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Introduction: As life expectancy increases, geriatric patients are affected by kidney disease; nephrologists are increasingly faced with a geriatric population requiring kidney biopsy (KB). Objective: To analyze geriatric patients’ histopathological diagnosis, clinical presentation, and biopsy indications. Methods: All patients who underwent native KB in our center between 2017 and 2023 were included. Histopathological diagnosis, clinical presentation, and biopsy indications in geriatric patients were compared with the non-geriatric group. Results: Among the 511 included patients, those older than 65 years (n:81, 15.8%) were analyzed and compared with those aged 18–64 years (n:430, 84.2%). The median age of the patients was 68 (IQR 66-72) years, and 56.8% were male. Non-nephrotic proteinuria was the most common biopsy indication in the geriatric group (27.2%, p: 0.004). The most frequent primer glomerular disease (PGD) was membranous glomerulonephritis (MGN). MGN (33.3%) was the leading cause of nephrotic syndrome. The geriatric group’s most frequent Primary Glomerular Disease (PGD) histopathological patterns were MGN, FSGS, and pauci-immune GN. The frequency of acute kidney injury was significantly higher in the geriatric group (19.8%) compared to the non-geriatric group (11.6%) (p = 0.046). Secondary glomerular diseases (SGD) were more common than PGD and tubulointerstitial nephritis. Diabetic nephropathy was the most common SGD in both the geriatric and non-geriatric groups (24.7% and 15.6%). Conclusions: The spectrum of biopsy-proven kidney disease in the geriatric patients seen in our study differs from that of the non-geriatric population. KB provides valuable information with diagnostic, therapeutic, and prognostic implications in these patients, Introducción: A medida que aumenta la esperanza de vida, los pacientes geriátricos se ven afectados por la enfermedad renal; los nefrólogos se enfrentan cada vez más a una población geriátrica que requiere biopsia renal (BR). El objetivo de este estudio fue analizar el diagnóstico histopatológico, la presentación clínica y las indicaciones de biopsia en pacientes geriátricos. Materiales y métodos: Se incluyeron todos los pacientes sometidos a BR nativa en nuestro centro entre 2017 y 2023. Se comparó el diagnóstico histopatológico, la presentación clínica y las indicaciones de biopsia en pacientes geriátricos con el grupo no geriátrico. Resultados: De los 511 pacientes incluidos, se analizaron los mayores de 65 años (n:81, 15,8%) y se compararon con los que tenían entre 18 y 64 años (n:430, 84,2%). La edad media de los pacientes fue de 68 (IQR 66-72) años, y el 56,8% eran varones. La proteinuria no nefrótica fue la indicación de biopsia más frecuente en el grupo geriátrico (27,2%, p: 0,004). La enfermedad glomerular primaria (PGD) más frecuente fue la glomerulonefritis membranosa (GNM). La GNM (33,3%) fue la principal causa de síndrome nefrótico. Los patrones histopatológicos más frecuentes de PGD en el grupo geriátrico fueron GNM, GEFS y GN pauciinmune. La frecuencia de lesión renal aguda fue significativamente mayor en el grupo geriátrico (19,8%) en comparación con el grupo no geriátrico (11,6%) (p = 0,046). Las enfermedades glomerulares secundarias (EGS) fueron más frecuentes que la PGD y la nefritis tubulointersticial. La nefropatía diabética fue la EGS más frecuente tanto en el grupo geriátrico como en el no geriátrico (24,7% y 15,6%). Conclusiones: El espectro de la enfermedad renal probada mediante biopsia en los pacientes geriátricos observados en nuestro estudio difiere del de la población no geriátrica. La BR aporta información útil con implicaciones diagnósticas, terapéuticas y pronósticas en estos pacientes

AIM: The Swedish Renal Registry (SRR) is a unique national quality registry that monitors the clinical trajectory of patients with chronic kidney disease (CKD). We have validated the biopsy data registered in the SRR for IgA Nephropathy (IgAN) diagnosis. METHODS: In total 25% of all patients (n = 142), registered with IgAN in the SRR after having performed a kidney biopsy during 2015-2019, were randomly selected. We obtained original biopsy and medical records for 139 (98%) patients. We evaluated the IgAN diagnosis using a standardized template, calculated its positive predictive value (PPV) with 95% confidence interval (CI) and reported clinical features at the time of diagnosis. RESULTS: A histological and clinical diagnosis of IgAN was confirmed in 132 of the 139 patients, yielding a PPV of 95% (95% CI 90-98%). Median age was 46 years (range: 18-85) and the male:female ratio was 2.1:1. The median creatinine level was 123 µmol/L, with a corresponding estimated glomerular filtration rate (eGFR) level of 51 mL/min/1.73m2. Histological features of IgA deposits were seen in all patients, hypercellularity in 102/132 (77.2%), C3 deposits in 98/132 (72.4%) and C1q deposits in 27/132 (20.5%) of the cases. CONCLUSION: Validating data is not research per se, but continuous validation of medical registries is an important feature necessary to ensure reliable data and the foundation of good epidemiological data for future research. Our validation showed a high PPV (95%) for IgAN diagnosis registered in the SRR. Clinical characteristics were consistent with previous reports. The biopsy data in the SRR will be a valuable resource in future IgAN research.

ntroduction: This study aims to examine the patients who underwent kidney biopsies due to urinary abnormalities and/or kidney failure in our unit and whether there was a change in the distribution of glomerular diseases before and after the coronavirus disease-2019 pandemic. Materials and Methods: The patients were divided into pre-pandemic (group-1) and post-pandemic (group-2). The frequency of renal pathology results and the representative clinical syndrome were compared between groups. Results: 452 patients [median age: 48 years (IQR: 36.25- 58), 54.8% male], (group-1, n:215; 47.57%), (group-2, n:237; 52,43%)) were included in the study. Non-nephrotic proteinuria was the most common indication in both two groups. The frequency of nephrotic syndrome was significantly higher in group-1 (19.5%, p:0.007). The acute or rapidly progressive renal failure frequency was significantly higher in group-2 (p:0.021). The median 24-hour urine protein level was 1354 (IQR:521-3000) mg/day, significantly lower in group-2 (p: 0,001). Primary glomerular disease was the most common category (42.19%), followed by secondary glomerular diseases (35.02%) and tubulointerstitial nephropathies (6.32%) in group-2. The frequency of primary glomerular disease was significantly higher in group-1 (p:0.022). Hypertensive nephrosclerosis (6.80%) was common in group-2 compared to group-1 (p:0,026). Conclusion: We did not detect an increase in the prevalence of primary glomerular disease; on the contrary, there was a decrease in the prevalence of primary glomerular disease in the post-pandemic period. The acute or rapidly progressive renal failure frequency was significantly higher in the post-pandemic period. Further multicenter studies are needed to determine the effect of the COVID-19 pandemic on glomerular diseases., Introducción: El objetivo de este estudio es examinar a los pacientes sometidos a biopsia renal por anomalías urinarias y/o insuficiencia renal en nuestra unidad y, examinar si hubo un cambio en la distribución de las enfermedades glomerulares antes y después de la pandemia por coronavirus-2019. Material y métodos: Los pacientes se dividieron en dos grupos: prepandémicos (grupo 1) y postpandémicos (grupo 2). Se comparó la frecuencia de los resultados de la patología renal y el síndrome clínico representativo entre los grupos. Resultados: Se incluyeron en el estudio 452 pacientes [mediana de edad: 48 años (IQR: 36,25- 58), 54,8% varones], (grupo-1, n:215; 47,57%), (grupo-2, n:237; 52,43%)). La proteinuria no nefrótica fue la indicación más frecuente en ambos grupos. La frecuencia de síndrome nefrótico fue significativamente mayor en el grupo-1 (19,5%, p:0,007). La frecuencia de insuficiencia renal aguda o rápidamente progresiva fue significativamente mayor en el grupo-2 (p:0,021). La mediana del nivel de proteínas en orina de 24 horas fue de 1354 (IQR:521-3000) mg/día y fue significativamente menor en el grupo-2 (p:0,001). La enfermedad glomerular primaria fue la categoría más frecuente (42,19%), seguida de las enfermedades glomerulares secundarias (35,02%) y las nefropatías tubulointersticiales (6,32%) en el grupo-2. La frecuencia de enfermedad glomerular primaria fue significativamente mayor en el grupo-1 (p:0,022). La nefroesclerosis hipertensiva (6,80%) fue más frecuente en el grupo-2 (p:0,026). Conclusiones: No se detectó un aumento de la prevalencia de la enfermedad glomerular primaria, al contrario, hubo una disminución de la prevalencia de la enfermedad glomerular primaria en el período pospandémico. La frecuencia de insuficiencia renal aguda o rápidamente progresiva fue significativamente mayor en el periodo postpandémico. Se necesitan más estudios multicéntricos para determinar el efecto de la pandemia de COVID-19 en las enfermedades glomerulares.

Nephrotic syndrome (NS) in children responds well to steroid therapy, therefore kidney biopsy before treatment is often avoided. However, the indications for kidney biopsy in children with NS with microscopic hematuria are controversial. In the present study, the indications for pretreatment kidney biopsy at the onset of pediatric patients with NS with microscopic hematuria were evaluated. Clinicopathologic correlations were retrospectively examined from patients enrolled in a database from January 2005 to December 2018. Fifty-nine pediatric patients with NS were enrolled. Among them, 6 with hypocomplementemia, gross hematuria, or onset at less than 1 year of age were excluded. Of the 53 enrolled patients, 38 without hematuria were assigned to Group A, and 15 patients with microscopic hematuria comprised Group B. There was a significant difference in the renal biopsy rate between Group A (n = 19, 50%) and Group B (n = 13, 87%) (P = 0.01). Two patients in Group B avoided biopsy. Pathology results for patients in Group B included 4 patients with minimal change disease, 2 with focal segmental glomerulosclerosis, 6 with mesangial proliferative glomerulonephritis (non-IgA), and 1 with membranous lupus nephritis (LN). The first three are commonly found in pediatric patients with NS, and all are treated with steroid therapy. LN could be diagnosed by kidney biopsy at the time of steroid resistance. LN presenting with nephrotic syndrome is also treated with steroids. Thus, the treatment strategy would not have changed even if the kidney biopsy had been performed before treatment. These results suggest that renal biopsy is not always mandatory during the initial stage for pediatric patients with NS with microscopic hematuria.

Introduction: Biopsy is an important diagnostic technique for the treatment of patients with kidney disease. It is possible to make an etiological diagnosis, in addition to determining the prognosis and the probability of response to treatment. Objective: Determine the main indications and the most frequent histopathological findings in renal biopsies performed in the Department of Adult Nephrology of the Hospital de Clínicas from April 2016 to November 2022. Methods: Observational, retrospective, cross-sectional study. Results: 130 biopsies were performed in the period studied, 50.7% in female patients. The main reasons were: nephrotic syndrome 34.6%, systemic lupus ery- thematosus 31.5% and transplant patients with suspected rejection 18.4%. The following most frequent histopathological diagnoses were obtained according to the different indications: focal and segmental glomerulosclerosis-FSGS (24), stage IV lupus nephritis (24) and graft rejection (16), respectively. 0.7% of patients pre- sented nephrectomy as a complication and retroperitoneal hematoma in an equal percentage. Conclusion: 130 renal biopsies were performed, with no important difference between sexes. The main indications were: nephrotic syndrome, systemic lupus erythematosus and suspected graft rejection, with the most frequent histopathological diagnoses being FSGS, stage IV lupus nephritis and rejection, respectively. Complications occurred in 1.4%., Introducción: La biopsia es una técnica de diagnóstico primordial para el tratamiento del paciente con afectación renal. Es posible realizar un diagnóstico etiológico, determinar el pronóstico y la probabilidad de respuesta al tratamiento. Objetivo: Determinar las principales indicaciones y los hallazgos histopatológicos más frecuentes en las biopsias renales realizadas en el Departamento de Nefrología Adultos del Hospital de Clínicas desde abril de 2016 a noviembre de 2022. Métodos: Estudio observacional, retrospectivo, corte transversal. Resultados: Se realizaron 130 biopsias en el período estudiado, 50,7% en pacientes de sexo femenino. Los principales motivos fueron: síndrome nefrótico 34,6%, lupus eritematoso sistémico 31,5% y pacientes trasplantados con sospecha de rechazo 18,4%. Se obtuvieron los siguientes diagnósticos histopatológicos más frecuentes según las diferentes indicaciones: glomeruloesclerosis focal y segmentaria-GEFS (24), nefritis lúpica estadio IV (24) y rechazo del injerto (16). El 0,7% de los pacientes presentó como complicación la nefrectomía e igual porcentaje un hematoma retroperitoneal. Conclusión: Se realizaron 130 biopsias renales, no habiendo diferencia importante entre ambos sexos. Las principales indicaciones fueron: síndrome nefrótico, lupus eritematoso sistémico y sospecha de rechazo del injerto, siendo los diagnósticos histopatológicos más frecuentes GEFS, nefritis lúpica estadio IV y rechazo, respectivamente. Se presentaron complicaciones en 1,4%.

Introduction: Biopsy is an important diagnostic technique for the treatment of patients with kidney disease. It is possible to make an etiological diagnosis, in addition to determining the prognosis and the probability of response to treatment. Objective: Determine the main indications and the most frequent histopathological findings in renal biopsies performed in the Department of Adult Nephrology of the Hospital de Clínicas from April 2016 to November 2022. Methods: Observational, retrospective, cross-sectional study. Results: 130 biopsies were performed in the period studied, 50.7% in female patients. The main reasons were: nephrotic syndrome 34.6%, systemic lupus ery- thematosus 31.5% and transplant patients with suspected rejection 18.4%. The following most frequent histopathological diagnoses were obtained according to the different indications: focal and segmental glomerulosclerosis-FSGS (24), stage IV lupus nephritis (24) and graft rejection (16), respectively. 0.7% of patients pre- sented nephrectomy as a complication and retroperitoneal hematoma in an equal percentage. Conclusion: 130 renal biopsies were performed, with no important difference between sexes. The main indications were: nephrotic syndrome, systemic lupus erythematosus and suspected graft rejection, with the most frequent histopathological diagnoses being FSGS, stage IV lupus nephritis and rejection, respectively. Complications occurred in 1.4%., Introducción: La biopsia es una técnica de diagnóstico primordial para el tratamiento del paciente con afectación renal. Es posible realizar un diagnóstico etiológico, determinar el pronóstico y la probabilidad de respuesta al tratamiento. Objetivo: Determinar las principales indicaciones y los hallazgos histopatológicos más frecuentes en las biopsias renales realizadas en el Departamento de Nefrología Adultos del Hospital de Clínicas desde abril de 2016 a noviembre de 2022. Métodos: Estudio observacional, retrospectivo, corte transversal. Resultados: Se realizaron 130 biopsias en el período estudiado, 50,7% en pacientes de sexo femenino. Los principales motivos fueron: síndrome nefrótico 34,6%, lupus eritematoso sistémico 31,5% y pacientes trasplantados con sospecha de rechazo 18,4%. Se obtuvieron los siguientes diagnósticos histopatológicos más frecuentes según las diferentes indicaciones: glomeruloesclerosis focal y segmentaria-GEFS (24), nefritis lúpica estadio IV (24) y rechazo del injerto (16). El 0,7% de los pacientes presentó como complicación la nefrectomía e igual porcentaje un hematoma retroperitoneal. Conclusión: Se realizaron 130 biopsias renales, no habiendo diferencia importante entre ambos sexos. Las principales indicaciones fueron: síndrome nefrótico, lupus eritematoso sistémico y sospecha de rechazo del injerto, siendo los diagnósticos histopatológicos más frecuentes GEFS, nefritis lúpica estadio IV y rechazo, respectivamente. Se presentaron complicaciones en 1,4%.

SCOPUS: ed.j, info:eu-repo/semantics/published

Membranous nephropathy is an uncommon cause of nephrotic syndrome in pediatrics. We 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. Sixteen 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. Our 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.

The kidney is commonly involved in multiple myeloma and other disorders producing monoclonal immunoglobulins. Crystalglobulinemia is a rare condition characterized by spontaneous crystallization and deposition of monoclonal immunoglobulins within the microvasculature of the kidney and other organs, leading to inflammation, ischemia, and end-organ damage. The present case and literature review highlight the clinical spectrum, diagnostic challenges, management, and outcomes of this underrecognized complication of monoclonal gammopathy. Crystalglobulin-associated kidney disease should be suspected in patients with rapidly progressive kidney disease associated with hematuria, proteinuria, extrarenal lesions (ie, skin and joints), and monoclonal gammopathy. Kidney biopsy is critical to the diagnosis, which relies on the identification by ultrastructural analysis of electron-dense crystalline structures composed of a monoclonal immunoglobulin within the kidney microvasculature. Conventional immunofluorescence on frozen tissue frequently fails to detect monoclonal protein deposits, and pronase-based antigen retrieval on paraffin-embedded material or immunoelectron microscopy is required to unmask antigenic epitopes located within crystalline inclusions. Early intervention combining treatment of clonal cell proliferation and plasma exchanges is warranted to reduce the burden of this rare but dramatic complication of monoclonal gammopathy.

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.

There are few published studies examining cytomorphologic alterations in endothelial cells in human tissue. One fascinating but largely unexplored endothelial morphologic variant is large multinucleated variant endothelial cells (MVECs). To our knowledge, there are no published reports of MVECs identified in the kidney. Here, we present a case series of 4 kidney biopsies from allograft kidneys whose microvasculature contained MVECs. Electron microscopy confirmed the endothelial identity in all cases. A broad immunohistochemical panel used in 1 case was also confirmatory of an endothelial cell origin. All cases occurred in the setting of chronic, active, antibody-mediated rejection, and alternative etiologies, such as viral infections, were excluded. Two patients were positive for concurrent donor-specific antibodies, and 3 of the 4 cases occurred in second kidney allografts. We speculate that MVECs are a rare or often overlooked finding often confused for megakaryocytes and may be associated with chronic endothelial cell injury in the setting of chronic antibody-mediated rejection.

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.

Introduction Anticoagulant-related nephropathy (ARN) is a relatively novel recognized entity characterized by hematuria-associated acute kidney injury (AKI) in the context of overanticoagulation. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to evaluate underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed. Methods Retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. Results A total of 26 patients were included with a median age of 75 years (62–80) and a follow-up period of 10.1 months. Of the patients, 80% were male, and most cases (92%) were on anticoagulation with vitamin K antagonists (VKAs). At admission, median serum creatinine (SCr) level was 4.2 mg/dl (2.8–8.2), median international normalized ratio (INR) 2.4 (1.5–3.4), and 11 patients (42%) required acute dialysis during hospitalization. Kidney biopsy results revealed that all patients except 1 had an underlying nephropathy: IgA nephropathy (IgAN) in 19, probable IgAN in 1, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1. At 12 weeks after discharge, only 6 subjects (24%) attained complete kidney recovery whereas 7 (28%) remained on chronic dialysis. Conclusion IgAN was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.

Introduction Anticoagulant-related nephropathy (ARN) is a relatively novel recognized entity characterized by hematuria-associated acute kidney injury (AKI) in the context of overanticoagulation. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to evaluate underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed. Methods Retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. Results A total of 26 patients were included with a median age of 75 years (62–80) and a follow-up period of 10.1 months. Of the patients, 80% were male, and most cases (92%) were on anticoagulation with vitamin K antagonists (VKAs). At admission, median serum creatinine (SCr) level was 4.2 mg/dl (2.8–8.2), median international normalized ratio (INR) 2.4 (1.5–3.4), and 11 patients (42%) required acute dialysis during hospitalization. Kidney biopsy results revealed that all patients except 1 had an underlying nephropathy: IgA nephropathy (IgAN) in 19, probable IgAN in 1, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1. At 12 weeks after discharge, only 6 subjects (24%) attained complete kidney recovery whereas 7 (28%) remained on chronic dialysis. Conclusion IgAN was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.

BackgroundThe 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.MethodsWe 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 <50%). Interstitial fibrosis and tubular atrophy scores from kidney biopsy reports were used as ground-truth.ResultsThe two machine learning models demonstrated similar positive predictive value (0.886 versus 0.935) and accuracy (0.831 versus 0.879).ConclusionsIn summary, machine learning algorithms are a promising noninvasive diagnostic tool to quantify kidney fibrosis from CT scans. The clinical utility of these prediction tools, in terms of avoiding renal biopsy and associated bleeding risks in patients with severe fibrosis, remains to be validated in prospective clinical trials.

Introduction: In Mexico, chronic kidney disease (CKD) represents a major health problem, and glomerulopathies (GP) represent the third leading cause of CKD. Aim: From a database of native kidney biopsies (KB), describe the different morphological patterns of GP in Mexico. Methods: Records of native KB in a nephropathology referral center were evaluated by a single nephropathologist. The final diagnosis in each case was based on clinical parameters and histopathological findings. Results: 2084 KB were analyzed, patients were 34.4±17.6 years of age, there were 1085 KB (52.1%) in females; nephrotic syndrome was most frequent in males (p<0.001), and nephritic syndrome was more frequent in females (p <0.001). Primary GP and túbulo-interstitial diseases were most diagnosed in males (p <0.01). Lupus nephritis (LN) was the most-reported secondary GP. Focal and segmental glomerulosclerosis (FSGS) was the primary GP most often diagnosed in both genders. The most frequently detected vascular disease was immunoglobulin A vasculitis. Nephrotic syndrome was the most frequent indication for KB (42.9%), followed by: nephritic syndrome (23.9%), isolated proteinuria (16.4%), acute kidney injury (8.7%), asymptomatic urinary alterations (6.2%), and CKD (1.8%). Conclusions: The most frequently observed primary GP was FSGS, and LN was the most frequent secondary GP, predominantly in females, and IgA nephropathy was observed more frequently in comparison with other series published in Mexico. There were significant differences in GP presentation in relation to patient sex and age., Introducción: En México, la enfermedad renal crónica (ERC) representa un gran problema de salud y las glomerulopatías (GP) representan la tercera causa de ERC. Objetivo:Describir, desde una base de datos de biopsias renales (BR) nativas, los diferentes patrones morfológicos de GP en México. Métodos: Se analizaron registros de BR de riñón nativo en un centro de referencia en nefropatología, todas las BR fueron evaluadas por una única nefropatóloga (AVP). El diagnóstico final en cada caso se basó en parámetros clínicos e histopatológicos. Resultados: Fueron revisadas 2084 BR, con edad de 34.4 ± 17.6 años. 1085 BR (52.1%) en género femenino; el síndrome nefrótico fue más frecuente en hombres (p<0.001) y síndrome nefrítico fue más frecuente en mujeres (p<0.001). GP primarias y nefropatías túbulo-intersticiales fueron más diagnosticadas en hombres (p<0.01). Nefritis lúpica (NL) fue la GP secundaria más reportada. La glomeruloesclerosis focal y segmentaria (GEFS) fue la GP primaria diagnosticada con mayor frecuencia en ambos géneros. Vasculitis por inmunoglobulina A fue la enfermedad vascular más frecuentemente detectada. Síndrome nefrótico fue la indicación más frecuente de BR (42.9%), seguido de: síndrome nefrítico (23.9%), proteinuria aislada (16.4%), daño renal agudo (8.7%), alteraciones urinarias asintomáticas (6.2%) y ERC (1.8%). Conclusiones: La GP primarias con mayor frecuencia fueron GEFS. Las GP secundarias más frecuentemente reportadas fueron NL, predominantemente en mujeres. Se observó nefropatía IgA con mayor frecuencia en comparación con otras series publicadas en México. Hubo diferencias significativas en la presentación de GP en relación con el género y la edad del paciente.

Introduction Anticoagulant-related nephropathy (ARN) is a relatively novel recognized entity characterized by hematuria-associated acute kidney injury (AKI) in the context of overanticoagulation. Preexisting or underlying kidney disease seems to be a predisposing factor; however, few studies have described histologic findings in patients with ARN. We aimed to evaluate underlying kidney pathology in patients on oral anticoagulation who presented an episode of AKI with hematuria in whom a kidney biopsy was performed. Methods Retrospective observational multicenter case study in patients treated with oral anticoagulants who developed macroscopic or intense hematuria followed by AKI. Only patients with available kidney biopsy specimens were included. Histologic findings and clinical data throughout follow-up were analyzed. Results A total of 26 patients were included with a median age of 75 years (62–80) and a follow-up period of 10.1 months. Of the patients, 80% were male, and most cases (92%) were on anticoagulation with vitamin K antagonists (VKAs). At admission, median serum creatinine (SCr) level was 4.2 mg/dl (2.8–8.2), median international normalized ratio (INR) 2.4 (1.5–3.4), and 11 patients (42%) required acute dialysis during hospitalization. Kidney biopsy results revealed that all patients except 1 had an underlying nephropathy: IgA nephropathy (IgAN) in 19, probable IgAN in 1, diabetic nephropathy in 3, nephrosclerosis in 1, and idiopathic nodular glomerulosclerosis in 1. At 12 weeks after discharge, only 6 subjects (24%) attained complete kidney recovery whereas 7 (28%) remained on chronic dialysis. Conclusion IgAN was the most common underlying kidney disease in our biopsy-proven series of ARN, in which a significant percentage of patients did not achieve kidney function recovery.

Introduction: Kidney biopsy is performed to assess if an extended criteria graft can be used for transplantation. It may be performed before or after cross-clamping during organ procurement. This study aims to evaluate whether the timing of biopsy may modify cold ischemia times (CIT) and/or graft outcomes. Methods: Kidney transplants performed in our center from January 2007 to December 2017 were analyzed. Grafts with preimplantation kidney biopsy were included. Biopsies were performed during surgical back table (ex situ kidney biopsy [ESKB]) until 2012 and since then before the aortic cross-clamping (in situ kidney biopsy [ISKB]). To overcome biases owing to different distributions, a propensity score model was developed. The study population consists in 322 patients, 115 ESKB, and 207 ISKB. Results: CIT was significantly lower for ISKB (730 min ISKB vs. 840 min ESKB, p value = 0.001). In both crude (OR 0.27; 95% confidence interval, 95% CI 0.12-0.60; p value = 0.002) and adjusted analyses (OR 0.37; 95% CI 0.14-0.94; p value = 0.039), ISKB was associated with a reduced odd of graft loss when compared to ESKB. Discussion/Conclusion: Performing preimplantation kidney biopsy during the recovery, prior to the aortic cross-clamping, may be a strategy to reduce CIT and improve transplant outcomes.

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., Funding agencies:King Gustaf V's 80-year Foundation FAI-2019-0635Professor Nanna Svartz Foundation 2019-00290Ulla and Roland Gustafsson Foundation 2019-12Fondation Saint-LucFonds de la Recherche Scientifique - FNRS

Introduction: Kidney biopsy is performed to assess if an extended criteria graft can be used for transplantation. It may be performed before or after cross-clamping during organ procurement. This study aims to evaluate whether the timing of biopsy may modify cold ischemia times (CIT) and/or graft outcomes. Methods: Kidney transplants performed in our center from January 2007 to December 2017 were analyzed. Grafts with preimplantation kidney biopsy were included. Biopsies were performed during surgical back table (ex situ kidney biopsy [ESKB]) until 2012 and since then before the aortic cross-clamping (in situ kidney biopsy [ISKB]). To overcome biases owing to different distributions, a propensity score model was developed. The study population consists in 322 patients, 115 ESKB, and 207 ISKB. Results: CIT was significantly lower for ISKB (730 min ISKB vs. 840 min ESKB, p value = 0.001). In both crude (OR 0.27; 95% confidence interval, 95% CI 0.12-0.60; p value = 0.002) and adjusted analyses (OR 0.37; 95% CI 0.14-0.94; p value = 0.039), ISKB was associated with a reduced odd of graft loss when compared to ESKB. Discussion/Conclusion: Performing preimplantation kidney biopsy during the recovery, prior to the aortic cross-clamping, may be a strategy to reduce CIT and improve transplant outcomes.

Background&objectives: Glomerular size has been demonstrated as an independent prognostic marker in IgA nephropathy. Using digital pathology, this study aims to determine reproducibility of GD measurement, defining minimum number of glomeruli required for accurate measurement, and correlating GD with MEST-C scores. Method(s): The diameter of all non-sclerosed glomeruli from renal biopsies of 420 patients with IgA nephropathy was measured independently by 3 pathologists, using the ruler device on Aperio ImageScope software. Inter-observer and intra-observer variability was then assessed using interclass correlation coefficient (ICC). Mean and maximum GD were correlated with Oxford Classification MEST- C scores, using the independent samples T test. Result(s): There was excellent interobserver (between 3 pathologists) and intra-observer (one pathologist measuring 2 levels from the same biopsy) correlation with ICC of >0.9. Accuracy of measurement ofmaximumand mean GD increased with number of glomeruli measured, levelling off between 12-15 non-sclerosed glomeruli. T score was the only MEST-C variable to significantly correlate with glomerular diameter. Conclusion(s): Use of the ruler device on digital slide viewing software provides a rapid and reproducible estimate of glomerular diameter. Greater than 12 non-sclerosed glomeruli are required to provide an accurate measurement of the glomerular diameter. Glomerulomegaly results from adaptive changes associated with hyperfiltration that is in part determined by the severity of chronic renal injury, reflected by correlation of GD with Oxford Classification T score.

Background: Lupus nephritis (LN) is a poor prognostic marker in children with Systemic Lupus Erythematosus (SLE). Treatment strategies are based on adult guidelines, involving multiple immunosuppressive agents. Aim(s): In children with LN at Monash Children's Hospital (MCH), to review induction treatment and immunosuppressive agents used compared to international guidelines, and to describe patient outcomes. Method(s): Retrospective chart review identified children diagnosed with SLE and LN at MCH from January 2002-June 2020. Demographic and clinical data were collected, including relapses or progression of LN and modalities of treatment. Result(s): Over the study period, 17 children with LN were treated at MCH. Data from 16 patients was available. 68.7% were female, with median age at diagnosis 12.5 years (range 8-17). 15 patients had LN at presentation: all had proteinuria (nephrotic range in 7), 14 had haematuria and no patient had renal impairment. All had systemic features, most commonly rash, fever and arthritis. 15 of 16 patients underwent renal biopsy, with proliferative LN in 66.6%. All patients received oral hydroxychloroquine and glucocorticoids. 81.2% received intravenous methylprednisolone and 75% commenced mycophenolate mofetil at induction. 8 of 15 had at least one further kidney biopsy, with a change in LN class observed in five patients. Three patients had progressive LN- requiring treatment with cyclophosphamide, rituximab and ultimately dialysis (median age 15, median time to dialysis 5 years). Excluding the 3 patients with end stage kidney disease, the median eGFR at last follow-up (median 2.25 years) was 108 mL/min/1.73 m2 (2 patients had an eGFR <90 mL/min/1.73 m2). Conclusion(s): Induction treatment of paediatric patients with LN at MCH aligned with recommendations of current international guidelines. End stage kidney disease developed in 18.7% of patients.

Purpose: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Method(s): We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Result(s): ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion(s): In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.Copyright © 2020, The Author(s).

Aim: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected GKD. Background(s): Genetic kidney disease (GKD) is increasingly recognized as an important cause of CKD and can be difficult to accurately diagnose using traditional diagnostic strategies. There is a paucity of data on the clinical utility of genomic testing in kidney disease patients. Method(s): We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Result(s): ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis following ES. A diagnosis on ES was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%) and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion(s): In this pragmatic paediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.

Background: Lupus nephritis (LN) is a poor prognostic marker in children with Systemic Lupus Erythematosus (SLE). Treatment strategies are based on adult guidelines, involving multiple immunosuppressive agents. Aim(s): In children with LN at Monash Children's Hospital (MCH), to review induction treatment and immunosuppressive agents used compared to international guidelines, and to describe patient outcomes. Method(s): Retrospective chart review identified children diagnosed with SLE and LN at MCH from January 2002-June 2020. Demographic and clinical data were collected, including relapses or progression of LN and modalities of treatment. Result(s): Over the study period, 17 children with LN were treated at MCH. Data from 16 patients was available. 68.7% were female, with median age at diagnosis 12.5 years (range 8-17). 15 patients had LN at presentation: all had proteinuria (nephrotic range in 7), 14 had haematuria and no patient had renal impairment. All had systemic features, most commonly rash, fever and arthritis. 15 of 16 patients underwent renal biopsy, with proliferative LN in 66.6%. All patients received oral hydroxychloroquine and glucocorticoids. 81.2% received intravenous methylprednisolone and 75% commenced mycophenolate mofetil at induction. 8 of 15 had at least one further kidney biopsy, with a change in LN class observed in five patients. Three patients had progressive LN- requiring treatment with cyclophosphamide, rituximab and ultimately dialysis (median age 15, median time to dialysis 5 years). Excluding the 3 patients with end stage kidney disease, the median eGFR at last follow-up (median 2.25 years) was 108 mL/min/1.73 m2 (2 patients had an eGFR <90 mL/min/1.73 m2). Conclusion(s): Induction treatment of paediatric patients with LN at MCH aligned with recommendations of current international guidelines. End stage kidney disease developed in 18.7% of patients.

Purpose: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Method(s): We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Result(s): ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion(s): In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.Copyright © 2020, The Author(s).

Background&objectives: Glomerular size has been demonstrated as an independent prognostic marker in IgA nephropathy. Using digital pathology, this study aims to determine reproducibility of GD measurement, defining minimum number of glomeruli required for accurate measurement, and correlating GD with MEST-C scores. Method(s): The diameter of all non-sclerosed glomeruli from renal biopsies of 420 patients with IgA nephropathy was measured independently by 3 pathologists, using the ruler device on Aperio ImageScope software. Inter-observer and intra-observer variability was then assessed using interclass correlation coefficient (ICC). Mean and maximum GD were correlated with Oxford Classification MEST- C scores, using the independent samples T test. Result(s): There was excellent interobserver (between 3 pathologists) and intra-observer (one pathologist measuring 2 levels from the same biopsy) correlation with ICC of >0.9. Accuracy of measurement ofmaximumand mean GD increased with number of glomeruli measured, levelling off between 12-15 non-sclerosed glomeruli. T score was the only MEST-C variable to significantly correlate with glomerular diameter. Conclusion(s): Use of the ruler device on digital slide viewing software provides a rapid and reproducible estimate of glomerular diameter. Greater than 12 non-sclerosed glomeruli are required to provide an accurate measurement of the glomerular diameter. Glomerulomegaly results from adaptive changes associated with hyperfiltration that is in part determined by the severity of chronic renal injury, reflected by correlation of GD with Oxford Classification T score.

Aim: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected GKD. Background(s): Genetic kidney disease (GKD) is increasingly recognized as an important cause of CKD and can be difficult to accurately diagnose using traditional diagnostic strategies. There is a paucity of data on the clinical utility of genomic testing in kidney disease patients. Method(s): We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Result(s): ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis following ES. A diagnosis on ES was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%) and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion(s): In this pragmatic paediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.

Kidney failure is common in patients with Coronavirus Disease-19 (COVID-19), resulting in increased morbidity and mortality. In an international collaboration, 284 kidney biopsies were evaluated to improve understanding of kidney disease in COVID-19. Diagnoses were compared to five years of 63,575 native biopsies prior to the pandemic and 13,955 allograft biopsies to identify diseases that have increased in patients with COVID-19. Genotyping for APOL1 G1 and G2 alleles was performed in 107 African American and Hispanic patients. Immunohistochemistry for SARS-CoV-2 was utilized to assess direct viral infection in 273 cases along with clinical information at the time of biopsy. The leading indication for native biopsy was acute kidney injury (45.4%), followed by proteinuria with or without concurrent acute kidney injury (42.6%). There were more African American patients (44.6%) than patients of other ethnicities. The most common diagnosis in native biopsies was collapsing glomerulopathy (25.8%), which was associated with high-risk APOL1 genotypes in 91.7% of cases. Compared to the five-year biopsy database, the frequency of myoglobin cast nephropathy and proliferative glomerulonephritis with monoclonal IgG deposits was also increased in patients with COVID-19 (3.3% and 1.7%, respectively), while there was a reduced frequency of chronic conditions (including diabetes mellitus, IgA nephropathy, and arterionephrosclerosis) as the primary diagnosis. In transplants, the leading indication was acute kidney injury (86.4%), for which rejection was the predominant diagnosis (61.4%). Direct SARS-CoV-2 viral infection was not identified. Thus, our multi-center large case series identified kidney diseases that disproportionately affect patients with COVID-19 and demonstrated a high frequency of APOL1 high-risk genotypes within this group, with no evidence of direct viral infection within the kidney.

BackgroundInterstitial fibrosis (IF) on kidney biopsy is one of the most potent risk factors for kidney disease progression. The furosemide stress test (FST) is a validated tool that predicts the severity of acute kidney injury (especially at 2 h) in critically ill patients. Since furosemide is secreted through the kidney tubules, the response to FST represents the tubular secretory capacity. To our knowledge there is no data on the correlation between functional tubular capacity assessed by the FST with IF on kidney biopsies from patients with chronic kidney disease (CKD). The aim of this study was to determine the association between urine output (UO), Furosemide Excreted Mass (FEM) and IF on kidney biopsies after a FST.MethodsThis study included 84 patients who underwent kidney biopsy for clinical indications and a FST. The percentage of fibrosis was determined by morphometry technique and reviewed by a nephropathologist. All patients underwent a FST prior to the biopsy. Urine volume and urinary sodium were measured in addition to urine concentrations of furosemide at different times (2, 4 and 6 h). We used an established equation to determine the FEM. Values were expressed as mean, standard deviation or percentage and Pearson Correlation.ResultsThe mean age of the participants was 38 years and 44% were male. The prevalence of diabetes mellitus, hypertension and diuretic use was significantly higher with more advanced degree of fibrosis. Nephrotic syndrome and acute kidney graft dysfunction were the most frequent indications for biopsy. eGFR was inversely related to the degree of fibrosis. Subjects with the highest degree of fibrosis (grade 3) showed a significant lower UO at first hour of the FST when compared to lower degrees of fibrosis (p = 0.015). Likewise, the total UO and the FEM was progressively lower with higher degrees of fibrosis. An inversely linear correlation between FEM and the degree of fibrosis (r = - 0.245, p = 0.02) was observed.ConclusionsOur

BACKGROUND: Untreated microangiopathic hemolytic anemia in pregnancy is associated with adverse maternal and perinatal outcomes. Accurate diagnosis is challenging owing to nonspecific clinical features and pathologic findings. Timely initiation of appropriate management is essential to optimize maternal and perinatal outcomes. CASE: A 26-year-old primiparous woman presented at 20 weeks of gestation with new-onset microangiopathic hemolytic anemia on a background of poorly controlled type 1 diabetes. She received eculizumab for presumed atypical hemolytic uremic syndrome. At 24 weeks of gestation, she developed superimposed early-onset preeclampsia; she delivered at 27 weeks of gestation after continuing eculizumab. CONCLUSION(S): Eculizumab may prolong pregnancy in early-onset preeclampsia. Additional research is needed to assess short-term and long-term maternal and newborn outcomes.Copyright © 2019 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.

Background In Australia, Lupus Nephritis (LN) affects a culturally diverse population of patients. We established the Lupus Nephritis Australian Registry (LUNAR) to better understand the population of patients receiving Myfortic and other immunosuppressants, and to analyse the safety and efficacy of the treatments they received. Methods A non-interventional, multicentre, registry of patients with biopsy-proven ISN/RPS class III, IV or V LN, treated with Myfortic or other immunosuppressants, was established. We collected baseline demographic and 6-monthly follow-up data over a 5-year period (2013-2018), including clinical data, laboratory tests and safety outcomes. Results 149 patients were enrolled in LUNAR across 8 sites, with 83.7% female and a mean age of 38.8 years. Most patients were Caucasian (45.2%) - patients of Asian ethnicity (29.6%) and Aboriginal/Torres Strait Islander or Maori/Pacific Islander descent (10.4%) were significantly over-represented compared to the general population. The mean and median duration of SLE was 8.6 and 6 years, respectively (range 0-42 years), and of LN was 5.4 and 3.9 years, respectively (range 0-30 years). Most patients had class IV LN on their initial kidney biopsy (59.3%), with 21.5% having class III and 11.1% having class V LN. Immunosuppressants used prior to screening included corticosteroids (68.9%), mycophenolate mofetil ((MMF) 61.5%), Myfortic (41.5%) and cyclophospha-mide (32.6%). At enrolment or during the study, most patients were treated with Myfortic (76.3%), MMF (65.2%) and/or hydroxychloroquine (67.4%). Rituximab and azathio-prine were each started in 8.9% of patients during the study period. Kidney function was stable/improved for most patients over the study period and mycophenolate-based therapy was well-tolerated. Conclusions LUNAR is the first study outlining the demographics, outcomes and practice patterns in the management of patients with LN in Australia.

Background: Rapid genomic sequencing with results available in clinically meaningful timeframes is becoming feasible. Its role in the diagnosis and management of patients with kidney disease is unclear. Method(s): Patients were recruited prospectively for rapid whole exome sequencing (WES) with analysis of a pre-determined phenotype specific list of genes of interest and results available in less than 2 weeks. This followed review by a nephrologist, clinical geneticist and genetic counsellor who considered inclusion if a result was likely to significantly impact clinical management, particularly avoiding kidney biopsies in younger children. Full author list online at KidGen.org.au Results: Ten patients (7 pediatric, 5 female) were recruited ranging in age from 1 month to 55 years. Indications for rapid testing were to avoid a renal biopsy (8) and to facilitate transplant planning (2). Five patients received a definitive diagnosis (ADPKD, Dent disease, primary hyperoxaluria, Alport syndrome and ciliopathy), 1 received a diagnosis which was likely unrelated to their kidney disease (MIRAGE syndrome). One patient's negative result facilitated sibling donor workup. The most significant result in this cohort was an unexpected diagnosis of primary hyperoxaluria in a 6-month old presenting in renal failure. WES results were available within 5 days informing conversion from peritoneal dialysis to hemodialysis and planning for a sequential liver-kidney transplant. This avoided the significant morbidity of oxalate deposition in extra-renal tissues leading to fractures, visual impairment and heart failure and recurrence of the disease if an isolated renal transplant had been performed. Conclusion(s): Rapid genomic sequencing has high diagnostic utility in selected patients with renal disease and can inform clinical management within meaningful timeframes. It has the potential to transform the diagnostic pathway for young children, particularly where invasive renal biopsies can

Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (TRM) cells persist in peripheral organs and provide immune protection against reinfection. However, whether TRM cells participate in responses unrelated to the primary infection, such as autoimmune inflammation, is unknown. By using high-dimensional single-cell analysis, we identified CD4+ TRM cells with a TH17 signature (termed TRM17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal TRM17 cells were induced by pathogens infecting the kidney, such as Staphylococcus aureus, Candida albicans, and uropathogenic Escherichia coli, and persisted after the clearance of infections. Upon induction of experimental glomerulonephritis, these kidney TRM17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced TRM17 cells have a previously unrecognized function in aggravating autoimmune disease.Copyright © 2020 American Association for the Advancement of Science. All rights reserved.

Introduction: Proteinuria is a common kidney presentation. Historically, diagnostic workup of patients with isolated proteinuria involved thorough urinalysis, imaging and blood sampling before potentially proceeding to renal biopsy. However recent advances have resulted in reduced cost and increased availability of genomic sequencing for establishing clinical diagnoses. Case Description: An 8year old boy was referred with an incidental finding of persistent proteinuria during investigation for nonspecific abdominal pain. He had no haematuria and had normal serum albumin. All other investigations including blood analysis for haematological, biochemical and immunological parameters, renal ultrasound, ophthalmology and audiology assessment were unremarkable. Further assessment revealed consanguineous family history and a brother also with isolated proteinuria. Renal biopsy demonstrated normal light microscopy and global uniform thinning of the glomerular basement membrane on electron microscopy. Chromosomal microarray revealed long continuous stretches of homozygosity (LCSH) representing ~4.5 of the genome. Shared regions of LCSH between the brothers were identified using the Genomic Oligoarray and single nucleotide polymorphism (SNP) Evaluation tool. Examination of these regions implicated CUBN, on chromosome 10p12.31. Research whole genome sequencing of both affected individuals was performed with informed consent (HREC/15/ QRCH/126). This revealed a homozygous stop-gain variant in CUBN (NM-001081.3, c.4689-4690delTAinsAT, p.(CysIle1263*), ACMG Class 5). Discussion(s): CUBN mutations have been implicated as a hereditary cause of megaloblastic anaemia and variable proteinuria. This is the second reported family with isolated proteinuria due to biallelic CUBN variants in the absence of megaloblastic anaemia, demonstrating the utility of genomics to identify single gene causes of nephropathy, and in doing so, to expand the associated phenotypic spectrum. Therefore, geno

Background: Genomic technologies enable rapid and cost-effective sequencing of DNA and have demonstrated a definitive diagnosis in several patient groups such as childhood syndromes and oncology. We sought to determine the diagnostic and clinical utility of WES in a cohort of adults and children with clinically suspected genetic kidney disease who were reviewed in multidisciplinary renal genetics clinic (RGC). Method(s): Sequential patients were prospectively recruited through five tertiary academic centres in Australia. Patients were referred by their treating nephrologist to a dedicated RGC. Following review by a multidisciplinary team consisting of a nephrologist, clinical geneticist and genetic counsellor, patients underwent genomic sequencing with analysis for a pre-determined phenotype specific list of genes of interest. We measured the diagnostic yield and the effect on short term clinical management. Full author list online at KidGen.org.au Results: We performed WES in 204 patients (82 paediatric and 122 adults) with CKD. The median age at time of recruitment was 29 years (0-72). Preliminary results demonstrate a genetic diagnosis in 77 patients (38%). This includes (69) pathogenic variants and (25) likely pathogenic variants. When comparing the a priori clinical diagnosis at referral in patients with WES diagnoses, 48 (62%) had their suspected clinical diagnosis confirmed and 29 patients (38%) had a subsequent change in diagnosis. 42 patients (54%) with positive diagnoses had recommended changes to clinical management. This included the avoidance of immunosuppression, avoidance of renal biopsy, initiation of surveillance for extra-renal disease and facilitating transplant and reproductive decisions. In addition, at least 26 patients (13%) had a clinically relevant negative result with management implications. Conclusion(s): To our knowledge this is the first study to report diagnostic and clinical utility of genomic sequencing in a pragmatic clinical settin

BACKGROUND: Untreated microangiopathic hemolytic anemia in pregnancy is associated with adverse maternal and perinatal outcomes. Accurate diagnosis is challenging owing to nonspecific clinical features and pathologic findings. Timely initiation of appropriate management is essential to optimize maternal and perinatal outcomes. CASE: A 26-year-old primiparous woman presented at 20 weeks of gestation with new-onset microangiopathic hemolytic anemia on a background of poorly controlled type 1 diabetes. She received eculizumab for presumed atypical hemolytic uremic syndrome. At 24 weeks of gestation, she developed superimposed early-onset preeclampsia; she delivered at 27 weeks of gestation after continuing eculizumab. CONCLUSION(S): Eculizumab may prolong pregnancy in early-onset preeclampsia. Additional research is needed to assess short-term and long-term maternal and newborn outcomes.Copyright © 2019 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.

Although it is well established that microbial infections predispose to autoimmune diseases, the underlying mechanisms remain poorly understood. After infection, tissue-resident memory T (TRM) cells persist in peripheral organs and provide immune protection against reinfection. However, whether TRM cells participate in responses unrelated to the primary infection, such as autoimmune inflammation, is unknown. By using high-dimensional single-cell analysis, we identified CD4+ TRM cells with a TH17 signature (termed TRM17 cells) in kidneys of patients with ANCA-associated glomerulonephritis. Experimental models demonstrated that renal TRM17 cells were induced by pathogens infecting the kidney, such as Staphylococcus aureus, Candida albicans, and uropathogenic Escherichia coli, and persisted after the clearance of infections. Upon induction of experimental glomerulonephritis, these kidney TRM17 cells rapidly responded to local proinflammatory cytokines by producing IL-17A and thereby exacerbate renal pathology. Thus, our data show that pathogen-induced TRM17 cells have a previously unrecognized function in aggravating autoimmune disease.Copyright © 2020 American Association for the Advancement of Science. All rights reserved.

Background In Australia, Lupus Nephritis (LN) affects a culturally diverse population of patients. We established the Lupus Nephritis Australian Registry (LUNAR) to better understand the population of patients receiving Myfortic and other immunosuppressants, and to analyse the safety and efficacy of the treatments they received. Methods A non-interventional, multicentre, registry of patients with biopsy-proven ISN/RPS class III, IV or V LN, treated with Myfortic or other immunosuppressants, was established. We collected baseline demographic and 6-monthly follow-up data over a 5-year period (2013-2018), including clinical data, laboratory tests and safety outcomes. Results 149 patients were enrolled in LUNAR across 8 sites, with 83.7% female and a mean age of 38.8 years. Most patients were Caucasian (45.2%) - patients of Asian ethnicity (29.6%) and Aboriginal/Torres Strait Islander or Maori/Pacific Islander descent (10.4%) were significantly over-represented compared to the general population. The mean and median duration of SLE was 8.6 and 6 years, respectively (range 0-42 years), and of LN was 5.4 and 3.9 years, respectively (range 0-30 years). Most patients had class IV LN on their initial kidney biopsy (59.3%), with 21.5% having class III and 11.1% having class V LN. Immunosuppressants used prior to screening included corticosteroids (68.9%), mycophenolate mofetil ((MMF) 61.5%), Myfortic (41.5%) and cyclophospha-mide (32.6%). At enrolment or during the study, most patients were treated with Myfortic (76.3%), MMF (65.2%) and/or hydroxychloroquine (67.4%). Rituximab and azathio-prine were each started in 8.9% of patients during the study period. Kidney function was stable/improved for most patients over the study period and mycophenolate-based therapy was well-tolerated. Conclusions LUNAR is the first study outlining the demographics, outcomes and practice patterns in the management of patients with LN in Australia.

Background: Rapid genomic sequencing with results available in clinically meaningful timeframes is becoming feasible. Its role in the diagnosis and management of patients with kidney disease is unclear. Method(s): Patients were recruited prospectively for rapid whole exome sequencing (WES) with analysis of a pre-determined phenotype specific list of genes of interest and results available in less than 2 weeks. This followed review by a nephrologist, clinical geneticist and genetic counsellor who considered inclusion if a result was likely to significantly impact clinical management, particularly avoiding kidney biopsies in younger children. Full author list online at KidGen.org.au Results: Ten patients (7 pediatric, 5 female) were recruited ranging in age from 1 month to 55 years. Indications for rapid testing were to avoid a renal biopsy (8) and to facilitate transplant planning (2). Five patients received a definitive diagnosis (ADPKD, Dent disease, primary hyperoxaluria, Alport syndrome and ciliopathy), 1 received a diagnosis which was likely unrelated to their kidney disease (MIRAGE syndrome). One patient's negative result facilitated sibling donor workup. The most significant result in this cohort was an unexpected diagnosis of primary hyperoxaluria in a 6-month old presenting in renal failure. WES results were available within 5 days informing conversion from peritoneal dialysis to hemodialysis and planning for a sequential liver-kidney transplant. This avoided the significant morbidity of oxalate deposition in extra-renal tissues leading to fractures, visual impairment and heart failure and recurrence of the disease if an isolated renal transplant had been performed. Conclusion(s): Rapid genomic sequencing has high diagnostic utility in selected patients with renal disease and can inform clinical management within meaningful timeframes. It has the potential to transform the diagnostic pathway for young children, particularly where invasive renal biopsies can

Introduction: Proteinuria is a common kidney presentation. Historically, diagnostic workup of patients with isolated proteinuria involved thorough urinalysis, imaging and blood sampling before potentially proceeding to renal biopsy. However recent advances have resulted in reduced cost and increased availability of genomic sequencing for establishing clinical diagnoses. Case Description: An 8year old boy was referred with an incidental finding of persistent proteinuria during investigation for nonspecific abdominal pain. He had no haematuria and had normal serum albumin. All other investigations including blood analysis for haematological, biochemical and immunological parameters, renal ultrasound, ophthalmology and audiology assessment were unremarkable. Further assessment revealed consanguineous family history and a brother also with isolated proteinuria. Renal biopsy demonstrated normal light microscopy and global uniform thinning of the glomerular basement membrane on electron microscopy. Chromosomal microarray revealed long continuous stretches of homozygosity (LCSH) representing ~4.5 of the genome. Shared regions of LCSH between the brothers were identified using the Genomic Oligoarray and single nucleotide polymorphism (SNP) Evaluation tool. Examination of these regions implicated CUBN, on chromosome 10p12.31. Research whole genome sequencing of both affected individuals was performed with informed consent (HREC/15/ QRCH/126). This revealed a homozygous stop-gain variant in CUBN (NM-001081.3, c.4689-4690delTAinsAT, p.(CysIle1263*), ACMG Class 5). Discussion(s): CUBN mutations have been implicated as a hereditary cause of megaloblastic anaemia and variable proteinuria. This is the second reported family with isolated proteinuria due to biallelic CUBN variants in the absence of megaloblastic anaemia, demonstrating the utility of genomics to identify single gene causes of nephropathy, and in doing so, to expand the associated phenotypic spectrum. Therefore, geno

Background: Genomic technologies enable rapid and cost-effective sequencing of DNA and have demonstrated a definitive diagnosis in several patient groups such as childhood syndromes and oncology. We sought to determine the diagnostic and clinical utility of WES in a cohort of adults and children with clinically suspected genetic kidney disease who were reviewed in multidisciplinary renal genetics clinic (RGC). Method(s): Sequential patients were prospectively recruited through five tertiary academic centres in Australia. Patients were referred by their treating nephrologist to a dedicated RGC. Following review by a multidisciplinary team consisting of a nephrologist, clinical geneticist and genetic counsellor, patients underwent genomic sequencing with analysis for a pre-determined phenotype specific list of genes of interest. We measured the diagnostic yield and the effect on short term clinical management. Full author list online at KidGen.org.au Results: We performed WES in 204 patients (82 paediatric and 122 adults) with CKD. The median age at time of recruitment was 29 years (0-72). Preliminary results demonstrate a genetic diagnosis in 77 patients (38%). This includes (69) pathogenic variants and (25) likely pathogenic variants. When comparing the a priori clinical diagnosis at referral in patients with WES diagnoses, 48 (62%) had their suspected clinical diagnosis confirmed and 29 patients (38%) had a subsequent change in diagnosis. 42 patients (54%) with positive diagnoses had recommended changes to clinical management. This included the avoidance of immunosuppression, avoidance of renal biopsy, initiation of surveillance for extra-renal disease and facilitating transplant and reproductive decisions. In addition, at least 26 patients (13%) had a clinically relevant negative result with management implications. Conclusion(s): To our knowledge this is the first study to report diagnostic and clinical utility of genomic sequencing in a pragmatic clinical settin

Lymphomatous infiltration of kidney parenchyma is a frequent complication of systemic hematologic malignancies and often shows subtle clinical presentation. Diffuse large B-cell lymphoma represents the most frequent form involving the kidney, with advanced stage at diagnosis, poor outcome, and risk for central nervous system relapse if not adequately treated. Kidney biopsy can provide specific and early detection of these cases, helping in the differential diagnosis with more frequent entities. Finally, further hematologic workup (bone marrow biopsy, complete blood cell count, and positron emission tomography) can distinguish secondary involvement of the kidney from the rarer kidney-limited forms, especially in patients without a previous diagnosis of lymphoma. Making a prompt and correct diagnosis directs the management of these cases and may improve the outcome, as described in the present report.

RATIONALE & OBJECTIVE: Membranous nephropathy (MN) is characterized by the deposition of immune complexes along glomerular basement membranes. M-Type phospholipase A2 receptor (PLA2R), thrombospondin type 1 domain-containing 7A (THSD7A), exostosin 1 and 2 (EXT1/2), and neural epidermal growth factor-like 1 protein (NELL-1) have been identified as established or potential podocyte antigens in MN. We investigated the association of podocyte antigen staining with MN clinical phenotype and outcomes. STUDY DESIGN: Multicenter retrospective cohort study. SETTING & PARTICIPANTS: 177 consecutive patients with MN unrelated to lupus erythematosus, identified after screening of 3,875 native kidney biopsies performed in the Belgian UCLouvain Kidney Disease Network from 2000 through 2018. PREDICTOR: Positive immunostaining for podocyte antigens on archived kidney biopsy samples. OUTCOMES: Association with different phenotypes (baseline characteristics of patients and pathologic findings on kidney biopsy), time to cancer and to kidney failure. ANALYTICAL APPROACH: Kaplan-Meier estimates and Cox regression analyses to assess time to cancer and kidney failure. RESULTS: 177 patients were followed up for a median of 4.0 (IQR, 1.3-8.0) years. Diagnosis of PLA2R-positive (PLA2R+), THSD7A+, and double-negative (PLA2R-/THSD7A-) MN was made in 117 (66.1%), 6 (3.4%), and 54 (30.5%) patients, respectively. Progression to kidney failure was similar in all groups. Although the number of patients with THSD7A+MN was small, they showed a higher incidence (50%) and increased risk for developing cancer during follow-up (adjusted HR, 5.0 [95% CI, 1.4-17.9]; P=0.01). 8% and 5% of patients with double-negative MN stained positively for EXT1/2 and NELL-1, respectively. Most patients with EXT1/2+MN were women, had features of systemic autoimmunity, and showed glomerular C1q deposits. LIMITATIONS: Retrospective design; small number of patients in the THSD7A group; lack of evaluation of immunoglobulin G

BackgroundInterstitial fibrosis (IF) on kidney biopsy is one of the most potent risk factors for kidney disease progression. The furosemide stress test (FST) is a validated tool that predicts the severity of acute kidney injury (especially at 2 h) in critically ill patients. Since furosemide is secreted through the kidney tubules, the response to FST represents the tubular secretory capacity. To our knowledge there is no data on the correlation between functional tubular capacity assessed by the FST with IF on kidney biopsies from patients with chronic kidney disease (CKD). The aim of this study was to determine the association between urine output (UO), Furosemide Excreted Mass (FEM) and IF on kidney biopsies after a FST.MethodsThis study included 84 patients who underwent kidney biopsy for clinical indications and a FST. The percentage of fibrosis was determined by morphometry technique and reviewed by a nephropathologist. All patients underwent a FST prior to the biopsy. Urine volume and urinary sodium were measured in addition to urine concentrations of furosemide at different times (2, 4 and 6 h). We used an established equation to determine the FEM. Values were expressed as mean, standard deviation or percentage and Pearson Correlation.ResultsThe mean age of the participants was 38 years and 44% were male. The prevalence of diabetes mellitus, hypertension and diuretic use was significantly higher with more advanced degree of fibrosis. Nephrotic syndrome and acute kidney graft dysfunction were the most frequent indications for biopsy. eGFR was inversely related to the degree of fibrosis. Subjects with the highest degree of fibrosis (grade 3) showed a significant lower UO at first hour of the FST when compared to lower degrees of fibrosis (p = 0.015). Likewise, the total UO and the FEM was progressively lower with higher degrees of fibrosis. An inversely linear correlation between FEM and the degree of fibrosis (r = - 0.245, p = 0.02) was observed.ConclusionsOur