Post-transplant recurrence of focal segmental glomerular sclerosis: consensus statements

Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review. Focal segmental glomerular sclerosis (FSGS) is 1 of the primary causes of nephrotic syndrome in both pediatric and adult patients, which can lead to end-stage kidney disease. Recurrence of FSGS after kidney transplantation significantly increases allograft loss, leading to morbidity and mortality. Currently, there are no consensus guidelines for identifying those patients who are at risk for recurrence or for the management of recurrent FSGS. Our work group performed a literature search on PubMed/Medline, Embase, and Cochrane, and recommendations were proposed and graded for strength of evidence. Of the 614 initially identified studies, 221 were found suitable to formulate consensus guidelines for recurrent FSGS. These guidelines focus on the definition, epidemiology, risk factors, pathogenesis, and management of recurrent FSGS. We conclude that additional studies are required to strengthen the recommendations proposed in this review. •We recommend that the diagnosis of recurrent focal segmental glomerular sclerosis (FSGS) in the transplanted kidney be made in patients with history of primary FSGS in native kidneys, both children and adults, who show:○Nephrotic-range proteinuria > 3.5 g/24 h or protein-to-creatinine ratio > 3g/g (>300 mg/mmol) in adults, and first morning or 24-hour protein-to-creatinine ratio >2 g/g (>200 mg/mmol) or > 3+ on urine dipstick in children, AND hypoalbuminemia (serum albumin <3.0 g/dl) (1A). (Supplementary Table S1 explains the grading system for the recommendations.)○Allograft biopsy showing FSGS pattern of injury and widespread podocyte effacement (1A).•We recommend that all patients with FSGS undergoing kidney transplantation be monitored for recurrent FSGS. Patients may be monitored for proteinuria and serum creatinine daily for 1 week, twice weekly in week 2, weekly for 4 weeks, monthly for the first year, and every 3 months thereafter; preferably with use of a first morning void urine sample (1B). •We recommend that if the recipient is known to possess a causal pathogenic variant associated with FSGS, potential living-related donors should undergo genetic testing before being accepted as kidney donors, to preclude the donor from a risk of chronic kidney disease, and although uncommon, to assess the risk of development of FSGS in transplanted kidney (1A).•We recommend kidney transplantation in patients with primary FSGS after the risk of recurrence is discussed with the recipient (2C).•Recurrent FSGS leading to loss of a prior allograft is associated with a high risk of recurrence in a subsequent allograft. In such a situation, candidacy for a subsequent kidney transplant (especially a living donor transplant) should be carefully considered. •We recommend prompt initial therapy of recurrent FSGS with plasmapheresis (2A).•We recommend not providing prophylactic plasmapheresis or rituximab before the kidney transplant (2C).