Post renal transplant collapsing glomerulopathy is associated with poor outcomes

Abstract

Introduction: Collapsing glomerulopathy (CG) is a distinct morphologic pattern of proliferative renal parenchymal injury. It differ from focal segmental glomerulosclerosis (FSGS) by clinicopathologic pattern and its adverse outcome. The clinical significance of CG in renal allograft biopsies is not yet clear due to scant data and less occurrence of CG in renal transplant recipients. We conducted this single-center retrospective study to evaluate the prevalence, clinicopathological features, and outcome of post renal transplant CG. Subjects and Methods: We studied 127 renal allograft biopsies performed over a period of 45 months (Jan 2015–Oct 2018). A diagnosis of CG was made if at least one glomerulus demonstrated global or segmental collapse of the glomerular capillary walls, associated marked hyperplasia, and hypertrophy of the overlying visceral epithelial cells. We analyzed clinical, biochemical, and pathological characteristics and its impact on renal allograft outcome. Statistical analysis was performed and continuous variables were expressed as means ± standard deviation (SD) or medians (interquartile range and noncontinuous data were expressed in percentage and numerical values. Results: The prevalence of CG was 5.3% (7/127) of allograft biopsies. Out of the seven patients, six patients had undergone live donor transplant and one patient had undergone deceased donor renal transplant. The native kidney disease was unknown in these patients except one (IgA nephropathy). The median duration of diagnosis for CG was 17 months after transplantation (range 5–132months). Presenting symptoms were pedal edema and hypertension in 71.4% (5) patients each. All patients had proteinuria of more than 1 gm and renal allograft dysfunction and median serum creatinine of 3.05 mg/dl (1.5–4.8 mg/dl). All patients received standard triple immunosuppression. Over a period of 2–20 months, 57.14% (4) patients developed a graft failure and 43% (3) of the other patients had functioning grafts with serum creatinine of 1.5–4.2 mg/dl. Conclusions: CG presents with moderate to severe proteinuria and may lead to rapid graft dysfunction and subsequent graft failure in most of the patients.

CMV‐associated collapsing focal segmental glomerulosclerosis after kidney transplant in a pediatric patient

“…Collapsing FSGS after kidney transplantation is associated with poor clinical outcomes 2,5 . In our case, diarrhea on presentation may have been a manifestation of gastrointestinal CMV disease, but since it abated after 3 days and prior to the kidney transplant biopsy, we deferred endoscopy to obtain tissue biopsy for a formal diagnosis of CMV disease.…”

“…This proposed T‐cell mediated mechanism is supported by our patient's biopsy results which demonstrated acute T‐cell mediated rejection changes but had negative CMV viral staining. Other phenotypic switches, from IgA nephropathy to collapsing FSGS, are also reported after kidney transplantation in a retrospective study by Karthikeyan et al; however, it is unknown whether CMV induced the immune response in their study due to the lack of data on donor CMV status 5 …”

“…Other phenotypic switches, from IgA nephropathy to collapsing FSGS, are also reported after kidney transplantation in a retrospective study by Karthikeyan et al; however, it is unknown whether CMV induced the immune response in their study due to the lack of data on donor CMV status. 5 APOL1 kidney risk variants, including G1/G1, G1/G2, and G2/ G2, can also predispose patients to collapsing FSGS. In the native kidney, high-risk APOL1 has been reported in patients who developed COVID-19-associated nephropathy (COVAN).…”

“…Collapsing FSGS is associated with various etiologies including infectious, such as human immunodeficiency virus (HIV), COVID‐19, Epstein–Barr virus (EBV), and cytomegalovirus (CMV), in addition to genetic mutations in the APOL1 gene, malignancies, and ischemic events 1–4 . Among patients who have undergone kidney transplantation, immunosuppression increases the risk for infectious insult from CMV, which may predispose patients to collapsing FSGS 5,6 . This report describes the first known case of pediatric collapsing FSGS in the setting of CMV viremia after kidney transplantation.…”

“…increases the risk for infectious insult from CMV, which may predispose patients to collapsing FSGS. 5,6 This report describes the first known case of pediatric collapsing FSGS in the setting of CMV viremia after kidney transplantation.…”