Glomerular disease tied to increased CVD risk

Adults with glomerular disease have a more than twofold risk of cardiovascular (CV) events compared with the general population, with the risk varying by type of glomerular disease, according to a retrospective study presented at ASN Kidney Week 2020. 

The researchers identified 1,912 adults (median age 50.6 years, 59.5 percent male) with glomerular disease from a centralized kidney pathology registry between 2000 and 2012 in British Columbia, Canada. These included incidents of focal segmental glomerulosclerosis (FSGS; n=540), IgA nephropathy (n=759), membranous nephropathy (n=387), and minimal change disease (n=226). Patients with end-stage kidney disease (ESKD) at biopsy were excluded.

A hospital discharge registry was used to assess the primary outcome which was a composite of major adverse CV events or revascularization procedure, including coronary artery, cerebrovascular, and peripheral vascular disease. Patients were followed up for a median 6.8 years during which time 338 CV events occurred.

The overall risk of CV events at 10 years was 16 percent, with an event rate of 24.7 per 1,000 person-years. This risk varied by glomerular disease type with the highest risk noted with FSGS (27.0 percent), followed by membranous nephropathy (19.4 percent), minimal change disease (13.2 percent), and IgA nephropathy (7.7 percent), with event rates of 46.1, 26.4, 16.4, and 12.2 per 1,000 person-years, respectively. [ASN Kidney Week 2020, abstract SA-OR36]

Univariate analysis showed that compared with IgA nephropathy, membranous nephropathy (hazard ratio [HR], 2.6, 95 percent confidence interval [CI], 1.7–3.9) and FSGS (HR, 3.7, 95 percent CI, 2.6–5.3; p<0.01 for both), but not minimal change disease (HR, 1.3, 95 percent CI, 0.8–2.4; p=0.29), were associated with a higher risk of CV events.

Traditional CV risk factors were also significantly associated with an increased CV risk, as were proteinuria and estimated glomerular filtration rate (eGFR). However, in the multivariable analysis, the significance was lost for multiple factors, including glomerular disease type, though proteinuria (HR, 1.3 per doubling of g/d) and eGFR (HR, 0.8 per 15 mL/min/1.73 m²) remained significant (p<0.01 for both).

This suggests that the increased CV risk among these patients cannot be fully explained by traditional CV risk factors, where some of the risk is accounted for by proteinuria and eGFR, said lead author Heather Gunning from the University of British Columbia in Vancouver, Canada.

Patients with glomerular disease also had a higher risk of CV events compared with the general population (standardized incidence ratio [SIR], 2.46, 95 percent CI, 2.12–2.82). This risk was highest among patients with FSGS (SIR, 3.98, 95 percent CI, 3.19–4.91), followed by membranous nephropathy (SIR, 3.03, 95 percent CI, 2.23–4.03), minimal change disease (SIR, 1.76, 95 percent CI, 1.03–2.82), and IgA nephropathy (SIR, 1.38, 95 percent CI, 1.01–1.85).

“Chronic kidney disease (CKD) is associated with increased CV risk,” said Gunning. While proteinuria and reduced eGFR are strong, independent CV risk factors, patients with glomerular disease may have an additional risk due to nephrotic syndrome, systemic inflammation, endothelial dysfunction, and immunosuppressive therapies, she said. However, there is little data on CV risk in the different types of glomerular disease.

“These results demonstrate that … patients with glomerular disease are at high risk of cardiovascular disease (CVD), both before and after ESKD onset … with 10-year risk exceeding 10 percent,” said Gunning.

The CV risk for all glomerular disease subtypes was higher than the general population,” said Gunning and co-authors. This highlights the need for CVD prevention strategies in patients with glomerular disease.

“Consideration of glomerular disease-specific factors can help improve CV risk prediction. Failure to take these novel factors into account will lead to underestimation of CV risk and underutilization of CV primary prevention strategies,” Gunning noted.

Research is ongoing to examine the effect of long-term glomerular disease activity and immunosuppressive treatment on CV risk. “This will allow better understanding of the impact of glomerular disease on CV risk and whether treatment may modify this,” she added.