Collagen biomarkers are associated with decline in renal function independently of blood pressure and other cardiovascular risk factors: The Multi-Ethnic Study of Atherosclerosis Study

Objective:We studied associations of circulating collagen type I carboxy-Terminal telopeptide (ICTP) and procollagen type III N-Terminal propeptide (PIIINP) with long-Term renal function decline.Methods:In the Multi-Ethnic Study of Atherosclerosis, we included 2492 participants initially aged 45-84 years and free of clinical cardiovascular disease (CVD), excluding people with estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m² or urine albumin/creatinine (UAC) at least 30 mg/g. The primary outcome in median 9.4-year follow-up was renal function decline (≥30% decline in eGFR between any two exams or incident UAC ≥ 30 mg/g). The associations of baseline plasma ICTP and PIIINP with renal function decline were estimated using Poisson regression, adjusting for baseline variables race/ethnicity, sex, age, and continuous eGFR and UAC, with further adjustment for CVD risk factors and medications.Results:Baseline serum ICTP was 3.27 ± 1.43 μg/l and PIIINP was 5.43 ± 1.85 μg/l. Mean baseline eGFR was 91.5 ± 18.4 ml/min per 1.73 m². Renal function decline occurred in 19.5% during 9.4-year follow-up. The renal function decline outcome was positively associated with serum ICTP and PIIINP: relative incidence density (95% confidence interval) per SD 1.22 (1.11-1.33) and 1.27 (1.16-1.40), respectively. Additional adjustment for other risk factors did not greatly alter findings.Conclusion:High collagen biomarker concentrations in serum were associated with future decline in renal function in people initially free of CVD and with normal eGFR, consistent with collagen production signaling renal decline. The continuous association observed for ICTP which, unlike PIIINP, is filtered by the kidney, may owe to its double status as a sensitive marker of glomerular function and collagen degradation.