Biomarkers of Kidney Tubule Disease and Risk of End-Stage Kidney Disease in Persons With Diabetes and CKD.
Biomarkers of Kidney Tubule Disease and Risk of End-Stage Kidney Disease in Persons With Diabetes and CKD.
复制标题
糖尿病和慢性肾病患者中肾小管疾病的生物标志物和终末期肾病的风险。
DOI：
10.1016/j.ekir.2022.03.033
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发表时间：
2022-07
影响因子：
6
通讯作者：
Ix, Joachim H.
中科院分区：
文献类型：
--
作者：
Amatruda, Jonathan G.;Katz, Ronit;Sarnak, Mark J.;Gutierrez, Orlando M.;Greenberg, Jason H.;Cushman, Mary;Waikar, Sushrut;Parikh, Chirag R.;Schelling, Jeffrey R.;Jogalekar, Manasi P.;Bonventre, Joseph, V;Vasan, Ramachandran S.;Kimmel, Paul L.;Shlipak, Michael G.;Ix, Joachim H.
估计的肾小球滤过率(EGFR)和蛋白尿很难反映糖尿病和慢性肾脏疾病(CKD)的肾小管间质损害。肾脏健康的尿液生物标记物可能更好地阐明糖尿病和慢性肾脏病患者的疾病进展。根据病例队列设计，我们从1092名成人糖尿病患者中随机选择了560名中风地理和种族差异(CONTS)研究参与者的子队列，基线EGFR为每1.73平方米60毫升/分钟，并在4.3±2.7年的平均随访期间登记了161例终末期肾病(ESKD)病例(亚队列93例；亚队列外68例)。我们测定了尿液中反映肾小管损伤(肾损伤分子-1[KIM-1])、炎症和纤维化(单核细胞趋化蛋白-1[MCP-1])、修复(几丁质酶-3-样蛋白1[YKL-40])和肾小管功能的生物标志物，包括重吸收(α-1-微球蛋白[α1M])和合成能力(表皮生长因子[EGF]和尿调蛋白[UMOD])。加权COX回归模型估计了人口统计学、ESKD危险因素、基线EGFR和尿白蛋白调整后的ESKD风险。最小绝对收缩和选择算子(LASSO)回归确定了与ESKD最相关的生物标记物的子集。在基线时，亚队列参与者的平均年龄为70±9岁，平均每1.73m2的EGFR为40±13ml/分钟，尿白蛋白/肌酐的中位数比率为33(四分位数范围为10-213)mg/g。调整基线的EGFR和蛋白尿后，尿金-1(危险比：1.43[95%CI：1.17-1.75])、α1M(危险比=1.47[1.19-1.82])分别高出2倍。和MCP-1(危险比=1.27[1.06-1.53])与ESKD独立相关。套索保留了KIM-1和α1M与ESKD的联系。在糖尿病和慢性肾脏病患者中，每1.73m2尿液中KIM-1、α-1M和单核细胞趋化蛋白-1升高与肾脏病的发生独立相关，为糖尿病和慢性肾脏病患者肾脏疾病的进展提供了洞察力。
Tubulointerstitial damage in diabetes and chronic kidney disease (CKD) is poorly captured by estimated glomerular filtration rate (eGFR) and albuminuria. Urine biomarkers of kidney health may better elucidate disease progression in persons with diabetes and CKD. Per case-cohort design, we randomly selected a subcohort of 560 study participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study from 1092 adults with diabetes and baseline eGFR <60 ml/min per 1.73 m2 and registered a total of 161 end-stage kidney disease (ESKD) cases (n = 93 from the subcohort; n = 68 from outside the subcohort) during 4.3 ± 2.7 years mean follow-up. We measured urine biomarkers of kidney tubule injury (kidney injury molecule—1 [KIM-1]), inflammation and fibrosis (monocyte chemoattractant protein—1 [MCP-1]), repair (chitinase-3–like protein 1 [YKL-40]), and tubule function, including reabsorption (alpha-1-microglobulin [α1m]) and synthetic capacity (epidermal growth factor [EGF] and uromodulin [UMOD]). Weighted Cox regression models estimated ESKD risk adjusting for demographics, ESKD risk factors, and baseline eGFR and urine albumin. Least absolute shrinkage and selection operator (LASSO) regression identified a subset of biomarkers most strongly associated with ESKD. At baseline, subcohort participants had mean age of 70 ± 9 years, mean eGFR of 40 ±13 ml/min per 1.73 m2, and median urine albumin-to-creatinine ratio of 33 (interquartile range 10–213) mg/g. Adjusting for baseline eGFR and albuminuria, each 2-fold higher urine KIM-1 (hazard ratio = 1.43 [95% CI: 1.17–1.75]), α1m (hazard ratio = 1.47 [1.19–1.82]), and MCP-1 (hazard ratio = 1.27 [1.06–1.53]) were independently associated with ESKD. LASSO retained KIM-1 and α1m for associations with ESKD. Among adults with diabetes and eGFR <60 ml/min per 1.73 m2, higher urine KIM-1, α1m, and MCP-1 are independently associated with incident ESKD, providing insight into kidney disease progression in persons with diabetes and CKD.
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DOI：
10.1056/nejmoa1306033
发表时间：
2013-12-26
期刊：
The New England journal of medicine
影响因子：
--
作者：
de Zeeuw D;Akizawa T;Audhya P;Bakris GL;Chin M;Christ-Schmidt H;Goldsberry A;Houser M;Krauth M;Lambers Heerspink HJ;McMurray JJ;Meyer CJ;Parving HH;Remuzzi G;Toto RD;Vaziri ND;Wanner C;Wittes J;Wrolstad D;Chertow GM;BEACON Trial Investigators
通讯作者：
BEACON Trial Investigators
DOI：
10.1111/dom.13301
发表时间：
2018-08
期刊：
Diabetes, obesity & metabolism
影响因子：
--
作者：
Dekkers CCJ;Petrykiv S;Laverman GD;Cherney DZ;Gansevoort RT;Heerspink HJL
通讯作者：
Heerspink HJL
DOI：
10.2215/cjn.03220314
发表时间：
2015-01-01
影响因子：
9.8
作者：
Jotwani, Vasantha;Scherzer, Rebecca;Shlipak, Michael G.
通讯作者：
Shlipak, Michael G.
影响因子：
6
作者：
Dubin, Ruth F.;Judd, Suzanne;Peralta, Carmen A.
通讯作者：
Peralta, Carmen A.
影响因子：
120.7
作者：
Kramer, HJ;Nguyen, QD;Hsu, CY
通讯作者：
Hsu, CY