A National Registry Study of Patient and Renal Survival in Adult Nephrotic Syndrome

Abstract

Introduction: We aimed to determine the mortality rate, cause of death, and rate of end-stage kidney disease (ESKD) in adults with nephrotic syndrome (NS).

Methods: We conducted a national registry-based study, including all 522 adults who had a kidney biopsy for NS in Scotland in 2014-2017. We linked the Scottish Renal Registry to death certificate data. We performed survival and Cox proportional hazards analyses, accounting for competing risks of death and ESKD. We compared mortality rates with those in the age- and sex-matched general population.

Results: A total of 372 patients had primary NS; 150 had secondary NS. Over a median follow-up of 866 days, 110 patients (21%) died. In patients with primary NS, observed versus population 3-year mortality was 2.1% (95% CI 0.0%-4.6%) versus 0.9% (0.8%-1.0%) in patients aged <60 years and 24.9% (18.4%-30.8%) versus 9.4% (8.3%-10.5%) in those aged ≥60 years. In secondary NS, this discrepancy was 17.1% (5.6%-27.2%) versus 1.1% (0.9%-1.2%) in <60-year-olds and 49.4% (36.6%-59.7%) versus 8.1% (6.6%-9.6%) in ≥60-year-olds. In primary NS, cardiovascular causes accounted for 28% of deaths, compared with 18% in the general population. Eighty patients (15%) progressed to ESKD. Incidence of ESKD by 3 years was 8.4% (95% CI 4.9%-11.7%) in primary and 35.1% (24.3%-44.5%) in secondary NS. Early remission of proteinuria and the absence of early acute kidney injury (AKI) were associated with lower rates of death and ESKD.

Conclusions: Adults with NS have high rates of death and ESKD. Cardiovascular causes account for excess mortality in primary NS.

Keywords: ESKD; cardiovascular disease; glomerular disease; minimal-change nephropathy; mortality; nephrotic syndrome.

Graphical abstract

Figure 1

Patient survival curves, stratified by cause of nephrotic syndrome (NS) and age. Check-marks denote times at which patients were censored from the analysis (end of follow-up). P value is for comparison between groups by log-rank test.

Figure 2

Cox proportional hazards models for risk of death. Multivariable models were constructed to test the association between predictor baseline variables and death for (a) the whole study cohort and (b) the subgroup with primary nephrotic syndrome aged ≥60 years. Alb, serum albumin concentration; eGFR, estimated glomerular filtration rate calculated by CKD-EPI equation; FSGS, focal segmental glomerulosclerosis; Hb, hemoglobin concentration; MCD, minimal-change nephropathy; MCGN, mesangiocapillary glomerulonephritis; NS, nephrotic syndrome; SIMD, Scottish Index of Multiple Deprivation.

Figure 3

Proportion with end-stage kidney disease (ESKD), stratified by age and cause of nephrotic syndrome (NS). (a) Event curves were drawn using a Fine-Gray model, accounting for the competing risk of death. Patients were censored at the end of the follow-up period (check-marks). (b) Cumulative incidence of death or ESKD, stratified by age and cause of NS.

Figure 4

Cox proportional hazards model for risk of end-stage kidney disease (ESKD) in older patients with primary nephrotic syndrome (NS). A multivariable model was constructed to test the association between predictor baseline variables and the onset of ESKD for the cohort with primary NS aged ≥60 years. The model accounts for the competing risk of death. Alb, serum albumin concentration; eGFR, estimated glomerular filtration rate calculated by CKD-EPI equation; FSGS, focal segmental glomerulosclerosis; Hb, hemoglobin concentration; MCD, minimal-change nephropathy; MCGN, mesangiocapillary glomerulonephritis; SIMD, Scottish Index of Multiple Deprivation.