Glomerular and Tubular Damage Markers Are Elevated in Patients With Diabetes

April 2011
Diabetes Care;Apr2011, Vol. 34 Issue 4, p975
Academic Journal
OBJECTIVE--We investigated in a cross-sectional study the levels of serum and urinary damage markers in diabetic patients (n = 94) and nondiabetic control subjects (n = 45) to study the association of glomerular (IgG), proximal tubular (kidney injury molecule [KIM]-1, N-acetyl-β-D-glucosaminidase [NAG], neutrophil gelatinase-associated lipocalin [NGAL], and cystatin C), and distal tubular (heart fatty acid-binding protein [H-FABP]) damage markers with kidney disease severity, as assessed by albuminuria and estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS--Damage markers were measured in triplicate in fresh morning urine samples and in plasma. RESULTS--Of the diabetic patients, 41 were normoalbuminuric, 41 were microalbuminuric, and 12 were macroalbuminuric. Urinary NAG (ninefold), NGAL (1.5-fold), and H-FABP (3.5-fold) were significantly elevated in normoalbuminuric diabetic patients compared with nondiabetic control subjects. Urinary concentrations of all markers increased per albuminuria stratum, except KIM-1. All urinary damage markers, except KIM-1, were significantly associated with albuminuria, independent of age, sex, and plasma concentrations of the corresponding biomarker (standard βs between 0.35 and 0.87: all P ≤ 0.001). All urinary, damage markers, except KIM-1, were significantly associated with the eGFR in univariate models (standard βs between -0.38 and -0.21: all P < 0.04). After adjusting for age, sex, plasma concentration of the corresponding damage marker, and albuminuria, only the association of H-FABP with eGFR remained significant (standard β -0.26; P = 0.037). CONCLUSIONS--Glomerular and tubular markers are associated with albuminuria, independently of eGFR, suggesting that albuminuria reflects both glomerular and tubulointerstitial damage. Only urinary H-FABP is associated with eGFR independently of albuminuria and, therefore, may be a promising urinary damage marker to assess diabetic kidney disease.


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