Initiation of renin-angiotensin system inhibitors and first complete remission in patients with primary nephrotic syndrome: a nationwide cohort study

Clin Exp Nephrol. 2023 May;27(5):480-489. doi: 10.1007/s10157-023-02331-3. Epub 2023 Feb 25.

Abstract

Background: Evidence on renin-angiotensin system inhibitors (RASis) effect in reducing urinary protein levels in patients with nephrotic syndrome is insufficient. We determined whether RASis can induce complete remission (CR) in patients on immunosuppressive therapy.

Methods: This cohort study included 84 adults (median age, 65 years; males, 57%) with primary nephrotic syndrome (excluding minimal change disease) not receiving RASis during enrollment in the Japanese Nephrotic Syndrome Cohort Study from January 2009 to December 2010, and were followed up for 5 years. Exposure and outcome were RASi initiation and first CR, respectively. Marginal structural models and Poisson regression were used to account for time-varying covariates and estimate causal effects of RASis on CR.

Results: Overall, 51 (61%), 73 (87%), and 55 (66%) patients had membranous nephropathy, were prescribed immunosuppressive agents at baseline (1-month post-renal biopsy and/or at start of immunosuppressive therapy), and were prescribed RASis during the study period, respectively. Sixty-five patients experienced first CR (incidence 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 lower (aIRR: 0.17, 95% CI 0.04-0.68) first CR in patients with membranous nephropathy and other pathologies, respectively.

Conclusion: RASis are beneficial as adjuvant therapy for inducing remission in patients with membranous nephropathy.

Keywords: Glomerular disease; Membranous nephropathy; Nephrotic syndrome; Renin–angiotensin system.

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents
  • Cohort Studies
  • Enzyme Inhibitors / pharmacology
  • Glomerulonephritis, Membranous* / pathology
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Nephrotic Syndrome* / complications
  • Renin-Angiotensin System

Substances

  • Immunosuppressive Agents
  • Antihypertensive Agents
  • Enzyme Inhibitors