Urine Collagen Fragments and CKD Progression—The Cardiovascular Health Study

Abstract

Tubulointerstitial fibrosis is common with ageing and strongly prognostic for ESRD but is poorly captured by eGFR or urine albumin to creatinine ratio (ACR). Higher urine levels of procollagen type III N-terminal propeptide (PIIINP) mark the severity of tubulointerstitial fibrosis in biopsy studies, but the association of urine PIIINP with CKD progression is unknown. Among community-living persons aged $65 years, we measured PIIINP in spot urine specimens from the 1996 to 1997 Cardiovascular Health Study visit among individuals with CKD progression (30% decline in eGFR over 9 years, n=192) or incident ESRD (n=54) during follow-up, and in 958 randomly selected participants. We evaluated associations of urine PIIINP with CKD progression and incident ESRD. Associations of urine PIIINP with cardiovascular disease, heart failure, and death were evaluated as secondary end points. At baseline, mean age (6SD) was 7865 years, mean eGFR was 63618 ml/min per 1.73 m 2 , and median urine PIIINP was 2.6 (interquartile range, 1.4-4.2) mg/L. In a case-control study (192 participants, 231 controls), each doubling of urine PIIINP associated with 22% higher odds of CKD progression (adjusted odds ratio, 1.22; 95% confidence interval, 1.00 to 1.49). Higher urine PIIINP level was also associated with incident ESRD, but results were not significant in fully adjusted models. In a prospective study among the 958 randomly selected participants, higher urine PIIINP was significantly associated with death, but not with incident cardiovascular disease or heart failure. These data suggest higher urine PIIINP levels associate with CKD progression independently of eGFR and ACR in older individuals.

Acetyl‐11‐keto‐β‐boswellic acid ameliorates renal interstitial fibrosis via Klotho/TGF‐β/Smad signalling pathway

“…Renal interstitial fibrosis, characterized by excessive accumulation of extracellular matrix (ECM), is the final common pathway of chronic kidney disease (CKD) progress to end‐stage renal disease (ESRD), irrespective of the initiating pathology 1. Inhibiting the progression of interstitial fibrosis is considered as a potential strategy to protect the kidney from the deleterious effects of CKD.…”

Urinary Markers of Fibrosis and Risk of Cardiovascular Events and Death in Kidney Transplant Recipients: The FAVORIT Trial

“…(13) PINP and PIIINP are cleaved from type 1 and type 3 collagen fibrils during collagen deposition, which is an important step in fibrogenesis. (14) Urine PIIINP is the N-terminal fragment of type III collagen and is released during newly deposited collagen type III and is correlated with interstitial fibrosis (11) and kidney function decline(15) in patients with CKD of different etiologies (16) and in KTRs. (11)…”

Spot urine sodium measurements do not accurately estimate dietary sodium intake in chronic kidney disease 1,2

“…Given the technical difficulties and challenges, few largescale epidemiologic studies have obtained even a single 24-h urine collection, and many fewer have collected multiple samples from the same individual over time (8,20,21). Many more have obtained spot urine specimens (22,23). In an effort to develop a reliable method of estimating sodium intake that does not require multiple 24-h urine collections and is not prone to the errors of collection accuracy or recall, researchers have published numerous equations that attempt to estimate sodium intake with the use of spot urine samples (24)(25)(26).…”