Incidence of remission and relapse of proteinuria, end-stage kidney disease, mortality, and major outcomes in primary nephrotic syndrome: the Japan Nephrotic Syndrome Cohort Study (JNSCS)

Abstract

Background: Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan.

Methods: A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model.

Results: Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN.

Conclusions: Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.

Keywords: Cohort study; Diabetes; End-stage kidney disease; Infection; Mortality; Primary nephrotic syndrome.

Fig. 1

Flow diagram of patients in the Japan Nephrotic Syndrome Cohort Study (JNSCS). *Including two patients who were diagnosed with MCD at the first kidney biopsy but re-diagnosed with FSGS (NOS variant) at the second biopsy 33 and 1344 days after the first biopsy

Fig. 2

Cumulative probabilities of major clinical outcomes: incomplete remission type 1 (a) and 2 (b), complete remission (c), relapse of proteinuria after complete remission (d), 50% and 100% increase in serum creatinine and/or end-stage kidney disease (ESKD) (e, f), ESKD (g), all-cause mortality (h), and use of diabetic drugs (i)

Fig. 2

Cumulative probabilities of major clinical outcomes: incomplete remission type 1 (a) and 2 (b), complete remission (c), relapse of proteinuria after complete remission (d), 50% and 100% increase in serum creatinine and/or end-stage kidney disease (ESKD) (e, f), ESKD (g), all-cause mortality (h), and use of diabetic drugs (i)

Fig. 3

Incidence rates of major outcomes in primary nephrotic syndrome; causes of mortality included infection (N = 6, 5, and 1 in MCD, MN, and FSGS, respectively), malignancy (N = 1, 5, and 1 in MCD, MN, and other glomerulonephritides, respectively), cardiovascular disease (N = 1 and 1 in MCD and MN, respectively) and others (N = 1, 1, and 1 in MCD, MN, and other glomerulonephritides, respectively)