Incidence and risk factors for end-stage kidney disease in patients with clinically manifest vascular disease; results from the UCC-SMART cohort study
Authors: Oestergaard H.B , Verhaar M.C , Bots M.L , Asselbergs F.W , De Borst G.J , Kappelle L.J , Visseren F.L.J , Van Der Leeuw J 
Published: November 2020

Abstract

Background
Patients with cardiovascular disease are at increased risk of developing chronic kidney disease, potentially leading to end-stage kidney disease (ESKD). On the other hand, kidney disease is associated with an increased risk of adverse cardiovascular outcomes and mortality. Previous studies have identified several risk factors for ESKD in the general population. However, little is known about the impact of these risk factors for ESKD in patients with clinically manifest cardiovascular disease.

Purpose
The aim of this study was to determine the incidence rates of ESKD in patients with clinically manifest cardiovascular disease and to assess the relation between risk of ESKD and risk factors, including systolic blood pressure (SBP), type 2 diabetes mellitus, estimated glomerular filtration rate (eGFR) and albuminuria (urinary albumin/creatinine ratio (uACR)), body mass index (BMI), dyslipidemia (non-HDL cholesterol), smoking, kidney length and exercise, in this high-risk population.

Methods
Patients (n=8402) from the ongoing UCC-SMART cohort (1996–2018) with clinically manifest cardiovascular disease were included. Occurrence of ESKD during follow up was defined as kidney transplantation, chronic dialysis or chronic kidney disease stage 5 (persistent eGFR &lt;15 mL/min/1.73m2). Incidence rates for ESKD were determined and stratified according to vascular disease location. Cox proportional hazard models were used to assess the risk of ESKD for every determinant adjusted for potential confounders.

Results
A total of 65 events of ESKD were observed in 75,282 person-years (median follow-up time 8.6 years, IQR 4.7–12.8 years). The overall incidence rate for ESKD was 0.9 per 1000 person-years and was lower in patients with only cerebrovascular (0.6 per 1000 person-years) or cardiovascular disease (0.6 per 1000 person-years). A higher incidence rate was observed in patients with polyvascular disease (1.8 per 1000 person-years) (Figure 1A). Presence of type 2 diabetes (HR 1.83; 95% CI 1.06–3.16) and higher SBP (HR 1.37; 95% CI 1.24–1.52 per 10 mmHg) were associated with an elevated risk of ESKD. Lower eGFR and higher uACR were associated with a higher risk of ESKD (Figure 1B). Kidney length was inversely associated with risk of ESKD. Smoking, physical exercise, BMI and non-HDL cholesterol were not related to ESKD.

Conclusions
The incidence of ESKD is higher in patients with polyvascular disease compared to patients with cerebrovascular or cardiovascular disease. Type 2 diabetes, SBP, eGFR, uACR and kidney length are associated with a higher risk of ESKD. In patients with symptomatic vascular disease, secondary cardiovascular prevention focused at these risk factors may also reduce the risk of ESKD.
Figure 1

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): University Medical Center Utrecht