Collapsing FSGS Post Non Renal Solid Organ Transplantation

Abstract

Introduction: Collapsing focal and segmental glomerulosclerosis (cFSGS) is a rare and aggressive form of FSGS. It occurs in a variety of clinical settings and is usually associated with a heavy proteinuria and very poor renal outcome. We describe the clinical and histological characteristics of 10 cases of cFSGS occurring at our institution after non-renal solid organ transplantation. Methods: We performed a retrospective review of all cases of biopsy proven cFSGS occurring post non-renal solid organ transplantation at our institution. Results are given as mean ±SEM. Results: We identified 10 cases of cFSGS post non-renal solid organ transplantation occurring over the last 20 years at our institution. 5 cases occurred post heart transplantation, 3 cases post combined heart and lung transplantation, 1 case post liver transplantation and 1 post lung transplantation. Two patients were female, the rest (8) were male. All had well preserved renal function and minimal proteinuria prior to transplantation. 3/10 of the patients had been smokers prior to transplantation, 5/10 patients had developed diabetes post transplantation and 7/10 were being treated for hypertension at the time of renal biopsy. 9/10 patients were treated with a calcineurin inhibitor (CNI) based immunosuppressive regimen post transplantation and 1/10 was treated with an everolimus based immunosuppressive regimen without CNI. The mean age of patients at the time of renal biopsy was 44±4.73. Mean time in years between transplantation and renal biopsy was 8.1±1.81. Mean serum creatinine at the time of biopsy was 261±30μmol/L. Mean proteinuria at the time of renal biopsy was 6.6±1.35g/24hours and mean serum albumin at the time of biopsy was 31.1±1.88g/L. On biopsy the mean percentage of glomeruli with global sclerosis was 45±7%. Remaining glomeruli showed changes constant with cFSGS. All biopsies showed moderate to severe interstitial fibrosis and atrophy, mostly in a striped pattern consistent with chronic CNI nephrotoxicity. At diagnosis many patients were converted to non-CNI based immunosuppressive regimens. Despite this all but 1 patient progressed to end-stage renal failure (ESRF) within a mean of 20±8.3 months of diagnosis. The only patient not to progress to ESRF has had only 4 months follow-up. Conclusion: cFSGS is a rare complication occurring late post non-renal solid organ transplantation. It occurs in the setting of prolonged exposure to CNIs and in association with other vascular risk factors. It presents with heavy proteinuria and moderate degrees of renal failure. The prognosis, as with most forms of FSGS, is almost universally poor. Late amendment to immunosuppressive therapy, in particular withdrawal of CNIs has little effect on the progression of disease which is characterised by chronic and irreversible biopsy changes. Close monitoring of renal parameters in the post transplant period, particularly regular monitoring for the onset of proteinuria may allow earlier detection of the lesion and improve outcome with earlier changes to immunosuppressive regimens.