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Glomerular disease is an important complication in patients undergoing hematopoietic stem cell transplantation (HSCT), impacting approximately 1%–2% of all HSCT recipients and equating to 700–1400 cases per year worldwide. Development of kidney disease in HSCT recipients is often multifactorial and a kidney biopsy is required to identify the underlying disease etiology and pathology. While glomerular disease is an important toxicity following HSCT, there are few kidney biopsy studies examining this complication, with the majority being limited to small series and case reports. A range of glomerular diseases may occur in association with HSCT. The study by Yap et al. defines this disease spectrum, which includes (in descending order) thrombotic microangiopathy (38.7%), membranous nephropathy (25.8%), mesangial proliferative glomerulonephritis (12.9%), minimal change disease (9.7%), focal segmental glomerulosclerosis (9.7%) and membranoproliferative glomerulonephritis (3.2%). In this editorial, we summarize the study and prior studies looking at glomerular diseases associated with HSCT.

With the advancement in immunosuppressive management and graft versus host disease prophylaxis, hematopoietic stem cell transplantation from a haploidentical donor is increasingly used and has become a standard donor option for patients lacking an appropriately matched sibling or unrelated donor. Inflammatory cytokines released by activated lymphocytes and innate cells in the context of cellular therapy can cause fever, vasodilatation, and end-organ damage, collectively known as cytokine release syndrome, is a common complication in patients undergoing haploidentical stem cell transplant and in this setting referred as “haplostorm.” We present a case of acute kidney injury induced by haplostorm after receiving a haploidentical hematopoietic stem cell transplant. The patient was managed with tocilizumab and conservatively without the need for kidney replacement therapy. Over the course, the patient had a successful kidney recovery.

The following cell cycle arrest urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP-7), have been used for early detection of acute kidney injury (AKI) in critically ill patients. The purpose of this study is to validate the use of these urinary biomarkers in patients undergoing open heart surgery.In a single-center prospective observational study, urine samples were collected in 108 consecutive patients who underwent open heart surgery immediately after separation from cardiopulmonary bypass and on postoperative day 1, and were sent for the biomarker [TIMP-2]*[IGFBP7] analysis. Acute kidney injury was defined based on KDIGO criteria, and levels of [TIMP-2]*[IGFBP7] were analyzed for the ability to predict AKI.Of the 108 patients, 19 (17.6%) patients developed postoperative AKI within 48 hours of surgery. At the threshold of0.3 (ng/mL)Urinary [TIMP-2]*[IGFBP7] was not predictive of the risk of AKI after cardiac surgery in this single-center study population.

Background: Immune check point inhibitors (ICPi) have become the first line treatment for most of the cancers and have shown promising results. However, they can provoke reactions, the most feared being immune related adverse events (irAE). Case presentation: We present a series of three cases, of patients recieving ICPi. All three patients developed AKI after administration of SARS-CoV-2 mRNA vaccine. Two patients had kidney-biopsy-proven acute interstitial nephritis (AIN) which responded to ICPi discontinuation and treatment with steroids. One had presumed AIN based on the high levels of CRP and urine retinol binding protein to creatinine ratio and responded to cessation of ICPi alone. Conclusion: These three cases demonstrate that a strong immune response from the SARS-CoV-2 mRNA vaccine combined with an uninhibited immune system under influence of ICPi led to an amplification of autoimmunity leading to AKI presenting as AIN.

Advances in cancer therapy have significantly improved overall patient survival; however, AKI remains a common complication in patients with cancer, occurring in anywhere from 11% to 22% of patients, depending on patient-related or cancer-specific factors. Critically ill patients with cancer as well as patients with certain malignancies (

Systemic AA amyloidosis is associated with systemic inflammatory processes such as autoimmune disorders or chronic infections. In addition, AA amyloidosis can develop in a localized or systemic form in patients with malignant neoplastic disorders, and usually involves kidneys impacting renal function. Among solid tumors, renal cell carcinoma (RCC) appears to be responsible for one-quarter to half of all cancers associated with amyloidosis. Among other solid cancers, various clinical presentations and pathological types of lung cancer and basal cell carcinoma skin were reported with AA amyloidosis more often than isolated case reports on other cancers with AA amyloidosis. Symptoms from kidney involvement rather than from the tumor per se were the presenting manifestations in cases of RCC associated with AA amyloidosis. Among hematological malignancies, clonal B cell/plasma cell dyscrasias such as monoclonal gammopathy and lymphoma were noted to be associated with AA amyloidosis. In addition, AA amyloidosis was reported in a substantial number of cases treated with immune checkpoint inhibitors such as pembrolizumab and nivolumab. The mechanism of association of cancer and AA amyloidosis seems to be mediated by the immune response exacerbated from the tumor and its microenvironment or immune therapy. The mainstay of treatment consists of therapy directed against the underlying malignancy or careful withdrawal of the offending agent. This review will discuss this rare but highly morbid clinical condition.

Background Recent improvement in treatment and patient survival has opened the eligibility of kidney transplantation to patients who developed end-stage kidney disease (ESKD) from plasma cell dyscrasias (PCDs). Data on clinical outcomes in this population are lacking. Methods We conducted a retrospective study of United Network for Organ Sharing/Organ Procurement and Transplantation Network dataset (2006–2018) to compare patient and graft outcomes of kidney transplant recipients with ESKD due to PCD versus other causes. Results Among 168 369 adult first kidney transplant recipients, 0.22–0.43% per year had PCD as the cause of ESKD. The PCD group had worse survival than the non-PCD group for both living and deceased donor types {adjusted hazard ratio [aHR] 2.24 [95% confidence interval (CI) 1.67–2.99] and aHR 1.40 [95% CI 1.08–1.83], respectively}. The PCD group had worse survival than the diabetes group, but only among living donors [aHR 1.87 (95% CI 1.37–2.53) versus aHR 1.16 (95% CI 0.89–1.2)]. Graft survival in patients with PCD were worse than non-PCD in both living and deceased donors [aHR 1.72 (95% CI 1.91–2.56) and aHR 1.30 (95% CI 1.03–1.66)]. Patient and graft survival were worse in amyloidosis but not statistically different in multiple myeloma compared with the non-PCD group. Conclusion The study data are crucial when determining kidney transplant eligibility and when discussing transplant risks in patients with PCD.

Systemic mastocytosis (SM) is a disorder of excessive mast cell accumulation in tissues due to a somatic gain-of-function mutation, commonly in the KIT gene, which prevents apoptosis of mast cells. Whereas bone marrow, skin, lymph nodes, spleen, and gastrointestinal tract are commonly involved, kidneys are rarely involved directly by SM. However, there are increasing reports of indirect kidney involvement in patients with SM. Novel anti-neoplastic agents to treat advanced forms of SM include non-specific tyrosine kinase inhibitors, which are reported to be associated with kidney dysfunction in some patients. SM is also associated with immune-mediated glomerulonephritis (GN) like mesangioproliferative GN, membranous nephropathy, and diffuse proliferative GN. Kidney injury, in the form of monoclonal deposition disease and primary light chain amyloidosis, is reported in SM associated with plasma cell dyscrasia. In this narrative review, we discuss the various ways kidneys (and the urinary tract) are involved in patients with SM.

High institutional transplant volume is associated with improved outcomes in isolated heart and kidney transplant. The aim of this study was to assess trends and outcomes of simultaneous heart-kidney transplant (SHKT) nationally, as well as the impact of institutional heart and kidney transplant volume on survival. All adult patients who underwent SHKT between 2005–2019 were identified using the United Network for Organ Sharing (UNOS) database. Annual institutional volumes in single organ transplant were determined. Univariate and multivariable analyses were conducted to assess the impact of demographics, comorbidities, and institutional transplant volumes on 1-year survival. 1564 SHKT were identified, increasing from 54 in 2005 to 221 in 2019. In centers performing SHKT, median annual heart transplant volume was 35.0 (IQR 24.0–56.0) and median annual kidney transplant volume was 166.0 (IQR 89.5–224.0). One-year survival was 88.4%. In multivariable analysis, increasing heart transplant volume, but not kidney transplant volume, was associated with improved 1-year survival. Increasing donor age, dialysis requirement, ischemic times, and bilirubin were also independently associated with reduced 1-year survival. Based on this data, high-volume heart transplant centers may be better equipped with managing SHKT patients than high-volume kidney transplant centers.

Lung cancer is the leading cause of cancer-related mortality and approximately 5% of non–small-cell lung cancer (NSCLC) patients are positive for anaplastic lymphoma kinase (ALK) gene rearrangement or fusion with echinoderm microtubule-associated protein-like 4. ALK inhibitors are the mainstay treatment for patients with NSCLC harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update. Several ALK-1 inhibitors are used in clinical practice, including crizotinib, ceritinib and alectinib. According to the package insert and published literature, treatment with several ALK-1 inhibitors appears to be associated with the development of peripheral edema and rare electrolyte disorders, kidney failure, proteinuria and an increased risk for the development and progression of renal cysts. This review introduces the different types of ALK inhibitors, focusing on their detailed kidney-related side effects in clinical practice.

In the last decade, immune checkpoint inhibitors (ICI) have become a cornerstone in the treatment of a wide range of malignancies. It is well established that ICI are associated with multiple immune-related adverse events, a spectrum of autoimmune toxicities, that can also affect the kidney. In this issue of Clinical Kidney Journal, Kanbay et al. report the first meta-analysis and systematic review evaluating the impact of ICI-related acute kidney injury (ICI-AKI) on long-term kidney and patient outcomes (including mortality). The authors report a high incidence of ICI-AKI (mostly mild AKI episodes) with high rates of recovery resulting in a good kidney outcomes. However, the occurrence of ICI-AKI has a significant impact on mortality in ICI-treated patients probably related to temporary or definitive cessation of ICI. Additional studies are needed to establish the safety of ICI re-challenging in patients with ICI-AKI, and to determine the optimal treatment strategy for them.

Introduction: Immune checkpoint inhibitors (ICI) are changing the way we treat cancer. However, these novel agents have various systemic adverse events that may preclude its use and cause poor patient outcomes. ICI-associated acute kidney injury is an emerging complication of this treatment. While tubulointerstitial disease is the most common pathologic finding of patients with ICI-associated AKI, there is sparse data in medical literature describing its association with glomerular disease. Case report: Here, we present a patient with metastatic lung adenocarcinoma who developed acute kidney injury and significant proteinuria after receiving pembrolizumab. The kidney biopsy revealed a membranoproliferative and diffuse segmental endocapillary proliferative pattern of glomerular injury. Management and outcome: Pembrolizumab was then held and high-dose prednisone was initiated, resulting in a rapid and dramatic improvement in kidney function and proteinuria. Discussion: We highlight a report of a patient diagnosed with immune-complex mediated glomerulonephritis associated with the use of pembrolizumab, who was successfully treated with drug withdrawal and corticosteroids.

Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with neoplasms in advanced stages. On the other hand, ICIs have immune-related adverse events. These adverse events affect mostly other organs than the kidney, such as skin or gastrointestinal tract. The incidence of nephrotoxicity with monotherapy with any ICI is about 2%, which increases to 5% in combination therapy. Acute tubulointerstitial nephritis (AIN) is the most common pattern of kidney damage related to ICIs. Globally, without considering ICI nephrotoxicity, AIN is estimated to account for 15% to 20% of cases of acute kidney injury (AKI). This is crucial because patients who are treated with ICIs, may also be taking other drugs that potentially cause AIN, and therefore, knowing the particularities about ICI-related AIN could be helpful in clinical practice to better understand the phenotypic differences between the 2 types of AIN. In addition, several studies have now shown that being on proton pump inhibitors is a risk factor for AIN from ICI therapy.

ORIGINAL INVESTIGATIONCOVID-19 Vaccination and new onset glomerular disease: Results from the IRocGN2 International registryWaldman, Meryl1,a; Sinaii, Ninet2; Lerma, Edgar V.3; Kurien, Anila Abraham4; Jhaveri, Kenar D.5; Uppal, Nupur N.5; Wanchoo, Rimda5; Avasare, Rupali6; Jonathan E, Zuckerman7; Liew, Adrian8; Gallan, Alexander J9; El-Meanawy, Ashraf10; Yagil, Yoram11; Lebedev, Larissa11; Baskaran, Krishoban12,13; Vilayur, Eswari12; Seung, Adrienne Wai12; Weerasinghe, Nethmi12; Petrakis, Ioannis14; Stylianou, Kostas15; Gakiopoulou, Hariklia16; Hamilton, Alexander J17; Edney, Naomi18; Millner, Rachel19; Marinaki, Smaragdi20; Rein, Joshua L21; Killen, John Paul22,23; Rodríguez Chagolla, Jose Manuel24; Bassil, Claude25; Lopez del Valle, Ramon26; Evans, Jordan27; Urisman, Anatoly28; Zawaideh, Mona29; Baxi, Pravir V.30; Rodby, Roger30; Vankalakunti, Mahesha31; Mejia Vilet, Juan M.32; Ramirez Andrade, Silvia E.33; Homan, Mal34; Jiménez, Enzo Vásquez35; Perinpanayagam, Natasha36; Carlos Q Velez, Juan37,38; Mohamed, Muner M.B.37,38; Mohammed, Khalid M.G39; Sekar, Arjun40; Ollila, Laura41; Aron, Abraham W42; Arellano Arteaga, Kevin Javier43; Islam, Mahmud44; Berrio, Esperanza Moral45; Maoujoud, Omar46; Morales, Rebecca Ruf47; Seipp, Regan48; Schulze, Carl E49; Yenchek, Robert H50; Vancea, Irina51; Muneeb, Muhammad52; Howard, Lilian1; Caza, Tiffany N53Author InformationKidney360 ():10.34067/KID.0006832022, December 16, 2022. | DOI: 10.34067/KID.0006832022OPENPAPMetricsAbstractBackground: Cases of de novo glomerular disease with various renal histologies have been reported after vaccination against SARS-CoV-2. Causality has not been established and the long-term outcomes are not known. To better characterize the glomerular diseases and clinical course/outcomes, we created the International Registry of COVID-19 vaccination and Glomerulonephritis (IRocGN2) to study in aggregate de novo glomerulonephritis cases suspected after COVID-19 vaccine exposure.:Methods: A RedCap survey was used for anonymized data collection. Detailed information on vaccination type and timing and glomerular disease histology were recorded in the registry. We collected serial information on laboratory values (before and after vaccination and during follow-up), treatments, and kidney-related outcomes.Results: Ninety-eight glomerular disease cases were entered into the registry over eleven months from 44 centers throughout the world. Median follow-up was 89 days after diagnosis. IgA nephropathy (IgAN) and minimal change disease (MCD) were the most the common kidney diseases reported. Recovery of kidney function and remission of proteinuria was more likely in IgAN and MCD at 4-6 months than with pauci immune glomerulonephritis /vasculitis and membranous nephropathy.Conclusions: Development of glomerular disease after vaccination against SARS-CoV-2 may be a very rare adverse event. Temporal association is present for IgAN and MCD, but causality is not firmly established. Kidney outcomes for IgAN and MCD are favorable. No changes in vaccination risk-benefit assessment is recommended based on these findings.

Purpose of review Nearly 20 years ago, vascular endothelial growth factor (VEGF)inhibitors (VEGFi) were adapted from systemic use from antiangiogenesis roles to intravitreal uses. Initially bevacizumab a murine immunoglobulin was injected 'off label' as a treatment for diabetic macular edema and age-related macular degeneration. Throughout the following decade aflibercept and finally ranibizumab were adapted and obtained Food and Drug Administration approval for intravitreal use. Initially systemic absorption was thought to be quite low after intravitreal injections and was quoted as being 200-fold lower than levels postulated to induce significant VEGF inhibition. Pharmacodynamic studies obtained in 2014 and again in 2017 revealed significant systemic absorption and detectable VEGF inhibition, this has since been confirmed in multiple subsequent studies. Recent findings A few case reports of renal dysfunction and glomerular disease related to VEGFi were initially identified. Mixed findings on effects on blood pressure were noted in studies. More recently, 32 cases of de-novo glomerular disease and/or proteinuria exacerbation were identified. New studies have corroborated increased blood pressure, proteinuria exacerbation in patients with pre-existing nephrotic syndrome, and systemic VEGF depletion. Further, the most common lesion of systemic VEGFi nephrotoxicity, thrombotic microangiopathy, has recently been reported by our group. Summary We will review the pharmacokinetic, translational, and epidemiological data that year upon year establish the finite-yet real risk of intravitreal VEGFi.

Chemotherapeutic agents used to treat cancer generally have narrow therapeutic indices along with potentially serious adverse toxicities. Many cancer drugs are at least partially excreted through the kidney and, thus, the availability of accurate data on safe and effective dosing of these drugs in patients with chronic kidney disease (CKD) is essential to guide treatment decisions. Typically, during drug development, initial clinical studies only include patients with normal or only mildly impaired kidney function. In subsequent preregistration studies, a limited number of patients with more severe kidney dysfunction are included. Data obtained from patients with either severe kidney dysfunction (here defined as an estimated glomerular filtration rate [eGFR] < 30 ml/min or stage 4G CKD) or end-stage kidney disease (ESKD) requiring kidney replacement treatment are particularly limited before drug registration and only a minority of new drug applications to the US Food and Drug Administration (FDA) include data from this population. Unfortunately, limited data and/or other safety concerns may result in a manufacturer statement that the drug is contraindicated in patients with advanced kidney disease, which hinders access to potentially beneficial drugs for these patients. This systemic exclusion of patients with CKD from cancer drug trials remains an unsolved problem, which prevents provision of optimal clinical care for these patients, raises questions of inclusion, diversity, and equity. In addition, with the aging of the population, there are increasing numbers of patients with CKD and cancer who face these issues. In this review, we evaluate the scientific basis to exclude patients with CKD from cancer trials and propose a comprehensive strategy to address this problem. ispartof: KIDNEY INTERNATIONAL REPORTS vol:7 issue:9 pages:1939-1950 ispartof: location:United States status: published

Introduction: The prevalence of chronic kidney disease (CKD) is high among kidney neoplasm patients because of the overlapping risk factors. Our purpose is to identify kidney cancer survivors with higher CKD risk. Methods: We studied a retrospective cohort of 361 kidney tumor patients with partial or radical nephrectomy. Linear mixed model was performed. Results: Of patients with follow-up >3 months, 84% were identified retrospectively to fulfill criteria for CKD diagnosis, although CKD was documented in only 15%. Urinalysis was performed in 205 (57%) patients at the time of nephrectomy. Multivariate analysis showed interstitial fibrosis and tubular atrophy (IFTA) >25% ( p = 0.005), severe arteriolar sclerosis ( p = 0.013), female gender ( p = 0.024), older age ( p = 0.012), BMI ⩾ 25 kg/m2 ( p < 0.001), documented CKD ( p < 0.001), baseline eGFR ⩽ 60 ml/min/1.73 m2 ( p < 0.001), and radical nephrectomy ( p < 0.001) were independent risk factors of lower eGFR at baseline and during follow-up. Average eGFR decreased within 3 months post nephrectomy. However, patients with different risk levels showed different eGFR time trend pattern at longer follow-ups. Multivariate analysis of time × risk factor interaction showed BMI, radical nephrectomy and baseline eGFR had time-dependent impact. BMI ⩾ 25 kg/m2 and radical nephrectomy were associated with steeper eGFR decrease slope. In baseline eGFR > 90 ml/min/1.73 m2 group, eGFR rebounded to pre-nephrectomy levels during extended follow-up. In partial nephrectomy patients with baseline eGFR ⩾ 90 ml/min/1.73 m2 ( n = 61), proteinuria ( p < 0.001) and BMI ( p < 0.001) were independent risk factors of decreased eGFR during follow up. Conclusions: As have been suggested by others and confirmed by our study, proteinuria and CKD are greatly under-recognized. Although self-evident as a minimum workup for nephrectomy patients to include SCr, eGFR, urinalysis, and proteinuria, the need for uniform applications of this practice should be reinforced. Non-neoplastic histology evaluation is valuable and should include an estimate of global sclerosis% (GS) and IFTA%. Patients with any proteinuria and/or eGFR ⩽ 60 at the time of nephrectomy or in follow-up with urologists, and/or >25% GS or IFTA, should be referred for early nephrology consultation.

Intravitreal vascular endothelial growth factor (VEGF) receptor blockade is used for a variety of retinal pathologies. These include age-related macular degeneration (AMD), diabetic macular edema (DME) and central retinal vein obstruction. Reports of absorption of intravitreal agents into systemic circulation have increased in number and confirmation of depletion of VEGF has been confirmed. Increasingly there are studies and case reports showing worsening hypertension, proteinuria, renal dysfunction and glomerular disease. The pathognomonic findings of systemic VEGF blockade, thrombotic microangiopathies (TMAs), are also being increasingly reported. One lesion that occurs in conjunction with TMAs that has been described is collapsing focal segmental glomerulosclerosis (cFSGS). cFSGS has been postulated to occur due to TMA-induced chronic glomerular hypoxia. In this updated review we discuss the mechanistic, pharmacological, epidemiological and clinical evidence of intravitreal VEGF toxicity. We review cases of biopsy-proven toxicity presented by our group and other investigators. We also present the third reported case of cFSGS in the setting of intravitreal VEGF blockade with a chronic TMA component that was crucially found on biopsy. This patient is a 74-year-old nondiabetic male receiving aflibercept for AMD. Of the two prior cases of cFSGS in the setting of VEGF blockade, one had AMD and the other had DME. This case solidifies the finding of cFSGS and its association with chronic TMA as a lesion that may be frequently encountered in patients receiving intravitreal VEGF inhibitors.

Capillary leak syndrome (CLS) is a rare condition typically presenting with profound hypotension, edema, and hemoconcentration. While there are some known, yet rare causes of CLS described, there is very limited data available with use of monoclonal antibodies and immune checkpoint inhibitors. This study aimed to look for the reported side effect of CLS with the use of targeted monoclonal antibodies and immune checkpoint inhibitors (ICI). FDA adverse event reporting system (FAERS) database was searched from first quarter 2010 to fourth quarter 2021 for targeted monoclonal antibodies and ICI. Other literature search including PubMed and case reports/series were also performed. Only 22 cases of CLS with novel anti-cancer treatments were reported in FAERS. Anti-CD20 was the most common class with nine cases of CLS with Rituximab. Six cases with ICI and four cases of CLS with anti-VEGF therapy were also documented. PubMed search showed anti-programmed cell death protein 1 (anti-PD1) as the most common class associated with CLS with five reported cases. CLS is a known complication of anticancer agents such as gemcitabine, clofarabine, cyclophosphamide, platinum-based therapy, colony stimulating factors, and CAR-T therapy, however CLS is not that common with newer monoclonal antibodies and ICIs. This study demonstrates that clinicians need to be aware of this rare fatal side effect of these drugs.

Background: Immune checkpoint inhibitors (ICI) are a fast growing therapy used in several types of malignancies. The majority of immune related adverse events observed in the kidney are due to acute interstitial nephritis. Glomerular diseases although less common have also been described. Case Presentation: We present a case of phospholipase A2 receptor positive membranous nephropathy triggered by ICI therapy cemiplimab (PD1 inhibitor) in a 88 year old man with no prior history of proteinuria or glomerular disease. The patient responded to steroid monotherapy with rapid clinical and immunological remission. Conclusion: While patients undergoing ICI therapy warrant close monitoring of systemic immune related adverse events, physicians should remain vigilant of kidney related events and obtain a kidney biopsy if clinically indicated.