Correlations between biomarkers of kidney injury, adiponectin, and TGF‐β1 in African American men with diabetes

Diabetic nephropathy (DN), the most common complication of diabetes, develops in about one‐third of diabetic patients. The prevalence of diabetes is higher in ethnic minorities, affecting approximately 13% of African Americans, 9.5% of Hispanics, and 15% of Native Americans, primarily with type 2 diabetes. African‐American men are underrepresented in research studies used to develop biomarkers for diagnosis and early detection of DN. Previous studies have developed more sensitive and reliable proteomic markers of kidney injury, which include neutrophil gelatinase‐associated lipocalin (NGAL), cystatin C, and kidney injury molecule‐1 (KIM‐1). Accumulating evidence suggests that transforming growth factor β1 (TGF‐β 1 ) is involved in the development of renal scarring. Meanwhile, adiponectin is an adipokine that has been shown to have reno‐protective effects through AMPK‐activated pathways, resulting in the prevention of albuminuria. The goal of the current study was to determine the correlation between proteomic biomarkers of kidney injury, adiponectin, and TGF‐β1 in African American men with diabetes. To this end, fasting blood and urine samples were collected from African American men aged 18 to 62 years. Three groups were compared, namely: diabetics (n=43), diabetics with diagnosed diabetic nephropathy (n=7), and non‐diabetic controls (n=28). Enzyme‐linked immunosorbent assays (ELISA) were used to determine the plasma and urine levels of proteomic markers of kidney injury (creatinine, cystatin C, NGAL, and KIM‐1), as well as the levels of adiponectin, and TGF‐β1. The data were analyzed by 2‐way ANOVA (GraphPad Prism). Plasma NGAL levels were significantly higher in patients with diagnosed DN when compared to diabetics without kidney injury and non‐diabetic controls (p≤0.01). Similarly, plasma cystatin C levels were significantly higher in patients with DN when compared to non‐diabetic controls and diabetics without known kidney injury (p≤0.01). Diabetic patients had a modest but significant increase in plasma cystatin C when compared to non‐diabetic controls (p≤0.05). In contrast, the urinary cystatin C levels were lower in all diabetic patients when compared to non‐diabetic controls. There was no significant difference in urine creatinine levels among the non‐diabetic and diabetic patients evaluated. There was a significant increase in urinary adiponectin levels in patients with DN when compared to non‐diabetic controls and diabetic patients without known kidney injury (p≤0.01). A modest increase in adiponectin was also observed in diabetic patients without DN when compared to non‐diabetic controls. However, there was no significant difference in TGF‐β1 levels between the three groups analyzed. Our data shows an increase in plasma cystatin C levels in diabetic African American men. This increase may be indicative of early onset of kidney disease, suggesting that cystatin C could be a suitable marker for early diagnosis of DN. The data also shows that adiponectin and/or adiponectin‐mediated pathways may play a role in the progression of DN in African American men. Support or Funding Information This study was supported by the Minority Men's Health Initiative (MMHI) through NIH/NIMHD Center Award # U54MD008621 (CFDA 93.307), Sub‐Awards # HU140004 and HU150006. Ava Boston is supported by the RISE program under NIH/NIGMS Grant # R25GM076162 to Goldie S Byrd