Ix Joachim H, Biggs Mary L, Mukamal Kenneth, Djousse Luc, Siscovick David, Tracy Russell, Katz Ronit, Delaney Joseph A, Chaves Paulo, Rifkin Dena E, Hughes-Austin Jan M, Garimella Pranav S, Sarnak Mark J, Shlipak Michael G, Kizer Jorge R
Division of Nephrology-Hypertension, University of California San Diego and Veterans Affairs San Diego Healthcare System, San Diego, California;
Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, Washington;
J Am Soc Nephrol. 2015 Oct;26(10):2494-503. doi: 10.1681/ASN.2014070696. Epub 2015 Feb 5.
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.
肾小管间质纤维化随年龄增长而常见，是终末期肾病（ESRD）的强预后因素，但估算肾小球滤过率（eGFR）或尿白蛋白与肌酐比值（ACR）对其反映不佳。在活检研究中，尿中III型前胶原N端前肽（PIIINP）水平升高标志着肾小管间质纤维化的严重程度，但尿PIIINP与慢性肾脏病（CKD）进展之间的关联尚不清楚。在≥65岁的社区居住人群中，我们在1996年至1997年心血管健康研究访视时，对随访期间出现CKD进展（9年内eGFR下降30%，n = 192）或新发ESRD（n = 54）的个体以及958名随机选择的参与者的即时尿标本中的PIIINP进行了测量。我们评估了尿PIIINP与CKD进展和新发ESRD之间的关联。将尿PIIINP与心血管疾病、心力衰竭和死亡之间的关联作为次要终点进行评估。基线时，平均年龄（±标准差）为78±5岁，平均eGFR为63±18 ml/min/1.73 m²，尿PIIINP中位数为2.6（四分位间距，1.4 - 4.2）μg/L。在一项病例对照研究（192名参与者，231名对照）中，尿PIIINP每增加一倍，CKD进展的几率就高出22%（调整后的比值比，1.22；95%置信区间，1.00至1.49）。尿PIIINP水平升高也与新发ESRD相关，但在完全调整模型中结果不显著。在对958名随机选择的参与者进行的前瞻性研究中，尿PIIINP升高与死亡显著相关，但与新发心血管疾病或心力衰竭无关。这些数据表明，在老年人中，尿PIIINP水平升高与CKD进展相关，且独立于eGFR和ACR。
