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Associations of Biomarkers of Tubular Injury and Inflammation with Biopsy Features in Type 1 Diabetes

医学 肾功能 2型糖尿病 内科学 糖尿病 肌酐 泌尿科 四分位间距 活检 胃肠病学 生物标志物 肾脏疾病 蛋白尿 内分泌学 病理 生物化学 化学
作者
Christine P. Limonte,David K. Prince,Andrew N. Hoofnagle,Andrzej T. Gałecki,Irl B. Hirsch,Frances Tian,Sushrut S. Waikar,Helen C. Looker,Robert G. Nelson,Alessandro Doria,Michael Mauer,Bryan Kestenbaum,Ian H. de Boer
出处
期刊:Clinical Journal of The American Society of Nephrology [American Society of Nephrology]
卷期号:19 (1): 44-55 被引量:2
标识
DOI:10.2215/cjn.0000000000000333
摘要

Background Whether biomarkers of tubular injury and inflammation indicate subclinical structural kidney pathology early in type 1 diabetes remains unknown. Methods We investigated associations of biomarkers of tubular injury and inflammation with kidney structural features in 244 adults with type 1 diabetes from the Renin-Angiotensin System Study, a randomized, placebo-controlled trial testing effects of enalapril or losartan on changes in glomerular, tubulointerstitial, and vascular parameters from baseline to 5-year kidney biopsies. Biosamples at biopsy were assessed for kidney injury molecule 1 (KIM-1), soluble TNF receptor 1 (sTNFR1), arginine-to-citrulline ratio in plasma, and uromodulin and epidermal growth factor (EGF) in urine. We examined cross-sectional correlations between biomarkers and biopsy features and baseline biomarker associations with 5-year changes in biopsy features. Results Participants' mean age was 30 years (SD 10) and diabetes duration 11 years (SD 5); 53% were women. The mean GFR measured by iohexol disappearance was 128 ml/min per 1.73 m 2 (SD 19) and median urinary albumin excretion was 5 μ g/min (interquartile range, 3–8). KIM-1 was associated with most biopsy features: higher mesangial fractional volume (0.5% [95% confidence interval (CI), 0.1 to 0.9] greater per SD KIM-1), glomerular basement membrane (GBM) width (14.2 nm [95% CI, 6.5 to 22.0] thicker), cortical interstitial fractional volume (1.1% [95% CI, 0.6 to 1.6] greater), fractional volume of cortical atrophic tubules (0.6% [95% CI, 0.2 to 0.9] greater), and arteriolar hyalinosis index (0.03 [95% CI, 0.1 to 0.05] higher). sTNFR1 was associated with higher mesangial fractional volume (0.9% [95% CI, 0.5 to 1.3] greater) and GBM width (12.5 nm [95% CI, 4.5 to 20.5] thicker) and lower GBM surface density (0.003 μ m 2 / μ m 3 [95% CI, 0.005 to 0.001] lesser). EGF and arginine-to-citrulline ratio correlated with severity of glomerular and tubulointerstitial features. Baseline sTNFR1, uromodulin, and EGF concentrations were associated with 5-year glomerular and tubulointerstitial feature progression. Conclusions Biomarkers of tubular injury and inflammation were associated with kidney structural parameters in early type 1 diabetes and may be indicators of kidney disease risk. Clinical Trial registry name and registration number Renin Angiotensin System Study (RASS/B-RASS), NCT00143949 Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_11_17_CJN0000000000000333.mp3
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