Biomarkers of kidney injury and indicators of renal inflammation in African American men with diabetes and diabetic nephropathy

Abstract

Diabetic nephropathy (DN) is a progressive kidney disease caused by damage to the capillaries in the kidneys' glomeruli due to changes in glomerular hemodynamics, causing renal lesions and fibrosis. Oxidative stress and inflammatory responses represent underlying causes for developing chronic kidney damage. Treatment outcomes for DN are poor because many patients with DN are diagnosed late due to lack of clinical tests based on sensitive biomarkers. Monocyte chemoattractant protein‐1 (MCP‐1) is a major promoter of inflammation, renal injury, and fibrosis in diabetic nephropathy. In the United States, minority ethnic communities bear a disproportionate burden of complications of diabetes and are at a higher risk of developing end stage renal disease. Participation in biomedical research by African American men is especially low due to historical mistrust with the research institutions. The objective of this study is to assess correlations between biomarkers of kidney injury and indicators of inflammation among three groups of African American men: 1) diabetic patients without DN, 2) diabetic patients with diagnosed DN, and 3) non‐diabetic controls. Fasting blood and urine samples were collected from patients recruited through a community health clinic. Surveys were administered to establish patient profiles and family history. Enzyme‐linked immunosorbent assays (ELISA) were used to determine the levels of plasma MCP‐1 and the levels of three biomarkers of kidney injury, namely, cystatin C, neutrophil gelatinase‐associated lipocalin (NGAL), and kidney injury molecule 1 (KIM‐1). The data were analyzed by 2‐way ANOVA. The data showed that the levels of serum cystatin C were significantly higher in patients with diagnosed DN compared to non‐diabetic controls (p<0.01). Additionally, diabetic patients showed a significant increase in serum cystatin C levels relative to the non‐diabetic controls (p<0.05). In contrast, urine cystatin C levels were significantly lower in patients with DN compared to the other two groups. Plasma NGAL levels were significantly higher in patients with DN compared to both non‐diabetic and diabetic patients (p<0.01). However, there was no significant difference in the levels of urine KIM‐1 among the three groups. In conclusion, serum MCP‐1 exhibited higher levels in patients with DN compared to both diabetic patients and non‐diabetic controls (p<0.0001). The significant increase in serum MCP‐1 levels suggests that inflammation is an underlying cause of kidney injury in African American men who have DN. Furthermore, the data suggest that a significant number of diabetic African American men may have undiagnosed kidney injury as shown by elevated cystatin C levels.Support or Funding InformationThis study was supported by the Minority Men's Health Initiative (MMHI) through NIH/NIMHD Center Award # U54MD008621 (CFDA 93.307), Sub‐Award # HU140004 and sub‐award #HU150006.