Dataset Information

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 (±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) ?g/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.

SUBMITTER: Ix JH

PROVIDER: S-EPMC4587692 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Urine Collagen Fragments and CKD Progression-The Cardiovascular Health Study.

Ix Joachim H JH Biggs Mary L ML Mukamal Kenneth K Djousse Luc L Siscovick David D Tracy Russell R Katz Ronit R Delaney Joseph A JA Chaves Paulo P Rifkin Dena E DE Hughes-Austin Jan M JM Garimella Pranav S PS Sarnak Mark J MJ Shlipak Michael G MG Kizer Jorge R JR

Journal of the American Society of Nephrology : JASN 20150205 10

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 Hea ...[more]

PMID: 25655067

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Project description:Key Points The extent to which racial and ethnic disparities noted in older adult populations with CKD are present in young adulthood is unknown. Young adults with CKD who identify as Black or Hispanic have a higher burden of cardiovascular risk factors, some of which are modifiable. Rates of cardiovascular disease and CKD progression are higher in young adults who identify as Black or Hispanic. Visual Abstract Background Significant racial and ethnic disparities in cardiovascular (CV) and kidney function outcomes in older adults with chronic kidney disease (CKD) have been reported. However, little is known about the extent to which these disparities exist in patients with CKD during the foundational period of young adulthood. The objective of this study was to determine risk factors and rates of CV disease and CKD progression in young adults with CKD across racial and ethnic groups. Methods We studied all participants aged 21–40 years of age enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study (n=317). Baseline CV risk factors were described across racial and ethnic groups. Results Outcomes included CV events or death (first incidence of heart failure, myocardial infarction, and stroke or death) and CKD progression (>50% decline in eGFR from baseline or end stage kidney disease [ESKD]). Incidence rate ratios (IRRs) were compared as a secondary analysis for participants identifying as Black or Hispanic with those identifying as White or another race and ethnicity. Adjusted models included age, sex, and per APOL1 high-risk allele. CV risk factors were higher in Black and Hispanic participants, including mean SBP, BMI, median UACr, and LDL. Black and Hispanic participants had higher incidence rates of HF (17.5 versus 5.1/1000 person-years), all-cause mortality (15.2 versus 7.1/1000 person-years), and CKD progression (125 versus 59/1000 person-years). Conclusions In conclusion, we found a higher prevalence of CV risk factors, some modifiable, in young adults with CKD who identify as Black or Hispanic. Future strategies to ameliorate the racial and ethnic inequality in health outcomes earlier in life for patients with CKD should be prioritized.

Project description:Rationale & objectiveSingle measurements of urinary biomarkers reflecting kidney tubule health are associated with chronic kidney disease (CKD) risk in HIV infection, but the prognostic value of repeat measurements over time is unknown.Study designCohort study.Setting & participants647 women living with HIV infection enrolled in the Women's Interagency Health Study.Exposures14 urinary biomarkers of kidney tubule health measured at 2 visits over a 3-year period.OutcomeIncident CKD, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 at two 6-month visits and an average eGFR decline ≥ 3% per year.Analytical approachWe used multivariable generalized estimating equations adjusting for CKD risk factors to evaluate baseline, time-updated, and change-over-time biomarker associations with incident CKD. We compared CKD discrimination between models with and without a parsimoniously selected set of biomarkers.ResultsDuring a median 7 years of follow-up, 9.7% (63/647) developed CKD. In multivariable-adjusted analyses, 3 of 14 baseline biomarkers associated with incident CKD. In contrast, 10 of 14 time-updated biomarkers and 9 of 14 biomarkers modeled as change over time associated with incident CKD. Urinary epidermal growth factor (EGF), α1-microglobulin (A1M), and albumin were selected using penalized regression methods. In the time-updated model, lower urinary EGF (risk ratio [RR] per 2-fold higher time-updated biomarker levels, 0.69; 95% CI, 0.58-0.81), higher urinary A1M (RR, 1.47; 95% CI, 1.25-1.73), and higher urinary albumin excretion (RR, 1.21; 95% CI, 1.03-1.42) were jointly associated with increased risk for CKD. Compared with a base model (C statistic, 0.75), CKD discrimination improved after adding urinary EGF, A1M, and albumin values across baseline (C = 0.81), time-updated (C = 0.83), and change-over-time (C = 0.83) models (P < 0.01 for all).LimitationsObservational design, incident CKD definition limited to eGFR.ConclusionsRepeat urinary biomarker measurements for kidney tubule health have stronger associations with incident CKD compared with baseline measurements and moderately improve CKD discrimination in women living with HIV infection.

Dataset Information

Urine Collagen Fragments and CKD Progression-The Cardiovascular Health Study.

Publications

Urine Collagen Fragments and CKD Progression-The Cardiovascular Health Study.

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