Published in

American Society of Nephrology, Clinical Journal of the American Society of Nephrology, 2023

DOI: 10.2215/cjn.0000000000000333

Links

Tools

Export citation

Search in Google Scholar

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

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

Full text: Unavailable

Green circle
Preprint: archiving allowed
Green circle
Postprint: archiving allowed
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

Abstract

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 tumor necrosis factor receptor 1 (sTNFR1), and arginine-to-citrulline ratio in plasma; uromodulin (UMOD) and epidermal growth factor (EGF) in urine. We examined cross-sectional correlations between biomarkers and biopsy features and baseline biomarker associations with 5-year change in biopsy features. Results Participants’ mean age was 30 years (SD 10) and diabetes duration 11 years (SD 5); 53% were female. Mean iohexol-GFR was 128ml/min/1.73m2 (SD 19) and median urinary albumin excretion was 5μg/min (IQR 3,8). KIM-1 was associated with most biopsy features: higher mesangial fractional volume (0.5% [95% CI 0.1,0.9] greater per SD KIM-1), glomerular basement membrane width (14.2nm [95% CI 6.5,22.0] thicker), cortical interstitial fractional volume (1.1% [95% CI 0.6,1.6] greater), fractional volume of cortical atrophic tubules (0.6% [95% CI 0.2,0.9] greater), and arteriolar hyalinosis index (0.03 [95% CI 0.1,0.05] higher). sTNFR1 was associated with higher mesangial fractional volume (0.9% [95% CI 0.5,1.3] greater) and glomerular basement membrane width (12.5nm [95% CI 4.5,20.5] thicker), and lower glomerular basement membrane surface density (0.003μm2/μm3 [95% CI 0.005,0.001] lesser). EGF and arginine-to-citrulline ratio correlated with severity of glomerular and tubulointerstitial features. Baseline sTNFR1, UMOD, 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 early type 1 diabetes and may be indicators of kidney disease risk.