Glomerulopathies

Minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) are histological manifestations of idiopathic nephrotic syndrome (iNS). Characteristics of iNS include nephrotic syndrome and podocyte injury. The response to corticosteroids and other immunosuppressive drugs is variable, although FSGS is in general more steroid resistent. Progressive renal failure is typically observed in patients with steroid resistant and relapsing iNS progress to end-stage kidney disease. Importantly, iNS recurs immediately after kidney transplantation in 50% of high-risk patients.
Post-transplant iNS recurrence is often treated with plasmapheresis in addition to standard immunosuppressive treatment. If instituted early, many patients respond with temporary to combined treatment. The early recurrence after transplantation and response to plasmapheresis provide indirect evidence for circulating permeability factors (CPF) in iNS pathogenesis. It is likely that the same CPF(s) are involved in iNS in the native kidneys, and that native kidney iNS may also be respond to plasmapheresis. However, few studies have addressed efficacy of plasmapheresis for iNS in the native kidneys.
Over the last decade, we have permormed plasmapheresis in 17 patients with complicated and/or mult-drug resistant iNS.

References:
1. Maas, R.J., Deegens, J.K., Smeets, B., Moeller, M.J. & Wetzels, J.F. Minimal change disease and idiopathic FSGS: manifestations of the same disease. Nat Rev Nephrol 12, 768-776 (2016).
2. Maas, R.J., Deegens, J.K., van den Brand, J.A., Cornelissen, E.A. & Wetzels, J.F. A retrospective study of focal segmental glomerulosclerosis: clinical criteria can identify patients at high risk for recurrent disease after first renal transplantation. BMC Nephrol 14, 47 (2013).
3. Maas, R.J., Deegens, J.K. & Wetzels, J.F. Permeability factors in idiopathic nephrotic syndrome: historical perspectives and lessons for the future. Nephrol Dial Transplant 29, 2207-2216 (2014).
4. Moret, L., Ganea, A, Dao, M, et al. Apheresis in adult with refractory idiopathic nephrotic syndrome on native kidneys. Kidney Int Rep 6, 2134-43 (2021)
5. Feld, S.M., Figueroa, P, Savin, V. et al. Plasmapheresis in the treatment of steroid-resistant focal segmental glomerulosclerosis in native kidneys. Am J Kid Dis 32: 230-7 (1998)

We have treated 17 patients with treatment refractory and/or complicated iNS with plasmpheresis. Our objective is to compare clinical outcomes in these patients with matched controls from ERK Reg. Our hypothesis is that plasmapheresis is of added benefit for some patients with iNS in the native kidneys.

Plasmapheresis group (Radboudumc, n=17):

• adult patients (>18 years) with iNS (with biopsy-confirmed MCD or FSGS) - indications for plasmapheresis: steroid resistant nephrotic syndrome
• fixed protocol for plasmapheresis treatment

Control group (other ERK Reg participants):  controls matched for disease status and duration, age, eGFR and proteinurie

Data Sources: ERKReg and Local database Radboudumc (Castor file)

Data Elements:

• primary renal diagnosis: iNS based on presentation with nephrotic syndrome and MCD/FSGS on biopsy
• age at diagnosis: adult patients
• lab values of interest: creatinine / eGFR, serum albumin, proteinuria (PCR)
• outcome data: partial and complete remission, renal failure (persistent creatinine > 3.5 mg/dL, dialysis or transplantation)

Treatment response (complete and partial remissions) and time to response will be compared in plasmapheresis and non- plasmapheresis group, respectively. Similarly, long-term outcome will be compared between groups (eGFR slope, proportion reaching renal failure, stable remission with and without immunosuppressive medication).