Urinary podocyte mRNAs precede microalbuminuria as a progression risk marker in human type 2 diabetic nephropathy.
Urinary podocyte mRNAs precede microalbuminuria as a progression risk marker in human type 2 diabetic nephropathy.
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DOI：
10.1038/s41598-020-75320-1
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发表时间：
2020-10-23
影响因子：
4.6
通讯作者：
Fujimoto S
中科院分区：
文献类型：
--
作者：
Fukuda A;Minakawa A;Kikuchi M;Sato Y;Nagatomo M;Nakamura S;Mizoguchi T;Fukunaga N;Shibata H;Naik AS;Wiggins RC;Fujimoto S
及早发现糖尿病肾病的进展风险将允许及早干预以减少进展。尿小球足细胞mRNA是比微量白蛋白尿更敏感的进展风险标记物的假设得到了检验。纳入了165名2型糖尿病患者和41名年龄和性别匹配的对照组的横断面队列。测定大量白蛋白尿组、微量白蛋白尿组和正常白蛋白尿组的足细胞应激(尿小球podocin：neparin m RNA比率)、足细胞脱离(尿小球podocin m RNA：肌酐比：UPPod：cr)和肾小管标志物(尿小球水通道蛋白2：肌酐比)。在124名糖尿病受试者中，4年后重新评估了EGFR。横断面分析显示，所有糖尿病组尿小球足细胞和肾小管上皮细胞的mRNA标志物均升高。经4年随访，单因素和多因素模型分析显示，与EGFR斜率显著相关的尿标志物仅有UPPod：cr(P <； 0.01)和蛋白尿(P <； 0.01)。使用K倍交叉验证预测 ≥ 的EGFR丢失的AUC分析显示，UPod：CR和蛋白尿都类似地改善了AUC值，结合临床变量，它们给出了AUC值 = 为0.70。足细胞标志物和蛋白尿有重叠的AUC贡献，如果足细胞耗竭导致蛋白尿，正如预期的那样。在正常白蛋白尿队列(n = 75)中，基线UPPod：cr与白蛋白尿的发生相关(P = 0.007)，在肾功能正常(EGFR84 ± 11.7ml/m in/1.73m2)和基线白蛋白尿正常的三联体中，UPod：cr与EGFr丢失率相关(P = 0.003)。在有微量或大量蛋白尿的2型糖尿病患者中，UPod：CR和蛋白尿同样能预测EGFR的丢失。对于蛋白尿正常的2型糖尿病患者，UPPod：CR可预测蛋白尿和EGFR丢失。
Earlier detection of progression risk in diabetic nephropathy will allow earlier intervention to reduce progression. The hypothesis that urinary pellet podocyte mRNA is a more sensitive progression risk marker than microalbuminuria was tested. A cross sectional cohort of 165 type 2 diabetics and 41 age and sex-matched controls were enrolled. Podocyte stress (Urinary pellet podocin:nephrin mRNA ratio), podocyte detachment (Urinary pellet podocin mRNA:creatinine ratio: UPPod:CR) and a tubular marker (Urinary pellet aquaporin 2:creatinine ratio) were measured in macro-albuminuric, micro-albuminuric and norm-albuminuric groups. eGFR was reassessed after 4 years in 124 available diabetic subjects. Urinary pellet podocyte and tubular mRNA markers were increased in all diabetic groups in cross-sectional analysis. After 4 years of follow-up univariable and multivariate model analysis showed that the only urinary markers significantly related to eGFR slope were UPPod:CR (P < 0.01) and albuminuria (P < 0.01). AUC analysis using K-fold cross validation to predict eGFR loss of ≥ 3 ml/min/1.73m2/year showed that UPPod:CR and albuminuria each improved the AUC similarly such that combined with clinical variables they gave an AUC = 0.70. Podocyte markers and albuminuria had overlapping AUC contributions, as expected if podocyte depletion causes albuminuria. In the norm-albuminuria cohort (n = 75) baseline UPPod:CR was associated with development of albuminuria (P = 0.007) and, in the tertile with both normal kidney function (eGFR 84 ± 11.7 ml/min/1.73m2) and norm-albuminuria at baseline, UPPod:CR was associated with eGFR loss rate (P = 0.003). In type 2 diabetics with micro- or macro-albuminuria UPPod:CR and albuminuria were equally good at predicting eGFR loss. For norm-albuminuric type 2 diabetics UPPod:CR predicted both albuminuria and eGFR loss.
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影响因子：
16.2
作者：
Kamijo-Ikemori A;Sugaya T;Yasuda T;Kawata T;Ota A;Tatsunami S;Kaise R;Ishimitsu T;Tanaka Y;Kimura K
通讯作者：
Kimura K
影响因子：
16.2
作者：
Lopes-Virella MF;Baker NL;Hunt KJ;Cleary PA;Klein R;Virella G;DCCT/EDIC Research Group
通讯作者：
DCCT/EDIC Research Group
影响因子：
2.5
作者：
Kriz, W
通讯作者：
Kriz, W
影响因子：
19.6
作者：
Ding F;Wickman L;Wang SQ;Zhang Y;Wang F;Afshinnia F;Hodgin J;Ding J;Wiggins RC
通讯作者：
Wiggins RC
影响因子：
8.2
作者：
Lytvyn, Yuliya;Xiao, Fengxia;Burger, Dylan
通讯作者：
Burger, Dylan