Rituximab in treatment of collapsing FSGS—A case series

Abstract

Background Collapsing focal segmental glomerulosclerosis (cFSGS) is an aggressive glomerular disease presenting as a nephrotic syndrome that has lower rates of remission with conventional immunosuppressive therapy and rapidly progresses to end‐stage‐renal‐disease (ESRD). We report eight cases of HIV‐negative cFSGS treated with rituximab. Methods The current report is a retrospective case series of cFSGS treated with rituximab from January 2011 to March 2020, at varying phases of the disease. Results Eight out of the 70 cFSGS patients received rituximab. The median age of patients was 30 years (IQR 24.25‐37.5); five patients were males. The median serum creatinine, mean serum albumin and median 24 hours urinary protein at presentation was 0.9 (IQR 0.66‐1.27) mg/dL, 2.95 ± 1.15 g/dL, 4.87 (IQR 1.64‐5.75) g/day, respectively. Two patients were steroid‐resistant, one steroid and tacrolimus dependent, one steroid and cyclosporine dependent, two steroids and tacrolimus resistant, one steroid, tacrolimus, cyclophosphamide, mycophenolate mofetil resistant and one steroid‐resistant and tacrolimus dependent before rituximab therapy. Rituximab was given either as targeted therapy (after an initial dose of 375 mg/m2; patients having CD‐19 levels >5/μL or >1% at 1 month received additional low‐dose [100 mg] of rituximab), or weekly regimen. Five patients received CD‐19 targeted rituximab; three received weekly doses of 375 mg/m2, cumulative doses being 820 ± 228.03 mg, and 1800 ± 721.11 mg, respectively. At the end of median follow‐up of 15 months, five (62.5%) patients were in remission (three partial, two complete remissions), two (25%) were resistant to therapy; one (12.5%) progressed to ESRD. Conclusion Rituximab is reasonably safe and achieves/maintains remission in 60% of cFSGS cases.

Immunosuppression for adult steroid-dependent or frequently relapsing nephrotic syndrome: A systematic review and meta-analysis

“…Our study included a total of 574 patients across 28 studies [ 26 – 53 ], of which 330 from 19 studies [ 27 – 31 , 33 – 34 , 36 – 40 , 42 – 44 , 46 – 47 , 49 , 52 ] received rituximab, 61 from four studies [ 32 , 41 , 51 , 53 ] received cyclosporine, 59 received from five studies [ 26 , 33 , 35 , 48 , 51 ] received cyclophosphamide, 90 from four studies [ 26 , 33 , 50 , 51 ] received mycophenolate mofetil, and 34 from four studies [ 26 , 45 , 48 , 51 ] received tacrolimus. There are 9 prospective studies [ 27 , 39 , 42 , 44 – 46 , 48 – 49 , 52 ] and 19 retrospective studies [ 26 , 28 – 38 , 40 – 41 , 43 , 47 , 50 – 51 , 53 ].…”

“…There are 9 prospective studies [ 27 , 39 , 42 , 44 – 46 , 48 – 49 , 52 ] and 19 retrospective studies [ 26 , 28 – 38 , 40 – 41 , 43 , 47 , 50 – 51 , 53 ]. Five studies were conducted in USA [ 28 , 33 , 36 – 37 , 51 ], six studies in India [ 26 , 31 , 35 , 45 , 49 , 52 ], five in China [ 30 , 41 , 44 , 47 , 48 ], four studies in Japan [ 34 , 39 , 42 , 46 ], two each in France [ 40 , 43 ] and Spain [ 29 , 50 ] as well as one each in Netherlands [ 38 ], Sweden [ 27 ], Tunisia [ 32 ] and Pakistan [ 53 ].…”

“…21 studies [ 28 – 35 , 37 , 39 – 40 , 42 – 48 , 50 – 51 , 53 ] reported the baseline creatinine level of patients. 9 studies [ 28 , 29 , 31 , 32 , 35 , 40 , 43 , 51 , 53 ] reported a mean baseline creatinine of 1.08 mg/dL, 2 [ 33 , 34 ] studies reported a median baseline creatinine level of 0.69mg/dL and 0.9 mg/dL respectively whereas the other 10 studies [ 30 , 37 , 39 , 42 , 44 – 48 , 50 ] did not mention whether baseline creatinine level was calculated in mean or median. Extracted data from 11 studies [ 26 – 28 , 35 , 41 , 46 – 48 , 50 – 52 ] reported a mean rate of relapse of 33.33%, while the duration of remission from 6 studies [ 27 , 37 , 41 , 44 , 48 , 51 ] ranges between 1 to 43 months.…”

“…For previous therapies, 8 studies [ 27 , 28 , 34 , 37 , 38 , 43 , 48 , 51 ] reported the use of cyclophosphamide, 11 studies [ 27 , 28 , 31 , 34 , 37 – 39 , 43 , 48 , 51 , 53 ] reported the use of cyclosporine, 10 studies [ 27 , 28 , 34 , 37 – 40 , 43 , 47 , 48 ] reported the use of mycophenolate mofetil, 7 studies [ 27 , 28 , 31 , 34 , 37 , 39 , 43 ] reported the use of tacrolimus, 3 studies [ 27 , 38 , 43 ] reported the use of levamisole and 2 studies [ 34 , 39 ] reported the use of mizoribine. Azathioprine, abatacept, rituximab, mechlorethamine, basiliximab, chimeric antigen receptor (CAR), chlorambucil, pefloxacin were reported in 1 study respectively [ 28 , 30 , 43 ].…”

Membranous nephropathy with collapse in a HIV negative patient; a case report with a 34-month follow-up

“…Although the patient evolved with partial remission, she became cyclosporine dependent. In light of the new recommendations for MN and the favorable reports of rituximab use in cFSGS unresponsive to other immunosuppressive treatments (17), we decided to maintain a low-dose of cyclosporine and start a trial of rituximab (two doses of 1 g, two weeks apart). At six months, she maintained partial remission and a positive PLA 2 R but at a lower titer of 10.…”