Limy Wong

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. This study thus characterized a large C3 glomerulopathy cohort and identified clinicopathologic predictors of renal outcome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS All patients with kidney biopsies fulfilling criteria for C3 glomerulopathy from two quaternary renal centers within the United Kingdom and Ireland between 1992 and 2012 were retrospectively reviewed. We recorded histologic, demographic, and clinical data and determined predictors of ESRD using the Cox proportional hazards model. RESULTS Eighty patients with C3 glomerulopathy were identified: 21 with DDD and 59 with C3GN. Patients with DDD were younger, more likely to have low serum C3 levels, and more likely to have crescentic GN than patients with C3GN. Patients with C3GN were older and had more severe arteriolar sclerosis, glomerular sclerosis, and interstitial scarring than patients with DDD. Of 70 patients with available follow-up data, 20 (29%) progressed to ESRD after a median of 28 months. Age >16 years, DDD subtype, and crescentic GN were independent predictors of ESRD within the entire cohort. Renal impairment at presentation predicted ESRD only among patients with DDD. CONCLUSIONS Although detailed serologic and genetic data are lacking, this study nevertheless identifies important clinicopathologic distinctions between patients with DDD and C3GN. These include independent predictors of renal outcome. If replicated in other cohorts, these predictors could be used to stratify patients, enabling application of emerging mechanism-based therapies to patients at high risk for poor renal outcome.

Getting the balance right: adverse events of therapy in anti-neutrophil cytoplasm antibody vasculitis

Antineutrophil cytoplasm antibody associated systemic vasculitides (AASV) have traditionally been managed with a combination of cyclophosphamide and glucocorticoids during the induction phase, followed by azathioprine in the maintenance phase. Whilst these therapies have markedly improved the prognosis in AASV, treatment related adverse events remain a major challenge and include complications such as infection, glucocorticoid related side effects, malignancy, cardiovascular disease, infertility and death. Newer biologic therapies have been shown to demonstrate equivalent efficacy as cyclophosphamide for remission but the hoped for reduction in adverse events has yet to be realised. More recent efforts have been focused on refining existing therapeutic regimens and strategies, tailoring individual treatment to disease severity, patient age and kidney function to derive maximum treatment efficacy while minimising treatment toxicity. In particular, current interventional trials are targeting a reduction in corticosteroid exposure in an effort to make induction and maintenance regimens safer.

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.

The Irish Kidney Gene Project - Prevalence of Family History in Patients with Kidney Disease in Ireland

Background: The prevalence of kidney disease (KD) due to inherited genetic conditions in Ireland is unknown. The aim of this study was to characterise an adult kidney disease population in Ireland and to identify familial clusters of kidney disease within the population. Methods: This was a multicenter cross-sectional study of patients with kidney disease in the Republic of Ireland, from January 2014 to September 2014, recruiting from dialysis units and out-patient renal departments. A survey was performed by collecting data on etiology of kidney disease and whether a family history of kidney disease exists. Medical records were cross-referenced to confirm the etiology of kidney disease. Results: A total of 1,840 patients were recruited with a mean age of 55.9 years (range 17-94.5) and a male predominance (n = 1,095; 59.5%). A positive family history was reported by 629 participants (34.2%). Excluding polycystic kidney disease (n = 134, 7.3%), a positive family history was reported by 495 participants (26.9%). Kidney disease due to an unknown etiology was the commonest etiology in the non-polycystic kidney disease group with a positive family history (10.6%, n = 67). Kidney diseases that are not classically associated with familial inheritance including tubulo-interstitial kidney disease, congenital abnormalities of the kidney and urinary tract and glomerulonephritis demonstrated familial clustering. Conclusion: In an Irish non-polycystic kidney disease population, 26.9% reports a positive family history. The commonest etiology of kidney disease in the positive family history cohort, excluding autosomal dominant polycystic kidney disease, was kidney disease due to unknown etiology. Examining families with kidney disease provides an opportunity to better understand disease pathogenesis and potentially identify genetic predispositions to kidney disease.

Recurrence of anti-neutrophil cytoplasmic antibody-associated vasculitis in appropriately immunosuppressed renal transplant patients: a discussion of two cases.

Background: Granulomatosis with polyangiitis (GPA) (formerly known as Wegener’s granulomatosis) is a multisystem autoimmune disease of unknown aetiology. Renal disease manifests as a crescentic glomerulonephritis, with varying degrees of renal failure. Ten percent of patients progress to end-stage kidney disease. Relapse of GPA in renal transplant patients is rare, with a rate of 0.09 relapses per patient per year. Patients and Methods: We describe two cases of GPA relapse in immunosuppressed renal transplant patients. Results: These patients presented with new-onset graft disfunction, having previously had an uncomplicated posttransplant course. Both patients were on appropriate doses of immunosuppressive agents at the time of relapse, with therapeutic target levels of tacrolimus. We describe the background history and management of both patients. Conclusion: The cases described inform us that although recurrence of anti-neutrophil cytoplasmic antibody vasculitis in transplant patients is rare, it should remain on our list of differential diagnoses in allograft disfunction.

Successful kidney transplantation normalizes platelet function

Abstract Background Uraemic platelet dysfunction is not completely understood, in part due to non-physiological platelet function assays. We have developed a physiological flow-based assay that quantifies platelet function in microlitre volumes of blood under arterial shear. The aim of this study was to characterize platelet function before and after kidney transplantation. Methods Ten patients scheduled for living donor kidney transplant surgery and nine healthy controls were analysed using the assay. The motional parameters of platelet behaviour on von Willebrand factor (VWF) were recorded using customized platelet tracking software. The assay was repeated 3–8 weeks post-transplant in the transplant group and at an interval of >3 weeks in normal healthy volunteers. Results Platelet–VWF interactions were markedly reduced in the 10 pre-transplant patients compared with the healthy controls. In seven patients with immediate graft function, dynamic platelet function returned to normal (despite a small decrease in haemoglobin and haematocrit), but remained markedly abnormal in the three patients with delayed graft function (DGF). Conclusions Dynamic platelet function returned to normal following transplantation in those with immediate graft function. This early improvement was not observed in those with DGF. There may be important clinical implications, as patients with DGF are more likely to undergo invasive procedures, including transplant biopsies and insertion of central venous catheters.

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. We discuss the diagnostic challenges faced in this presentation and also explore possible differential diagnoses. This rare presentation highlights the importance of renal biopsy in the diagnosis and treatment of acute renal failure and the atypical presentation of tuberculosis.

Temporal fossa intra-extracranial dumbbell schwannoma

Intra-extracranial schwannomas arising unrelated to major cranial nerves are exceedingly rare neoplasms. We report the case of a 23-year-old male who presented with a 9 month history of progressive temporal swelling which was excised and found histologically to be a schwannoma. A succinct review of the relevant literature is presented.