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Atypical hemolytic uremic syndrome (aHUS) is a subtype of thrombotic microangiopathy (TMA) characterized by a dysregulation of the alternative complement pathway. Here, we report a previously healthy 38-year-old woman in whom aHUS developed after a COVID-19 vaccine booster. One day after receipt of a booster dose of mRNA-1273 vaccine, she felt ill. Because of persistent headache, nausea, and general malaise, she went to her general practitioner, who referred her to the hospital after detecting hypertension and acute kidney injury. A diagnosis of TMA was made. Her treatment consisted of blood pressure control, hemodialysis, plasma exchange, and respiratory support. Kidney biopsy confirmed the diagnosis of acute TMA. The patient was referred for treatment with eculizumab, and kidney function improved after initiation of this therapy. Genetic analysis revealed a pathogenic C3 variant. SARS-CoV-2 infection as a trigger for complement activation and development of aHUS has been described previously. In addition, there is one reported case of aHUS occurring after receipt of the adenovirus-based COVID-19 vaccine ChAdOx1 nCoV-19, but, to our knowledge, this is the first case of aHUS occurring after a booster dose of an mRNA COVID-19 vaccine in a patient with an underlying pathogenic variant in complement C3. Given the time frame, we hypothesize that the vaccine probably was the trigger for development of aHUS in this patient. ispartof: AMERICAN JOURNAL OF KIDNEY DISEASES vol:81 issue:3 pages:364-367 ispartof: location:United States status: published

Background: The Flemish Collaborative Glomerulonephritis Group (FCGG) registry is a population-based kidney biopsy registry that has been including all native kidney biopsies performed in children in Flanders (Belgium), since 2017. Methods: From 2017 to 2020, 148 pediatric (< 18 years) native kidney biopsies were included. Each biopsy received a histopathological and final nephrological diagnosis, and concordance between both was assessed. Disease chronicity, summarized by the Mayo Clinic Chronicity Score, was determined on 122 biopsies with > 5 glomeruli. Results: Kidney biopsy rate was high (29.0 biopsies per million children per year), median age was 10.0 years (IQR 5.8–14.7), and boys predominated (56.1% males). A total of 140 biopsies (94.6%) showed a representative pathology result. Glomerular disease was most prevalent, with IgA nephropathy/IgA vasculitis (43 biopsies, 29.1%) and minimal change disease (MCD) (29 biopsies, 19.6%) being the overall most frequent diagnoses. In general, diagnostic concordance was high (80.7%). In Alport syndrome and focal segmental glomerulosclerosis (FSGS), concordance was lower, as the nephrological diagnosis was often determined by results of genetic analysis. Nephrotic syndrome was the most frequent indication for kidney biopsy (31.8%) and was mainly caused by MCD and FSGS. The degree of disease chronicity on kidney biopsies was generally low, although 27.3% of biopsies with a diagnosis of FSGS showed moderate-to-severe chronic damage. Conclusions: The presented epidemiological findings validate data from previous European registry studies and may inspire kidney biopsy registries worldwide to implement novel features such as clinicopathological concordance and chronicity grading. Graphical abstract: [Figure not available: see fulltext.]

Background and objectives: C3 glomerulopathy and idiopathic Ig-associated membranoproliferative GN are kidney diseases characterized by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients develop kidney failure within 10 years. Design, setting, participants, & measurements: To improve identification of patients with poor prognosis, we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histologic scoring system, we analyzed 156 native diagnostic kidney biopsies from a retrospective cohort of 123patients with C3 glomerulopathy and 33 patients with Ig-associated membranoproliferative GN. We used linear regression, survival analysis, and Cox proportional hazards models to assess the relationship between histologic and clinical parameters with outcome. Results: Frequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane double contours, and endocapillary hypercellularity. Multivariable analysis showed negative associations between eGFR and crescents, interstitial inflammation, and interstitialfibrosis/tubular atrophy. Proteinuria positively associated with endocapillary hypercellularity and glomerular basement membrane double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at the time of biopsy, cellular/fibrocellular crescents, segmental sclerosis, and interstitial fibrosis/tubular atrophy scores. Conclusions: Our detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and interstitial fibrosis/tubular atrophy scores were significant determinants of deterioration in kidney function.

Background The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. Methods The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. Results Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08–1.17], liver disease (OR 2.27, 95% CI 1.21–4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07–1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92–0.99) were protective. Conclusions This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes.

BackgroundMembranous nephropathy is an uncommon cause of nephrotic syndrome in pediatrics.MethodsWe reviewed our kidney biopsy records for patients ≤ 20 years of age with membranous nephropathy without evidence of systemic lupus erythematosus within 6 months of biopsy (January 1995-September 2020). Staining for PLA2R, NELL1, THSD7A, SEMA3B, EXT2 (3 biopsies), and IgG-subclass were performed.ResultsSixteen children (≤ 12 years) and 25 adolescents (13-20 years) were identified. Four children and 15 adolescents showed autoantigen positivity: PLA2R+/SEMA3B- (13), SEMA3B+/PLA2R+ (2), SEMA3B+/PLA2R- (1), NELL1 (1),EXT2+ (2), and THSD7A (0). Co-morbidities associated with PLA2R positivity included IPEX syndrome, active hepatitis B, Von Hippel Lindau syndrome, solitary kidney, type 1 diabetes, hyperuricemia, pregnancy (1), obesity (3), type II diabetes, H. pylori, viral prodrome, and nephrolithiasis. The SEMA3B+/PLA2R- adolescent was pregnant, the NELL1+ adolescent was obese, and the two EXT2+ adolescents eventually met the clinical criteria for lupus (4, 9 years post-biopsy). Co-morbidities among the remaining 24 patients included remote hepatitis B (2), Down's syndrome, lysinuric protein intolerance, recurrent UTIs, hypothyroidism, pregnancy (3), and obesity (2). Follow-up data was available for 12 children and 16 adolescents. Of the 12 children, 6 achieved complete remission, 4 achieved partial remission, and 2 had no response to treatment (1 transplant). Of the 16 adolescents, 4 achieved complete remission, 4 achieved partial remission, and 8 had no response to treatment (3 transplants). A child with "full-house" immunofluorescence staining achieved spontaneous disease remission.ConclusionOur non-lupus membranous nephropathy cohort represents one of the largest pediatric studies to date. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acute kidney injury (AKI) frequently complicates corona virus disease 2019 (COVID-19) and is associated with significant mortality. Kidney disease in COVID-19 is usually due to acute tubular injury, but a variety of glomerular processes, especially collapsing glomerulopathy, have been increasingly described. Until recently, proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) had not been reported in the setting of COVID-19. We present a case of dialysis-dependent AKI developing soon after symptomatic COVID-19 which, on kidney biopsy, was found to be due to PGNMID with IgG3 kappa deposits. As is typical of PGNMID, a search for evidence of extra-renal monoclonal immunoglobulin or clonal lymphocyte population was negative. However, the patient had a favorable response to anti-plasma cell therapy and was ultimately able to stop hemodialysis. Though monoclonal gammopathy of renal significance (MGRS) is usually not associated with infection, other cases of post-viral MGRS, including PGNMID, have been previously reported. PGNMID has recently been linked specifically to COVID-19, with this representing one of only four cases reported thus far. Though causality between the preceding viral infection and the subsequent glomerulonephritis cannot be proven in these reports, nephrologists should be aware that not all kidney disease occurring in the aftermath of COVID-19 is due to tubular injury or collapsing glomerulopathy. As such, kidney biopsy should be routinely considered in the setting of COVID-19-associated glomerular disease as findings may change management. In the case of COVID-19-associated PGNMID data to guide treatment are limited, but our report suggests that anti-plasma cell therapy may be effective.

BACKGROUND: The goal of the Artificial Intelligence in Renal Scarring (AIRS) study is to develop machine learning tools for noninvasive quantification of kidney fibrosis from imaging scans. METHODS: We conducted a retrospective analysis of patients who had one or more abdominal computed tomography (CT) scans within 6 months of a kidney biopsy. The final cohort encompassed 152 CT scans from 92 patients, which included images of 300 native kidneys and 76 transplant kidneys. Two different convolutional neural networks (slice-level and voxel-level classifiers) were tested to differentiate severe versus mild/moderate kidney fibrosis (≥50% versus

Background Transplant nephropathology is a highly specialized field of pathology comprising both the evaluation of organ donor biopsy for organ allocation and post-transplant graft biopsy for assessment of rejection or graft damage. The introduction of digital pathology with whole-slide imaging (WSI) in clinical research, trials and practice has catalyzed the application of artificial intelligence (AI) for histopathology, with development of novel machine-learning models for tissue interrogation and discovery. We aimed to review the literature for studies specifically applying AI algorithms to WSI-digitized pre-implantation kidney biopsy. Methods A systematic search was carried out in the electronic databases PubMed-MEDLINE and Embase until 25th September, 2021 with a combination of the key terms “kidney”, “biopsy”, “transplantation” and “artificial intelligence” and their aliases. Studies dealing with the application of AI algorithms coupled with WSI in pre-implantation kidney biopsies were included. The main theme addressed was detection and quantification of tissue components. Extracted data were: author, year and country of the study, type of biopsy features investigated, number of cases, type of algorithm deployed, main results of the study in terms of diagnostic outcome, and the main limitations of the study. Results Of 5761 retrieved articles, 7 met our inclusion criteria. All studies focused largely on AI-based detection and classification of glomerular structures and to a lesser extent on tubular and vascular structures. Performance of AI algorithms was excellent and promising. Conclusion All studies highlighted the importance of expert pathologist annotation to reliably train models and the need to acknowledge clinical nuances of the pre-implantation setting. Close cooperation between computer scientists and practicing as well as expert renal pathologists is needed, helping to refine the performance of AI-based models for routine pre-implantation kidney biopsy clinical practice.

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in clinically significant multi-system disease including involvement in the kidney. The underlying histopathological processes were unknown at the start of the pandemic. As case reports and series have been published describing the underlying renal histopathology from kidney biopsies, we have started to gain an insight into the renal manifestations of this novel disease. AIM To provide an overview of the current literature on the renal histopathological features and mechanistic insights described in association with coronavirus disease 2019 (COVID-19) infection. METHODS A systematic review was performed by conducting a literature search in the following websites-‘PubMed’, ‘Web of Science’, ‘Embase’ and ‘Medline-ProQuest’ with the following search terms-“COVID-19 AND kidney biopsy”, “COVID-19 AND renal biopsy”, “SARS-CoV-2 AND kidney biopsy” and “SARS-CoV-2 AND renal biopsy”. We have included published data up until February 15, 2021, which includes kidney biopsies (native, transplant and postmortem) from patients with COVID-19. Data on clinical presentation, histopathological features, management and outcome was extracted from the reported studies. RESULTS The total number of biopsies reported on here is 288, of which 189 are postmortem, 84 native and 15 transplants. The results are varied and show underlying pathologies ranging from collapsing glomerulopathy and acute tubular injury (ATI) to anti-nuclear cytoplasmic antibody associated vasculitis and pigment nephropathy. There was variation in the specific treatment used for the various renal conditions, which included steroids, hydroxychloroquine, eculizumab, convalescent plasma, rituximab, anakinra, cyclophosphamide and renal replacement therapy, amongst others. The pathological process which occurs in the kidney following COVID-19 infection and leads to the described biopsy findings has been hypothesized in some conditions but not others (for example, sepsis related hypoperfusion for ATI). It is important to note that this represents a very small minority of the total number of cases of COVID-19 related kidney disease, and as such there may be inherent selection bias in the results described. Further work will be required to determine the pathogenetic link, if any, between COVID-19 and the other renal pathologies. CONCLUSION This report has clinical relevance as certain renal pathologies have specific management, with the implication that kidney biopsy in the setting of renal disease and COVID-19 should be an early consideration, dependent upon the clinical presentation.

A 67-year-old female with Type 2 diabetes mellitus developed nephrotic syndrome within 1 week of receiving the first dose of severe acute respiratory syndrome coronavirus 2 CoronaVac vaccine. A kidney biopsy was consistent with minimal change nephrotic syndrome and treatment was symptomatic with antiproteinuric therapy and improvement in proteinuria. Oedema returned within 1 week of the second dose of CoronaVac. On this occasion, acute kidney injury and massive proteinuria were noted. In kidney biopsy, glomeruli were normal, but tubulointerstitial inflammation consistent with acute tubulointerstitial nephritis was noted. Pulse followed by oral steroids was followed by recovery of kidney function. Proteinuria decreased after initiation of cyclosporine A.

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

Background Soluble tumor necrosis factor receptor (sTNFR)-1, sTNFR-2, YKL-40, monocyte chemoattractant protein (MCP)-1, and soluble urokinase plasminogen activator receptor (suPAR) have emerged as promising biomarkers of inflammation but have not been evaluated across diverse types of kidney diseases. Methods We measured these plasma biomarkers in 523 individuals enrolled into a prospective, observational cohort study of patients undergoing clinically indicated native kidney biopsy at 3 tertiary care hospitals. Two kidney pathologists adjudicated biopsy specimens for semiquantitative scores of histopathology. Proportional hazard models tested associations between biomarkers and risks of kidney disease progression (composite of ≥40% estimated glomerular filtration rate [eGFR] decline or end-stage kidney disease [ESKD]) and death. Results Mean eGFR was 56.4±36 ml/min per 1.73 m2 and the median proteinuria (interquartile range) was 1.6 (0.4, 3.9) g/g creatinine. The most common primary clinicopathologic diagnoses were proliferative glomerulonephritis (29.2%), nonproliferative glomerulopathy (18.1%), advanced glomerulosclerosis (11.3%), and diabetic kidney disease (11.1%). sTNFR-1, sTNFR-2, MCP-1, and suPAR were associated with tubulointerstitial and glomerular lesions. YKL-40 was not associated with any histopathologic lesions after multivariable adjustment. During a median follow-up of 65 months, 182 participants suffered kidney disease progression and 85 participants died. After multivariable adjustment, each doubling of sTNFR-1, sTNFR-2, YKL-40, and MCP-1 was associated with increased risks of kidney disease progression, with hazard ratios ranging from 1.21 to 1.47. Each doubling of sTNFR-2, YKL-40, and MCP-1 was associated with increased risks of death, with hazard ratios ranging from 1.33 to 1.45. suPAR was not significantly associated with kidney disease progression or death. Conclusions sTNFR-1, sTNFR-2, YKL-40, MCP-1, and suPAR are associated with underlying histopathologic lesions and adverse clinical outcomes across a diverse set of kidney diseases., Graphical abstract

Background: The simultaneous occurrence of impaired kidney function and paraproteinemia is common in our constantly aging society. Both can be independent entities; however, renal insufficiency can also be caused by the paraprotein. We assessed all kidney biopsies in patients with monoclonal gammopathy in our clinic over the past 20 years and evaluated the histological results. Methods: Biopsies were systematically performed in nearly all patients with paraproteinemia and impaired kidney function (n = 178). The histological findings were systematically evaluated and correlated with the initial clinical diagnosis. Results: We found cast nephropathy (CN) in n = 66 (37.1%) biopsies, AL amyloidosis in n = 31 (17.4%) biopsies, monoclonal immunoglobulin deposition disease (MIDD) in n = 7 (3.9%) biopsies and other renal diseases (ORDs) in n = 74 (41.6%) biopsies. In the latter group, paraprotein-associated changes were found in 37 of 74 (50%) patients, whereas paraprotein-independent changes were found in the other half. Whereas, in the group of patients with MGUS, the findings were heterogenous, most of the patients with known multiple myeloma (MM) or B-NHL showed malignancy-associated changes in the kidney. The biopsy changed the diagnoses in a significant proportion of the patients: The group of patients with MM grew from 71 to 112 patients, whereas, in the MGUS group, only 31 of 44 patients remained. Conclusion: Kidney biopsies in patients with paraproteinemia and renal impairment show a wide range of findings that can lead to a change in diagnosis.

Background: Fabry disease (FD) is a rare lysosomal storage disease causing progressive loss of target organ function. All renal cell types are involved from the early stages, even before clinical signs can be detected. FD-specific therapies can stop/mitigate disease progression. Thus, it is important to validate early markers of renal lesions so that they can be adopted as criteria for timely treatment initiation. Materials and methods: We retrospectively analyzed and extensively evaluated 21 FD case patients; this evaluation included a kidney biopsy. We looked for the influence of pathological findings on the management of FD patients. In addition, we investigated the association between general and FD-specific features and long-term patients’ outcomes. We defined a combined endpoint as being at least one of the following: 50% decrease of estimated glomerular filtration rate (eGFR) from baseline, kidney failure (KF), end-stage kidney disease (ESKD), or death and mortality. Results: Our cohort of 21 FD patients (11 males and 10 females) was stratified according to the presence of the combined endpoint: group 1 (n = 15) included patients without the combined endpoint, while group 2 (n = 6) patients reached the combined endpoint outcome. Patients from group 2 presented lower mean baseline eGFR (72.2 ± 38.7 mL/min/1.73 m2 vs. 82.5 ± 26.4 mL/min/1.73 m2) without statistical significance (p = 0.44), but significantly (p = 0.22) higher median baseline proteinuria (2.7 g/24 h vs. 0.4 g/24 h). Specific lysosomal deposits were identified in all patients. Segmental sclerosis was present in all patients with the combined endpoint and in only 33% of patients without the combined endpoint (p = 0.009). Global sclerosis and interstitial fibrosis were present in both groups, with no significant differences. A total of 15 out of the 16 treatment-naïve patients (7 males and 9 females) started FD-specific therapy after kidney biopsy. Treatment was initiated in all male FD patients and in 8 female patients. In 2 females, pathological findings in kidney biopsy offered important reasons to start FD treatment, although specific criteria of the Romanian protocol for prescription of FD-specific therapy were still not fulfilled. Cox univariate analysis showed that every increase in 24 h proteinuria with 1 g is associated with a 65% risk of developing the combined endpoint (HR = 1.65; 95%CI: 1.05–2.58; p = 0.02), and that the presence of segmental sclerosis increased the risk of developing the combined endpoint by 51.3 times (HR = 51.3; 95% CI: 95% CI: 1.67–103.5; p = 0.01). Kaplan–Meier analysis showed that the cumulative risk of developing the combined endpoint was higher in patients in whom segmental sclerosis (100% vs. 0%, log-rank test, p = 0.03) was present. Conclusions: Histological evaluation is an important tool for the detection of early kidney involvement and provides additional support to the early initiation of FD-specific therapy. Presence of segmental sclerosis can predict the long-term outcomes of kidney disease deterioration and mortality and may be used as an early indicator of disease progression. Additionally, in the absence of other criteria according to current guidelines, specific FD renal lesions as revealed by kidney biopsy might become a distinct criterion to initiate FD therapy.

Introduction Kidney biopsy is an important tool for making diagnoses and for assessing the drug treatment requirements and disease prognosis in the management of kidney diseases. There are variations in the rate of complications associated with kidney biopsies across countries, and this depends on various clinical and technical factors. The aim of this study is to report on complications associated with kidney biopsy performed in low- and middle-income countries. Methods Two reviewers searched studies in MEDLINE, Embase, Cochrane Reviews, and African Journals Online. A random effects meta-analysis method was used to pool estimates of complications. Results We identified 39 studies reporting on 19,500 kidney biopsies with overall complications (major + minor) rate of 14.9% (95% confidence interval = 11.4%–18.7%). Fewer complications were reported in biopsies performed with real-time ultrasound scans compared to those pre-marked using ultrasound or blind procedures (12.4% vs. 14.9% vs. 24.5%; P = 0.037), respectively. Complications, albeit lower for procedures performed with automated needles (13.3%), were not significantly different from those performed with nonautomated needles (17.3%; P = 0.588). Major complications included macroscopic hematuria (1.48%), nephrectomy (0.04%), blood loss requiring red cell transfusion (0.24%), angiographic intervention (0.22%), and death (0.01%). Conclusion Complications associated with kidney biopsy in low- and middle-income countries are low, are comparable to those in other settings, and occur more sparingly when real-time ultrasound techniques or automated kidney biopsy needles are used. This suggests the need to expand the use of this procedure to improve diagnosis of kidney pathologies and choice of therapy when indicated., Graphical abstract

Introduction: Kidney biopsies (KBs) are performed in patients with type 2 diabetes (T2D) to diagnose non-diabetic or hypertensive kidney disease (NDHKD) potentially requiring specific management compared to diabetic and or hypertensive nephropathy (absence of NDHKD). Indications for KB are based on the presence of atypical features compared to the typical course of diabetic nephropathy. In this study, we assessed the association of different patterns of atypical features, or KB indications, with NDHKD. Methods: Native KBs performed in patients with T2D were analyzed. Data were collected from the patients’ records. KB indications were determined according to the presence of different atypical features considered sequentially: (1) presence of any feature suggesting NDHKD which is not among the following ones, (2) recent onset of nephrotic syndrome, (3) low or rapidly declining estimated glomerular filtration rate (eGFR), (4) rapid increase in proteinuria, (5) short duration of diabetes, (6) presence of hematuria, or (7) normal retinal examination. Results: Among the 463 KBs analyzed, NDHKD was diagnosed in 40% of the total population and 54, 40, 24, and 7% of the KBs performed for indications 1–4 respectively. Conversely, no patient who underwent KB for indications 5–7 displayed NDHKD. Logistic regression analyses identified eGFRCKD-EPI >15 mL/min/1.73 m2, urinary protein-to-Cr ratio

Immunoglobulin A nephropathy (IgAN) is the most common chronic glomerulopathy with variable clinical manifestations. IgAN diagnostics became possible in Latvia in 2013. The study aim was to describe IgAN manifestations in the Latvian population by analysing epidemiological, clinical, histological data, and reveal factors that might determine the course of the disease. The retrospective, one-centre study included biopsy-proven IgAN patients over a five-year period in the Nephrology Centre at Pauls Stradiņš Clinical University Hospital. Data from inpatient and outpatient medical records were collected. The study included 69 patients with histologically confirmed IgAN (23% of all renal biopsies): 52% men with mean age of 37. More than a half of them had hypertension, changes in urinalysis and kidney structure, and GFR < ml/min before the biopsy. Pathology data stratified by MEST-C score were: M1 (93%), E1 (5%), S1 (81%), T1 and T2 (24%), C1 (18%). 20% started renal replacement therapy (RRT). Proteinuria, obesity, hyperuricemia, high total MEST-C score, and low serum C3 were associated with a worse prognosis. As a significant part of patients start RRT in the five-year period after the biopsy, the disease course is not benign. IgAN in the study population was diagnosed with clinical and histological signs of advanced disease.

Rationale & Objective Anorexia nervosa is often intractable and induces various physical disorders, including kidney disease and mineral disorders, occasionally progressing to kidney failure. No consensus-based clinical practice guidelines have been established for patients with anorexia nervosa referred to a nephrologist. Study Design Patients with anorexia nervosa–associated kidney disease diagnosed were analyzed retrospectively. Kidney outcomes were defined as doubling of serum creatinine level and/or progression to end-stage kidney disease. Setting & Participants Patients with a history of anorexia nervosa with kidney disease, including electrolyte abnormalities, who were referred to our hospital between 1992 and 2017 were included. Results 14 female patients were included. The time from anorexia nervosa onset to the initial visit with a nephrologist was 17.8 years. At the first visit, median body mass index was 13.4kg/m2, median serum creatinine level was 1.9mg/dL, and median serum potassium level was 2.7mmol/L. All patients showed hypokalemia and addictive vomiting or diuretic/laxative abuse. During the median observation period of 3.1 years, kidney outcomes occurred in 9 patients, and 2 died due to their anorexia nervosa. 4 patients underwent kidney biopsy. The kidney biopsy findings of these patients included hypertrophy of the juxtaglomerular apparatus, advanced glomerular collapse, and interstitial fibrosis, consistent with ischemic kidney injury and hypokalemic nephropathy. Limitations The sample size was small, and kidney function was assessed based on serum creatinine levels in patients with anorexia nervosa with low muscle mass. Conclusions Most patients with anorexia nervosa referred to nephrologists had kidney disease at the time of the first visit. Improving kidney outcomes of patients with anorexia nervosa may require earlier collaboration between psychiatrists and nephrologists.

Background The incidence of acute tubulointerstitial nephritis (ATIN) related to drugs has dramatically increased over recent years. A new subtype of ATIN, apparently different from classical drug-related ATIN, has emerged that has been related to the administration of immune checkpoint inhibitors (ICIs). We investigated these differences between ICI-related ATIN (ICI ATIN) and non-ICI-related ATIN in terms of clinical features, response to treatment with steroids and the evolution of kidney function. Methods A total of 47 patients diagnosed with ATIN from two centres were recruited. Of these, 13 patients presented with ATIN during ICI treatment and 34 were diagnosed with ATIN attributed to other drugs. The main demographic, clinical and analytical variables such as gender, age and current medication were recorded. The type of malignancy, oncological treatment, ICI dose and presence of extrarenal immune-related adverse events were also reviewed. Renal biopsy diagnosis, time to drug withdrawal and ATIN-specific treatment, as well as laboratory data during follow-up, were also studied. Results Patients diagnosed with ICI ATIN presented with lower creatinine (ICI ATIN 3.8 ± 1.03 versus classical ATIN 5.98 ± 4.15 mg/dL, P = 0.007) at diagnosis and higher urinary leucocyte counts (ICI ATIN 263.2 ± 418.04 versus classical ATIN 133.55 ± 284.62, P = 0.048) compared with patients with non-ICI-related ATIN. Time from initiation of the culprit drug to ATIN diagnosis was longer in patients with ICI ATIN than in those with classical ATIN (197.07 ± 184.99 versus 114.4 ± 352.16 days, P = 0.006). In addition, during follow-up, the slope of decreasing creatinine over time was lower for ICI ATIN compared with non-ICI-related ATIN. Conclusions In this study, we analysed differences between ICI ATIN and classical ATIN. We found that patients with ICI ATIN presented with a larger latency period after culprit drug initiation, milder acute kidney injury and slower creatinine amelioration compared with those with classical ATIN. These results may, in part, be ascribed to potential differences in the pathological mechanisms involved in ATIN development, suggesting that ICI and classical ATIN may be different diseases with similar renal histologies.

Oliguric acute kidney injury (AKI) with minimal change nephrotic syndrome (MCNS) has long been recognized. Several mechanisms such as hypovolemia due to hypoalbuminemia and the nephrosarca hypothesis have been proposed. However, the precise mechanism by which MCNS causes AKI has not been fully elucidated. Herein, we describe an elderly patient with AKI caused by MCNS who fully recovered after aggressive volume withdrawal by hemodialysis and administration of a glucocorticoid. A 75-year-old woman presented with diarrhea and oliguria, and laboratory examination revealed nephrotic syndrome (NS) and severe azotemia. Fluid administration had no effect on renal dysfunction, and hemodialysis was initiated. Her renal function improved upon aggressive fluid removal through hemodialysis. Renal pathological findings revealed minimal change disease with faint mesangial deposits of IgA. After administration of methylprednisolone pulse therapy followed by oral prednisolone, she achieved complete remission from NS. The clinical course of this case supports the nephrosarca hypothesis regarding the mechanism of AKI caused by MCNS. Furthermore, appropriate fluid management and kidney biopsy are also important in elderly patients with AKI caused by NS.

Monoclonal gammopathy of renal significance (MGRS) is a new nosology in modern nephrology and oncohematology. MGRS is defined as kidney injury due to nephrotoxic monoclonal immunoglobulin produced by the B-cell line clone which does not reach the hematological criteria for specific treatment initiation. Monoclonal proteins pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: 1) limited knowledge about the MGRS among hematologists and nephrologists; 2) lack of necessary diagnostic resources in most health-care facilities; 3) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. Consensus document comprises the opinion of experts leading nephrologists and hematologists of Russian Federation on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy, 1516 of March 2019, Pavlov First Saint Petersburg State Medical University. The present Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses.Моноклональная гаммапатия ренального значения (МГРЗ) представляет собой новую нозологическую группу в современной нефрологии и онкогематологии. Под МГРЗ понимают поражение почек, обусловленное действием нефротоксичного моноклонального иммуноглобулина, продуцируемого клоном В-клеточной линии, который не достигает критериев, необходимых для начала противоопухолевой терапии по онкогематологическим показаниям. Результатом воздействия моноклонального белка на почечную паренхиму является неуклонное прогрессирование дисфункции почек вплоть до утраты функции органа, что в соответствии с единой позицией международного консенсуса гематологов и нефрологов определенно указывает на необходимость клон-ориентированного лечения МГРЗ, несмотря на отсутствие критериальных онкогематологических показаний. Основной проблемой МГРЗ в Российской Федерации является недоступность для большинства пациентов своевременной диагностики и лечения данной патологии, что обусловлено, во-первых, недостаточной осведомленностью гематологов и нефрологов страны в отношении МГРЗ, во-вторых, отсутствием в большинстве медицинских учреждений необходимых диагностических ресурсов, в-третьих, отсутствием утвержденных рекомендаций и медико-экономических стандартов лечения этой болезни. Текст настоящего консенсуса заключает в себе мнение специалистов РФ в отношении нозологической классификации, диагностики и подходов к терапии МГРЗ и основан на итогах проведенного совместного совещания ведущих гематологов и нефрологов страны. Совещание состоялось 1516 марта 2019 г. в рамках симпозиума Плазмоклеточные дискразии и лимфопролиферативные заболевания: новые подходы к терапии, проведенного в ФГБОУ ВО Первый СПбГМУ им. акад. И.П. Павлова. Настоящий консенсус гематологов и нефрологов призван наметить основные практические пути решения проблемы МГРЗ в РФ, которые кратко сформулированы в виде заключительных положений.

Apolipoprotein L1 (APOL1) risk variants G1 and G2 are known to result in risk for kidney disease in patients of African ancestry. APOL1-associated nephropathy typically occurs in association with certain environmental factors or systemic diseases. As such, there has been increasing evidence of the role of interferon (IFN) pathways in the pathogenesis of APOL1-associated collapsing glomerulopathy in patients with human immunodeficiency virus (HIV) infection and systemic lupus erythematosus, 2 conditions that are associated with high IFN levels. Collapsing glomerulopathy has also been described in patients receiving exogenous IFN therapy administered for various medical conditions. We describe a patient with a genetic condition that results in an increased IFN state, stimulator of IFN genes (STING)-associated vasculopathy with onset in infancy (SAVI), who developed collapsing glomerulopathy during a flare of his disease. The patient was found to have APOL1 G1 and G2 risk variants. This case supports the role of IFN in inducing APOL1-associated collapsing glomerulopathy.

Thrombotic microangiopathy (TMA) can sometimes manifest only histologically. Our aim was to retrospectively compare biopsy-proven adult TMA patients showing only histological (h-TMA) or both histological and clinical (c-TMA) TMA in 2006–2017. All native kidney biopsies with TMA were included. Biopsies were re-evaluated by light and electron microscopy, and immunofluorescence. Clinical characteristics, laboratory variables, and treatments were recorded from the electronic medical database. Patients were categorized into h-TMA and c-TMA and these groups were compared. In total, 30 biopsy-proven cases among 7943 kidney biopsies were identified and, of these, 15 had h-TMA and 15 c-TMA. Mean follow-up was 6.3 y, and 73.3% had secondary hemolytic uremic syndrome (HUS) and the rest were atypical HUS. Patient characteristics, treatments, and kidney, and patient survival in the groups were similar. Statistically significant differences were found in histological variables. Vascular myxoid swelling and vascular onion-skinning were almost exclusively detected in c-TMA and, thus, vascular occlusive changes indicate clinically apparent rather than merely histological TMA. In addition, regardless of clinical presentation, kidney and patient survival times were similar in the patient groups highlighting the importance of a kidney biopsy in the case of any kidney-related symptoms.

Background: Galectin-3 (Gal-3) is a multifunctional glycan-binding protein shown to be linked to chronic inflammation and fibrogenesis. Plasma Gal-3 is associated with proteinuria and renal dysfunction, but its role has never been confirmed with kidney biopsy results. In our study, we aimed to explore the expression of Gal-3 in biopsy-proven patients, and we tested the hypothesis that chronic kidney disease (CKD) leads to upregulation of plasma Gal-3 expression in corresponding biopsy findings and RNA sequencing analysis.Method: In 249 patients (male/female: 155/94, age: 57.2 ± 16.3 years) who underwent kidney biopsy, plasma levels of Gal-3 were measured to estimate the association of renal fibrosis. Relationships between plasma Gal-3 levels, estimated glomerular filtration rate (eGFR) and renal histology findings were also assessed. We further examined the gene expression of Gal-3 in RNA-sequencing analysis in biopsy-proven patients.Results: Compared to patients without CKD, CKD patients had higher levels of plasma Gal-3 (1,016.3 ± 628.1 pg/mL vs. 811.6 ± 369.6 pg/ml; P = 0.010). Plasma Gal-3 was inversely correlated with eGFR (P = 0.005) but not with proteinuria. Higher Gal-3 levels were associated with interstitial fibrosis, tubular atrophy and vascular intimal fibrosis. RNA-sequencing analysis showed the upregulation of Gal-3 in fibrotic kidney biopsy samples, and the differentially expressed genes were mainly enhanced in immune cell activation and the regulation of cell-cell adhesion.Conclusions: Plasma Gal-3 levels are inverse correlated with eGFR but positively correlated with renal fibrosis, which may be involved in the immune response and associated pathways. These findings support the role of Gal-3 as a predictive marker of renal fibrosis.

Kidney involvement, termed lupus nephritis (LN), develops in 35–60% of patients with systemic lupus erythematosus, often early during the disease course. When not treated promptly and efficiently, LN may lead to rapid and severe loss of kidney function, being the reason why it is considered one of the most severe lupus manifestations. Despite improved pharmacotherapy, 5–20% of LN patients develop end-stage kidney disease within ten years from the LN diagnosis. While the principal ground of LN therapy is prevention of renal function worsening, resembling a race against nephron loss, consensual agreement upon outcome measures and clinically meaningful short- and long-term targets of LN therapy have yet to be determined. Literature points to the importance of inclusion of tissue-based approaches in the determination of those targets, and evidence accumulates regarding the importance of per-protocol repeat kidney biopsies in the evaluation of the initial phase of therapy and prediction of long-term renal prognosis. The latter leads to the hypothesis that the information gleaned from repeat biopsies may contribute to optimised therapeutic decision making, and, therefore, increased probability to attain complete renal response in the short term, and a more favourable renal prognosis within a longer prospect. The multinational project ReBioLup was recently designed to serve as a key contributor to form evidence about the role of per-protocol repeat biopsies in a randomised fashion and aspires to unify the global LN community towards improved kidney and patient survival.

The relationship between focal segmental glomerulosclerosis (FSGS) and pregnancy is complex and not completely elucidated. Pregnancy in patients with FSGS poses a high risk for complications, possibly due to hemodynamic factors, imbalance between angiogenic and antiangiogenic factors, and hormonal conditioning. Although poor clinical outcomes associated with collapsing FSGS are common outside of pregnancy, the prognosis during pregnancy is not well documented. We report 3 patients who developed collapsing FSGS during pregnancy, 2 of whom had presumed underlying FSGS. Two patients underwent biopsy during pregnancy, and 1, during the puerperium. None of the 3 patients improved spontaneously after delivery, and 1 experienced a rapid deterioration in kidney function and proteinuria after delivery. Aggressive immunosuppressive therapy led to a full response in 1 case (without chronic lesions) and to partial responses in the remaining 2 cases. These cases suggest that collapsing lesions should be considered in patients with FSGS who develop a rapid increase in serum creatinine level or proteinuria during pregnancy and that these lesions may at least partially respond to treatment.

BACKGROUND The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the biopsy. AIM To report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive medications. METHODS In a single-center observational study, we characterized the histopathological findings of allograft biopsies in kidney transplant recipients with graft failure within one year after the biopsy. RESULTS We identified 329 patients with graft failure that met the selection criteria between January 1, 2006 and December 31, 2016. The three most common biopsy findings were interstitial fibrosis and tubular atrophy (IFTA, 53%), acute rejection (AR, 43%) and transplant glomerulopathy (TG, 33%). Similarly, the three most common causes of graft failure based on the primary diagnosis were AR (40%), TG (17%), and IFTA (13%). Most grafts failed within two years of post-transplant (36%). Subsequently, approximately 10%-15% of grafts failed every two years: > 2-4 years (16%), > 4-6 years (13%), > 6-8 years (11%), > 8-10 years (9%) and > 10 years (16%). AR was the most common cause of graft failure in the first six years (48%), whereas TG was the most prevalent cause of graft failure after 6 years (32%) of transplant. CONCLUSION In the current era of immunosuppression, AR is still the most common cause of early graft failure, while TG is the most prevalent cause of late graft failure.

Introduction: Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE), resulting in increased morbidity and mortality. The gold standard for diagnosis of LN is a renal biopsy. Considering the importance of the biopsy in determining long-term prognostication and treatment decisions, it is crucial to assess renal histopathology with utmost accuracy and precision. This review represents a systematic search of published literature to estimate the degree of interpathologist reproducibility in current assessment of LN. Methods: Using the PubMed and Google Scholar search engines, studies analyzing the agreement of 4 or more pathologists assessing LN slides using the ISN/Renal Pathology Society (RPS) classification, activity index, and chronicity index were selected for analysis in this systematic review. Results: In reviewing 6 qualifying studies (those analyzing the agreement of 4 or more pathologists using the ISN/RPS classification, activity index, and chronicity index) for the assignment of ISN/RPS class was 0.325 (interquartile range [IQR] 0.2405–0.425), which is “poor.” The median interpathologist concordance values for the assigned activity index and chronicity index were “moderate”: 0.52 (IQR 0.51–0.69) and 0.49 (IQR 0.36–0.58), respectively. Conclusion: Thus, the current scoring using the ISN/RPS classification system and activity and chronicity indices for LN exhibits poor interpathologist agreement, which limits its use in clinical practice. Given that this can have severe repercussions on a patient’s treatment and prognosis, efforts to update pathology assessment guidelines, objectively measurable biomarkers, and deep learning approaches are strongly warranted. Keywords: chronic kidney disease, glomerulonephritis, inflammation, kidney biopsy, lupus

Rationale & Objective In 2009, the first case of acute kidney injury and occlusive red blood cell (RBC) tubular casts associated with a high international normalized ratio in a patient receiving warfarin was identified. This entity, named warfarin-related nephropathy, was later renamed anticoagulant-related nephropathy (ARN) after similar cases with other anticoagulants were described. We provide our 10-year experience with ARN based on a single-center kidney biopsy laboratory. Study Design The kidney pathology database at the Ohio State University Wexner Medical Center (OSUWMC) was searched for native kidney biopsy cases consistent with ARN. Clinical data were obtained from patient medical records. Setting & Participants Native kidney biopsies evaluated between January 1, 2009, and December 31, 2017 at OSUWMC. Results Among 8,636 native kidney biopsies reviewed at the OSUWMC, there were 41 (0.5%) patients for whom deterioration in kidney function could not be explained by kidney biopsy findings alone if anticoagulation was not considered. There were 63% men and 95% were white; average age was 62 ± 14 years. Most were on warfarin therapy (N = 28), although cases were also attributed to direct-acting anticoagulants (N = 2), antiplatelet medications (N = 1), heparin or enoxaparin (N = 4), and disseminated intravascular coagulopathy (N = 6). Morphologically, there was acute tubular necrosis and RBC casts. The majority of biopsies had an underlying glomerular disease and many patients had positive serologic test results. In all these cases, the severity of kidney failure, RBC tubular casts, and hematuria were disproportionate to glomerular morphologic changes. Limitations Selection bias in the decision to perform a kidney biopsy. Conclusions ARN is an uncommon diagnosis in kidney pathology practice, but it should be considered when the number of RBC tubular casts is disproportionate to the severity of glomerular changes in a kidney biopsy in patients either receiving anticoagulation therapy or who presented with acute coagulopathy. Our data suggest that anticoagulation aggravates underlying glomerular diseases rather than directly affecting the glomerular filtration barrier., Graphical abstract

Background Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant disease caused by mutations in APOE, the gene which encodes apolipoprotein E. LPG mainly affects Asian individuals, however occasional cases have also been described in Americans and Europeans. Herein we report two unrelated Brazilian patients with LPG in whom genetic analyses revealed the APOE-Osaka/Kurashiki variant. Case presentation - case 1 A 29-year-old Caucasian male sought medical attention with complaints of face swelling and foamy urine for the last 3 months. He denied a family history of kidney disease, consanguinity, or Asian ancestry. His tests showed proteinuria of 12.5 g/24 h, hematuria, serum creatinine 0.94 mg/dL, albumin 2.3 g/dl, total cholesterol 284 mg/dL, LDL 200 mg/dL, triglycerides 175 mg/dL, and negative screening for secondary causes of glomerulopathy. A kidney biopsy revealed intraluminal, laminated deposits of hyaline material in glomerular capillaries consistent with lipoprotein thrombi. These findings were confirmed by electron microscopy, establishing the diagnosis of LPG. His apolipoprotein E serum level was 72 mg/dL and genetic analysis revealed the APOE pathogenic variant c.527G > C, p.Arg176Pro in heterozygosis, known as the Osaka/Kurashiki mutation and positioned nearby the LDL receptor binding site. Case 2 A 34-year-old Caucasian man sought medical assessment for renal dysfunction and hypertension. He reported intermittent episodes of lower-limb edema for 3 years and a family history of kidney disease, but denied Asian ancestry. Laboratorial tests showed BUN 99 mg/dL, creatinine 10.7 mg/dL, total cholesterol 155 mg/dL, LDL 79 mg/dL, triglycerides 277 mg/dL, albumin 3.1 g/dL, proteinuria 2.7 g/24 h, and negative screening for secondary causes of glomerulopathy. His kidney biopsy was consistent with advanced chronic nephropathy secondary to LPG. A genetic analysis also revealed the Osaka/Kurashiki variant. He was transplanted a year ago, displaying no signs of disease relapse. Conclusion We report two unrelated cases of Brazilian patients with a diagnosis of lipoprotein glomerulopathy whose genetic assessment identified the APOE-Osaka/Kurashiki pathogenic variant, previously only described in eastern Asians. While this is the second report of LPG in Latin America, the identification of two unrelated cases by our medical team raises the possibility that LPG may be less rare in this part of the world than currently thought, and should definitely be considered when nephrotic syndrome is associated with suggestive kidney biopsy findings.

Background The diagnosis of antibody-mediated rejection (AMR) is reached using the Banff Classification for Allograft Pathology, which now includes gene expression analysis. In this study, we investigate the application of ‘increased expression of thoroughly validated gene transcripts/classifiers strongly associated with AMR’ as diagnostic criteria. Method We used quantitative real-time polymerase chain reaction for 10 genes associated with AMR in a retrospective cohort of 297 transplant biopsies, including biopsies that met the full diagnostic criteria for AMR, even without molecular data (AMR, n = 27), biopsies that showed features of AMR, but that would only meet criteria for AMR with increased transcripts [suspicious for AMR (AMRsusp), n = 49] and biopsies that would never meet criteria for AMR (No-AMR, n = 221). Results A 10-gene AMR score trained by a receiver-operating characteristic to identify AMR found 16 cases with a high score among the AMRsusp cases (AMRsusp-high) that had significantly worse graft survival than those with a low score (AMRsusp-low; n = 33). In both univariate and multivariate Cox regression analysis, the AMR 10-gene score was significantly associated with an increased hazard ratio (HR) for graft loss (GL) in the AMRsusp group (HR = 1.109, P = 0.004 and HR = 1.138, P = 0.012, respectively), but not in the whole cohort. Net reclassification index and integrated discrimination improvement analyses demonstrated improved risk classification and superior discrimination, respectively, for GL when considering the gene score in addition to histological and serological data, but only in the AMRsusp group, not the whole cohort. Conclusions This study provides evidence that a gene score strongly associated with AMR helps identify cases at higher risk of GL in biopsies that are suspicious for AMR but do not meet full criteria.

Background: Although several renal biopsy registry reports have been published worldwide, there are no data on primary glomerular disease trends in Turkey. Methods: Three thousand eight-hundred fifty-eight native kidney biopsy records were assessed in the Turkish Society of Nephrology Primary Glomerulopathy Working Group (TSN-GOLD) Registry. Secondary disease and transplant biopsies were not recorded in the registry. These records were divided into four periods, before 2009, 2009 to 2013, 2013–2017, and 2017–current. Results: A total of 3858 patients (43.6% female, 6.8% elderly) were examined. Nephrotic syndrome was the most common biopsy indication in all periods (58.6%, 53%, 44.1%, 51.6%, respectively). In the whole cohort, IgA nephropathy (IgAN) (25.7%) was the most common PGN with male predominance (62.7%), and IgAN frequency steadily increased through the periods (× 2 = 198, p < 0.001). MGN was the most common nephropathy in the elderly (> 65 years), and there was no trend in this age group. An increasing trend was seen in the frequency of overweight patients (× 2 = 37, p < 0.0001). Although the biopsy rate performed with interventional radiology gradually increased, the mean glomeruli count in the samples did not change over the periods. Conclusions: In Turkey, IgAN is the most common primary glomerulonephritis, and the frequency of this is increasing. © 2022, The Author(s), under exclusive licence to Springer Nature B.V.

Background Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults worldwide. A growing body of evidence indicates a pathogenic and autoimmune correlation between Helicobacter pylori infection, MN, and autoimmune liver disease. Case presentation A 47-year-old African American woman presented to our institution with epigastric pain and vomiting. In-patient hospital workup included a thorough abdominal evaluation including esophagogastroduodenoscopy and liver biopsy, which revealed active H. pylori infection and autoimmune hepatitis. The patient was incidentally also found to have nephrotic-range proteinuria. Renal workup including kidney biopsy established the diagnosis of MN. Proteinuria improved after initiation of triple therapy for H. pylori infection. Conclusion This case adds to the growing evidence of a correlation between H. pylori infection, MN, and autoimmune liver disease. This report demonstrates a unique case of a patient with MN, autoimmune hepatitis (AIH)/primary biliary cholangitis (PBC), and HP who underwent triple-eradication antibiotic treatment that resulted in an ultimate resolution of all these conditions.

Objectives: To analyze the clinical characteristics and renal pathological manifestations of patients with monoclonal gammopathy (MG) and kidney injury.Methods: This was a multicenter retrospective cohort study conducted at four tertiary hospitals in China. The study population comprised patients with MG admitted from January 1 2013 to December 31 2020. Hospitalization records, laboratory data, and kidney biopsy reports of all patients were collected from the electronic hospital information systems. The study outcomes included kidney disease progression and major hemorrhagic complications after kidney biopsy.Results: We identified 1,164 patients with MG, 782 (67.2%) of whom had underlying kidney injury. Of 101 patients who underwent kidney biopsy, 16 had malignant neoplasms. Amyloid nephropathy was the most common finding (n = 34, 33.7%), followed by membranous nephropathy (n = 18, 17.8%) and membranoproliferative nephritis (n = 8, 7.9%). Among 85 patients with non-malignant hematologic conditions who underwent kidney biopsy, 43 had MG of renal significance (MGRS) related lesions and 42 had MG-unrelated lesions. The risk of kidney disease progression was higher in patients with kidney injury than in patients without kidney injury.Conclusion: Among patients with MG and kidney injury, only 12.9% underwent kidney biopsy and more than 40% of these patients had MG-unrelated lesions. A kidney biopsy is safe and essential to maximize the possibility of correct diagnosis for patients with clinically suspected MG of renal significance (MGRS).

Light chain deposition disease (LCDD) is characterized by the deposition of monoclonal immunoglobulin light chains in the kidney, which can cause end-stage kidney disease if not treated. While kidney biopsy is required for definitive diagnosis, choosing an appropriate biopsy method may be problematic when examining patients with atrophic kidneys. A 66-year-old Japanese man was referred to our institution with a three-month history of leg edema. Clinical investigations revealed proteinuria levels of 7.5 g/day. CT-guided percutaneous kidney biopsy was selected as the biopsy method because atrophic kidneys were poorly visualized on ultrasonography. Kidney biopsy revealed nodular glomerulosclerosis, exclusive deposition of the κ chain, and powdery electron-dense deposits, all of which were indicative of LCDD. Bence-Jones protein was detected in the urine. The patient also had an abnormal serum-free light chain ratio. Bone marrow biopsy revealed multiple myeloma; therefore, the patient was diagnosed to have LCDD with multiple myeloma. The patient was treated with daratumumab, bortezomib, cyclophosphamide, and dexamethasone. After a one-year follow-up, the patient had hematological and renal responses without any treatment-related adverse effects. Our case demonstrates the effectiveness of daratumumab as a treatment for LCDD with nephrotic-range proteinuria. Additionally, we suggest that CT-guided kidney biopsy should be considered as a diagnostic test in patients with kidney atrophy when making a definitive diagnosis.

Introduction The risk of bleeding associated with transjugular kidney biopsies is unclear, and which patients are the best candidates for this route is unknown. Methods This was a retrospective cohort study comparing proportion of bleeding associated with transjugular versus percutaneous native kidney biopsies in all patients in France in the 2010–2019 period. Major bleeding at day 8 (i.e., blood transfusions, hemorrhage/hematoma, angiographic intervention, nephrectomy) and risk of death at day 30 were assessed, and we used a bleeding risk score initially developed for the percutaneous route. Results Our analysis included 60,331 patients (transjugular route: 5305; percutaneous route: 55,026 patients). The observed proportion of major bleeding varied widely (transjugular vs. percutaneous): 0.4% versus 0.5% for the lowest risk scores (0–4) to 19.1% versus 30.8% for the highest risk scores (≥35). Transjugular was more frequently used than percutaneous route (39% vs. 24%) when the risk score was ≥20 (15,133/60,331; 25% of all patients). Transjugular was associated with a lower risk of major bleeding than percutaneous route in multivariate analyses (odds ratio [OR]: 0.88 [0.78–0.99]), especially for scores ≥20 (OR: 0.83 [0.72–0.96], (i.e., 25% of patients). Major bleeding was associated with an increased risk of death both for transjugular (OR: 1.77 [1.00–3.14]) and percutaneous (OR: 1.80 [1.43–2.28]) routes. Conclusions The transjugular route is independently associated with a lower risk of bleeding than the percutaneous route, especially in high-risk patients identified by a preprocedure risk score ≥20 (i.e., 25% of patients). Major bleeding is associated with an increased risk of death for both routes., Graphical abstract

Background Smart lens is a magnifying device that turns the smartphone into a microscopic exploring instrument. It is a convenient and inexpensive tool as an on-site evaluation device for the kidney biopsy specimen. We demonstrate the benefit of using a handheld smartphone microscope compared to the standard procedure in allograft kidney specimens. Material and methods This was a cohort study of allograft kidney biopsies performed between June 2015 and November 2017 in Srinagarind Hospital, Khon Kaen University, Thailand. The clinical utility of the “Chula smart lens” applied to the smartphone as an on-site evaluation device was studied. Clinical data, diagnostic quality, and complications were retrospectively reviewed and compared between the smart lens group and the standard group. Results The study cohort consisted of 93 allograft kidney biopsies (standard:47, smart lens:46). The mean age was 40.6 (18–48) years, and 63 patients (67.7%) were male. By using the smart lens device, the number of obtained tissue cores was higher (3.5 vs 2.9, p = 0.019) and the inadequacy rate for diagnosis was significantly lower (7% vs 21.3%, p = 0.05). Conclusion Using a handheld smartphone microscope as an on-site evaluation device resulted in more positive glomeruli and diagnostic yield compared to the standard procedure., Kidney transplantation; Kidney biopsy; Smart lens; Microscopy; Yield

Background Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare hereditary disease caused by a variety of genetic mutations. Carriers of a mutation in the responsible genes are at risk of reaching end-stage kidney disease typically in middle age. The frequency of this disease is assumed to be underestimated because of a lack of disease-specific signs. Pathological findings obtained from kidney of uromodulin related ADTKD (ADTKD-UMOD) patients are regarded as non-specific and less-informative for its diagnosis. This research was undertaken to evaluate the significance of kidney biopsy in ADTKD-UMOD patients. Methods Thirteen patients from 10 families with nine identified uromodulin (UMOD) gene mutations who underwent kidney biopsy in the past were studied. Their kidney tissues were stained with anti-UMOD antibody in addition to conventional methods such as PAS staining. When positive, the numbers of tubules with visible UMOD protein accumulations were calculated based on the total numbers of UMOD expressing tubules. Pathological findings such as tubulointerstitial fibrosis, atrophy, inflammation and glomerulosclerosis were also evaluated and analyzed. Results Interstitial fibrosis and tubular atrophy were present in all 13 patients. Most atrophic tubules with thickening and lamellation of tubular basement membranes showed negative UMOD staining. In all but two patients with C94F mutations, massive accumulation of UMOD proteins was observed in the renal endoplasmic reticulum. UMOD accumulations were also detectable by PAS staining as polymorphic unstructured materials in the 11 patients at frequencies of 2.6–53.4%. 80.4% of the UMOD accumulations were surrounded by halos. The detection rate of UMOD accumulations positively correlated with eGFR. Glomerulosclerosis was detected in 11/13 patients, with a frequency of 20.0 to 61.1%, while no cystic dilatations of glomeruli were detected. Conclusions Massively accumulated UMOD proteins in ADTKD-UMOD kidneys are detectable not only by immunostaining using anti-UMOD antibody but also by conventional methods such as PAS staining, although their detection is not easy. These findings can provide important clues to the diagnosis of ADTKD-UMOD. Kidney biopsy in ADTKD-UMOD may be more informative than assumed previously.

Renal biopsy is an important diagnostic test which is used to extract kidney tissue with the help of a biopsy needle. It is frequently performed under ultrasonography or CT guidance. As with every other procedure, renal biopsy also carries some risks. Common complications of renal biopsy are damage to adjacent organs. Hemothorax is an exceedingly rare complication of renal biopsy. We report a case of a middle-aged female who developed a left-sided hemothorax after undergoing percutaneous renal biopsy with ablation and conducted a literature review of this rare complication.

12 p.-4 fig.-4 tab., Rationale & objective: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population., Study design: Multicenter, retrospective cohort study., Setting & participants: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN)., Predictors: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score., Outcome: Time to kidney failure., Analytical approach: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines., Results: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure., Limitations: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding., Conclusions: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure., Work in this study was supported by the Instituto de Salud Carlos III /Fondo Europeo de Desarrollo Regional (ISCIII/FEDER) grant PI16/01685 and Red de Investigación Renal (RedInRen) (RD12/0021/0029) (to MP), the Autonomous Region of Madrid (S2017/BMD-3673) (to MP); EGdeJ is supported by the Spanish “Ministerio de Ciencia, Innovación y Universidades" (RYC-2013-13395 and RTI2018-095955-B-100).

Renal failure or acute/chronic kidney damage may present as a clinical manifestation of rheumatic diseases. In addition treatment with DMARDs or biologic drugs may induce nephrotoxicity. In this case-based review, we present two patients with SpA under anti-TNF-α treatment admitted to our hospital because of renal failure and proteinuria. We review previously published yet isolated cases of TNF-α blocker-induced glomerular disease in patients with SpA. Renal manifestations are occasionally seen in patients with ankylosing spondylitis and psoriatic arthritis with IgA nephropathy being the most common of them. Anti-TNF-α agents although reportedly used for the treatment of glomerular nephropathy as a disease manifestation, they have been considered responsible for provoking renal damage in some cases. A diagnostic approach for patients with SpA treated with anti-TNF-α agents presenting with renal manifestations is proposed herein.

Background A kidney biopsy is being increasingly performed for the diagnosis of renal diseases. It is a reasonably safe procedure that helps not only to reach the correct diagnosis based on histopathological findings but also helps in predicting the clinical course and outcome. The pattern of kidney diseases varies not only in far apart geographical regions but also in the same country. This study was done to evaluate the demographic pattern and spectrum of kidney diseases in renal biopsy-proven cases in an admitted patient of a tertiary care hospital of northern India. Results The mean age of patients was 41.3 years ± 18.39 years, and the male-to-female ratio was 1.7:1. The most common indication for biopsy in this study was nephrotic syndrome (40.5%). The primary glomerular disease was most common, accounting for 57.5% of cases. Membranous nephropathy (MN) was the most frequently observed histopathological diagnosis not only in the primary glomerular disease category (22.9%) but of all cases (13.2%) as well. Among secondary cases, diabetic nephropathy was most frequent, constituting 43.4% cases. Interstitial and vascular diseases accounted for 18.8% and 1.8% of total cases, respectively. While minimal change disease (MCD) was the most common diagnosis in < 18-year age group, membranous nephropathy was most common above this age. Regarding the gender factor, membranoproliferative glomerulonephritis had an equal distribution among both genders, while MCD had a female preponderance. Conclusions Primary glomerular disease is the predominant kidney disease in northern India with MN being the most common histopathological diagnosis. The spectrum of kidney diseases varied with patient’s age and gender.

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Background Anti-low density lipoprotein receptor-related protein 2 (LRP2) nephropathy/anti-brush border antibody (ABBA) disease is a disorder characterized by acute tubulointerstitial injury associated with circulating antibodies to kidney proximal tubular brush border protein LRP2/megalin. Patients are typically elderly and present with acute kidney injury and subnephrotic proteinuria. They progress to end-stage renal disease with poor response to immunosuppressive therapies. Case presentation We report a case of a 29-year-old Chinese woman, who presented with nephrotic syndrome with normal kidney function. Kidney biopsy showed no obvious tubular injury or interstitial inflammation. Positive immunoglobulin G (IgG) staining was revealed along the brush border of proximal tubular cells. Anti-LRP2 antibody was identified in serum, consistent with a diagnosis of anti-LRP2 nephropathy. The patient achieved complete remission after receiving prednisone and cyclophosphamide. Conclusions Anti-LRP2 nephropathy can also present as nephrotic syndrome in young patients and complete remission from nephrotic syndrome may be achieved after immunosuppressive therapy.

Background While histopathologic changes correlate with functional impairment in cross-sectional studies of diabetic nephropathy (DN), whether these findings predict future rate of kidney function loss remains uncertain. We thus sought to examine the relationship between kidney histopathology, incidence of end-stage kidney disease (ESKD), and rate of estimated glomerular filtration rate (eGFR) loss in DN. Methods In this longitudinal cohort study, we studied 50 adults diagnosed with biopsy-proven DN. We analyzed the histopathologic parameters of each patient’s kidney biopsy, as defined by the Renal Pathology Society classification system for DN, and tracked all available eGFR measurements post-biopsy. We additionally collected baseline clinical parameters (at the time of biopsy), including eGFR, albumin-to-creatinine ratio (ACR), and hemoglobin A1c. Multivariable linear regression was used to assess the relationship between histologic and clinical parameters at the time of the biopsy and eGFR slope. Kaplan-Meier curves and Cox regression were used to evaluate the association between histologic and clinical parameters and ESKD incidence. Results Progression to ESKD was associated with worsening interstitial fibrosis score (p = 0.05), lower baseline eGFR (p = 0.02), higher ACR (p = 0.001), and faster eGFR decline (p .41). Conclusions Renal histology predicts ultimate progression to ESKD, but not the rate of progression. Future work is required to identify novel predictors of rapid functional decline in patients with diabetic nephropathy.

Background: In the absence of a histological diagnosis, persistent albuminuria is globally accepted as the main diagnostic criteria for diabetic kidney disease (DKD). Methods: In the present retrospective study, we evaluated data from an Italian cohort of 42 deceased diabetic donors (mainly with type 2 diabetes). Using the kidney biopsies obtained at the time of donation to evaluate single or double allocation based on Karpinski score, we determined the prevalence of histological lesions attributable to diabetes. Results: All 42 donors presented with proteinuria in the normal range and an estimated glomerular filtration rate (eGFR) (chronic kidney disease [CKD]-EPI) >60 mL/min/1.73 m2. A kidney biopsy was available for 36 patients; of these, one was not interpretable and 32 showed histopathological lesions consistent with DKD and encompassing all histological classes. Thus, we found a relatively high proportion of histologically proven DKD that had been clinically undiagnosed, as none of the patient had significant proteinuria and eGFR 2. Conclusions: The data we present here support the need to implement routine kidney biopsies in normoalbuminuric diabetic subjects in the early stages of CKD. Such strategy may help to improve risk stratification in diabetic patients and guide therapeutic decisions during the early stages of the disease.

Background Practice patterns and bleeding complications of percutaneous native kidney biopsy (PNKB) have not recently been investigated and the Japanese Society of Nephrology performed a nationwide questionnaire survey in 2018. Methods The survey consisted of nine sections about PNKB: (1) general indications; (2) indications for high-risk patients; (3) informed consent; (4) pre-biopsy evaluation; (5) procedures; (6) sedation; (7) post-biopsy hemostasis, bed rest, and examinations; (8) bleeding complications; and (9) specimen processing. A supplementary survey examined bleeding requiring transcatheter arterial embolization (TAE). Results Overall, 220 directors of facilities (nephrology facility [NF], 168; pediatric nephrology facility [PF], 52) completed the survey. Indications, procedures, and monitoring protocols varied across facilities. Median lengths of hospital stay were 5 days in NFs and 6 days in PFs. Gauge 14, 16, 18 needles were used in 5%, 56%, 33% in NFs and 0%, 63%, 64% in PFs. Mean limits of needle passes were 5 in NFs and 4 in PFs. The bed rest period was 16–24 h in 60% of NFs and 65% of PFs. Based on 17,342 PNKBs, incidence rates of macroscopic hematuria, erythrocyte transfusion, and TAE were 3.1% (NF, 2.8%; PF, 6.2%), 0.7% (NF, 0.8%; PF, 0%), and 0.2% (NF, 0.2%; PF, 0.06%), respectively. Forty-six percent of facilities processed specimens all for light microscopy, immunofluorescence, and electron microscopy, and 21% processed for light microscopy only. Timing of bleeding requiring TAE varied among PNKB cases. Conclusion Wide variations in practice patterns of PNKB existed among facilities, while PNKBs were performed as safely as previously reported. Electronic supplementary material The online version of this article (10.1007/s10157-020-01869-w) contains supplementary material, which is available to authorized users.