TO STUDY CALCINEURIN INHIBITOR SPARING STRATEGIES IN PATIENTS WITH STAEROID RESISTANT AND STEROID DEPENDENT NEPHROTIC SYNDROME

Introduction:

Steroid resistant nephrotic syndrome (SRNS) and steroid dependent nephrotic syndrome(SDNS), while uncommon, are associated with significant morbidity in children. Calcineurin inhibitors (CNIs) remain the first line recommended therapy for children with non-genetic forms of SRNS and have been used successfully in children with SDNS as well. Although the efficacy of these medications is acceptable, the adverse effects associated with these drugs limit their long term use. Thus, alternative therapies are needed for maintaining sustained remission in such patients on CNI. We studied various CNI sparing treatment strategies being used in SRNS and SDNS to maintain sustained remission. 

Methods:

It was an observational study, conducted retrospectively and prospectively over a period of 1 year to include patients below 18 years of age, with SRNS or SDNS; who had received a minimum of 12 months therapy with any of the calcineurin inhibitors (i.e. cyclosporine or tacrolimus) and were either in complete or partial remission at the time of enrolment. Patients with secondary or genetic forms of nephrotic syndrome were excluded.  Data abstracted included demographics, histopathology on renal biopsy, prior and concomitant use of other immunosuppressive agents, and serial clinical/laboratory data. Primary outcome measure was incidence of sustained remission (absence of relapse in twelve months period). The secondary objectives were to observe the incidence of relapses and side effects with the strategy used.

Results:

Our study included 18 children with SDNS and 11 with SRNS. The majority were male. It was observed that the most common CNI sparing agent used was rituximab in 19 (65%) followed by cyclophosphamide in 6 (20.7%), methotrexate in 2 (6.9%) while mycophenolate was used in only one patient of SDNS. All 29 patients were followed for 25 of these patients were followed up for 12 months. Sustained remission was seen in 9 out of 25 children (36%) and 66.6% of these patients were given Rituximab (3 infusions of 375 mg/m2 in majority) as CNI sparing agent. The mean time to first relapse was 5.6 months and there was a reduction in incidence relapse rate from 1.55 to 0.82 relapses/patient year. At twelve months follow up, all patients (n=17) on rituximab therapy were in remission (88.8% complete remission, 11.7% partial remission); 3 (75%) patients on oral cyclophosphamide were in CR while one was in PR; both patients on methotrexate were in complete remission; the only patient of SDNS who was given mycophenolate was in complete remission at 12 months with no relapse. Only one patient was in non remission at 1 year (SDNS patient; given cyclophosphamide). There was a significant decline in mean serum creatinine levels after switching therapy from CNI to other less nephrotoxic agents (p=0.001). No major side effects were seen with any of the therapy.

Comparative analysis of various treatment strategies used is attached as png image. 

Conclusions:

Rituximab was the most commonly used CNI sparing agent and appears to be an effective and safe option for maintaining remission in patients of SDNS and SRNS who have already received CNI for a long term; though further long term follow up studies are needed.  

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.