Diagnostic utility of genetic testing in patients undergoing renal biopsy.

High-throughput DNA testing is becoming established as a standard diagnostic test in the renal clinic. Previously published studies on cohorts of patients with unexplained chronic kidney disease of a suspected genetic aetiology have suggested a diagnostic yield for genomic sequencing of up to 18%. Here we determine the yield of targeted gene panel in a clinically unscreened cohort of patients referred for percutaneous native renal biopsy.

An Exome Sequencing Study of 10 Families with IgA Nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) is a heterogeneous disorder with a strong genetic component. The advent of whole exome sequencing (WES) has accelerated the discovery of genetic risk factors underlying familial disorders.

Objectives: We set out to test whether damaging variants in known kidney disease genes explain a proportion of IgAN cases recruited in Ireland.

Spatial and Temporal Clustering of Anti-Glomerular Basement Membrane Disease.

Background And Objectives: An environmental trigger has been proposed as an inciting factor in the development of anti-GBM disease. This multicenter, observational study sought to define the national incidence of anti-GBM disease during an 11-year period (2003-2014) in Ireland, investigate clustering of cases in time and space, and assess the effect of spatial variability in incidence on outcome.

Design, Setting, Participants, & Measurements: We ascertained cases by screening immunology laboratories for instances of positivity for anti-GBM antibody and the national renal histopathology registry for biopsy-proven cases.

Kidney transplant outcomes in familial C3 glomerulopathy.

C3 glomerulopathy, a newly designated entity, is characterized by glomerular disease associated with dysregulation of the alternative complement pathway and is a rare cause of end-stage kidney disease. Overall disease characteristics that include clinical presentation, laboratory assessment, histopathology and genetic background have only been unravelled in recent years and have led to the development of anti-complement therapies targeting different levels of the alternative pathway. We describe the long-term outcomes following kidney transplantation in an Irish family with familial C3 glomerulopathy due to a hybrid CFHR3-1 gene.

A De Novo Deletion in the Regulators of Complement Activation Cluster Producing a Hybrid Complement Factor H/Complement Factor H-Related 3 Gene in Atypical Hemolytic Uremic Syndrome.

The regulators of complement activation cluster at chromosome 1q32 contains the complement factor H (CFH) and five complement factor H-related (CFHR) genes. This area of the genome arose from several large genomic duplications, and these low-copy repeats can cause genome instability in this region. Genomic disorders affecting these genes have been described in atypical hemolytic uremic syndrome, arising commonly through nonallelic homologous recombination.

C3 glomerulopathy: clinicopathologic features and predictors of outcome.

Background And Objectives: The term C3 glomerulopathy describes renal disorders characterized by the presence of glomerular deposits composed of C3 in the absence of significant amounts of Ig. On the basis of electron microscopy appearance, subsets of C3 glomerulopathy include dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). The full spectrum of histologic change observed in C3 glomerulopathy has yet to be defined and pathologic predictors of renal outcome within this patient population remain largely unknown.

Clinical and pathologic characteristics of hereditary apolipoprotein A-I amyloidosis in Ireland.

Aim: Apolipoprotein A-I amyloidosis is a rare, autosomal dominant disorder characterized by progressive accumulation of amyloid fibrils in tissues, leading to renal and hepatic disease. We describe the clinical manifestations and pathologic features of kidney disease in three Irish families.

Methods: This observational study examines all known cases of chronic kidney disease due to hereditary apolipoprotein A-I amyloidosis in Ireland.

Acute renal failure secondary to tuberculosis: a diagnostic challenge.

Tuberculosis is a multiorgan disease with varied clinical presentations and is reemerging due to increasing immigration and globalization. We present the case of an immigrant female patient who developed acute renal failure with clinical and biochemical features suggestive of lupus nephritis but with a timely renal biopsy showing caseating granulomata in the renal parenchyma consistent with renal tuberculosis. Despite treatment with antituberculosis treatment and resolution of TB on repeat renal biopsy, she remained haemodialysis dependent.

Renal histology in the elderly: indications and outcomes.

Background: Renal disease is being increasingly diagnosed in the elderly. However, reports on biopsy-confirmed renal disease in this population are limited. The aim of this study was to give an overview of the most important indications, diagnoses and outcomes of renal biopsies in the elderly in our center.

Improved graft survival in highly sensitized patients undergoing renal transplantation after the introduction of a clinically validated flow cytometry crossmatch.

Background: Flow cytometric techniques are increasingly used in pretransplant crossmatching, although there remains debate regarding the clinical significance and predictive value of donor-specific antibodies detected by flow cytometry. At least some of the discrepancies between published studies may arise from differences in cutoffs used and lack of standardization of the test.

Methods: We selected cut-off values for pretransplant flow cytometric crossmatching (FCXM) based on the correlation of retrospective results with the occurrence of antibody-mediated rejection.

Plasmapheresis as rescue therapy in accelerated acute humoral rejection.

Accelerated acute humoral rejection (AHR) continues to occur in renal transplantation despite improved crossmatching, with potentially devastating consequences. Between 1 June 1998 and 31 December 2000, 440 renal transplants were performed in our center. AHR was diagnosed by the demonstration of typical pathological features on renal histology and positive direct immunofluorescence or detection of anti-HLA antibodies in serum.

International variation in histologic grading is large, and persistent feedback does not improve reproducibility.

Histologic grading systems are used to guide diagnosis, therapy, and audit on an international basis. The reproducibility of grading systems is usually tested within small groups of pathologists who have previously worked or trained together. This may underestimate the international variation of scoring systems.

Pathogenesis of acute renal failure associated with the HELLP syndrome: a case report and review of the literature.

Acute renal failure is a rare but serious complication of pregnancy. We describe a 31-year-old woman with haemolytic anemia, elevated liver enzymes, low platelets (HELLP syndrome) who developed acute peripartum renal failure. Renal biopsy performed 2 weeks later because of persistent oliguria revealed thrombotic microangiopathy and acute tubular necrosis.