Patients with primary membranous nephropathy are at high risk of cardiovascular events

Abstract

Here we conducted a retrospective study to examine the risk of cardiovascular events (CVEs) relative to that of end-stage renal disease (ESRD) in patients with primary membranous nephropathy, in a discovery cohort of 404 patients. The cumulative incidence of CVEs was estimated in the setting of the competing risk of ESRD with risk factors for CVEs assessed by multivariable survival analysis. The observed cumulative incidences of CVEs were 4.4%, 5.4%, 8.2%, and 8.8% at 1, 2, 3, and 5 years respectively in the primary membranous nephropathy cohort. In the first 2 years after diagnosis, the risk for CVEs was similar to that of ESRD in the entire cohort, but exceeded it among patients with preserved renal function. Accounting for traditional risk factors and renal function, the severity of nephrosis at the time of the event (hazard ratio 2.1, 95% confidence interval 1.1 to 4.3) was a significant independent risk factor of CVEs. The incidence and risk factors of CVEs were affirmed in an external validation cohort of 557 patients with primary membranous nephropathy. Thus early in the course of disease, patients with primary membranous nephropathy have an increased risk of CVEs commensurate to, or exceeding that of ESRD. Hence, reduction of CVEs should be considered as a therapeutic outcome measure and focus of intervention in primary membranous nephropathy.

Keywords: cardiovascular disease; glomerulonephritis; membranous nephropathy.

Figure 1 |. Number of cardiovascular events observed according to the duration of follow-up and the status of nephrotic syndrome in primary MN cohorts.

CVE, cardiovascular event; GDCN, Glomerular Disease Collaborative Network; MN, membranous nephropathy; TGNR, Toronto Glomerulonephritis Registry.

Figure 2 |. Estimates of cumulative incidence functions.

(a) Cumulative incidences of CVEs, ESRD, and death unrelated to CVE in the GDCN cohort. The cumulative incidence rate of CVE was calculated by accounting for the influence of competing risks of ESRD and death unrelated to CVE. (b) The incidence of CVEs is commensurate to or exceeds that of ESRD in the early period of follow-up for each category of baseline eGFR. Cumulative incidence probabilities of CVEs and ESRD were calculated by competing risk analysis. In patients with eGFR ≥60 ml/min per 1.73 m² at baseline (red lines), the incidence rate of CVEs (red solid line) is higher than that of ESRD (red dotted line) throughout the follow-up period. For patients with eGFR <60 ml/min per 1.73 m² at baseline, the cumulative incidences of CVEs (black solid line) and ESRD (black dotted line) are similar during the first 6 months after diagnosis. Later in the course of disease, the cumulative incidence of ESRD exceeds that of CVEs among patients with baseline eGFR <60 ml/min per 1.73 m². CVE, cardiovascular event; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; GDCN, Glomerular Disease Collaborative Network.

Figure 3 |. Comparison of outcomes between GDCN and TGNR cohorts.

CVE, cardiovascular event; ESRD, end-stage renal disease; GDCN, Glomerular Disease Collaborative Network; TGNR, Toronto Glomerulonephritis Registry.