223 results on '"myeloma cast nephropathy"'
Search Results
2. Kidney outcomes and prognostic factors of myeloma associated acute kidney injury in the contemporary era.
- Author
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Ratnayake, Chathri, Gibbs, Simon Douglas John, and Lee, Darren
- Subjects
- *
ACUTE kidney failure , *PROGNOSIS , *IMMUNOGLOBULIN light chains , *MULTIPLE myeloma , *ELECTRONIC health records - Abstract
Myeloma cast nephropathy (MCN) has historically been associated with poor kidney outcomes. We aimed to evaluate the kidney outcomes and identify prognostic factors of myeloma‐associated acute kidney injury (M‐AKI) in the contemporary era of anti‐plasma cell therapy. Patients who received anti‐myeloma therapy with M‐AKI (January 2012 to June 2020) from a single centre were identified from electronic medical records. Diagnosis of MCN was either biopsy confirmed (BC) or clinically suspected (CS), the latter defined as acute kidney injury with reduced estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and involved serum free light chains (iSFLC) >500 mg/L at diagnosis. Twenty‐six patients with M‐AKI were identified (BC: n = 13, CS: n = 13). Median eGFR at diagnosis was 12 (interquartile range 6–20) mL/min/1.73 m2. All six dialysis‐requiring patients achieved dialysis independence after 71 (43–208) days. The best‐achieved eGFR was 47 (32–67) mL/min/1.73 m2 after 120 (63–167) days post‐treatment, which was maintained at 47 (33–66) mL/min/1.73 m2 12 months post‐treatment. Patients with best‐achieved eGFR above the median were more likely to have achieved an iSFLC of <20 mg/L (above median group 62% versus below median group 0%; p <.001) and lower best post‐treatment iSFLC (20 (12–90) versus 67 (29–146) mg/L; p <.05). Best‐achieved iSFLC was a prognostic factor for superior eGFR following treatment for M‐AKI. Despite low eGFR at diagnosis, contemporary anti‐myeloma therapy can achieve significant recovery of kidney function. Summary at a glance: This retrospective single‐centre study of myeloma‐associated acute kidney injury identified that achieving a lower involved serum free light chain following contemporary anti‐plasma cell therapy is associated with superior kidney function despite low kidney function at diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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3. [Renal failure in multiple myeloma: Specific management issues].
- Author
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Try M and Harel S
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- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide therapeutic use, Dexamethasone therapeutic use, Immunoglobulin Light Chains, Kidney Transplantation, Lenalidomide therapeutic use, Prognosis, Renal Dialysis, Renal Insufficiency etiology, Renal Insufficiency therapy, Thalidomide therapeutic use, Uromodulin, Acute Kidney Injury etiology, Acute Kidney Injury therapy, Bortezomib therapeutic use, Multiple Myeloma therapy, Multiple Myeloma complications
- Abstract
Renal impairment is common during multiple myeloma and persistent reduction in kidney function strongly affects prognosis. Cast nephropathy, by monoclonal free light chains precipitation with uromodulin in renal tubules, is the main cause of acute kidney injury in multiple myeloma. Kidney biopsy, although not necessary for diagnosis, allows assessment of renal prognosis according to the extent of cast formation, tubular atrophy and interstitial fibrosis. Prevention and early diagnosis of acute kidney injury are essential to optimize management and avoid progression to chronic kidney disease. Rehydration, interruption of nephrotoxic treatments, correction of precipitating factors, anti-plasma cell chemotherapy can rapidly reduce the free light chains nephrotoxicity. The association of the proteasome inhibitor Bortezomib and high dose Dexamethasone is the reference treatment in newly diagnosed patients with renal impairment. Adding Cyclophosphamide or the immunomodulator Lenalidomide may improve the hematological response, but with a poorer tolerance. Use of anti-CD38 monoclonal antibodies is being evaluated in this population. Hemodialysis with high-flux or high-cut-off membranes, combined to chemotherapy, may improve renal function recovery. Management of multiple myeloma have to be adapted in patients with chronic kidney disease, dialysis or kidney transplantation. Because of improvement in global survival, kidney transplantation remains an option to consider in selected patients. Collaboration between hematologists and nephrologists is essential throughout the course of the disease., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
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- 2024
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4. Multiple myeloma and kidney disease
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Natalia Zarankiewicz, Katarzyna Kosz, Martyna Zielińska, Klaudia Remjasz, Aleksandra Kuchnicka, Julia Kuchnicka, Klaudia Sapuła, Jakub Aleksandrowicz, and Wojciech Siedlecki
- Subjects
multiple myeloma ,myeloma cast nephropathy ,bortezomib ,RANKL ,Education ,Sports ,GV557-1198.995 ,Medicine - Abstract
Abstract Background: Multiple myeloma is a clonal plasma cell neoplasm which affects 1% of all malignancies. In this article we reviewed epidemiology, symptoms with particular attention to renal failure and its manifestation in multiple myeloma (MM). Material and methods: This paper was based on medical articles collected in PubMed from 2001 to 2022, medical websites and books. The research has been done by looking through key words such as: „multiple myeloma”, „myeloma cast nephropathy”, „bortezomib”, „RANKL” Results: Multiple myeloma has indolent course and many patients present renal disorders at the moment of diagnosis. The use of novel therapies can reverse renal failure. Conclusions: Treatment of the patients with MM and kidney disease is challenging for health care professionals. Doctors have to adjust treatment to provide the best therapeutic effects.
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- 2022
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5. Monoclonal Immunoglobulin-Associated Renal Lesions in Patients with Newly Diagnosed Multiple Myeloma: A Report from a Single Center
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Lin ZS, Yu XJ, Zhang X, Wang SX, Cen XN, Zhou FD, and Zhao MH
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kidney biopsy ,multiple myeloma ,myeloma cast nephropathy ,monoclonal immunoglobulin ,prognosis. ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Zi-Shan Lin,1,* Xiao-Juan Yu,1,* Xu Zhang,1,2 Su-Xia Wang,1,2 Xi-Nan Cen,3 Fu-De Zhou,1 Ming-Hui Zhao1,4 1Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University, Renal Pathology Center, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, People’s Republic of China; 2Laboratory of Electron Microscopy, Pathological Centre, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Hematology, Peking University First Hospital, Beijing, People’s Republic of China; 4Peking-Tsinghua Center for Life Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fu-De ZhouRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University; Renal Pathology Center, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of ChinaTel +86-13501162527Fax +86-10-83575694Email zhoufude1801@vip.sina.comBackground: Monoclonal immunoglobulin-associated renal lesions in patients with newly diagnosed myeloma vary. We aimed to determine the pathological spectrum and analyze associated prognostic factors.Methods: Fifty-six patients with newly diagnosed multiple myeloma and biopsy-proven renal lesions were enrolled. Kidney biopsies were reanalyzed, and the baseline clinical characteristics, treatments and outcomes were recorded.Results: Fifty-one patients had monoclonal immunoglobulin-associated renal lesions, with myeloma cast nephropathy (MCN) being the most common pattern. We divided our cohort into pure MCN, MCN+ other pathologies and non-MCN. Patients with MCN had more severe renal injury than those with non-MCN. In our cohort, none of the patients with pure MCN or MCN + other pathologies presented with nephrotic syndrome. Patients with non-MCN had better renal and overall survival than those with pure MCN but similar survivals to those with MCN + other pathologies. Number of myeloma casts (HR 1.08, p = 0.012) was the only independent prognostic factor for renal survival. Male sex (HR: 3.64; p = 0.015) and number of casts (HR: 1.17; p = 0.001) were independent prognostic factors for overall survival.Conclusion: Patients with MCN had more severe renal injury than those with non-MCN. Patients with non-MCN had better renal and overall outcomes than those with pure MCN, but their outcomes were similar to those with MCN + other pathologies. The independent predictors of overall survival were male sex and number of myeloma casts.Keywords: kidney biopsy, multiple myeloma, myeloma cast nephropathy, monoclonal immunoglobulin, prognosis
- Published
- 2021
6. Myeloma Cast Nephropathy an Unusual Association with HIV Infection Presenting with Renal Dysfunction.
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Subramanian, Kalaivani S., Srinivas, Bheemanathi H., Parapelli, Divya, Basu, Debdatta, Sivanpillai, Priyamvada P., and Parameswaran, Sreejith
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- *
HIV infections , *BIOPSY , *KIDNEYS , *STAINS & staining (Microscopy) , *INTERSTITIAL nephritis , *IMMUNOHISTOCHEMISTRY , *KIDNEY diseases , *FLUORESCENT antibody technique , *MULTIPLE myeloma , *HEMATURIA , *ACUTE diseases , *DISEASE complications - Abstract
Human immunodeficiency virus (HIV)-associated renal disease is a pan-nephropathy, causing glomerular, tubular, and interstitial changes. The common lesion is the collapsing variant of focal segmental glomerulosclerosis. Multiple myeloma presenting as light chain cast nephropathy in an HIV-positive patient is very rare. A 45-year-old female retropositive patient presented with one episode of hematuria. Kidney biopsy was performed with a clinical diagnosis of acute interstitial nephritis (AIN). Biopsy showed unremarkable glomeruli. Tubules were dilated and showed a few periodic acid--Schiff (PAS) positive and many PAS-negative fractured casts surrounded by histiocytic reaction. Immunofluorescence and immunohistochemistry (IHC) showed lambda restriction by the casts. Bone marrow aspirate showed an increase in plasma cells, and the biopsy showed nodular aggregates of atypical plasma cells, which showed lambda restriction by IHC. PAS-negative fractured tubular casts are known to be associated with HIV-related nephropathy and need detailed hematological workup to rule out an associated plasma cell dyscrasia. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Morphological and immunohistochemical predictors of renal response to therapy patients with myeloma cast nephropathy and dialysis-dependent acute kidney injury
- Author
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I. G. Rekhtina, E. V. Kazarina, E. S. Stolyarevich, A. M. Kovrigina, V. N. Dvirnyk, S. M. Kulikov, and L. P. Mendeleeva
- Subjects
myeloma cast nephropathy ,acute kidney injury ,multiple myeloma ,nephrobiopathy morphometry ,Medicine - Abstract
Aim.Reveal morphological and immunohistochemical predictors of reversibility of dialysis-dependent acute kidney injury (AKI) in patients with myeloma cast nephropathy (MCN) based on the study of kidney biopsy. Materials and methods.Renal pathological findings were studied in 36 patients with MCN and dialysis-dependent stage 3 AKI (AKIN, 2012). The study of biopsy samples was performed by a semi-quantitative and quantitative analysis using computer morphometry. The expression of E-cadherin, vimentin and-smooth muscle actin was determined immunohistochemically in the tubular cells and interstitium. Induction therapy for 26 patients was carried out to bortezomib-based programs; in 10 patients other schemes were used. A comparative analysis of morphological changes in nephrobiopathy depending on the renal response was performed in patients with achieved hematologic remission. Results.Improved renal function was observed only in patients with hematologic response to therapy. There were no differences in the number of sclerotic glomeruli, protein casts, the area of inflammatory interstitial infiltration, and the degree of acute tubular damage in patients with and without renal response. In patients with renal response compared with patients without improving renal function, the area of interstitial fibrosis was less (24.9% and 45.9%, respectively;p=0.001), and the area of E-cadherin expression was larger (15.9% and 7.1%, respectively;p=0.006). Interstitial fibrosis of 40% or more and/or the area of expression of E-cadherin less than 10% of the area of tubulo-interstitium have an unfavorable prognostic value in achieving a renal response in MCN. Conclusion.If the interstitial fibrosis area is 40% or more and the expression area of E-cadherin is less than 10%, the probability of the absence of a renal response is 93.3% (OR=24.5) even when a hematological response to induction therapy is achieved. The number of protein casts, the prevalence of acute tubular damage and inflammatory interstitial infiltration have not prognostic value.
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- 2020
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8. Crystals, crystals everywhere but not a clue till late… Light chain crystalline proximal tubulopathy with concomitant myeloma cast nephropathy
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Smita Mary Matthai, Suceena Alexander, Shibu Jacob, Neelaveni Duhli, Vinoi George David, and Santosh Varughese
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acute kidney injury ,crystalline tubulopathy ,crystal storing histiocytosis ,crystalline podocytopathy ,fanconi's anemia ,light chain deposition disease ,myeloma kidney ,myeloma cast nephropathy ,Pathology ,RB1-214 ,Microbiology ,QR1-502 - Abstract
The renal diseases commonly associated with myeloma include primary amyloidosis, cast nephropathy, and light chain deposition disease. Less frequent forms of renal involvement encountered in the course of myeloma are crystalline and non-crystalline proximal tubulopathies, neoplastic plasma cell infiltration, and immunoglobulin crystallization in interstitial histiocytes and glomerular cells including podocytes. Light chain proximal tubulopathy (LCPT) caused by aggregation of non-crystalline and rarely crystalline deposits of monoclonal light chains in the cytoplasm of proximal tubular epithelial cells, accounts for less than 5% of monoclonal gammopathy-associated kidney diseases. We report the case of a 48-year-old Indian woman with multiple myeloma, who presented with acute kidney injury and nephrotic syndrome, in whom the renal biopsy revealed widespread crystalline inclusions in extraglomerular and glomerular compartments. We present illustrative light microscopic (LM) and diagnostic electron microscopic (EM) findings of this case which enabled a diagnosis of crystalline LCPT, crystal storing histiocytosis, and crystalline podocytopathy occurring synchronously with myeloma cast nephropathy. While documenting this unique juxtapositioning of multicompartmental paraproteinemic renal injury in multiple myeloma, diagnosed after EM analysis of the patient's renal biopsy, we discuss the pathogenetic pathways of this condition along with the clinical implications. Due to intrinsic structural properties of the crystals, they frequently escape detection by routine LM, necessitating EM analysis for their diagnosis. Given the prognostic implications of tubulopathies complicating myeloma, LCPT is a critically important diagnosis, highlighting the need for a comprehensive renal biopsy evaluation inclusive of EM for the practice of precision medicine in such scenarios.
- Published
- 2020
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9. Effect of high cut-off dialysis for acute kidney injury secondary to cast nephropathy in patients with multiple myeloma: a systematic review and meta-analysis.
- Author
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Tarragón, Blanca, Ye, Nan, Gallagher, Martin, Sen, Shaundeep, Portolés, Jose Maria, and Wang, Amanda Y
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- *
ACUTE kidney failure , *MULTIPLE myeloma , *HEMODIALYSIS , *RANDOM effects model , *TREATMENT effectiveness , *HYPERPHOSPHATEMIA , *DIABETIC nephropathies - Abstract
Background Acute kidney injury (AKI) caused by cast nephropathy is associated with increased morbidity and mortality among patients with multiple myeloma (MM). High cut-off haemodialysis (HCO-HD) has proven to be effective in the removal of serum light chains but the effect on clinical outcomes, especially renal recovery, remains uncertain. Methods A systematic review and meta-analysis were performed examining all randomized controlled trials (RCTs) and observational studies (OBSs) assessing the effect of HCO-HD on clinical outcomes of patients with MM complicated by cast nephropathy–induced severe AKI. The primary outcome was all-cause mortality at the end of the study. The secondary outcomes included all-cause mortality at 12 months, HD independence and serum kappa and lambda light chain reduction. Pooled analysis was performed using random effects models. Results We identified five studies, comprising two RCTs and three retrospective cohort studies, including 276 patients with a mean follow-up of 18.7 months. The majority of the studies were of suboptimal quality and underpowered. Compared with patients treated with conventional HD, HCO-HD was not associated with a survival benefit at 12 months {five studies, 276 patients, relative risk [RR] 1.02 [95% confidence interval (CI) 0.76–1.35], I 2 = 33.9%} or at the end of the studies at an average of 34 months [five studies, 276 patients, RR 1.32 (95% CI 0.71–2.45), I 2 = 62.0%]. There was no difference in HD independence at 90 days [two trials, 78 patients, RR 2.23 (95% CI 1.09–4.55)], 6 months [two studies, 188 patients, RR 1.19 (95% CI 0.68–2.06)] or 12 months [two studies, 188 patients, RR 1.14 (95% CI 0.58–2.26)]. Patients receiving HCO dialysis, however, had a greater reduction in serum kappa [two studies, 188 patients, weighted mean difference (WMD) 46.7 (95% CI 38.6–54.7), I 2 = 52.0%] and lambda [two studies, 188 patients, WMD 50.3 (95% CI 21.4–79.3), I 2 = 95.1%] light chain levels. Conclusion Current evidence from RCTs and OBSs suggests HCO dialysis is able to reduce serum free light chains but makes no significant improvement in all-cause mortality and renal outcomes compared with conventional HD for patients with myeloma cast nephropathy. However, there is a trend towards better renal outcomes with the use of HCO dialysis. The lack of long-term data and the small sample sizes of the included studies limit this analysis. Therefore further large-scale RCTs with longer follow-up are needed to assess the effect of HCO dialysis on clinical outcomes in patients with myeloma cast nephropathy. [ABSTRACT FROM AUTHOR]
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- 2021
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10. Combined proximal tubulopathy, crystal-storing histiocytosis, and cast nephropathy in a patient with light chain multiple myeloma
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Chung-Kuan Wu, An-Hang Yang, Hung-Chih Lai, and Bing-Shi Lin
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Multiple myeloma ,Light chain proximal tubulopathy ,Crystal-storing histiocytosis ,Myeloma cast nephropathy ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Abstract Background The diagnosis of myeloma, a plasma dyscrasia, often results from the workup of unexplained renal disease. Persistent renal failure in myeloma is commonly caused by tubular nephropathy due to circulating immunoglobulins and free light chains. Myeloma cast nephropathy is characterized by crystalline precipitates of monoclonal light chains within distal tubules. Immunoglobulin crystallization rarely occurs intracellularly, within proximal tubular cells (light chain proximal tubulopathy) and interstitial histiocytes (crystal-storing histiocytosis). We present a case report of a rare simultaneous occurrence of light chain proximal tubulopathy, crystal-storing histiocytosis, and myeloma cast nephropathy in a patient with κ light chain multiple myeloma. Case presentation A 48-years-old man presented with uremia and anemia. Laboratory examination revealed low levels of serum IgG, IgA, and IgM. Serum and urine immunofixation electrophoresis showed a free κ monoclonal band. Bone marrow aspiration and biopsy revealed hypercellularity with marked plasmacytosis. Light microscopy revealed eosinophilic cuboid- and rhomboid-shaped crystals in the cytoplasm of proximal tubular epithelial cells, diffuse large mononuclear and multinuclear cells in the interstitium, and obstructed distal tubules with cast and giant cell reaction. Immunohistochemical examination indicated intense staining for κ light chains within casts, histiocytes, and tubular epithelial cells. Electron microscopy revealed electro-dense cuboid-, rhomboid-, or needle-shaped crystalline inclusions in proximal tubular epithelial cells and interstitial histiocytes. According to these results, we confirmed that this patient with myeloma exhibited simultaneous light chain proximal tubulopathy, crystal-storing histiocytosis, and myeloma cast nephropathy, which were attributed to monoclonal κ light chains. In addition to dialysis, the patient received induction chemotherapy with a combination of bortezomib, cyclophosphamide, and dexamethasone, followed by maintenance therapy with thalidomide. However, the patient did not regain renal function even when less than 5% plasma cells were detected in the bone marrow. Conclusion To the best of our knowledge, this is the first report of simultaneous light chain proximal tubulopathy, crystal-storing histiocytosis, and myeloma cast nephropathy in κ light chain multiple myeloma.
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- 2017
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11. Treatment of acute kidney injury in cancer patients
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Pauline Braet, Giulia Vanessa Re Sartò, Marta Pirovano, Ben Sprangers, and Laura Cosmai
- Subjects
Transplantation ,Science & Technology ,CAR T-cells ,TUMOR LYSIS SYNDROME ,RENAL-FAILURE ,MICROANGIOPATHIC HEMOLYTIC-ANEMIA ,MYELOMA CAST NEPHROPATHY ,GLOMERULAR-DISEASES ,BORTEZOMIB ,Urology & Nephrology ,chemotherapy ,urologic and male genital diseases ,GLUCARPIDASE ,multiple myeloma ,acute kidney injury ,Nephrology ,MULTIPLE-MYELOMA ,cancer ,HIGH-CUTOFF HEMODIALYSIS ,Life Sciences & Biomedicine ,checkpoint inhibitors ,renal replacement therapy ,ONCO-NEPHROLOGY - Abstract
Acute kidney injury (AKI), either of pre-renal, renal or post-renal origin, is an important complication in cancer patients, resulting in worse prognosis, withdrawal from effective oncological treatments, longer hospitalizations and increased costs. The aim of this article is to provide a literature review of general and cause-specific treatment strategies for AKI, providing a helpful guide for clinical practice. We propose to classify AKI as patient-related, cancer-related and treatment-related in order to optimize therapeutic interventions. In the setting of patient-related causes, proper assessment of hydration status and avoidance of concomitant nephrotoxic medications is key. Cancer-related causes mainly encompass urinary compression/obstruction, direct tumoural kidney involvement and cancer-induced hypercalcaemia. Rapid recognition and specific treatment can potentially restore renal function. Finally, a pre-treatment comprehensive evaluation of risks and benefits of each treatment should always be performed to identify patients at high risk of treatment-related renal damage and allow the implementation of preventive measures without losing the potentialities of the oncological treatment. Considering the complexity of this field, a multidisciplinary approach is necessary with the goal of reducing the incidence of AKI in cancer patients and improving patient outcomes. The overriding research goal in this area is to gather higher quality data from international collaborative studies. ispartof: CLINICAL KIDNEY JOURNAL vol:15 issue:5 pages:873-884 ispartof: location:England status: published
- Published
- 2021
12. Monoclonal Immunoglobulin-Associated Renal Lesions in Patients with Newly Diagnosed Multiple Myeloma: A Report from a Single Center
- Author
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Xinan Cen, Xiaojuan Yu, Suxia Wang, Xu Zhang, Fu-de Zhou, Zi-Shan Lin, and Ming-Hui Zhao
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0301 basic medicine ,medicine.medical_specialty ,kidney biopsy ,Single Center ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,myeloma cast nephropathy ,medicine ,Myeloma cast nephropathy ,Pathological ,Multiple myeloma ,Original Research ,Kidney ,monoclonal immunoglobulin ,business.industry ,medicine.disease ,multiple myeloma ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,Cancer Management and Research ,030220 oncology & carcinogenesis ,Monoclonal ,Cohort ,prognosis ,business ,Nephrotic syndrome - Abstract
Zi-Shan Lin,1,* Xiao-Juan Yu,1,* Xu Zhang,1,2 Su-Xia Wang,1,2 Xi-Nan Cen,3 Fu-De Zhou,1 Ming-Hui Zhao1,4 1Renal Division, Department of Medicine, Peking University First Hospital; Institute of Nephrology, Peking University, Renal Pathology Center, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, People’s Republic of China; 2Laboratory of Electron Microscopy, Pathological Centre, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Hematology, Peking University First Hospital, Beijing, People’s Republic of China; 4Peking-Tsinghua Center for Life Sciences, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fu-De ZhouRenal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University; Renal Pathology Center, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of ChinaTel +86-13501162527Fax +86-10-83575694Email zhoufude1801@vip.sina.comBackground: Monoclonal immunoglobulin-associated renal lesions in patients with newly diagnosed myeloma vary. We aimed to determine the pathological spectrum and analyze associated prognostic factors.Methods: Fifty-six patients with newly diagnosed multiple myeloma and biopsy-proven renal lesions were enrolled. Kidney biopsies were reanalyzed, and the baseline clinical characteristics, treatments and outcomes were recorded.Results: Fifty-one patients had monoclonal immunoglobulin-associated renal lesions, with myeloma cast nephropathy (MCN) being the most common pattern. We divided our cohort into pure MCN, MCN+ other pathologies and non-MCN. Patients with MCN had more severe renal injury than those with non-MCN. In our cohort, none of the patients with pure MCN or MCN + other pathologies presented with nephrotic syndrome. Patients with non-MCN had better renal and overall survival than those with pure MCN but similar survivals to those with MCN + other pathologies. Number of myeloma casts (HR 1.08, p = 0.012) was the only independent prognostic factor for renal survival. Male sex (HR: 3.64; p = 0.015) and number of casts (HR: 1.17; p = 0.001) were independent prognostic factors for overall survival.Conclusion: Patients with MCN had more severe renal injury than those with non-MCN. Patients with non-MCN had better renal and overall outcomes than those with pure MCN, but their outcomes were similar to those with MCN + other pathologies. The independent predictors of overall survival were male sex and number of myeloma casts.Keywords: kidney biopsy, multiple myeloma, myeloma cast nephropathy, monoclonal immunoglobulin, prognosis
- Published
- 2021
13. Kidney Injury in Multiple Myeloma: A Kidney Biopsy Teaching Case
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Itunu Owoyemi, Sanjeev Sethi, and Nelson Leung
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Kidney ,Pathology ,medicine.medical_specialty ,business.industry ,Acute kidney injury ,Glomerulonephritis ,lcsh:Diseases of the genitourinary system. Urology ,lcsh:RC870-923 ,medicine.disease ,Immunoglobulin light chain ,myeloma ,medicine.anatomical_structure ,Nephrology ,kidney injury ,Internal Medicine ,medicine ,Myeloma cast nephropathy ,business ,Multiple myeloma ,Acute tubular necrosis ,Kidney Biopsy Teaching Case ,Kidney disease - Abstract
Myeloma-related kidney disease has several manifestations; the 2 most common histologic diagnoses are myeloma cast nephropathy and acute tubular necrosis. We describe a case of different kidney pathologies occurring concomitantly in a patient found to have immunoglobulin A κ multiple myeloma. A White woman in her 70s presented with an 8-month history of back pain and was found to have nephrotic-range proteinuria and acute kidney injury. Serum calcium level was 12.6 mg/dL. Kidney biopsy showed κ light chain only proliferative glomerulonephritis with monoclonal immunoglobulin deposits, crystalglobulinemia, light chain proximal tubulopathy with κ light chain deposits, mild tubular atrophy, and interstitial fibrosis. Free κ light chain ratio was >1,000 mg/dL and free κ light chain level was 4,670 mg/dL. Within a week following treatment of hypercalcemia and initiation of chemotherapy, her acute kidney injury and hypercalcemia resolved. This case highlights the many kidney manifestations of multiple myeloma and that prompt management targeting these manifestations, including hypercalcemia, can improve clinical outcomes.
- Published
- 2021
14. Effect of high cut-off dialysis for acute kidney injury secondary to cast nephropathy in patients with multiple myeloma: a systematic review and meta-analysis
- Author
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Amanda Y. Wang, Nan Ye, Martin Gallagher, José Portolés, Blanca Tarragón, and Shaundeep Sen
- Subjects
medicine.medical_specialty ,high-cutoff hemodialysis ,medicine.medical_treatment ,030232 urology & nephrology ,Nephropathy ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,systematic review ,Randomized controlled trial ,law ,Internal medicine ,myeloma cast nephropathy ,Medicine ,AcademicSubjects/MED00340 ,Myeloma cast nephropathy ,Dialysis ,Transplantation ,business.industry ,Retrospective cohort study ,Original Articles ,medicine.disease ,meta-analysis ,acute kidney injury ,Nephrology ,030220 oncology & carcinogenesis ,Relative risk ,Meta-analysis ,Hemodialysis ,business - Abstract
Background Acute kidney injury (AKI) caused by cast nephropathy is associated with increased morbidity and mortality among patients with multiple myeloma (MM). High cut-off haemodialysis (HCO-HD) has proven to be effective in the removal of serum light chains but the effect on clinical outcomes, especially renal recovery, remains uncertain. Methods A systematic review and meta-analysis were performed examining all randomized controlled trials (RCTs) and observational studies (OBSs) assessing the effect of HCO-HD on clinical outcomes of patients with MM complicated by cast nephropathy–induced severe AKI. The primary outcome was all-cause mortality at the end of the study. The secondary outcomes included all-cause mortality at 12 months, HD independence and serum kappa and lambda light chain reduction. Pooled analysis was performed using random effects models. Results We identified five studies, comprising two RCTs and three retrospective cohort studies, including 276 patients with a mean follow-up of 18.7 months. The majority of the studies were of suboptimal quality and underpowered. Compared with patients treated with conventional HD, HCO-HD was not associated with a survival benefit at 12 months {five studies, 276 patients, relative risk [RR] 1.02 [95% confidence interval (CI) 0.76–1.35], I2 = 33.9%} or at the end of the studies at an average of 34 months [five studies, 276 patients, RR 1.32 (95% CI 0.71–2.45), I2 = 62.0%]. There was no difference in HD independence at 90 days [two trials, 78 patients, RR 2.23 (95% CI 1.09–4.55)], 6 months [two studies, 188 patients, RR 1.19 (95% CI 0.68–2.06)] or 12 months [two studies, 188 patients, RR 1.14 (95% CI 0.58–2.26)]. Patients receiving HCO dialysis, however, had a greater reduction in serum kappa [two studies, 188 patients, weighted mean difference (WMD) 46.7 (95% CI 38.6–54.7), I2 = 52.0%] and lambda [two studies, 188 patients, WMD 50.3 (95% CI 21.4–79.3), I2 = 95.1%] light chain levels. Conclusion Current evidence from RCTs and OBSs suggests HCO dialysis is able to reduce serum free light chains but makes no significant improvement in all-cause mortality and renal outcomes compared with conventional HD for patients with myeloma cast nephropathy. However, there is a trend towards better renal outcomes with the use of HCO dialysis. The lack of long-term data and the small sample sizes of the included studies limit this analysis. Therefore further large-scale RCTs with longer follow-up are needed to assess the effect of HCO dialysis on clinical outcomes in patients with myeloma cast nephropathy.
- Published
- 2020
15. Morphological and immunohistochemical predictors of renal response to therapy patients with myeloma cast nephropathy and dialysis-dependent acute kidney injury
- Author
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E.V. Kazarina, L P Mendeleeva, Alla M. Kovrigina, V N Dvirnyk, Sergei M. Kulikov, Ekaterina S Stolyarevich, and I G Rekhtina
- Subjects
History ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,030232 urology & nephrology ,Urology ,Renal function ,lcsh:Medicine ,nephrobiopathy morphometry ,Kidney ,Bortezomib ,03 medical and health sciences ,0302 clinical medicine ,Renal Dialysis ,Biopsy ,myeloma cast nephropathy ,medicine ,Humans ,Myeloma cast nephropathy ,Multiple myeloma ,medicine.diagnostic_test ,business.industry ,lcsh:R ,Acute kidney injury ,General Medicine ,medicine.disease ,Hematologic Response ,multiple myeloma ,medicine.anatomical_structure ,acute kidney injury ,030220 oncology & carcinogenesis ,Family Practice ,business ,medicine.drug - Abstract
Reveal morphological and immunohistochemical predictors of reversibility of dialysis-dependent acute kidney injury (AKI) in patients with myeloma cast nephropathy (MCN) based on the study of kidney biopsy.Renal pathological findings were studied in 36 patients with MCN and dialysis-dependent stage 3 AKI (AKIN, 2012). The study of biopsy samples was performed by a semi-quantitative and quantitative analysis using computer morphometry. The expression of E-cadherin, vimentin and-smooth muscle actin was determined immunohistochemically in the tubular cells and interstitium. Induction therapy for 26 patients was carried out to bortezomib-based programs; in 10 patients other schemes were used. A comparative analysis of morphological changes in nephrobiopathy depending on the renal response was performed in patients with achieved hematologic remission.Improved renal function was observed only in patients with hematologic response to therapy. There were no differences in the number of sclerotic glomeruli, protein casts, the area of inflammatory interstitial infiltration, and the degree of acute tubular damage in patients with and without renal response. In patients with renal response compared with patients without improving renal function, the area of interstitial fibrosis was less (24.9% and 45.9%, respectively;p=0.001), and the area of E-cadherin expression was larger (15.9% and 7.1%, respectively;p=0.006). Interstitial fibrosis of 40% or more and/or the area of expression of E-cadherin less than 10% of the area of tubulo-interstitium have an unfavorable prognostic value in achieving a renal response in MCN.If the interstitial fibrosis area is 40% or more and the expression area of E-cadherin is less than 10%, the probability of the absence of a renal response is 93.3% (OR=24.5) even when a hematological response to induction therapy is achieved. The number of protein casts, the prevalence of acute tubular damage and inflammatory interstitial infiltration have not prognostic value.Цель.Выявить морфологические и иммуногистохимические предикторы обратимости острого повреждения почек (ОПП) с потребностью в диализе у больных миеломной каст-нефропатией (МКН) на основании исследования биоптатов почек. Материалы и методы.Проведено исследование нефробиоптатов 36 пациентов с МКН и 3-й стадией ОПП (AKIN, 2012) с потребностью в диализе. Исследование биоптатов выполняли полуколичественным и количественным методом с применением компьютерной морфометрии. Иммуногистохимически в клетках эпителия канальцев и интерстиции определяли экспрессию Е-кадгерина, виментина,-гладкомышечного актина. Индукционная терапия 26 пациентам проводилась по бортезомибсодержащим программам, 10 больным использовали другие схемы. Сравнительный анализ морфологических изменений в нефробиоптатах в зависимости от почечного ответа выполнен у пациентов с достигнутой гематологической ремиссией. Результаты.Улучшение функции почек наблюдалось только у пациентов с гематологическим ответом на терапию. Не выявлено различий в количестве склерозированных клубочков, белковых цилиндров, площади клеточной воспалительной инфильтрации, а также степени острого повреждения канальцев у пациентов с почечном ответом и без него. У больных с почечным ответом по сравнению с пациентами без улучшения функции почек площадь интерстициального фиброза меньше (соответственно 24,9 и 45,9%;р=0,001), а площадь экспрессии E-кадгерина больше (соответственно 15,9 и 7,1%;p=0,006). Фиброз интерстиция 40% и более и/или площадь экспрессии Е-кадгерина менее 10% от площади тубулоинтерстиция имеют неблагоприятное прогностическое значение в достижении почечного ответа при МКН. Заключение.При площади фиброза интерстиция 40% и более и площади экспрессии Е-кадгерина менее 10% вероятность отсутствия почечного ответа составляет 93,3% (отношение шансов 24,5) даже при достижении гематологического ответа на индукционную терапию. Количество белковых цилиндров, распространенность острого повреждения канальцев и воспалительной инфильтрации интерстиция не имеют прогностического значения.
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- 2020
16. Serum free light chain level at diagnosis in myeloma cast nephropathy—a multicentre study
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Paul Cockwell, Nelson Leung, Paul W. Sanders, Insara Jaffer Sathick, Punit Yadav, Mark Cook, and Elizabeth E. Brown
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Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,030232 urology & nephrology ,Urology ,030204 cardiovascular system & hematology ,Kidney ,Glomerulonephritis, Membranous ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Medical research ,0302 clinical medicine ,Serum free ,hemic and lymphatic diseases ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,Myeloma cast nephropathy ,Dialysis ,Multiple myeloma ,Aged ,Aged, 80 and over ,Creatinine ,business.industry ,Hematology ,Translational research ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,3. Good health ,Oncology ,chemistry ,Female ,Immunoglobulin Light Chains ,Multiple Myeloma ,business ,Light chain level ,Cohort study - Abstract
Myeloma cast nephropathy (MCN) is a common cause of severe renal impairment in multiple myeloma (MM). The level of free light chain (FLC) that causes MCN varies substantially and there is uncertainty about the threshold level that should be used to inform clinical practice. In a multicentre cohort study of 103 patients with a diagnosis of MM and biopsy-confirmed MCN made between 2002–2014, we report prospectively measured levels of serum FLC at diagnosis obtained using a single nephelometric assay (Freelite®) and we explore the relationship between serum FLC level at diagnosis with renal outcome and patient survival. Using a landmark approach, overall survival (OS) was compared between patients who achieved independence from dialysis compared to those who remained dialysis dependent at 3-month, 6-month, 9-month, and 12-month time points. The median serum FLC level at diagnosis was 7531 mg/L (range 107–114600). Serum creatinine was 535 μmol/L (range 168–2993) and eGFR 7 ml/min/1.73 m2 (range 1–34). Six patients (5.8%) had an FLC level P = 0.003), 6-months (P = 0.035) and 9-months (P = 0.014); there was no survival benefit observed beyond 12 months (P = 0.146). Serum FLC level at diagnosis was neither associated with renal function recovery nor with OS. This is the largest reported cohort of patients with biopsy-confirmed MCN and prospectively measured serum FLC levels. These results indicate that a serum monoclonal FLC > 500 mg/L should be considered the threshold level associated with the development of MCN.
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- 2020
17. Gerontolizing Nephrology: Spectrum of Histopathological Findings of Kidney Biopsy in the Elderly
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Shikha Khandelwal, Dhananjai Agarwal, Nisha Gaur, Pankaj Beniwal, Parvati Joshi, Vinay Malhotra, Manish Sharma, Sanjeev Sharma, and Shailendra Kumar Singh
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Nephrology ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,nephrotic syndrome ,Acute kidney injury ,India ,lcsh:Diseases of the genitourinary system. Urology ,lcsh:RC870-923 ,medicine.disease ,urologic and male genital diseases ,Gastroenterology ,Focal segmental glomerulosclerosis ,Elderly ,Membranous nephropathy ,renal biopsy ,Internal medicine ,Biopsy ,medicine ,Original Article ,Renal biopsy ,Myeloma cast nephropathy ,business ,Kidney disease - Abstract
Introduction: The spectrum of renal disorder in the elderly differs from the younger population. There is a paucity of literature regarding kidney biopsy in elderly. This study aims to highlight the clinical profile and histopathological spectrum of the elderly patient undergoing a renal biopsy. Materials and Methods: This retrospective study included all patients (age ≥60 years) undergoing native renal biopsies from January 2012 to December 2017. The clinical profile, laboratory parameters, and renal biopsy findings of these patients were recorded from the case files. Results: Out of 1656 renal biopsies performed during the study period, 230 (13.9%%) performed on the elderly were included. Mean age was 64.02 ± 7.87 years (Range: 60-87 years), and males were predominant (70.4%). The commonest indication for biopsy was nephrotic syndrome (NS) (49.6%) followed by Rapidly progressive renal failure (RPRF) (20.9%) and Acute Kidney Injury (AKI) (15.7%). The most frequent histological diagnosis was membranous nephropathy (15.2%) followed by amyloidosis (13.9%) and Focal Segmental Glomerulosclerosis (FSGS) (13.0%). The commonest cause of NS was MGN (29.8%) followed by FSGS (24.6%) and amyloidosis (22.8%). The commonest cause of nephritic syndrome was Diffuse Proliferative Glomerulonephritis (29.4%) and Membranoproliferative Glomerulonephritis (29.4%). Hypertensive nephrosclerosis (40.0%) and diabetic nephropathy (26.7%)) were the commonest histological diagnosis in the patients who underwent renal biopsy for clinical Chronic kidney disease. Crescentic GN (35.4%) and Myeloma cast nephropathy 14.6%) were the commonest cause of RPRF while Acute Tubular Necrosis (41.7%) was the commonest cause of AKI. None of the patients had major complications. Conclusion: Renal biopsy is safe in the elderly and provides a wealth of information with regards to the diagnosis and prognosis of renal disorder.
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- 2020
18. Crystals, crystals everywhere but not a clue till late… Light chain crystalline proximal tubulopathy with concomitant myeloma cast nephropathy
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Suceena Alexander, Vinoi George David, Shibu Jacob, Smita Mary Matthai, Santosh Varughese, and Neelaveni Duhli
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Microbiology (medical) ,Pathology ,medicine.medical_specialty ,lcsh:QR1-502 ,Light chain deposition disease ,lcsh:Microbiology ,Pathology and Forensic Medicine ,Nephropathy ,myeloma cast nephropathy ,myeloma kidney ,lcsh:Pathology ,Medicine ,Myeloma cast nephropathy ,Multiple myeloma ,Kidney ,crystalline podocytopathy ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,Acute kidney injury ,light chain deposition disease ,General Medicine ,fanconi's anemia ,medicine.disease ,crystalline tubulopathy ,medicine.anatomical_structure ,acute kidney injury ,Renal biopsy ,crystal storing histiocytosis ,business ,lcsh:RB1-214 - Abstract
The renal diseases commonly associated with myeloma include primary amyloidosis, cast nephropathy, and light chain deposition disease. Less frequent forms of renal involvement encountered in the course of myeloma are crystalline and non-crystalline proximal tubulopathies, neoplastic plasma cell infiltration, and immunoglobulin crystallization in interstitial histiocytes and glomerular cells including podocytes. Light chain proximal tubulopathy (LCPT) caused by aggregation of non-crystalline and rarely crystalline deposits of monoclonal light chains in the cytoplasm of proximal tubular epithelial cells, accounts for less than 5% of monoclonal gammopathy-associated kidney diseases. We report the case of a 48-year-old Indian woman with multiple myeloma, who presented with acute kidney injury and nephrotic syndrome, in whom the renal biopsy revealed widespread crystalline inclusions in extraglomerular and glomerular compartments. We present illustrative light microscopic (LM) and diagnostic electron microscopic (EM) findings of this case which enabled a diagnosis of crystalline LCPT, crystal storing histiocytosis, and crystalline podocytopathy occurring synchronously with myeloma cast nephropathy. While documenting this unique juxtapositioning of multicompartmental paraproteinemic renal injury in multiple myeloma, diagnosed after EM analysis of the patient's renal biopsy, we discuss the pathogenetic pathways of this condition along with the clinical implications. Due to intrinsic structural properties of the crystals, they frequently escape detection by routine LM, necessitating EM analysis for their diagnosis. Given the prognostic implications of tubulopathies complicating myeloma, LCPT is a critically important diagnosis, highlighting the need for a comprehensive renal biopsy evaluation inclusive of EM for the practice of precision medicine in such scenarios.
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- 2020
19. Pauci-immune Crescentic Glomerulonephritis Due to MGRS Crystalline Nephropathy
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Benjamin Delprete, Samih H. Nasr, Faizan Babar, Shailendra Sharma, Amira Elshikh, and Samar M. Said
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Pathology ,medicine.medical_specialty ,business.industry ,Amyloidosis ,030232 urology & nephrology ,Glomerulonephritis ,030204 cardiovascular system & hematology ,medicine.disease ,Nephropathy ,03 medical and health sciences ,0302 clinical medicine ,Nephrology ,Glomerulopathy ,Pauci-immune ,Monoclonal ,medicine ,medicine.symptom ,business ,Myeloma cast nephropathy ,Nephrology Round ,Kidney disease - Abstract
There are several known mechanisms by which monoclonal Igs (MIg) or their subunits can cause kidney disease: (i) deposition in 1 or more kidney compartments, resulting in distinct clinicopathologic lesions, such as Ig-related amyloidosis, monoclonal Ig deposition disease, and a variety of glomerulonephritides, including cryoglobulinemic glomerulonephritis type I and II, immunotactoid glomerulonephritis, and proliferative glomerulonephritis with monoclonal immunoglobulin deposits; (ii) precipitation in tubular lumina (e.g., myeloma cast nephropathy); (iii) activation of the alternative pathway of complement (e.g., C3 glomerulopathy associated with monoclonal gammopathy, thrombotic microangiopathy associated with monoclonal gammopathy); (iv) cytokine activation (e.g., POEMS syndrome); and (v) crystallization in the renal vasculature (e.g., crystalglobulin-induced nephropathy).1, 2 Here, we describe an unusual case of monoclonal gammopathy of renal significance (MGRS)–associated crystalline nephropathy that does not conform to any of the previously described patterns of kidney involvement by monoclonal gammopathy.
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- 2019
20. Fabry disease associated with multiple myeloma: a case report
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Hirobumi Tokuyama, Yoichi Oshima, Hiroshi Itoh, Hiroyuki Yamakawa, Tomoaki Itoh, Akinori Hashiguchi, Shu Wakino, Keika Adachi, Hitoshi Sakuraba, and Tadayasu Togawa
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Nephrology ,Male ,medicine.medical_specialty ,Case Report ,Kidney ,Gastroenterology ,Bortezomib ,Internal medicine ,medicine ,Humans ,Myeloma cast nephropathy ,Multiple myeloma ,Aged ,medicine.diagnostic_test ,business.industry ,Acute kidney injury ,General Medicine ,medicine.disease ,Fabry disease ,Renal pathology ,Fabry Disease ,Female ,Kidney Diseases ,Renal biopsy ,business ,Multiple Myeloma ,medicine.drug - Abstract
Fabry disease (FD) is an X-linked genetic lysosomal disorder caused by alpha-galactosidase A (GLA) deficiency. Multiple myeloma (MM) predominately affects older adults, which ranks as the second commonest hematological malignancy. Their overlap has rarely been reported. We present a case of the coexistence of FD and MM in a patient. We report the case of a 68-year-old woman who was referred to our hospital for the evaluation of thoracic spine tumor with bone destruction. On admission, her serum creatinine (Cr) level was elevated to 12.70 mg/dL from the baseline value of 0.91 mg/dL. Bone marrow aspiration revealed MM. Renal biopsy showed myeloma cast nephropathy, which was the primary cause of acute kidney injury. Renal pathology also showed podocyte swelling and tubule myeloid bodies in a mosaic pattern compatible with female FD. Consequently, the patient was diagnosed as FD based on the germ line mutation in GLA. The patient was treated with bortezomib and dexamethasone therapy, which significantly improved the renal function. This is the second case demonstrating a potential pathogenic relationship between FD and MM. Since FD is one of the few genetic diseases for which there are therapeutic agents with fewer side effects, diagnostic value of FD is high. If an MM patient has multiple organ abnormalities or any familial history, the physician should suspect FD.
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- 2021
21. Prognostic value of kidney biopsy in myeloma cast nephropathy: a retrospective study of 70 patients.
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Ecotière, Laure, Thierry, Antoine, Debiais-Delpech, Céline, Chevret, Sylvie, Javaugue, Vincent, Desport, Estelle, Belmouaz, Simohamed, Quellard, Nathalie, Kaaki, Sihem, Goujon, Jean Michel, Fermand, Jean-Paul, Touchard, Guy, and Bridoux, Frank
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KIDNEY diseases , *RENAL biopsy , *MYELOMA proteins , *GLOMERULAR filtration rate , *RETROSPECTIVE studies - Abstract
Background. Light chain myeloma cast nephropathy (MCN) is the major cause of renal failure in multiple myeloma and strongly impacts patient survival. The role of kidney biopsy in the management of MCN is unclear. Methods. Renal pathological findings were retrospectively studied in 70 patients with multiple myeloma and MCN. Patients were categorized according to the achievement or not of renal response, as defined by estimated glomerular filtration rate (eGFR) =30 mL/min/1.73 m² and/or dialysis independence at 3 months. Results. Thirty-two patients (46%) achieved a renal response. In the whole study population, the following parameters differed significantly between patients with and without renal response, respectively: baseline median eGFR (13.3 versus 9.3 mL/min/1.73 m², P = 0.017), Acute Kidney Injury Network Stage 3 (68.8 versus 92.1%, P = 0.019), haematological response rate (94 versus 34%, P < 0.0001), median percentage of free light chain (FLC) reduction at Day 21 (92 versus 24%, P = 0.006) and median number of casts/10 fields (14 versus 25, P = 0.005). The extent of interstitial fibrosis and tubular atrophy was similar. In multivariate analysis, only FLC reduction at Day 21 was significantly associated with renal response. However, when considering only the subgroup of haematological responders, both median number of casts [odds ratio (OR) = 0.93, 95% confidence interval (95% CI): 0.88-0.98, P = 0.01] and extent of tubular atrophy (OR = 0.03, 95% CI: 0.00-0.52, P = 0.02) were independent predictors of renal response. Conclusions. In MCN, the presence of numerous casts and diffuse tubular atrophy is associated with poor renal prognosis. These data suggest that additional strategies to reduce FLC burden should be considered in patients with extensive cast formation. [ABSTRACT FROM AUTHOR]
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- 2016
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22. Clinical and prognostic differences among patients with light chain deposition disease, myeloma cast nephropathy and both.
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Zand, Ladan, Nasr, Samih H., Gertz, Morie A, Dispenzieri, Angela, Lacy, Martha Q., Buadi, Francis K., Kumar, Shaji, Kyle, Robert A., Fervenza, Fernando C., Sethi, Sanjeev, Dingli, David, Rajkumar, S. Vincent, Kapoor, Prashant, McCurdy, Arleigh, and Leung, Nelson
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KIDNEY disease diagnosis , *RENAL biopsy , *HEALTH outcome assessment , *MULTIPLE myeloma , *CREATININE , *IMMUNOFLUORESCENCE - Abstract
In some patients with light chain deposition disease (LCDD) there is also evidence of myeloma cast nephropathy (MCN) on renal biopsy. The purpose of this study was to evaluate the renal and survival outcome of patients with concomitant diagnosis of MCN and LCDD to LCDD and MCN alone. Eighty seven patients were identified and divided into LCDD (n= 45), MCN (n= 29), and LCDD+ MCN (n= 13). Patients with LCDD+ MCN had a worse overall survival (OS) compared to patients with LCDD (p= 0.03), but similar to patients with MCN (p= 0.4). Death-censored renal survival was no different amongst the groups. Presenting with acute renal failure at time of renal biopsy (HR 7.2,p= 0.0002) was an independent poor renal prognostic factor while older age (HR 1.06,p= 0.0002), presence of osteolytic lesions (HR 4.4,p< 0.0001), and requirement for dialysis or creatinine ≥ 5 mg/dL (HR 3.2,p= 0.0006) at time of renal biopsy were independent poor prognostic factors for OS. [ABSTRACT FROM AUTHOR]
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- 2015
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23. Myeloma Cast Nephropathy and COVID-19: A Case Report of Multiple Myeloma Presenting as Acute Kidney Injury in the Setting of COVID-19
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Selvaraj Muthusamy, Sindhura Bobba, Karishma Popli, Ayesha Akram, and Waqas Memon
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medicine.medical_specialty ,030204 cardiovascular system & hematology ,diagnosis of multiple myeloma ,Gastroenterology ,Nephropathy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Myeloma cast nephropathy ,Blood urea nitrogen ,Multiple myeloma ,Creatinine ,nephrotic syndrome ,Beta-2 microglobulin ,business.industry ,covid 19 ,General Engineering ,Acute kidney injury ,Hematology ,medicine.disease ,Bence Jones protein ,multiple myeloma ,chemistry ,Nephrology ,dialysis ,business ,030217 neurology & neurosurgery - Abstract
A 64-year-old African American male presented to the emergency department with subacute low back pain for two weeks and decreased urine output. He was found to have a potassium level of 9.2 mmol/L and was uremic with a creatinine level of 28.5 mg/dL and blood urea nitrogen (BUN) level of 201 mg/dL. He also tested positive for COVID-19. He was then started on continuous renal replacement therapy (CRRT). His urinalysis showed more than 500 mg/dL of protein. A workup for multiple myeloma was also conducted, and urine protein electrophoresis test was positive for free lambda light chains with a level of 17,700 mg/L and free kappa light chains with a level of 88.30 mg/L with a kappa:lambda free light chain ratio of 0.005. Additionally, serum Bence Jones protein level was elevated at 240 mg/dL, and serum beta-2 microglobulin level was elevated at 31.41 mg/L. An immunoglobulin (Ig) panel also showed low levels of IgG, IgA, and IgM. Kidney biopsy for this patient showed definite cast nephropathy and minimal chronic changes, with only one of over 20 glomeruli sclerosed and minimal interstitial deposits. The patient was started on chemotherapy with cyclophosphamide, bortezomib, and dexamethasone (CyBorD).
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- 2021
24. POS-212 THE ROLE OF KIDNEY BIOPSY AND QUANTITATIVE COMPUTER MORPHOMETRY IN PREDICTING THE REVERSIBILITY OF DIALYSIS-DEPEND ACUTE KIDNEY INJURY DUE TO MYELOMA CAST NEPHROPATHY
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A. Kovrigina, L. Mendeleeva, S. Kulikov, E. Stolyarevich, V. Dvirnyk, E. Kazarina, and I. Rekhtina
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Kidney ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Acute kidney injury ,Urology ,medicine.disease ,Diseases of the genitourinary system. Urology ,medicine.anatomical_structure ,Nephrology ,Biopsy ,medicine ,RC870-923 ,business ,Myeloma cast nephropathy ,Dialysis - Published
- 2021
25. Significance of urinary albumin excretion in patients with cast nephropathy
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Kenmei Takaichi, Masahiro Kawada, Aya Imafuku, Eiko Hasegawa, Atsushi Wake, Kenichi Ohashi, Hiroki Mizuno, Noriko Hayami, Ryo Nakagawa, Rikako Hiramatsu, Tatsuya Suwabe, Keiichi Sumida, Akinari Sekine, Masayuki Yamanouchi, Takeshi Fujii, Naoki Sawa, Junichi Hoshino, and Yoshifumi Ubara
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Male ,medicine.medical_specialty ,030232 urology & nephrology ,Serum albumin ,lymphoplasmacytic lymphoma/Waldenström macroglobulinemia ,Gastroenterology ,Nephropathy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,renal biopsy ,Internal medicine ,myeloma cast nephropathy ,Medicine ,Albuminuria ,Humans ,Myeloma cast nephropathy ,Multiple myeloma ,Serum Albumin ,Aged ,Retrospective Studies ,amyloidosis ,Creatinine ,medicine.diagnostic_test ,biology ,business.industry ,Amyloidosis ,Waldenstrom macroglobulinemia ,General Medicine ,Middle Aged ,medicine.disease ,multiple myeloma ,chemistry ,Nephrology ,biology.protein ,urinary albumin excretion ,Female ,Kidney Diseases ,Renal biopsy ,business ,Biomarkers ,Research Article - Abstract
Background This study was performed to determine whether the urinary albumin excretion rate (%UAE) could distinguish myeloma cast nephropathy (MCN) without glomerular amyloid deposition from MCN with glomerular amyloid deposition. Materials and methods We retrospectively reviewed clinicopathological data on 16 patients with MCN diagnosed by renal biopsy at Toranomon Hospital from 2004 to 2014. Results A total of 10 patients had pure MCN without glomerular amyloid deposition (group 1), and 6 patients had MCN with glomerular amyloid deposition (group 2). In all 10 patients from group 1, the underlying disease was multiple myeloma (MM), while 4 patients had MM, and 2 patients had lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia (LPL/WM) in group 2. Total protein did not show a significant difference between the two groups, but serum albumin was significantly higher in group 1 than group 2 (p = 0.0101). Serum-adjusted calcium did not show a significant difference between the groups, while serum creatinine (Cre) was significantly higher in group 1 than group 2 (p = 0.0343). Although urinary protein excretion did not differ significantly between the groups, the %UAE was significantly lower in group 1 than group 2 (p = 0.00198). In group 2, 3 of the 4 patients with MM died within 15 months of diagnosis, but the 2 patients with LPL/WM are alive after 32 months. In group 1, only 1 patient died (of unknown causes) within 15 months after diagnosis. Conclusion In patients with MCN, %UAE may be a useful marker for the detection of coexistence of glomerular lesions, such as amyloidosis, which are associated with a poor outcome.
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- 2019
26. High cutoff versus high-flux haemodialysis for myeloma cast nephropathy in patients receiving bortezomib-based chemotherapy (EuLITE): a phase 2 randomised controlled trial
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Julie Wessels, Markus Storr, Colin A. Hutchison, Mark Jesky, Paul Cockwell, Lesley Fifer, Christopher G. Winearls, Nils Heyne, Veronica Moroz, Julian D. Gillmore, Arthur R. Bradwell, Mark Cook, and Katja Weisel
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Adult ,Male ,medicine.medical_specialty ,Adolescent ,medicine.medical_treatment ,Population ,law.invention ,Nephropathy ,Bortezomib ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Renal Dialysis ,law ,Internal medicine ,medicine ,Humans ,education ,Myeloma cast nephropathy ,Dialysis ,Multiple myeloma ,Aged ,education.field_of_study ,business.industry ,Acute kidney injury ,Hematology ,Middle Aged ,medicine.disease ,Survival Analysis ,030220 oncology & carcinogenesis ,Female ,Immunoglobulin Light Chains ,Kidney Diseases ,Multiple Myeloma ,business ,030215 immunology ,medicine.drug - Abstract
Summary Background In multiple myeloma, severe acute kidney injury due to myeloma cast nephropathy is caused by pathogenic free light chain immunoglobulin in serum. High cutoff haemodialysis (HCO-HD) can remove large quantities of free light chain immunoglobulin from serum, but its effect on clinical outcomes is uncertain. We therefore aimed to assess whether HCO-HD could increase the frequency of renal recovery in patients with de novo multiple myeloma, severe acute kidney injury, and myeloma cast nephropathy relative to treatment with standard high-flux haemodialysis (HF-HD). Methods In this open-label, phase 2, multicentre, randomised controlled trial (EuLITE), we recruited patients with newly diagnosed multiple myeloma, biopsy-confirmed cast nephropathy, and acute kidney injury that required dialysis from renal services in 16 hospitals in the UK and Germany. Patients were randomly assigned (1:1) by random number generation to receive intensive HCO-HD (in sessions lasting 6–8 h) or standard HF-HD and they were stratified by age and centre. Patients and the medical staff treating them were not masked to treatment allocation. Patients received bortezomib, doxorubicin, and dexamethasone chemotherapy, and were then followed up for 2 years. The primary outcome was independence from dialysis at 90 days after random allocation to groups, which was assessed in an intention-to-treat population. The trial has completed follow-up, and is registered at the ISRCTN registry, number ISRCTN45967602. Findings Between June 7, 2008, and Sept 18, 2013, we recruited 90 patients, of whom 43 (48%) were randomly assigned to receive HCO-HD and 47 (52%) were randomly assigned to receive HF-HD. All 90 patients were included in the analysis of the primary outcome. One (2%) patient from the HF-HD group withdrew consent before receiving treatment. During treatment, nine (21%) patients from the HCO-HD group and two (4%) patients in the HF-HD group discontinued trial treatment. After 90 days, 24 (56%) patients in the HCO-HD group and 24 (51%) patients in the HF-HD group were independent from dialysis (relative risk 1·09, 95% CI 0·74–1·61; p=0·81). During the 2-year follow-up, 98 serious adverse events were reported in the HCO-HD group and 82 serious adverse events were reported in the HF-HD group. The most common serious adverse events were infections and adverse events related to the cardiovascular and thrombotic and musculoskeletal systems. During the first 90 days, 26 infections were reported in the HCO-HD group and 13 infections were reported in the HF-HD group, including 14 lung infections in the HCO-HD group and three lung infections in the HF-HD group. Interpretation In this phase 2 study, HCO-HD did not improve clinical outcomes for patients with de novo multiple myeloma and myeloma cast nephropathy who required haemodialysis for acute kidney injury and who received a bortezomib-based chemotherapy regimen relative to those receiving HF-HD. These results do not support proceeding to a phase 3 study for HCO-HD in these patients. Funding Gambro, Janssen, and Binding Site.
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- 2019
27. Massive generalized crystal-storing histiocytosis associated with extracellular crystalline nephropathy: clinical, immunohistochemical, and ultrastructural studies of a unique disorder and review of the literature
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Fransico Galeano-Valle, F. J. Díaz-Crespo, R. Melero-Martín, Jorge Del-Toro-Cervera, Pablo Demelo-Rodríguez, and J. E. Apaza-Chávez
- Subjects
Male ,Nephrology ,medicine.medical_specialty ,Pathology ,Fulminant ,030232 urology & nephrology ,Case Report ,030204 cardiovascular system & hematology ,Kidney ,Nephropathy ,03 medical and health sciences ,Fatal Outcome ,0302 clinical medicine ,Bone Marrow ,Internal medicine ,medicine ,Humans ,Myeloma cast nephropathy ,Histiocyte ,Aged ,business.industry ,General Medicine ,medicine.disease ,Histiocytosis ,medicine.anatomical_structure ,Liver ,Kidney Diseases ,Bone marrow ,business ,Spleen - Abstract
Crystal-storing histiocytosis (CSH) is a rare disorder characterized by the accumulation of nonneoplastic histiocytes containing intracytoplasmic crystallized immunoglobulins. In most cases, there is an associated underlying lymphoplasmacytic neoplasm expressing Ig kappa light chain. About 131 cases of CSH have been identified. There is a localized and a generalized form of CSH and it can involve several sites including bone marrow, lungs, lymph nodes, liver, spleen, gastrointestinal tract, and kidney. Generalized CSH is less frequent and involves multiple organs and tends to have a worst prognosis than localized CSH. Around 20 cases of renal involvement in CSH have been reported so far. Paraprotein-induced crystalline nephropathy can be divided into two categories based on whether the crystals in the kidney are intracellular (including light chain proximal tubulopathy with crystals and CSH) or extracellular (including the crystalline variant of myeloma cast nephropathy and crystalglobulin-induced nephropathy). The former tends to present with slowly worsening kidney dysfunction and generally has a good prognosis, whereas the latter usually presents with rapidly progressive renal failure and is associated with poor renal outcome. We present a case of generalized CSH associated with extracellular crystalline nephropathy with a fulminant and fatal clinical course. Kappa light-chain crystals were found exclusively extracellularly within the tubular lumen, not within the tubular epithelial cells nor the histiocytes, and the massive presence of those precipitates led to the acute renal failure. Consequently, we review the renal involvement in CSH in the literature and discuss the unique mechanism of renal injury in this case.
- Published
- 2019
28. Missed monoclonal disease manifesting in early post-renal transplant period
- Author
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Navin Pattanashetti, Kusum Joshi, Harbir Singh Kohli, Raja Ramachandran, K.L. Gupta, and Nirbhai Singh
- Subjects
medicine.medical_specialty ,medicine.medical_treatment ,030232 urology & nephrology ,Case Report ,030204 cardiovascular system & hematology ,lcsh:RC870-923 ,Diabetic nephropathy ,03 medical and health sciences ,0302 clinical medicine ,Tubulopathy ,medicine ,Myeloma cast nephropathy ,Cast nephropathy ,Dialysis ,Kidney transplantation ,Acute tubular necrosis ,business.industry ,medicine.disease ,lcsh:Diseases of the genitourinary system. Urology ,Surgery ,multiple myeloma ,tubulopathy ,Nephrology ,Azotemia ,Hemodialysis ,business - Abstract
A 63-year-old diabetic gentleman with microvascular complications presented with advanced azotemia and anemia. He was stabilized with blood transfusion and hemodialysis. With the probable diagnosis of diabetic nephropathy-related end-stage renal disease, he underwent kidney transplantation. He had delayed graft function. Graft biopsy done on the 2nd postoperative day showed acute tubular necrosis. Graft biopsy repeated after 2 weeks for persistent graft dysfunction showed myeloma cast nephropathy (MCN) and light chain proximal tubulopathy. Work-up for multiple myeloma was positive. He was started on plasmapheresis and chemotherapy. However, he suffered sudden cardiac death during dialysis after 1 week. The presence of MCN in the early graft biopsy implies that it must have been the cause for his native kidney failure. Thus, renal failure in a diabetic should not always be presumed to be due to diabetic nephropathy, and kidney biopsy should be done in diabetics with atypical features.
- Published
- 2019
29. Interstitial fibrosis and outcomes of acute kidney injury in myeloma cast nephropathy
- Author
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E.V. Kazarina, I G Rekhtina, L P Mendeleeva, V.N. Dvirnyk, S.M. Kulikov, E.S. Stolyarevich, and Artificial Organs
- Subjects
Pathology ,medicine.medical_specialty ,Nephrology ,business.industry ,Acute kidney injury ,medicine ,Interstitial fibrosis ,medicine.disease ,Myeloma cast nephropathy ,business - Published
- 2019
30. Infrared chemical imaging for histologic interpretation of renal tissue
- Author
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Rohit Bhargava, Kianoush Falahkheirkhah, Jennifer Pfister, Sergey V. Brodsky, Anjali A. Satoskar, Ghazal Azarfar, Meera Gopu, Georgina Cheng, and Tibor Nadasdy
- Subjects
Chemical imaging ,Modern medicine ,Pathology ,medicine.medical_specialty ,business.industry ,Amyloidosis ,medicine.disease ,Immunoglobulin light chain ,Diabetic nephropathy ,Monoclonal ,medicine ,business ,Myeloma cast nephropathy ,Kidney disease - Abstract
Applications of machine learning in pathology is an active research area in modern medicine. Here, we presented a classifier for label-free renal histopathology. Three frequently encountered categories of monoclonal gammopathy-associated kidney disease were studied, which included light chain amyloidosis, monoclonal light chain disease deposition (MIDD) and myeloma cast nephropathy. Biopsies with diabetic nephropathy and normal baseline transplant biopsies were used as control. The samples are imaged using a FTIR hyperspectral microscope. More than three million infrared spectra are adopted for the training and evaluation of the computational model. The model recognizes the pixels associated with the glomerulus, and diagnoses the disease based on infrared absorption features.
- Published
- 2021
31. Hypophosphatemic osteomalacia: an unusual clinical presentation of multiple myeloma.
- Author
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Reyskens, M., Sleurs, K., Verresen, L., Janssen, M., Berg, J., and Geusens, P.
- Subjects
- *
BACKACHE , *BIOPSY , *BLOOD testing , *BONE fractures , *MULTIPLE myeloma , *OSTEOMALACIA , *HYPOPHOSPHATEMIA - Abstract
An unusual case of a 75-year-old man is presented who had multiple stress fractures due to adult onset hypophosphatemic osteomalacia, which was the result of Fanconi syndrome, with light chain cast proximal tubulopathy due to multiple myeloma. A 75-year-old man presented with diffuse pain and muscle weakness. He had multiple stress fractures, low serum phosphate, decreased renal tubular reabsorption of phosphate, and normal PTH and FGF23, indicating adult onset hypophosphatemic osteomalacia. Phosphate supplements with calcitriol resulted in clinical recovery and healing of stress fractures. Because of proteinuria, a renal biopsy was performed that revealed Fanconi syndrome with light chain cast proximal tubulopathy and light kappa chains were found in serum and urine. A bone biopsy confirmed the diagnosis of multiple myeloma, and treatment with chemotherapy resulted in cytological and clinical recovery. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
32. Crystals in myeloma cast nephropathy
- Author
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Zi-Shan Lin and Fu-De Zhou
- Subjects
Pathology ,medicine.medical_specialty ,business.industry ,medicine ,Humans ,Immunoglobulin Light Chains ,Kidney Diseases ,General Medicine ,Acute Kidney Injury ,Multiple Myeloma ,Myeloma cast nephropathy ,medicine.disease ,business - Published
- 2021
33. Perspectives From an Onconephrology Interest Group: Conference Report
- Author
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Abhijat Kitchlu, Paul Tam, Christopher T. Chan, Sheron Latcha, Nelson Leung, and Sheldon Chen
- Subjects
Oncology ,medicine.medical_specialty ,030232 urology & nephrology ,lcsh:RC870-923 ,Nephrotoxicity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,myeloma cast nephropathy ,medicine ,cancer ,In patient ,Myeloma cast nephropathy ,onconephrology ,business.industry ,nephrotoxicity ,Cancer ,Conference Report ,medicine.disease ,lcsh:Diseases of the genitourinary system. Urology ,Nephrology ,030220 oncology & carcinogenesis ,Interest group ,Onconephrology ,business ,chronic kidney disease - Abstract
Onconephrology is a new and evolving field that deals with kidney complications in patients with cancer as well as the management of cancer in patients with preexisting kidney disease. With increasing numbers of patients with cancer with kidney-related complications, the field has garnered increased attention. Thus, an annual Greater Toronto Area Onconephrology Interest Group symposium was held in May 2019. The objective of the meeting was to demonstrate the junctures between oncology and nephrology by highlighting recent data regarding (1) kidney impairment in solid organ malignancies, (2) management and treatment of kidney cancer, (3) kidney impairment in hematologic malignancies, (4) malignancy and kidney transplantation, and (5) hyponatremia in patients with cancer.Through a structured presentation, the group explored key topics discussed at a Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on Onconephrology. Expert opinions, clinical trial findings, and publication summaries were used to illustrate patient and treatment-related considerations in onconephrology.Kidney complications in patients with cancer are a central theme in onconephrology. An estimated 12% to 25% of patients with solid organ malignancies have chronic kidney disease (CKD), although in certain cancers, the prevalence of CKD is higher. Kidney impairment is also a common complication of some hematologic malignancies. The incidence of renal failure in patients with multiple myeloma is estimated at 18% to 56% and light chain cast nephropathy is seen in approximately 30% of these patients. In addition, there appears to be a bidirectional relationship between kidney cancer and CKD, with some data sets suggesting the risk increases as kidney function declines. Cancer is also of concern in patients with preexisting kidney disease. Kidney transplant recipients have a greater risk of cancer and a higher risk of cancer-related mortality. Kidney complications have also been associated with novel cancer therapies, such as immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy. An estimated 2% to 4% of patients initiating an immune checkpoint inhibitor may develop nephrotoxicity, whereas up to 40% of patients on CAR T-cell therapy experience cytokine release syndrome (CRS). Tumor lysis syndrome and electrolyte abnormalities, such as hyponatremia, have also been reported with CAR T-cell therapy. While the incidence and prevalence of hyponatremia vary depending on the cancer type and serum sodium cutoff point, hyponatremia may be seen in up to 46% of patients hospitalized in cancer centers.Onconephrology is a developing field and the themes arising from this meeting indicate a need for greater collaboration between oncologists and nephrologists. Educational symposia and onconephrology fellowship programs may allow for improved cancer care for patients with kidney disease.L’onconéphrologie est une discipline nouvelle et évolutive qui traite les complications néphrologiques chez les patients atteints d’un cancer et assure également la prise en charge des patients soignés en oncologie et présentant une néphropathie préexistante. En mai 2019, le symposium duPar le biais d’une présentation structurée, le groupe s’est penché sur les thèmes clés discutés lors d’une conférence du KDIGO portant sur les controverses entourant l’onconéphrologie. Des avis d’experts, des résultats d’essais cliniques et des résumés de publications ont été utilisés pour illustrer les considérations relatives aux patients et aux traitements en onconéphrologie.Les complications rénales chez les patients atteints d’un cancer sont un thème central en onconéphrologie. On estime qu’environ 12 à 25 % des patients présentant une tumeur maligne touchant les organes solides sont atteints d’insuffisance rénale chronique (IRC), bien que la prévalence soit plus élevée pour certains cancers. L’insuffisance rénale s’avère également une complication fréquente de certaines tumeurs malignes hématologiques. L’incidence d’IRC chez les patients atteints d’un myélome multiple est estimée entre 18 et 56 %, et une néphropathie à chaînes légères est observée chez environ 30 % de ces patients. En outre, on soupçonne l’existence d’une relation bidirectionnelle entre le cancer du rein et l’IRC; certains ensembles de données suggérant que le risque de cancer augmenterait avec le déclin de la fonction rénale. Le cancer est également préoccupant chez les patients ayant une néphropathie préexistante. Enfin, les receveurs d’une greffe rénale présentent un risque accru de cancer et de mortalité liée au cancer. Les complications rénales ont également été associées aux nouveaux traitements contre le cancer, comme les inhibiteurs du point de contrôle immunitaire et les thérapies par cellules CAR T. Environ 2 à 4 % des patients amorçant un traitement par les inhibiteurs de point de contrôle immunitaire pourraient développer une néphrotoxicité, alors que jusqu’à 40 % des patients traités par cellules CAR T présentent un syndrome de relargage de cytokines. Le syndrome de lyse tumorale et des anomalies électrolytiques, comme l’hyponatrémie, ont également été observés chez les patients traités par cellules CAR T. Bien que l’incidence et la prévalence de l’hyponatrémie varient en fonction du type de cancer et du seuil de natrémie, jusqu’à 46 % des patients hospitalisés dans les centres de cancérologie présentent cette anomalie.L’onconéphrologie est une discipline en évolution et les thèmes issus de ce colloque soulignent le besoin d’accroître la collaboration entre les oncologues et les néphrologues. Les symposiums à caractère éducatif et les programmes de bourses d’études et de recherche en onconéphrologie pourraient améliorer les soins oncologiques prodigués aux patients atteints de néphropathies.
- Published
- 2020
34. Molecular mechanisms of crystal-related kidney inflammation and injury. Implications for cholesterol embolism, crystalline nephropathies and kidney stone disease.
- Author
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Mulay, Shrikant R., Evan, Andrew, and Anders, Hans-Joachim
- Subjects
- *
KIDNEY injuries , *INFLAMMATION , *ATHEROEMBOLISM , *KIDNEY stones , *CRYSTALS , *SILICOSIS , *ASBESTOSIS - Abstract
Crystals are particles of endogenous inorganic or organic composition that can trigger kidney injury when deposited or formed inside the kidney. While decades of research have focused on the molecular mechanisms of solute supersaturation and crystal formation, the pathomechanisms of crystal-induced renal inflammation remain largely unknown. The recent discovery of the intracellular NLRP3 inflammasome as a pattern recognition platform that translates crystal uptake into innate immune activation via secretion of IL-1β and IL-18 revised the pathogenesis of gout, silicosis, asbestosis, atherosclerosis and other crystal-related disorders. As a proof of concept, the NLRP3 inflammasome was now shown to trigger inflammation and acute kidney injury (AKI) in oxalate nephropathy. It seems likely that this and potentially other innate immunity mechanisms drive crystalline nephropathies (CNs) that are associated with crystals of calcium phosphate, uric acid, cysteine, adenine, certain drugs or contrast media, and potentially of myoglobin during rhabdomyolysis and of light chains in myeloma. Here, we discuss the proven and potential mechanisms of renal inflammation and kidney injury in crystal-related kidney disorders. In addition, we list topics for further research in that field. This perspective may also provide novel therapeutic options that can help to avoid progressive tissue remodeling and chronic kidney disease in patients with kidney stone disease or other CNs. [ABSTRACT FROM PUBLISHER]
- Published
- 2014
- Full Text
- View/download PDF
35. Myeloma cast nephropathy with diffuse amyloid casts without systemic amyloidosis: two cases report
- Author
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Ming-Hui Zhao, Fu-de Zhou, Zi-Shan Lin, Xiaojuan Yu, Suxia Wang, Zi-hao Yong, and Xinan Cen
- Subjects
Nephrology ,Male ,medicine.medical_specialty ,Pathology ,Amyloid ,Multiple cast nephropathy ,030232 urology & nephrology ,Case Report ,030204 cardiovascular system & hematology ,lcsh:RC870-923 ,Light chain deposition disease ,03 medical and health sciences ,0302 clinical medicine ,Multiple myeloma ,Internal medicine ,medicine ,Humans ,Myeloma cast nephropathy ,Kidney ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,Middle Aged ,lcsh:Diseases of the genitourinary system. Urology ,medicine.disease ,medicine.anatomical_structure ,Kidney Diseases ,Renal biopsy ,business - Abstract
Background Multiple myeloma (MM) is a plasma-cell derived hematologic malignant disease. The malignant proliferating plasma cells secrete massive monoclonal immunoglobulins which lead to various pathologic types of renal injury. Myeloma cast nephropathy (MCN) is the most common histopathologic lesion with the worst renal prognosis. Rarely, the free light chains in the protein casts can form amyloid fibrils. Here, we reported two rare cases of MCN with diffuse amyloid casts. Case presentation Case 1: A 54-year-old Chinese man presented with a 4-year history of multiple myeloma, proteinuria and hematuria. He had monoclonal IgAλ plus free λ spike in both serum and urine. He had been on chemotherapy for 4 years and maintained normal serum creatinine until 11 months ago. Then, his renal function deteriorated and he went on hemodialysis 4 months before admission. Renal biopsy showed diffuse amyloid casts in the tubular lumens, without any obvious amyloid deposits in other kidney compartments or signs of extra-renal amyloidosis. The amyloid fibrils formed around mononuclear cells which were CD68 negative. According to the morphology and location, these mononuclear cells were considered as tubular epithelial cells. The patient was maintained on chemotherapy and hemodialysis. He died 8 months after renal biopsy. Case 2: A 58-year-old Chinese man presented with a one-and-a-half-year history of proteinuria and slowly rising serum creatinine. He had monoclonal IgDλ spike in both serum and urine. Amyloid casts were observed in the tubular lumens and mononuclear cells could be identified in the center of some casts. There were no amyloid deposits in other kidney compartments and no sign of systemic amyloidosis. The patient also had fine granular deposits along the tubular basement membrane with λ linear staining along tubular basement membrane suggesting light chain deposition disease. He was treated with bortezomib-based chemotherapy followed by lenalidomide-based chemotherapy and achieved very good partial remission (VGPR). After 27 months of follow-up, the patient still showed no signs of systemic amyloidosis. Conclusions These 2 cases of MCN with diffuse amyloid casts have different histopathologic characteristics from the usual myeloma casts and tubular epithelial cells might play important roles in the pathogenesis.
- Published
- 2020
36. Myeloma Cast Nephropathy Manifesting only as Unexplained Acute Renal Failure
- Author
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Sarojini Raman and Nikunj Kishore Rout
- Subjects
medicine.medical_specialty ,business.industry ,Clinical Biochemistry ,Urology ,General Medicine ,medicine.disease ,multiple myeloma ,acute kidney injury ,Medicine ,business ,Myeloma cast nephropathy ,immunoglobulin kappa chain - Abstract
Multiple Myeloma (MM) is characterised by clonal B cell proliferation affecting elderly age group and involving various organ systems namely haematological, renal and skeletal system. Kidney may be affected in 50% of cases of MM. Though, Chronic Kidney Disease (CKD) is usually seen in MM, unusual presentations have been documented. The present case is of a 50-year-old female with complains of breathlessness and vague generalised symptoms. Routine tests showed blood urea level of 90 mg/dL and serum creatinine of 8.3 mg/dL. Further investigations revealed 24 hour protein level 48.5 gm/day, Erythrocyte Sedimentation Rate (ESR)-126 mm/1st hour, cast nephropathy in renal biopsy. Immunohistochemical (IHC) study on renal biopsy revealed kappa light chain deposits in tubules, raised kappa light chains (3280.00 mg/L) in serum Free Light Chain (FLC) assay and MM in bone marrow aspiration and biopsy study. So, MM should be considered in differential diagnosis in elderly patients presenting with acute severe renal failure.
- Published
- 2020
37. Randomized Trial Comparing Double Versus Triple Bortezomib-Based Regimen in Patients With Multiple Myeloma and Acute Kidney Injury Due to Cast Nephropathy
- Author
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Vincent Audard, Felipe Suarez, Salomon Manier, Frank Bridoux, Cécile Vigneau, Karine Augeul-Meunier, Bertrand Joly, Lionel Karlin, Bertrand Arnulf, Mourad Tiab, Nina Arakelyan-Laboure, Sophie Caillard, Alexandre Karras, Nolwenn Rabot, K. Belhadj, Bruno Royer, Margaret Macro, Sébastien Delbès, Jean Paul Fermand, P. Gobert, Damien Roos-Weil, Brigitte Pegourie, Emilie Cornec-Le Gall, Sylvie Chevret, Nicolas Blin, Denis Caillot, and Arnaud Jaccard
- Subjects
0301 basic medicine ,Male ,Cancer Research ,medicine.medical_specialty ,Urology ,Dexamethasone ,Nephropathy ,law.invention ,Bortezomib ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,In patient ,Myeloma cast nephropathy ,Cyclophosphamide ,Multiple myeloma ,Aged ,business.industry ,Acute kidney injury ,Acute Kidney Injury ,Middle Aged ,medicine.disease ,Regimen ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,business ,Multiple Myeloma ,medicine.drug - Abstract
PURPOSE We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and acute kidney injury (AKI) without need for dialysis. METHODS After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light chains (sFLCs) after 3 cycles, chemotherapy was reinforced with either cyclophosphamide (BD group) or thalidomide (C-BD group). RESULTS Ninety-two patients were enrolled in each group. At random assignment, characteristics of the 2 groups were similar, including median age (68 years) and serum creatinine level (305.5 and 273.5 µmol/L in BD and C-BD group, respectively). At 3 months, renal response rate (primary end point) was not different (41 v 47 responders in the BD and C-BD groups, respectively; relative risk [RR], 0.87; P = .46). Very good partial response (free light chain reduction ≥ 90%) or more was achieved in 36 and 47 patients, respectively (RR, 0.76; P = .10). After 1 cycle of chemotherapy, 69 in the BD group and 67 patients in the C-BD group had achieved sFLC level ≤ 500 mg/L. Serious adverse events were recorded in 30 and 40 patients, respectively. At 12 months, 19 patients had died (9 in the BD group v 10 in the C-BD group), including 10 (6 in the BD group and 4 in the C-BD group) from myeloma progression and 3 (0 in the BD group and 3 in the C-BD group) from infection. Within median follow-up of 27 months, 43 and 42 patients switched to new therapy, respectively. Overall, 50 patients (24 in the BD group and 26 in the C-BD group) had died. CONCLUSION This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial CN not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty.
- Published
- 2020
38. The interesting picture: simultaneous occurrence of myeloma cast nephropathy, light chain deposition disease and light chain proximal tubulopathy in a patient with multiple myeloma
- Author
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Ming-Hui Zhao, Fu-De Zhou, Zi-Shan Lin, Xiao-Juan Yu, and Suxia Wang
- Subjects
Nephrology ,Pathology ,medicine.medical_specialty ,business.industry ,Immunoglobulin light chain ,medicine.disease ,Light chain deposition disease ,Proximal Tubulopathy ,Internal medicine ,medicine ,Humans ,Immunoglobulin Light Chains ,Kidney Diseases ,Myeloma cast nephropathy ,business ,Multiple Myeloma ,Multiple myeloma - Published
- 2020
39. Myeloma light chain cast nephropathy, a review
- Author
-
Insara Jaffer Sathick, Nelson Leung, and Maria Eleni Drosou
- Subjects
Nephrology ,Oncology ,medicine.medical_specialty ,030232 urology & nephrology ,Context (language use) ,030204 cardiovascular system & hematology ,Plasma cell ,Kidney ,Nephropathy ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine ,Animals ,Humans ,Myeloma cast nephropathy ,Multiple myeloma ,business.industry ,Acute Kidney Injury ,Prognosis ,medicine.disease ,Review article ,medicine.anatomical_structure ,Immunoglobulin Light Chains ,Multiple Myeloma ,business - Abstract
Multiple Myeloma is a plasma cell proliferative disorder that commonly involves the kidney. Renal impairment is a serious complication during the course of the disease that is associated with increased morbidity and mortality. Light chain cast nephropathy is the predominant pattern of renal injury in Multiple Myeloma. This review article focuses on the pathophysiology and diagnostic approach of myeloma cast nephropathy. The management of precipitating factors as well as anti-plasma cell treatment modalities in the context of renal impairment are also discussed.
- Published
- 2018
40. Classification et prise en charge thérapeutique des gammapathies monoclonales de signification rénale
- Author
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I. Bouteau, Jean-Paul Fermand, J. Diolez, Nathalie Quellard, A. Colombo, Arnaud Jaccard, Jean-Michel Goujon, L. Ecotière, Frank Bridoux, Christophe Sirac, Vincent Javaugue, Estelle Desport, Guy Touchard, Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre National de Référence Maladies Rares: Amylose al et Autres Maladies à Dépôts d'Immunoglobulines Monoclonales, Université de Poitiers, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Electro-Fluido-Dynamique (EFD ), Département Fluides, Thermique et Combustion (FTC), Institut Pprime (PPRIME), ENSMA-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-ENSMA-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Institut Pprime (PPRIME), ENSMA-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-ENSMA-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], and CHU Limoges
- Subjects
Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,030232 urology & nephrology ,Clone (cell biology) ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] ,Internal Medicine ,medicine ,Myeloma cast nephropathy ,ComputingMilieux_MISCELLANEOUS ,Kidney transplantation ,Kidney ,Chemotherapy ,biology ,Gastroenterology ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,medicine.disease ,3. Good health ,medicine.anatomical_structure ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,Monoclonal ,biology.protein ,Antibody ,Complication - Abstract
Two categories of renal disorders associated with monoclonal gammopathies are to be distinguished, according to the characteristics of the underlying B-cell clone. The first group of renal diseases always occurs in the setting of high tumor mass with production of large amounts of monoclonal immunoglobulins. The main complication is the so-called myeloma cast nephropathy, which almost invariably complicates high tumor mass myeloma. The second group includes all renal disorders caused by a monoclonal immunoglobulin secreted by a nonmalignant B-cell clone, and currently referred as a "monoclonal gammopathy of renal significance (MGRS)". This term was introduced to distinguish monoclonal gammopathies that are responsible for the development of kidney damage from those that are truly benign. The spectrum of renal diseases in MGRS is wide and its classification relies on the localization of renal lesions, either glomerular or tubular, and on the pattern of ultrastructural organization of immunoglobulin deposits. Physicochemical characteristics of the pathogenic monoclonal immunoglobulin are probably involved in their propensity to deposit or precipitate in the kidney, as illustrated by the high rate of recurrence of each specific type after kidney transplantation. Early diagnosis and efficient chemotherapy targeting the causal B-cell clone are mandatory to improve renal prognosis and patient survival.
- Published
- 2018
41. Rapid reduction of extremely high kappa free light chains in a patient with myeloma cast nephropathy
- Author
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Christine L.H. Snozek, Theresa Kinard, and Jill Adamski
- Subjects
Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Urology ,Renal function ,Hematology ,General Medicine ,030204 cardiovascular system & hematology ,medicine.disease ,Nephropathy ,Tumor lysis syndrome ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,medicine ,Adjuvant therapy ,Hemodialysis ,business ,Myeloma cast nephropathy ,Multiple myeloma - Abstract
This report describes a patient with light chain myeloma and acute renal injury. Serum kappa free light chain (FLC) was extremely elevated, >33,000 mg/dL. Treatment with therapeutic plasma exchange (TPE) started day 2 for biopsy-confirmed cast nephropathy. Bortezomib-containing chemotherapy was initiated on day 5, and hemodialysis for tumor lysis syndrome on day 7. TPE alone decreased kappa FLC >70% by day 5, indicating direct FLC removal was successful in this patient. A total of 25 TPE procedures were performed in a 31-day hospitalization. Hemodialysis was discontinued after 3 months, and the patient's renal function and kappa FLC remain stable. Although the use of TPE for FLC removal is controversial, recent evidence supports its use as adjuvant therapy for acute renal injury secondary to myeloma cast nephropathy. TPE can be effective for rapidly reducing FLC; however, several TPE procedures might be required to reduce the risk of hemodialysis dependency.
- Published
- 2018
42. A Case of Myeloma Kidney With Glomerular C3 Deposition
- Author
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Asif Khan, Khine Lam, Suzanne El-Sayegh, and Elie El-Charabaty
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Acute kidney injury ,Urology ,medicine.disease ,Nephropathy ,Glomerulopathy ,Membranoproliferative glomerulonephritis ,Plasma Cell Myeloma ,medicine ,Renal biopsy ,business ,Myeloma cast nephropathy ,Kidney disease - Abstract
C3 glomerulonephritis is rare form of membranoproliferative glomerulonephritis, which result from defects in complement regulatory proteins that promotes excessive activation of alternative complement pathway. Kidney disease is common complication of multiple myeloma (MM). Most common renal complications in MM include monoclonal immunoglobulin deposition disease and myeloma cast nephropathy. Moreover, monoclonal Ig, through the interference of the complement alternative pathway has been shown to play the synergistic role towards renal damage. Up to 50% of MM patients present with renal impairment at diagnosis, 20% may present with acute kidney injury, and 10% require dialysis. In this case report, we describe a case of MM with cast nephropathy with mesangial staining for C3 consistent with C3 glomerulopathy, and the interrelationship between MM and complement system that leads to C3 glomerulopathy. A 59-year-old Trinidadian man with a 2-year history of hypertension presented with nausea and vomiting associated with a generalized weakness for the past 3 months. On admission laboratory results were as follows: hemoglobin 9.1 g/dL; red blood count 1.45 × 10 6 /mm 3 ; white cell count 3.2 × 10 3 /mm 3 ; platelet count 94 × 10 3 /mm 3 ; blood urea nitrogen 94 mg/dL; serum creatinine 10.47 mg/dL (patient had a baseline creatinine level of 1.5 mg/dL); sodium 130 mEq/L; potassium 6.2 mEq/L; bicarbonate 14 mEq/L; total protein 7.0 g/dL; albumin 2.9 g/dL; alkaline phosphatase 57; AST and ALT normal; lipase 102 U/L; urine analysis showed 2+ protein with bland urine sediment and microscopic hematuria (3 - 6/HPF). 24-h urine protein was 2 g/day. Renal ultrasound was significant for a right renal 0.6 cm cyst. The patient was admitted to ICU and was subsequently hemodialyzed due to worsening hyperkalemia and acute kidney injury. Serologies were notable for positive anti-dsDNA antibody and low levels of C3 (46 mg/dL) with normal C4 were observed. Immunofixation by electrophoresis showed free lambda. Serum plasma electrophoresis showed two M-spikes: Lambda light chains and IgG Lambda. A renal biopsy was performed and cast nephropathy was identified with mesangial staining for C3. Bone marrow biopsy was performed and showed CD 56-positive plasma cell myeloma. Patient was treated with Velcade, Cytoxan, and dexamethasone. The patient was subsequently discharged on chemotherapy and intermittent hemodialysis therapy. Follow-up evaluation of the alternative complement pathway showed normal activity level. This case illustrated myeloma kidney associated with mesangial C3 deposition in glomeruli and C3 hypocomplementemia. Our hypothesis is that in monoclonal gammopathy induced C3 glomerulopathy; paraprotein itself is acting as a trigger that excessively activates and dysregulates the AC pathway systemically. Thus, it is highly feasible to tailor the treatment to reduce the amount of paraproteins in C3 glomerulopathy associated with myeloma kidney, as opposed to conventional treatment for C3 glomerulopathy such as plasma exchange, rituximab/eculizumab, etc. Recognizing of the association between C3 GN and MM is important because it can be used as potential marker for hematological malignancy as well as the potential effective treatment for C3 G associated MM. World J Nephrol Urol. 2018;7(3-4):73-77 doi: https://doi.org/10.14740/wjnu359w
- Published
- 2018
43. Early use of PEPA dialyzer for light chains removal and for the recovery from myeloma cast nephropathy: A case report
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Gabriele Donati, Fulvia Zappulo, Elena Zamagni, Anna Laura Croci Chiocchini, Giorgia Comai, and Gaetano La Manna
- Subjects
medicine.medical_specialty ,Chemotherapy ,business.industry ,Bortezomib ,medicine.medical_treatment ,030232 urology & nephrology ,Urology ,Acute kidney injury ,Hematology ,030204 cardiovascular system & hematology ,medicine.disease ,Extracorporeal ,03 medical and health sciences ,0302 clinical medicine ,Nephrology ,Medicine ,Hemodialysis ,business ,Myeloma cast nephropathy ,Dialysis ,Multiple myeloma ,medicine.drug - Abstract
Chemotherapy and extracorporeal treatment reduce serum free light chains (FLCs) allowing the recovery of acute kidney injury (AKI) caused by myeloma cast nephropathy (MCN). We report the first case of recovery from AKI in a patient with MCN who underwent the removal of FLCs using the PEPA filter, with an undisclosed cut-off, combined with chemotherapy for multiple myeloma (MM).
- Published
- 2019
44. Coexistent amyloid fibrils in a patient with combined light chain deposition disease and light chain cast nephropathy
- Author
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Urmila Anandh, Anusha Patrick, and Alok Sharma
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Pathology ,medicine.medical_specialty ,030232 urology & nephrology ,Case Report ,030230 surgery ,Immunoglobulin light chain ,lcsh:RC870-923 ,Light chain deposition disease ,Nephropathy ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Myeloma cast nephropathy ,Amyloid fibrils ,medicine.diagnostic_test ,business.industry ,Amyloidosis ,light chain deposition disease ,medicine.disease ,lcsh:Diseases of the genitourinary system. Urology ,Nephrology ,Monoclonal ,cast nephropathy ,Renal biopsy ,business ,Monoclonal Immunoglobulin Deposition Disease - Abstract
Monoclonal secretion of light chains can affect the kidney with varied morphologic manifestations. Myeloma cast nephropathy, proximal tubulopathies, monoclonal immunoglobulin deposition disease, amyloidosis, and tubulointerstitial nephritis are often noted in the renal biopsy of these patients. Most often the histopathological manifestations affect only one compartment of the nephron (tubules, capillaries, glomerulus). Case reports of a combination of cast nephropathy and monoclonal light chain deposition disease are also reported in literature. Here we report an unusual case of coexisting cast nephropathy, light chain deposition disease, and deposition of amyloid fibrils in the biopsy of a lady with monoclonal kappa light chain excretion.
- Published
- 2019
45. AKI in Multiple Myeloma: Paraproteins, Metabolic Disturbances, and Drug Toxicity
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Mamta Shah and Mark A. Perazella
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Paraproteinemia ,medicine.medical_specialty ,business.industry ,030232 urology & nephrology ,Acute kidney injury ,030204 cardiovascular system & hematology ,urologic and male genital diseases ,medicine.disease ,Gastroenterology ,Light chain deposition disease ,Nephrotoxicity ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Paraproteins ,business ,Complication ,Myeloma cast nephropathy ,Multiple myeloma - Abstract
Acute kidney injury (AKI) is a frequent complication of multiple myeloma and is due predominantly to paraprotein-mediated nephrotoxicity. AKI occurs in myeloma patients due to a number of causes, including prerenal azotemia, metabolic nephrotoxicity from hypercalcemia and tumor lysis syndrome, proximal tubular injury, cast nephropathy, and drug-related nephrotoxicity. Importantly, AKI may develop in patients with known multiple myeloma or as an initial manifestation of this monoclonal disease. Diagnostic work-up includes the demonstration of monoclonal proteins, the search for the underlying B-cell clone, and a kidney biopsy, in many instances. Myeloma management involves treatment with chemotherapeutic agents to rapidly lower light chain levels, along with supportive measures that optimize volume status, correct metabolic disturbances, reduce proteinuria, and minimize nephrotoxin exposure. Extracorporeal therapies, such as plasma exchange and high-cutoff hemodialysis, have been employed, but their utility remain uncertain. The presence of AKI in myeloma patients appears to be associated with a higher mortality. Partial and full renal recovery are associated with better survival.
- Published
- 2017
46. Clinicopathologic Predictors of Reversibility Dialysis Dependent Acute Kidney Injury in Patients with Myeloma Cast Nephropathy
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Irina G. Rekhtina, Evgeniia V. Kazarina, Larisa P. Mendeleeva, Alla M. Kovrigina, Ekaterina S Stolyarevich, V N Dvirnyk, Valeriy G. Savchenko, and Sergei M. Kulikov
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Immunology ,Urology ,Acute kidney injury ,Lumen (anatomy) ,Renal function ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Hematologic Response ,medicine ,Renal biopsy ,Myeloma cast nephropathy ,business ,Dialysis ,Multiple myeloma - Abstract
Introduction: Myeloma cast nephropathy (MCN) is a main cause of acute kidney injury (AKI) at multiple myeloma (MM) onset. Wherein 5-9% of newly diagnosed MM patients are dialysis dependent. The introduction of novel agents has provided the achievement of rapid and deep hematologic response in most patients. However, the renal response in patients on dialysis is only 38-62.5%. The predictors of AKI reversibility in patients with MCN remain not enough studied. Aim: to determine clinical, morphological and immunohistochemical predictors of reversibility dialysis dependent AKI in patients with MCN. Materials and methods: 36 patients aged 38 to 74 years (median age=57 years) with newly diagnosed MM and dialysis dependent AKI stage 3 (AKIN, 2012) due to MCN were enrolled into the study from January 2006 till November 2019. The diagnosis of MM, hematologic and renal response were established according to the 2016 IMWG criteria. MCN was determined by renal biopsy performed prior to induction therapy. The assessment degree of acute tubular injury, tubular atrophy and interstitial fibrosis (IF/TA) were semi-quantitatively evaluated. The number of sclerotic glomerular were calculated manually. The median number of casts was defined by all casts in a section divided by number of fields observed (х100). Additionally, square of interstitial fibrosis, interstitial inflammation, expression of Immunohistochemical markers (E-cadherin, α-smooth muscle actin (α-SMA), vimentin) were measured by computerized quantitatively image analysis using the digital module Leica (Germany). The time from diagnosis of AKI to start of induction therapy did not exceed 3 months. Bortezomib based first line treatment regimen was used in 25 (69%) of patients; 9 (25%) patients received chemotherapeutic agents only, 2 (6%) dead before a start of induction therapy. Statistical software package SAS 9.4 was applied for calculations. Overall survival according to renal response was compared by using Kaplan-Meier curves. Also frequency, logistic, discriminant and ROC analysis were used. All estimates are shown with a 95%CI. Results: Hematologic partial response or better occurred in 19 (53%) of patients, median of 32 (13-129) days. Renal response - in 14 (39%). In 3 (8%) cases renal function improved after correction of dehydration before start of antimyeloma therapy, in the remaining 11 (30%) patients only when hematologic response was achieved (p = 0.001). The frequency of renal response was depending on start of antimyeloma therapy before and after 4 weeks from diagnosis of AKI and was 83% and 17%, respectively (p Patients with hematologic response were divided into two groups (Tab.). The main pathological findings associated with renal response were less frequent mild to severe IF/TA in patients with and without renal response (moderate 45% vs 75%, respectively, p=0.008), less area of interstitial fibrosis (24.9% vs 44.7%, respectively, p=0.001), percentage of proximal tubules with save epithelial phenotype and less area of expression E-cadherin at interstitium (15.9% vs 7.1%, respectively, p=0.006). The median number of casts per field was the same (6.4 and 6.3, p=0.64) as well as the percentage of tubule lumen obstruction by casts (13.6% and 15.1%, p=0.81). Statistically significant correlation between the expression area of E-cadherin and interstitial fibrosis was not found (Rs= -0.335, p= 0.065). Therefore, a combination of these factors can be used to predict renal response in the onset of AKI due to MCN (area under the ROC curve is 0.84). The prognostic model and logical rule allow to define groups of renal outcomes (Fig.). If expression area of E-cadherin is less than 10% and / or area of interstitial fibrosis is more than 40% of the interstitium, a renal response is unlikely (OR = 24.5) and will not be achieved in almost 90% of cases, despite hematological response. Discussion. Reversibility of dialysis dependent AKI due to MCN rely on the achievement of hematological response and the time from diagnosis of AKI to start of antimyeloma therapy. There are predictors of renal response of these patients determined by the severity of morphological changes: degree of IFTA, quantitative area of interstitial fibrosis and E-cadherin expression. Disclosures No relevant conflicts of interest to declare.
- Published
- 2020
47. Screening and Differential Diagnosis of Renal Light Chain-Associated Diseases.
- Author
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Gerth, Jens, Sachse, Anja, Busch, Martin, Illner, Nico, Muegge, Lars-Olof, Gröne, Hermann-Josef, and Wolf, Gunter
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- *
KIDNEY diseases , *PROTEIN research , *DIAGNOSIS , *DIFFERENTIAL diagnosis , *RESEARCH - Abstract
Background: Renal involvement in the light chain-associated diseases multiple myeloma (MM), amyloidosis (AL) and monoclonal immune position disease (MIDD) is common and differential diagnosis usually requires renal biopsy. The aim of this study was to investigate if noninvasive methods are viable to identify and differentiate between the various types of kidney diseases. Patients and Methods: All patients with a light chain-associated disease admitted to our center from 1996 to 2008 were retrospectively evaluated. Renal biopsy data were correlated with proteinuria findings. Results: Only the ratio of free κ/λ light chains showed a good sensitivity for myeloma cast nephropathy (MCN), AL and MIDD. The λ light chain was characteristic for AL, the κ light chain dominated in MIDD. Renal function at the time of diagnosis was worst in MIDD. MCN presented with a proteinuria of >3.5 g/g creatinine. In contrast, a higher proteinuria was found in AL or MIDD. Whereas the κ/λ ratio in the urine was pathological for all three diseases, extremely high or low ratios indicated the presence of MCN. However, in AL or MIDD, the ratio was only moderately elevated. Conclusion: A noninvasive differentiation between MCN and other forms of renal light chain disease is possible. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
48. Actualités dans le traitement du myélome avec insuffisance rénale.
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Moumas, Éric, Hanf, William, Desport, Estelle, Abraham, Julie, Delbès, Sébastien, Debiais, Céline, Lacotte-Thierry, Laurence, Touchard, Guy, Jaccard, Arnaud, Fermand, Jean-Paul, and Bridoux, Frank
- Subjects
MULTIPLE myeloma ,TREATMENT of chronic kidney failure ,CANCER chemotherapy ,CANCER complications ,DEXAMETHASONE ,HEMODIALYSIS ,KIDNEY function tests - Abstract
Copyright of Néphrologie & Thérapeutique is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2011
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- View/download PDF
49. Ig-Related Renal Disease in Lymphoplasmacytic Disorders: An Update.
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Ronco, Pierre, Plaisier, Emmanuelle, and Aucouturier, Pierre
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MONOCLONAL antibodies ,KIDNEY diseases ,CRYOGLOBULINEMIA ,AMYLOIDOSIS ,FANCONI syndrome ,DRUG efficacy ,PRECIPITIN reaction - Abstract
Summary: Ig-related renal diseases occurring in lymphoplasmacytic disorders (LPD) cover a wide spectrum of renal lesions. Except for cast nephropathy, which is almost specific for multiple myeloma, similar renal lesions caused by deposition or precipitation of monoclonal Ig-related material may occur in the various types of LPD. Because the secreted Ig provides the link between the LPD and the kidney disease, the renal outcome is linked to efficacy of chemotherapy. In the past 10 years, considerable advances have occurred in chemotherapy regimens with the advent of new classes of drugs, which already result in markedly improved renal and vital survival. [ABSTRACT FROM AUTHOR]
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- 2010
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- View/download PDF
50. Role of adjunct plasma exchange or high cut-off hemodialysis in the management of myeloma cast nephropathy: A systematic review
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Muhammad Umair Mushtaq, Abdul Rafae, Basel Abdelazeem, Faiz Anwer, Nazma Hanif, and Muhammad Khawar Sana
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Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Urology ,medicine.disease ,Immunoglobulin light chain ,Nephropathy ,Oncology ,medicine ,Hemodialysis ,business ,Complication ,Myeloma cast nephropathy ,Multiple myeloma - Abstract
e20032 Background: Renal impairment by cast nephropathy is a common complication in multiple myeloma. Tubulointerstitial injury results from precipitation of filtered free light chains (FLC) with Uromodulin in the distal convoluted tubules. Rapid reduction in serum FLC levels has shown to improve renal function in modeling studies. Extracorporeal light chain removal techniques such as plasma exchange (PEX) and high cut-off hemodialysis (HCO-HD) have been explored as potential adjunct treatment options for cast nephropathy in various clinical trials. Methods: PubMed, Cochrane library, and Clinicaltrials.gov were searched systematically for the use of plasma exchange and/or hemodialysis with chemotherapy in the treatment of myeloma cast nephropathy using their MeSH words and keywords. PRISMA guidelines were followed for screening and 5 out of 866 studies were finalized (N = 342). Results: Zucchelli et al. 1988 (n = 29) reported a dramatic reduction in Bence Jones protein (BJP) levels of 0.81 ± 0.46 g/day (P value < 0.01) and 1-year survival rate of 66% in the PEX group and decrease in BJP of 3.25 +/- 0.21 g/day (P-value < 0.05) with a survival rate of 28% in the control group. Clark et al. 2005 (n = 104) reported a primary composite response (patient alive at 6 months + dialysis independence + serum creatinine improvement of 50% at 6 months) in 57.9% of patients in the PEX group and 69.2% in the control group [95% CI, -8.3% to 29.1%]; P = 0.36. Johnson et al. 1990 (n = 21) reported a mean change of 880 μmol /L ± 260(SD) in serum creatinine in the PEX group and 570 μmol /L +/-240 in the control group. HD independence at 3 months was reported as 41.3% (n = 19) in the HCO-HD group and 33.3% (n = 16) in the conventional HD group (95% CI -12%–27.9%; P = 0.42) in the MYRE trial 2017 (n = 98). The EuLITE trial 2019 (n = 90) compared the efficacy of the high cut-off vs high flux hemodialysis (HF-HD) technique and concluded that there was no clinical benefit of one over the other. Independence from HD was achieved in 56% (n = 24) in the HCO-HD cohort vs 51% (n = 24) in HF-HD cohort (relative risk [RR] 1.09, 95% CI 0.74–1.61; P = 0.81). Conclusions: The use of high cut-off hemodialysis and plasma exchange as adjunct therapy did not show any significant survival benefit or improvement in clinical outcome. The role of routine use of PEX/HCO-HD in the management of cast nephropathy is still unclear and the decision to use these modalities should be made on an individual basis.
- Published
- 2021
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