Kidney Biopsy Studies Research Articles

Changes in the Spectrum of Kidney Diseases: A 14-Year Kidney Biopsy Study from a Single Center

Changes in the Spectrum of Kidney Diseases: A 14-Year Kidney Biopsy Study from a Single Center

An overview on the diagnostic role of electron microscopy for kidney diseases, study of 2006 native kidney biopsies in Iran

Introduction: Kidney diseases affect millions of people worldwide. Over several decades, electron microscopy has been an integral part of the kidney biopsy study repertoire. Objectives: In this study, we assessed the role of electron microscopy in the diagnosis of kidney diseases. Patients and Methods: This was a retrospective cross-sectional study conducted at a referral center over a 16-year period (2001-2016). The electron microscopy (EM), light microscopy (LM), and immunofluorescence (IF) profiles of the patients were assessed. The final diagnosis was based on EM, and the primary LM results were compared to those of EM in order to assess the contribution rate of EM to the final diagnosis. The role of EM was categorized as essential, helpful, or non-contributory. Results: A total of 2006 kidney biopsies were performed. Male subjects accounted for 44.3%, and adults for 74.1% of the cases. The most common diagnosis was lupus nephritis (LN) (20.7%), followed by focal segmental glomerulosclerosis (FSGS) (15.7%) and membranous glomerulonephritis (MGN) (14.5%). EM was the most contributory in hereditary nephritis and minimal change disease (MCD). Overall, EM was essential in 25.2%, helpful in 17.4%, and non-contributory in 57.4% of all 2006 cases. Conclusion: The common kidney disorders in this geographic area of Iran are LN, FSGS, and MGN. In about half of the patients, EM study played an important role in the more accurate diagnosis of kidney diseases and prevented misdiagnosis. This role has been found to be more prominent in inherited diseases. We recommend EM as a useful and indispensable tool for routine pathologic study of biopsies when possible.

Rationale and design of a prospective, clinical study of kidney biopsies in people with type 2 diabetes and severely increased albuminuria (the PRIMETIME 2 study)

IntroductionDiabetic kidney disease is a severe complication of diabetes. The diagnosis is based on clinical characteristics such as persistently elevated albuminuria, hypertension and decline in kidney function, although this definition...

Risk and Timing of Major Bleeding Complications Requiring Intervention of the Percutaneous Kidney Biopsy With a Short Observation Protocol: A Retrospective Chart Review

Background: We previously published a retrospective study of kidney biopsies performed in a tertiary care hospital in London, Ontario from 2012 to 2017. This study resulted in a change of practice in our institution to shorter postbiopsy monitoring for outpatients as well as the development of a risk calculator to predict serious bleeding complications. Objective: The primary objective of this study was to determine whether this shorter monitoring time is adequate in the outpatient setting. A secondary objective was to validate the bleeding risk calculator in both inpatients and outpatients. Design: This was a retrospective chart review. Setting: This study was performed at a tertiary academic hospital in London, Ontario, Canada. Participants: This was a retrospective study of 400 adult patients who underwent kidney biopsy between April 30, 2018 and February 25, 2022 at a tertiary academic hospital in London, Canada. Methods: We retrospectively assessed frequency and timing of major bleeding complications in patients who underwent kidney biopsy. In secondary analyses, we examined the prediction performance of the risk calculator in discrimination and calibration. Results: Major bleeding occurred in 7 patients (1.8%). Five of these patients required blood transfusions (1.3%) and 2 required embolization (0.5%). In the outpatient setting, any major bleeding events were identified immediately (1 patient) or on the routine 2-hour ultrasounds (1 patient). The risk calculator showed good discrimination (C-statistic, 0.91, 95% confidence interval [CI] = [0.84 to 0.95]) and calibration (slope, 1.10, 95% CI = [0.47 to 1.74]; intercept, 95% CI = −0.02 [−0.79 to 0.75]), but with much uncertainty in the estimates. Limitations: The occurrence of only a few major bleeding events limits the reliability of our assessment of our risk calculator. Conclusions: There appears to be little yield in extending observation beyond 2 hours after an outpatient kidney biopsy with the use of immediate and 2-hour postbiopsy ultrasounds. The bleeding risk calculator ( http://perioperativerisk.com/kbrc ) warrants further validation.

Urinary and Kidney Podocalyxin and Podocin Levels in Diabetic Kidney Disease: A Kidney Biopsy Study

Diabetic kidney diseases (DKDs) are the most common cause of dialysis-dependent kidney disease around the world. Previous studies have suggested that urinary level of podocyte-associated molecules may predict the prognosis of DKD. Observational cohort. 118 consecutive patientswith biopsy-proven DKD; 13 nondiabetic patients with hypertensive nephrosclerosis as controls. Urinary podocalyxin and podocin levels were obtained by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) and the corresponding intrarenal levels by western blotting. Dialysis-free survival; kidney event-free survival; rate of kidney function decline in 12 months. Correlation and time to event analysis. Urinary podocalyxin level was closely correlated with its messenger RNA (mRNA) level(r=0.562, P<0.001), but this did not predict the progression of DKD. Intrarenal podocalyxin level had only modest correlation with its urinary mRNA and ELISA levels, was an independent predictor of dialysis-free survival (adjusted HR, 1.85; 95% CI, 1.21-2.82; P=0.005), and showed an insignificant trend of predicting kidney event-free survival (adjusted HR, 1.36; 95% CI, 0.94-1.95; P=0.10). Urinary podocin level by ELISA had a modest correlation with the rate of kidney function decline (r=0.238, P=0.01) but did not predict dialysis-free survival. Small sample size; lack of serial measurement. Intrarenal podocalyxin level, but not its urinary level, was an independent predictor of dialysis-free survival, whereas urinary podocin level by ELISA correlated with the rate of kidney function decline. Although intrarenal podocalyxin level has prognostic value, it may not be suitable for routine clinical use.

MO325: Renal Glycosuria in Acute Kidney Injury Predicts the Diagnosis of Acute Interstitial Nephritis

Abstract BACKGROUND AND AIMS Acute interstitial nephritis (AIN) is one of the most frequent causes of acute kidney injury (AKI). Interstitial inflammation can lead to tubular epithelial infiltration producing tubular dysfunction, which could be clinically detected by glycosuria (with or without Fanconi syndrome), leukocyturia, microscopic haematuria or tubular proteinuria. The aim of this study was to determine the predictive value of renal glycosuria in AKI for the diagnosis of AIN. METHOD We conducted a retrospective study of kidney biopsies performed at out centre between May 1998 and December 2021, and included patients whose kidney biopsy was performed while presenting with AKI. We excluded patients with other indications for kidney biopsy, patients with diabetes mellitus and patients who presented a serum glucose level of &amp;gt; 120 mg/dL at presentation. We registered demographic, clinical and laboratory variables at presentation of AKI, and compared patients with a final diagnosis of AIN to patients with other causes of AKI. RESULTS The study included 211 patients; 39 patients (18.5%) with a diagnosis of AIN and 172 patients (81.5%) with other diagnoses for AKI. Eight patients with AIN presented with renal glycosuria (20.5%) compared with seven patients with other causes of AKI (4.1%) (P &amp;lt; .001). Patients with AIN presented less frequently haematuria (46.2% versus 86%; P &amp;lt; .001), lower albuminuria [86 (35–151) mg/g versus 694 (136–1414) mg/g; P &amp;lt; .001], proteinuria [0.43 (0.22–0.92) g/24 h versus 1.43 (0.76–2.97) g/24 h; P &amp;lt; .001], serum glucose (89.5 ± 12 versus 94.7 ± 12.5 mg/dL; P = .019) and uric acid (6.5 ± 2.5 versus 7.8 ± 2.3 mg/dL; P = .003), and more frequently metabolic acidosis (68.6% versus 33.3%; P &amp;lt; .001) and eosinophilia (17.9% versus 5.2%; P = .007) than in patients with other causes of AKI. There were no differences in age, sex, extrarenal manifestations, serum creatinine, potassium or phosphorus levels at presentation. The presence of at least traces (≥50 mg/dL) of glycosuria had a specificity of 96.5% (92.6–98.7) for the diagnosis of AIN, with a positive predictive value of 57.1% (32.9–78.3) and a negative predictive value of 84.3% (82%–86.3%). The positive likelihood ratio was 5.9 (2.2–16) and the negative likelihood ratio was 0.82 (0.7–0.97). The presence of &amp;gt; 100 mg/dL of glycosuria had a specificity of 99.4% for the diagnosis of AIN, with a positive predictive value of 75% (24.3–96.6) and a positive likelihood ratio of 13.2 (1.4–123.8). CONCLUSION AIN can lead to proximal tubular dysfunction, which can be clinically expressed as renal glycosuria. The presence of renal glycosuria in patients with AKI guides towards the diagnosis of AIN, with an excellent specificity when glycosuria &amp;gt; 100 mg/dL.

One-third of patients with lupus nephritis classified as complete responders continue to accrue progressive renal damage despite resolution of proteinuria

ObjectiveTreatment response in lupus nephritis (LN) is defined based on proteinuria, yet protocol kidney biopsy studies have shown that patients with lupus can have active nephritis in the absence of...

POS-906 TREATMENT WITH RECOMBINANT MUTATED HUMAN ANGIOPOIETIN-LIKE 4 AMELIORATES GLOMERULAR INJURY IN A MODEL OF THE COVID-19 CYTOKINE STORM

Some patients with COVID-19 infection develop proteinuria or Acute Kidney Injury, and cases of COVID-19 related Collapsing Glomerulopathy have also been reported. Three published human kidney biopsy studies did not find viral particles in the glomeruli or tubules. This raises the possibility of glomerular and kidney injury induced by the extensive cytokine storm documented early on in the pandemic in hospitalized COVID-19 patients. Mutated forms of Human Angiopoietin-like 4 (protein 8520) were previously shown to reduce proteinuria in rat models of FSGS and diabetic nephropathy (Clement LC, Mace C et al.

Fabry nephropathy before and after enzyme replacement therapy: important role of renal biopsy in patients with Fabry disease.

BackgroundIn Fabry disease, the presence of globotriaosylceramide (GL3) deposits in various kidney cells leads to progressive renal dysfunction. However, kidney biopsy studies in patients with Fabry disease are limited. In the present study, the pathologic findings of patients with Fabry nephropathy receiving enzyme replacement therapy (ERT) and untreated patients without albuminuria were investigated.MethodsThe present study included 15 patients with Fabry disease who underwent renal biopsy while receiving ERT (group 1: n = 9, age 19–58 years, two males and seven females) or before ERT initiation (group 2: n = 6, age 11–66 years, one male and five females). All patients in group 2 were normoalbuminuric.ResultsGroup 1 showed improved clinical symptoms, such as acroparesthesia. The ERT duration was 1.2 to 8 years and seven of the nine patients showed GL3 deposits in various kidney cells and segmental foot process effacement (FPE) of podocytes. GL3 deposits and FPE were not observed in the two remaining patients in group 1. Group 2 showed segmental FPE and podocyte GL3 deposits. Most patients in group 2 also showed GL3 deposits in the mesangium, endothelium, or tubular epithelium.ConclusionThe study results showed that segmental FPE and GL3 deposits can persist in Fabry nephropathy despite ERT. In addition, segmental FPE and GL3 deposits were observed in various kidney cells in normoalbuminuric patients with Fabry disease. These findings indicated that kidney biopsies at baseline and follow-up evaluation of Fabry nephropathy are essential for timely ERT initiation and ERT response assessment.

MO178DOES OBTAINING AN EXTRA CORE KIDNEY BIOPSY FOR RESEARCH PURPOSES INCREASE THE RISK OF COMPLICATIONS? A SINGLE CENTER EXPERIENCE

Abstract Background and Aims Kidney biopsy (KB) is the “gold standard” to diagnose nephropathies in our renal patients and it is a procedure with a low rate of complications. Obtaining material for kidney biopsy biobank requires the extraction of one more renal cylinder. The main objective of our study is to analyze the characteristics of a cohort of patients with KB, the safety of the establishment of a renal biopsy biobank with the objective to obtain at least one core of kidney biopsy for research purposes. Method Observational and prospective study of kidney biopsies performed in our center from January 2019 and 2020. We started a collection of kidney biopsy samples to obtain a biobank at January 2019. Therefore, in patients who accepted, instead of two cylinders, three cylinders were obtained during the procedure when possible. Clinical and laboratory data of the patients were reviewed and we looked for risk factors for complications, including the number of cylinders obtained in the procedure. Results We reviewed a cohort of 221 patients in whom we performed a kidney biopsy at our hospital. Eight patients (3.6%) underwent trans-jugular renal biopsy, which we have eliminated from the analysis. Of the remaining 213, 126 (59.2%) were men, the mean age was 56.8 (± 16.9) years, 122 (57.3%) patients had hypertension, 46 (23%) were diabetics, 14 (6.5%) were under anticoagulant treatment and 35 (16.4%) were under antiplatelet treatment. Regarding the analytical values, the mean creatinine was 2.22 (± 1.9) mg / dl, protein / creatinine urine ratio 1119.6 [448.3-2957.9] mg / gr, 44.6% (n = 95) had microhematuria, the median hemoglobin pre-KB was 12.1 (± 2.3) g / dL, 254380 (± 8873) platelets, INR 0.98 (± 0.09), prothrombin time of 11.8 (± 1.16) seconds, systolic blood pressure was 135 (± 24.3) mmHg, diastolic blood pressure was 76 (± 15.5) mmHg. The median kidney size was 11 (± 1.23) cm and cortical size was 1.7 (± 0.65) cm. In 113 (53.1%) patients the right kidney was biopsied. 69.5% (n = 148) of the patients 3 renal sample cylinders were obtained, 27.2% (n = 58) 2 cylinders and in 3.3% (n = 7) one cylinder. We did not found differences regarding of renal and cortical size in the patients according to the number of cylinders obtained. We observed that patients in whom 3 cylinders were had a higher percentage of renal biopsy in the left kidney (p = 0.028). We evidenced minor complications in 13.6% (n = 29) and 3.3% (n = 7) major complications. Patients with complications in KB were older (p = 0.039) and had a higher INR (p = 0.031). Patients with one renal cylinder Jin KB, presented a higher percentage of complications with 57.1% vs 17.2% two cylinders and 14.9% with three cylinder (p =0.014). We did not find differences in terms of complications according to the laterality of kidney biopsy (right vs left). Conclusion Kidney biopsy is a procedure with a low complication rate. Obtaining three renal biopsy cylinders for biobank has not shown an increase in the rate of complications, which remains similar than previously published reports. Our results suggest that the complications are observed mainly in the first and/or second cylinder, and in that case the third core is not performed.

COVID-19 effects on the kidney.

Apart from pulmonary disease, acute kidney injury (AKI) is one of the most frequent and most severe organ complications in severe coronavirus disease 2019 (COVID-19). The SARS-CoV‑2 virus has been detected in renal tissue. Patients with chronic kidney disease (CKD) before and on dialysis and specifically renal transplant patients represent a particularly vulnerable population. The increasing number of COVID-19 infected patients with renal involvement led to an evolving interest in the analysis of its pathophysiology, morphology and modes of virus detection in the kidney. Meanwhile, there are ample data from several autopsy and kidney biopsy studies that differ in the quantity of cases as well as in their quality. While the detection of SARS-CoV‑2 RNA in the kidney leads to reproducible results, the use of electron microscopy for visualisation of the virus is difficult and currently critically discussed due to various artefacts. The exact contribution of indirect or direct effects on the kidney in COVID-19 are not yet known and are currently the focus of intensive research.

COVID-19 effects on the kidney

Bei einer schweren Coronavirus-Erkrankung-2019 (COVID-19) ist neben der Lungenerkrankung selbst das akute Nierenversagen (ANV) eine der häufigsten und schwerwiegendsten Komplikationen. Das SARS-CoV-2-Virus konnte hierbei auch in der Niere nachgewiesen werden. Patienten mit chronischen Nierenerkrankungen (CKD), dialysepflichtige sowie v. a. nierentransplantierte Patienten scheinen eine besonders vulnerable Population darzustellen. Die zunehmende Anzahl SARS-CoV-2-infizierter Patienten hat das Interesse an der genauen Pathophysiologie und Morphologie der Nierenschädigung sowie am direkten Virusnachweis in der Niere geweckt, der im Gegensatz zur Lunge insgesamt schwieriger zu führen ist. Hierzu liegen mittlerweile Daten aus Autopsie- und Nierenbiopsiestudien mit unterschiedlichen Patientenzahlen und von sehr unterschiedlicher Qualität vor. Während der Nachweis von SARS-CoV-2-RNA im Nierengewebe mit gut reproduzierbaren Ergebnissen erfolgt, ist insbesondere der Virusnachweis mittels Elektronenmikroskopie schwierig und wird aufgrund zahlreicher Artefakte derzeit kritisch diskutiert. Die genauen direkten oder indirekten Effekte von SARS-CoV‑2 auf die Niere sind noch nicht im Detail bekannt und derzeit der Fokus intensiver Forschung.

COVID-19 and kidney involvement

Bei einer schweren COVID-19(„coronavirus disease 2019“)-Erkrankung ist neben der Lungenerkrankung das akute Nierenversagen eine der häufigsten und schwerwiegendsten Komplikationen. SARS-CoV‑2 („severe acute respiratory syndrome coronavirus 2“) konnte auch in der Niere nachgewiesen werden. Patienten mit chronischen Nierenerkrankungen und an der Dialyse wie auch nierentransplantierte Patienten scheinen eine besonders vulnerable Population darzustellen. Die zunehmende Anzahl SARS-CoV-2-infizierter Patienten hat das Interesse an der genauen Pathophysiologie und Morphologie der Nierenschädigung sowie am direkten Virusnachweis in der Niere geweckt, der im Gegensatz zur Lunge insgesamt schwieriger zu führen ist. Hierzu liegen mittlerweile Daten aus größeren Autopsie- und Nierenbiopsiestudien vor. Während der Nachweis von SARS-CoV-2-RNA im Gewebe zu gut reproduzierbaren Ergebnissen führt, wird insbesondere der Virusnachweis mittels Elektronenmikroskopie aufgrund zahlreicher Artefakte kritisch diskutiert. Die genauen und direkten Effekte von SARS-CoV‑2 auf die Niere sind noch nicht im Detail bekannt und derzeit im Fokus intensiver Forschung.

P0086FOCAL SEGMENTAL GLOMERULOSCLEROSIS AND TROMBOCYTOPENIA WITHOUT BLEEDING DIATHESIS: WHEN GENETICS MATTER

Abstract Background and Aims A 45-year old patient presented to our renal unit because of increased serum creatinine (2 mg/dL), proteinuria (2g/24h collection) and haematuria; platelets were 12000/mcL. His family history was negative. He had already undergone cataract surgery and was wearing a hearing device. Alport syndrome was suspected and kidney biopsy performed. Light microscopy showed focal segmental glomerulosclerosis (FSGS), while immunofluorescence was negative. Electron microscopy was not available. No specific treatment was undertaken and he progressed to end-stage renal disease (ESRD) in 10 years. The patient chose peritoneal dialysis. He was considered at high risk of bleeding but the Tenchkoff catheter was inserted without problems. After 3 months he received kidney transplant and again no pathological bleeding occurred. Method A genetic test was requested using next generation sequencing (NGS). Results A mutation of myosin heavy chain 9 (MYH9) gene which encodes the non-muscle myosin heavy chain-IIA (NMMH-IIA) was found. This mutation is associated with thrombocytopenia and proteinuria; platelets are giant and display normal aggregation, even in those patients who have a very low count. Proteinuria can be mild or in the nephrotic range, with or without microhaematuria. Kidney involvement is highly heterogeneous and leads to ESRD in half of the cases. Light microscopy shows FSGS as the prevalent pattern whereas electron microscopy is characterized by podocyte foot process effacement. In fact, NMMH-IIA is expressed in podocytes and controls cytoskeleton and cell migration. The differential diagnosis with Alport disease is challenging because additional features of MYH9 mutation are sensorineural deafness and pre-senile cataract. For all these reasons, accurate kidney biopsy study, family history and genetics are decisive. Conclusion Genetic testing has a pivotal role in understanding kidney diseases and should be more and more used.

The Impact of APOL1 on Chronic Kidney Disease and Hypertension.

Essential hypertension is a clinical diagnosis based on the presence of an elevated systemic blood pressure on physical examination without a clear inciting cause. It has multiple etiologies and is not a homogeneous disorder. Hypertension contributes to the development and progression of atherosclerotic cardiovascular diseases, and antihypertensive treatment reduces the risk of fatal and nonfatal myocardial infarction, stroke, and congestive heart failure. Although hypertension is frequently present in nondiabetic individuals with low levels of proteinuria and chronic kidney disease, reducing blood pressures in this population does not reliably slow nephropathy progression. Many of these patients with recent African ancestry have the primary kidney disease "solidified glomerulosclerosis" that is strongly associated with renal-risk variants in the apolipoprotein L1 gene (APOL1). This kidney disease contributes to secondarily elevated blood pressures. The APOL1-associated spectrum of nondiabetic nephropathy also includes proteinuric kidney diseases, idiopathic focal segmental glomerulosclerosis, collapsing glomerulopathy, severe lupus nephritis, and sickle cell nephropathy. This article reviews relationships between mild to moderate essential hypertension and chronic kidney disease with a focus on the role of APOL1 in development of hypertension. Available evidence strongly supports that APOL1 renal-risk variants associate with glomerulosclerosis in African Americans, which then causes secondary hypertension, not with essential hypertension per se.

Morphological and clinical findings in Sri Lankan patients with chronic kidney disease of unknown cause (CKDu): Similarities and differences with Mesoamerican Nephropathy.

In Sri Lanka, an endemic of chronic kidney disease of unknown origin (CKDu) is affecting rural communities. The endemic has similarities with Mesoamerican Nephropathy (MeN) in Central America, however it has not yet been clarified if the endemics are related diagnostic entities. We designed this study of kidney biopsies from patients with CKDu in Sri Lanka to compare with MeN morphology. Eleven patients with CKDu were recruited at the General Hospital, Polonnaruwa, using similar inclusion and exclusion criteria as our previous MeN studies. Inclusion criteria were 20–65 years of age and plasma creatinine 100–220 μmol/L. Exclusion criteria were diabetes mellitus, uncontrolled hypertension and albuminuria >1g/24h. Kidney biopsies, blood and urine samples were collected, and participants answered a questionnaire. Included participants were between 27–61 years of age and had a mean eGFR of 38±14 ml/min/1.73m2. Main findings in the biopsies were chronic glomerular and tubulointerstitial damage with glomerulosclerosis (8–75%), glomerular hypertrophy and mild to moderate tubulointerstitial changes. The morphology was more heterogeneous and interstitial inflammation and vascular changes were more common compared to our previous studies of MeN. In two patients the biopsies showed morphological signs of acute pyelonephritis but urine cultures were negative. Electrolyte disturbances with low levels of serum sodium, potassium, and/or magnesium were common. In the urine, only four patients displayed albuminuria, but many patients exhibited elevated α-1-microglobulin and magnesium levels. This is the first study reporting detailed biochemical and clinical data together with renal morphology, including electron microscopy, from Sri Lankan patients with CKDu. Our data show that there are many similarities in the biochemical and morphological profile of the CKDu endemics in Central America and Sri Lanka, supporting a common etiology. However, there are differences, such as a more mixed morphology, more interstitial inflammation and vascular changes in Sri Lankan patients.

Nationwide multicenter kidney biopsy study of Japanese patients with hypertensive nephrosclerosis.

Nephrosclerosis is an increasingly reason for dialysis in Japan. However, kidney biopsy specimens for hypertensive nephrosclerosis are very limited; thus, the pathologic evaluation of hypertensive nephrosclerosis currently remains unclear. Clinical and pathologic data of a total of 184 biopsy-confirmed hypertensive nephrosclerosis patients were collected from 13 centers throughout Japan. Seven pathological findings were assessed in this study. The outcomes of interest for this study were dialysis, composite kidney events, cardiovascular events, and all-cause mortality. The Green and Yellow (G&Y), Orange, and Red groups of the chronic kidney diseases (CKD) heat map contained 36, 57, and 91 cases, respectively. The mean observation period was 7.3±5.2 (median, IQR; 6.1, 2.6-9.7) years. Global glomerulosclerosis (GScle), interstitial fibrosis and tubular atrophy (IFTA), arteriolar hyalinosis in Red exhibited higher scores than those in G&Y and Orange. The incidence rates of the composite kidney end points in 100 person-years for the G&Y, Orange, and Red groups were 1.42, 2.16, and 3.98, respectively. In the univariate Cox analysis for the composite kidney end points, GScle, IFTA and interstitial cell infiltration exhibited statistically significant high hazard ratios (1.18, 1.84, 1.69, respectively). However, after adjustment for clinical and medication data, the Red group in the CKD heat map category was risk factor for the composite kidney end points (HR 9.51). In summary, although pathologic findings had minor impacts on the prediction of composite outcomes in this study, the clinical stage of the CKD heat map is a good predictor of composite kidney events.

Bile Cast Nephropathy in Patients with Acute Kidney Injury Due to Hepatorenal Syndrome: A Postmortem Kidney Biopsy Study.

Background and Aims: The role of bile cast nephropathy (BCN) in pathogenesis of hepatorenal syndrome (HRS) in decompensated cirrhosis and acute on chronic liver failure (ACLF) is unknown. This study aimed to determine the frequency of BCN detected on postmortem renal biopsy among patients with decompensated cirrhosis and ACLF who had been admitted with acute kidney injury due to HRS (HRA-AKI) and expired during that hospitalization.Methods: One-hundred-twenty-seven postmortem renal biopsies with adequate size (>1 cm in length) were included for analysis. These were obtained from 84 patients with decompensated cirrhosis and 43 patients with ACLF.Results: BCN was detected in 57 of the total 127 (44.8%) renal biopsy specimens. Patients with BCN had significantly higher levels of serum total bilirubin, total leukocyte count and model for end-stage liver disease score, as compared to those without BCN. BCN was detected in 32/43 (74.4%) of the patients with ACLF, as compared to 25/84 (29.7%) of the patients with decompensated cirrhosis (p < 0.001). On multivariate analysis, direct bilirubin (OR (95% CI): 1.27 (1121–1.698); p < 0.001) and presence of ACLF (OR (95% CI): 2.603 (1.054–7.111); p = 0.041) were found to be significant predictors of BCN on postmortem renal biopsy.Conclusion: BCN was found in 72.1% of patients with ACLF and 27.4% patients with decompensated cirrhosis who had been hospitalized with an admitting diagnosis of HRS-AKI and who expired during that hospitalization and underwent postmortem renal biopsy. Direct serum bilirubin and presence of ACLF were found to be significant predictors of BCN on postmortem renal biopsy.

Nationwide multicentre kidney biopsy study of Japanese patients with type 2 diabetes.

The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are diverse, but large-scale pathologic studies with long-term observations are limited. Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored. During the observation period, there were 304 composite kidney events [dialysis, doubling of creatinine or reduction of estimated glomerular filtration rate (eGFR) by half], 31 instances of chronic kidney disease (CKD) G5D, 76 cardiovascular events and 73 deaths. The mean observation period was 72.4 months. The distribution of CKD heat map categories for the 600 patients was 103 green or yellow, 149 orange and 348 red. Even in the cases in the green and yellow category, diffuse lesions (81.6%), polar vasculosis (42.6%) and subendothelial space widening (35.1%) were commonly detected. Cox proportional hazard analysis revealed that the presence of nodular lesions [hazard ratio (HR) 21.1, 95% confidence interval (CI) 5.3-84.6], exudative lesions (HR 5.1, 95% CI 1.3-20.3) and mesangiolysis (HR 7.6, 95% CI 2.0-28.8) in cases in the green and yellow category were associated with significantly great impact on composite kidney events after adjustment for clinical risk factors. This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients.

Renal Morphology, Clinical Findings, and Progression Rate in Mesoamerican Nephropathy

Mesoamerican nephropathy (MeN) is a chronic kidney disease affecting rural inhabitants in Central America. We have previously described the renal morphology in 8 patients from El Salvador. To confirm the renal pathology, we have studied kidney biopsies from patients with MeN in Nicaragua. Follow-up urine and blood samples from both biopsy studies were collected to investigate the natural history. Case series. In the kidney biopsy study, 19 male sugarcane workers in Nicaragua with suspected MeN were investigated with questionnaires, kidney biopsies, and blood and urine analysis. Inclusion criteria were age 20 to 65 years and plasma creatinine level of 1.13 to 2.49mg/dL or estimated glomerular filtration rate (eGFR) of 30 to 80mL/min/1.73m2. Exclusion criteria were proteinuria with protein excretion >3g/24 h, uncontrolled hypertension, diabetes mellitus, or other known kidney disease. In the follow up-study, blood and urine from the kidney biopsy study in Nicaragua (n=18) and our previous biopsy study of MeN cases in El Salvador (n=7) were collected 1 to 1.5 and 2 to 2.5 years after biopsy, respectively. Renal morphology, clinical, and biochemical characteristics, change in eGFR per year. eGFR was calculated using the CKD-EPI creatinine (eGFRcr), cystatin C (eGFRcys), and creatinine-cystatin C (eGFRcr-cys) equations. In the kidney biopsy study, participants had a mean eGFRcr of 57 (range, 33-96) mL/min/1.73m2. 47% had low plasma sodium and 21% had low plasma potassium levels. 16 kidney biopsies were representative and showed glomerulosclerosis (mean, 38%), glomerular hypertrophy, and signs of chronic glomerular ischemia. Mild to moderate tubulointerstitial damage and mostly mild vascular changes were seen. In the follow up-study, median duration of follow-up was 13 (range, 13-27) months. Mean change in eGFRcr was-4.4±8.4 (range,-27.7 to 10.2) mL/min/1.73m2 per year. Most patients had stopped working with sugarcane cultivation. 3 biopsy specimens had 4 or fewer glomeruli. This study confirms the renal morphology of MeN: chronic glomerular and tubulointerstitial damage with glomerulosclerosis and chronic glomerular ischemia. Follow-up data show that eGFRs, on average, deteriorated.