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 (±SD) was 78±5 years, mean eGFR was 63±18 ml/min per 1.73 m(2), and median urine
PIIINP was 2.6 (interquartile range, 1.4-4.2) μg/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.