Uromodulin, produced exclusively in the kidney’s thick ascending limb, is a biomarker of kidney tubular health. However, the relationship between urine uromodulin and histologic changes in the kidney tubulointerstitium has not been characterized. In this study, we test the association of urine uromodulin with kidney histologic findings in humans and mice.

We investigated the independent association of urine uromodulin measured at the time of kidney biopsy with histologic features in 364 participants at two academic medical centers from 2015 to 2018 using multivariable linear regression models. This relationship was further examined by comparison of uromodulin staining in murine models of kidney fibrosis and repair.

We found urine uromodulin to be correlated with serum creatinine (rho=–0.43; P<0.001), bicarbonate (0.20; P<0.001), and hemoglobin (0.11; P=0.03) at the time of biopsy but not with urine albumin (–0.07; P=0.34). Multivariable models controlling for prebiopsy GFR, serum creatinine at biopsy, and urine albumin showed higher uromodulin to be associated with lower severity of interstitial fibrosis/tubular atrophy and glomerulosclerosis (interstitial fibrosis/tubular atrophy: –3.5% [95% confidence intervals, –5.7% to –1.2%] and glomerulosclerosis: –3.3% [95% confidence intervals, –5.9% to –0.6%] per two-fold difference in uromodulin). However, when both interstitial fibrosis/tubular atrophy and glomerulosclerosis were included in multivariable analysis, only interstitial fibrosis/tubular atrophy was independently associated with uromodulin (interstitial fibrosis/tubular atrophy: –2.5% [95% confidence intervals, –4.6% to –0.4%] and glomerulosclerosis: –0.9% [95% confidence intervals, –3.4% to 1.5%] per two-fold difference in uromodulin). In mouse kidneys, uromodulin staining was found to be lower in the fibrotic model than in normal or repaired models.

Higher urine uromodulin is independently associated with lower tubulointerstitial fibrosis in both human kidney biopsies and a mouse model of fibrosis.

This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_08_10_CJN04360422.mp3.

尿调节蛋白仅在肾脏的粗升肢中产生，是肾小管健康的生物标志物。然而，尿液尿调节素与肾小管间质组织学变化之间的关系尚未得到表征。在这项研究中，我们测试了尿液尿调节素与人类和小鼠肾脏组织学结果的关联。

我们使用多变量线性回归模型研究了 2015 年至 2018 年两个学术医疗中心的 364 名参与者在肾活检时测量的尿液尿调节蛋白与组织学特征的独立关联。通过比较小鼠肾纤维化和修复模型中的尿调节素染色，进一步检验了这种关系。

我们发现尿调节蛋白与活检时的血清肌酐（rho=–0.43； P <0.001）、碳酸氢盐（0.20；P <0.001）和血红蛋白（0.11；P = 0.03）相关，但与尿白蛋白无关（ –0.07；P =0.34）。控制活检前 GFR、活检时血清肌酐和尿白蛋白的多变量模型显示，较高的尿调节素与间质纤维化/肾小管萎缩和肾小球硬化的较低严重程度相关（间质纤维化/肾小管萎缩：–3.5% [95% 置信区间，–5.7] % 至 –1.2%] 和肾小球硬化症：–3.3% [95% 置信区间，–5.9% 至 –0.6%] 每尿调节素差异两倍）。然而，当间质纤维化/肾小管萎缩和肾小球硬化均纳入多变量分析时，只有间质纤维化/肾小管萎缩与尿调节素独立相关（间质纤维化/肾小管萎缩：–2.5% [95% 置信区间，–4.6% 至 –0.4] %] 和肾小球硬化：尿调节素每两倍差异 –0.9% [95% 置信区间，–3.4% 至 1.5%]。在小鼠肾脏中，发现纤维化模型中的尿调节素染色低于正常或修复模型。

在人肾活检和小鼠纤维化模型中，较高的尿液尿调节素与较低的肾小管间质纤维化独立相关。

本文包含 https://www.asn-online.org/media/podcast/CJASN/2022_08_10_CJN04360422.mp3 上的播客。