Initiation of Renin-Angiotensin System Inhibitors and the Incidence of First Complete Remission in Patients with Primary Nephrotic Syndrome: A Nationwide Cohort Study

Abstract Background Renin-angiotensin system inhibitors (RASis) are recommended as the first-line therapy to reduce proteinuria in primary nephrotic syndrome. It is unclear whether RASis can induce complete remission (CR) in patients on immunosuppressive therapy. Methods This retrospective cohort study included adults with primary nephrotic syndrome from causes other than minimal change disease who were enrolled in the Japanese Nephrotic Syndrome Cohort Study from January 2009 to December 2010, with a 5-year follow-up period, and were not on RASis at enrolment. The exposure was a new RASi prescription, and the outcome was the first CR, defined as a urinary protein level < 0.3 g/day. Marginal structural models and Poisson regression were used to account for time-varying covariates and to estimate the causal effects of RASis on CR. Results Of the 84 eligible patients (median age, 65 years; males, 57%), 51 (61%) had membranous nephropathy. At baseline (1 month after renal biopsy and/or starting immunosuppressive therapy), 87% and 33% of patients were prescribed corticosteroids and calcineurin inhibitors, respectively. RASis were prescribed to 66% of patients during the study period. Sixty-five patients experienced CR during a median follow-up of 9.0 months (incidence remission rate, 5.05/100 person-months). RASi use was associated with a higher (adjusted incidence rate ratio [aIRR]: 2.27, 95% confidence interval [CI]: 1.06–4.84), and a lower (aIRR: 0.17, 95% CI: 0.04–0.68) CR rate in patients with membranous nephropathy and other pathologies, respectively. Conclusion RASis are beneficial as an adjuvant therapy for inducing remission in patients with membranous nephropathy.