scholarly journals Utility of Genomic Testing after Renal Biopsy

2019 ◽  
Vol 51 (1) ◽  
pp. 43-53
Author(s):  
Susan L. Murray ◽  
Anthony Dorman ◽  
Katherine A. Benson ◽  
Dervla M. Connaughton ◽  
Caragh P. Stapleton ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Renal Biopsy ◽  
Focal Segmental Glomerulosclerosis ◽  
Alport Syndrome ◽  
Kidney Biopsy ◽  
Genetic Diagnosis ◽  
Pathological Diagnosis ◽  
Genetic Sequencing ◽  
Segmental Glomerulosclerosis

Background: Renal biopsy is the mainstay of renal pathological diagnosis. Despite sophisticated diagnostic techniques, it is not always possible to make a precise pathological diagnosis. Our aim was to identify a genetic cause of disease in patients who had undergone renal biopsy and determine if genetic testing altered diagnosis or treatment. Methods: Patients with suspected familial kidney disease underwent a variety of next-generation sequencing (NGS) strategies. The subset of these patients who had also undergone native kidney biopsy was identified. Histological specimens were reviewed by a consultant pathologist, and genetic and pathological diagnoses were compared. Results: Seventy-five patients in 47 families underwent genetic sequencing and renal biopsy. Patients were grouped into 5 diagnostic categories based on pathological diagnosis: tubulointerstitial kidney disease (TIKD; n = 18); glomerulonephritis (GN; n = 15); focal segmental glomerulosclerosis and Alport Syndrome (n = 11); thrombotic microangiopathy (TMA; n = 17); and nonspecific pathological changes (n = 14). Thirty-nine patients (52%) in 21 families (45%) received a genetic diagnosis; 13 cases (72%) with TIKD, 4 (27%) with GN, 6 (55%) with focal segmental glomerulosclerosis/Alport syndrome, and 10 (59%) with TMA and 6 cases (43%) with nonspecific features. Genetic testing resulted in changes in understanding of disease mechanism in 21 individuals (54%) in 12 families (57%). Treatment would have been altered in at least 26% of cases (10/39). Conclusions: An accurate genetic diagnosis can result in changes in clinical diagnosis, understanding of pathological mechanism, and treatment. NGS should be considered as a complementary diagnostic technique to kidney biopsy in the evaluation of patients with kidney disease.

scholarly journals Hydroxypropyl-β-cyclodextrin protects from kidney disease in experimental Alport syndrome and focal segmental glomerulosclerosis

2018 ◽  
Vol 94 (6) ◽  
pp. 1151-1159 ◽  
Author(s):  
Alla Mitrofanova ◽  
Judith Molina ◽  
Javier Varona Santos ◽  
Johanna Guzman ◽  
Ximena A. Morales ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Alport Syndrome ◽  
Segmental Glomerulosclerosis

scholarly journals The Association between Glomerular Diameter and Secondary Focal Segmental Glomerulosclerosis in Chronic Kidney Disease

2021 ◽  
pp. 1-8
Author(s):  
Ryo Zamami ◽  
Kentaro Kohagura ◽  
Kojiro Kinjyo ◽  
Takuto Nakamura ◽  
Takanori Kinjo ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Biopsy ◽  
Focal Segmental Glomerulosclerosis ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Glomerular Hypertrophy ◽  
Glomerular Lesion ◽  
Segmental Glomerulosclerosis ◽  
Glomerular Size

<b><i>Introduction:</i></b> When nephron loss occurs, the glomerular filtration rate (GFR) is suggested to be maintained by glomerular hypertrophy, but excessive hypertrophy can rather lead to the formation of focal segmental glomerulosclerosis (FSGS), thereby causing progressive kidney damage. However, it is not clear how much glomerular hypertrophy leads to the formation of FSGS. We examined the association between glomerular diameter and FSGS lesions in chronic kidney disease (CKD) patients. <b><i>Methods:</i></b> We recruited 77 patients who underwent renal biopsy during 2016–2017; however, those identified with primary FSGS and glomerulonephritis with active glomerular lesion were excluded. We evaluated the maximal glomerular diameter (Max GD), an indicator of glomerular size, in each renal biopsy specimen and examined its association with FSGS lesion. <b><i>Results:</i></b> The median age, blood pressure, and estimated GFR of the patients were 53 years, 122/70 mm Hg, and 65 mL/min/1.73 m<sup>2</sup>, respectively. The optimal cutoff threshold of Max GD for predicting the presence of FSGS lesions, assessed by receiver operating characteristic curve analysis, was determined to be at 224 μm (area under the curve, 0.81; sensitivity, 81%; specificity, 72%). Multivariate logistic regression analyses demonstrated that Max GD ≥224 μm was significantly associated with the presence of FSGS lesions, independent of other confounding factors (odds ratio, 11.70; 95% confidence interval, 1.93–70.84). <b><i>Discussion/Conclusion:</i></b> Glomerular hypertrophy (Max GD ≥224 μm) has been associated with FSGS lesions in CKD patients and may reflect the limits of the compensatory process.

scholarly journals Clinical manifestations of focal segmental glomerulosclerosis in Japan from the Japan Renal Biopsy Registry: age stratification and comparison with minimal change disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takaya Ozeki ◽  
Shoichi Maruyama ◽  
Toshiyuki Imasawa ◽  
Takehiko Kawaguchi ◽  
Hiroshi Kitamura ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Renal Biopsy ◽  
Focal Segmental Glomerulosclerosis ◽  
Clinical Diagnosis ◽  
Clinical Characteristics ◽  
Minimal Change Disease ◽  
Multivariable Analysis ◽  
Laboratory Data ◽  
Minimal Change ◽  
Segmental Glomerulosclerosis

AbstractFocal segmental glomerulosclerosis (FSGS) is a serious condition leading to kidney failure. We aimed to investigate the clinical characteristics of FSGS and its differences compared with minimal change disease (MCD) using cross-sectional data from the Japan Renal Biopsy Registry. In Analysis 1, primary FSGS (n = 996) were stratified by age into three groups: pediatric (< 18 years), adult (18–64 years), and elderly (≥ 65 years), and clinical characteristics were compared. Clinical diagnosis of nephrotic syndrome (NS) was given to 73.5% (97/132) of the pediatric, 41.2% (256/622) of the adult, and 65.7% (159/242) of the elderly group. In Analysis 2, primary FSGS (n = 306) and MCD (n = 1303) whose clinical diagnosis was nephrotic syndrome (NS) and laboratory data were consistent with NS, were enrolled. Logistic regression analysis was conducted to elucidate the variables which can distinguish FSGS from MCD. On multivariable analysis, higher systolic blood pressure, higher serum albumin, lower eGFR, and presence of hematuria associated with FSGS. In Japanese nationwide registry, primary FSGS patients aged 18–64 years showed lower rate of NS than those in other ages. Among primary nephrotic cases, FSGS showed distinct clinical features from MCD.

scholarly journals Dapagliflozin in focal segmental glomerulosclerosis: a combined human-rodent pilot study

2018 ◽  
Vol 314 (3) ◽  
pp. F412-F422 ◽  
Author(s):  
Harindra Rajasekeran ◽  
Heather N. Reich ◽  
Michelle A. Hladunewich ◽  
Daniel Cattran ◽  
Julie A. Lovshin ◽  
...  
Keyword(s):  
Pilot Study ◽  
Kidney Disease ◽  
Focal Segmental Glomerulosclerosis ◽  
Plasma Flow ◽  
Renal Plasma Flow ◽  
Short Term Treatment ◽  
Segmental Glomerulosclerosis ◽  
Renal Hemodynamic ◽  
Hemodynamic Function ◽  
The Impact

Focal segmental glomerulosclerosis (FSGS) is an important cause of nondiabetic chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibition (SGLT2i) therapy attenuates the progression of diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in nondiabetic CKD such as FSGS. The primary aim of this pilot study was to determine the effect of 8 wk of dapagliflozin on glomerular filtration rate (GFR) in humans and in experimental FSGS. Secondary end points were related to changes in renal hemodynamic function, proteinuria, and blood pressure (BP). GFR (inulin) and renal plasma flow (para-aminohippurate), proteinuria, and BP were measured in patients with FSGS ( n = 10), and similar parameters were measured in subtotally nephrectomized (SNx) rats. In response to dapagliflozin, changes in GFR, renal plasma flow, and 24-h urine protein excretion were not statistically significant in humans or rats. Systolic BP (SBP) decreased in SNx rats (196 ± 26 vs. 165 ± 33 mmHg; P < 0.001), whereas changes were not statistically significant in humans (SBP 112.7 ± 8.5 to 112.8 ± 11.2 mmHg, diastolic BP 71.8 ± 6.5 to 69.6 ± 8.4 mmHg; P = not significant), although hematocrit increased (0.40 ± 0.05 to 0.42 ± 0.05%; P = 0.03). In archival kidney tissue from a separate patient cohort, renal parenchymal SGLT2 mRNA expression was decreased in individuals with FSGS compared with controls. Short-term treatment with the SGLT2i dapagliflozin did not modify renal hemodynamic function or attenuate proteinuria in humans or in experimental FSGS. This may be related to downregulation of renal SGLT2 expression. Studies examining the impact of SGLT2i on markers of kidney disease in patients with other causes of nondiabetic CKD are needed.

RENAL BIOPSY IN CHILDREN

PEDIATRICS ◽  
1958 ◽  
Vol 22 (6) ◽  
pp. 1033-1034
Author(s):  
ROBERT L. VERNIER ◽  
ROBERT A. GOOD
Keyword(s):  
Kidney Disease ◽  
Renal Biopsy ◽  
Needle Biopsy ◽  
Kidney Biopsy ◽  
Therapeutic Agents ◽  
Renal Diseases ◽  
Kidney Cortex ◽  
Percutaneous Needle Biopsy ◽  
Surgical Exploration ◽  
Renal Biopsies

RENAL biopsy offers invaluable aid in the clinical diagnosis of kidney disease and is an important technique in research designed to clarify the etiology, pathogenesis, and evaluation of therapeutic agents, in a variety of renal diseases. The majority of the scientific reports describing renal biopsy have concerned adult patients. The few available reports of renal biopsy in children do not discuss the risks attending the procedure or the specific problems peculiar to kidney biopsy in children. A review of our experience in 150 renal biopsies in children may afford a basis for evaluation of these questions. The available techniques of renal biopsy include: 1) surgical exploration and removal of a segment of kidney cortex, and 2) percutaneous needle biopsy.

Kidney Biopsy

2020 ◽  
Author(s):  
Adina Voiculescu ◽  
Gearoid McMahon
Keyword(s):  
Kidney Disease ◽  
Renal Biopsy ◽  
Kidney Transplant ◽  
Kidney Biopsy ◽  
Bleeding Risk ◽  
Renal Transplant Recipients ◽  
Outpatient Basis ◽  
Transplant Recipients ◽  
Renal Biopsies ◽  
Careful Assessment

The introduction of renal biopsies has transformed practice in nephrology, particularly with regard to glomerular disease and the care of kidney transplant recipients. A biopsy can provide information about the diagnosis and prognosis of kidney disease while most importantly often leading to changes in therapy that can be life saving. Four groups of patients benefit most from renal biopsy: those with nephrotic syndrome, those with acute nephritic syndromes with rapid deterioration of renal function, those with unexplained acute kidney injury and renal transplant recipients. Non-nephrotic range proteinuria and/or hematuria or unexplained chronic kidney disease represent indications in selected cases. The evaluation of patients prior to undergoing a kidney biopsy requires a careful assessment that includes a detailed history to confirm the relative benefit of a biopsy in making an accurate diagnosis compared with individual’s risk of bleeding. The use of real-time ultrasound or CT-guidance with gun-mounted biopsy needles is paramount for the successful performance of the biopsy and reduction of risks. renal biopsies are mostly done as an inpatient but can be performed on an outpatient basis in selected cases. A renal biopsy has a bleeding risk of up to 5% and is considered a “high bleeding risk procedure”. For patients receiving -antithrombotic therapy, the approach to periprocedural use of antithrombotic agents needs to be individualized. Because it is a high-risk procedure, all efforts must be undertaken to minimize the risk including a careful assessment of the patient's specific situation, and only experienced operators at institutions that can care for post-biopsy complications should perform the procedure. This review contains 7 tables, 7 figures and 83 references Key words: kidney biopsy, native kidney, transplant kidney, indications, preparation, performing biopsy, ultrasound guidance, transjugular, CT-guided, complications

scholarly journals Clinical Genetic Screening in Adult Patients with Kidney Disease

2020 ◽  
Vol 15 (10) ◽  
pp. 1497-1510 ◽  
Author(s):  
Enrico Cocchi ◽  
Jordan Gabriela Nestor ◽  
Ali G. Gharavi
Keyword(s):  
Genetic Testing ◽  
Kidney Disease ◽  
Massively Parallel Sequencing ◽  
Kidney Diseases ◽  
Chromosomal Microarray ◽  
Ethical Considerations ◽  
Clinical Genetic ◽  
Genetic Sequencing ◽  
Sequencing Technologies ◽  
Potential Benefits

Expanded accessibility of genetic sequencing technologies, such as chromosomal microarray and massively parallel sequencing approaches, is changing the management of hereditary kidney diseases. Genetic causes account for a substantial proportion of pediatric kidney disease cases, and with increased utilization of diagnostic genetic testing in nephrology, they are now also detected at appreciable frequencies in adult populations. Establishing a molecular diagnosis can have many potential benefits for patient care, such as guiding treatment, familial testing, and providing deeper insights on the molecular pathogenesis of kidney diseases. Today, with wider clinical use of genetic testing as part of the diagnostic evaluation, nephrologists have the challenging task of selecting the most suitable genetic test for each patient, and then applying the results into the appropriate clinical contexts. This review is intended to familiarize nephrologists with the various technical, logistical, and ethical considerations accompanying the increasing utilization of genetic testing in nephrology care.

P0066KIDNEYCODE: A GENETIC TESTING PROGRAM FOR PATIENTS WITH CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Prasad Devarajan ◽  
Geoffrey Block ◽  
Keisha Gibson ◽  
Jim McKay ◽  
Colin Meyer ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Genetic Testing ◽  
Kidney Disease ◽  
Exome Sequencing ◽  
Polycystic Kidney Disease ◽  
Whole Exome Sequencing ◽  
Alport Syndrome ◽  
Polycystic Kidney ◽  
Accuracy And Precision ◽  
Whole Exome

Abstract Background and Aims Knowledge about genetic causes of chronic kidney disease (CKD) is one of the key gaps in global kidney research and recent International Society of Nephrology recommendations encourage the adoption of genetic testing to enable a goal of providing precision medicine based on individual risk (1). A recent whole-exome sequencing study showed that genetic inheritance may be responsible for up to 10% of CKD diagnoses, many of which may be previously undiagnosed or mis-diagnosed (2). Continued advances in DNA sequencing technology have made genetic testing, even whole-exome sequencing, applicable to routine clinical diagnoses. In order to test the hypothesis that genetic testing can provide valuable information to increase the accuracy and precision of diagnosis in CKD, we designed a gene panel to prospectively provide genetic testing in a subset of patients with CKD defined by a specific set of inclusion criteria. Method Reata Pharmaceuticals is partnering with Invitae on a program called KidneyCode, which provides no-charge genetic testing to enable diagnosis of three specific rare monogenic causes of CKD: Alport syndrome (AS), autosomal dominant polycystic kidney disease (ADPKD) due to PKD2 mutations, and focal segmental glomerulosclerosis (FSGS), as well as detection of variants in one of the autosomal recessive polycystic kidney disease gene, PKHD1. Invitae’s renal disease panel includes 17 genes (ACTN4, ANLN, CD2AP, COL4A3, COL4A4, COL4A5, CRB2, HNF1A, INF2, LMX1B, MYO1E, NPHS1, NPHS2, PAX2, PKD2, PKHD1, and TRPC6), and its assay includes both full-gene sequencing and intragenic deletion/duplication analysis using next-generation sequencing (NGS). The assay targets the coding exons and flanking 10bp of intronic sequences. Invitae’s method of variant classification uses a systematic process for assessing evidence based on guidelines published by the American College of Medical Genetics (3). Patients in the US at risk for hereditary CKD (eGFR ≤ 90 mL/min/1.73m2 plus hematuria or a family history of CKD) or with a known diagnosis of AS or FSGS are eligible. Family members of those with suspected or known AS or FSGS are also eligible. All participants in the KidneyCode program have access to genetic counseling follow-up at no additional charge. Results In the first five months of the KidneyCode program, 152 genetic tests have been completed. A genetic variant was reported in 87 patients. Of those 87 patients, 67 patients had 75 variants in COL4A3, 4, or 5 genes (34 Pathogenic/Likely Pathogenic (P/LP), 41 Variants of Uncertain Significance (VUS)), 20 patients had 24 variants in genes associated with FSGS (3 P/LP, 21 VUS), 15 patients had 20 variants in PKHD1 (1 P/LP, 19 VUS), and 2 patients had variants in PKD2 (1 P/LP, 1 VUS). Of the 34 patients with Pathogenic or Likely Pathogenic COL4A variants, 19 reported a previous diagnosis of Alport syndrome. Other diagnoses in patients with COL4A mutations included FSGS, thin basement membrane disease, and familial hematuria. Extra-renal manifestations such as hearing loss and eye disease were reported in 7 of the 34 patients with COL4A variants. Conclusion Initial results with the KidneyCode panel demonstrate the utility of NGS and support the hypothesis that combining genetic testing with clinical presentation and medical history can significantly improve accuracy and precision of diagnosis in patients with hereditary CKD.

P0132DIAGNOSIS OF HYPEROXALURIA FROM RENAL BIOPSY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Marwa Omrane ◽  
Raja Aoudia ◽  
Mondher Ounissi ◽  
Nada Sellami ◽  
Mouna Jerbi ◽  
...  
Keyword(s):  
Renal Failure ◽  
Kidney Disease ◽  
Renal Biopsy ◽  
Kidney Biopsy ◽  
Interstitial Fibrosis ◽  
Renal Pathology ◽  
Crystal Deposition ◽  
Biopsy Specimens ◽  
Initial Symptoms ◽  
History Of

Abstract Background and Aims Crystal-induced kidney disease refers to kidney injury caused by intratubular crystal deposition. The most common forms of crystalline nephropathy encountered in renal pathology are nephrocalcinosis and oxalate nephropathy. The purpose of our study is to determine the epidemiological and clinical characteristics of hyperoxaluria diagnosed from renal biopsy. Method We retrospectively reviewed all kidney biopsy specimens evaluated at renal pathology laboratory, from 1976 to 2019. The biopsy specimens were received from multiple medical department and medical centers. We studied 8900 biopsy specimens and we were focused on patients whose diagnosis of hyperoxaluria was made from renal biopsy Results We identified 25 cases (15 children and 10 adults) with a sex ratio H / F of 0.9. Mean age at diagnosis was 17.2 years old [4 months-73 years old]. Most patients were offspring of consanguineous mating (14 of 25) with intermarriage of first-degree cousins being the most common pattern. A family history of chronic kidney disease was found in 13 patients: indeterminated nephropathy (n = 6) and renal stone (n = 5) and primary hyperoxaluria (n=2). Among our patients, five had a history of urolithiasis. One patient had a history of chronic diarrhea related to Crohn's disease and one patient had a history of cephalic pancreatectomy and ileal resection. Initial symptoms and signs were dominated by renal failure (n = 25) with mean creatinine of 789.5 μmol / l [306-1832μmol / l], associated with proteinuria in 10 patients and hematuria in 11 patients. Arterial hypertension was present in 4 patients. Oligo anuria was reported in 4 patients without dilation of the urinary excretory pathways. In our patients, the diagnosis of crystalin nephropathy was revealed by renal biopsy. In one case, the diagnosis was made after renal transplant. In 4 cases the diagnosis was made by postmortem kidney biopsy. In all cases, the kidney biopsy specimen showed extensive intratubular crystal deposition and tubulointerstitial mononuclear cell infiltration with features of tubular injury and interstitial fibrosis. Examination of histologic slides showed colorless refractile crystals of polygonal appearance. Multicolored birefringence under polarized light identified these crystals as calcium oxalate. After different investigations (genetic and biological analysis), the diagnosis of hyperoxaluria was confirmed. Hyperoxaluria was primary in 23 patients and secondary in 2 patients. Conclusion Hyperoxaluria is a rare condition, often serious, involving renal prognosis and sometimes life-threatening, especially in early-onset forms. Early diagnosis and treatment should be done as soon as possible to slow the progression to end-stage renal failure. In patients with renal insufficiency, the diagnosis of hyperoxaluria is difficult. Renal biopsy can help when clinical and radiological data are not sufficient.

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