Inflammation and Kidney Injury in Diabetic African American Men.

African Americans are disproportionately burdened by diabetic kidney disease (DKD). However, little is known about the cellular and molecular mechanisms underlying the onset and progression of DKD in this population. The goal of the current study was to determine the association between specific inflammation markers and kidney injury in diabetic African American men. To this end, we recruited diabetic patients either with (n = 20) or without (n = 87) diagnosed kidney disease along with age-matched nondiabetic controls (n = 81). Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFR) were used for biochemical assessment of kidney function. We then measured plasma and urinary levels of seven inflammatory markers, including adiponectin, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), TNF receptor 1 (TNFR1), TNF receptor 2 (TNFR2), interleukin-6 (IL-6), and intercellular cell adhesion molecule-1 (ICAM-1). Plasma levels of TNF-α, TNFR1, and TNFR2 were significantly higher in diabetics with macroalbuminuria compared to nondiabetic controls and diabetics with normoalbuminuria or microalbuminuria. Likewise, urinary levels of ICAM-1 were higher in diabetics with macroalbuminuria compared to the other groups. Indeed, urinary ICAM-1, plasma TNF-α, and adiponectin had moderate positive correlations with UACR while plasma TNFR1 and TNFR2 levels were strongly correlated with kidney injury, indicated by multiple biomarkers of kidney injury. In contrast, though plasma CRP was elevated in diabetic subjects relative to nondiabetic controls, its levels did not correlate with kidney injury. Together, these data suggest that inflammation, particularly that mediated by the TNF-α/NF-κB signaling axis, may play a role in the pathogenesis of DKD in African American men.

Undiagnosed Kidney Injury in Uninsured and Underinsured Diabetic African American Men and Putative Role of Meprin Metalloproteases in Diabetic Nephropathy.

Diabetes is the leading cause of chronic kidney disease. African Americans are disproportionately burdened by diabetic kidney disease (DKD) and end stage renal disease (ESRD). Disparities in DKD have genetic and socioeconomic components, yet its prevalence in African Americans is not adequately studied. The current study used multiple biomarkers of DKD to evaluate undiagnosed DKD in uninsured and underinsured African American men in Greensboro, North Carolina. Participants consisted of three groups: nondiabetic controls, diabetic patients without known kidney disease, and diabetic patients with diagnosed DKD. Our data reveal undiagnosed kidney injury in a significant proportion of the diabetic patients, based on levels of both plasma and urinary biomarkers of kidney injury, namely, urinary albumin to creatinine ratio, kidney injury molecule-1, cystatin C, and neutrophil gelatinase-associated lipocalin. We also found that the urinary levels of meprin A, meprin B, and two kidney meprin targets (nidogen-1 and monocytes chemoattractant protein-1) increased with severity of kidney injury, suggesting a potential role for meprin metalloproteases in the pathophysiology of DKD in this subpopulation. The study also demonstrates a need for more aggressive tests to assess kidney injury in uninsured diabetic patients to facilitate early diagnosis and targeted interventions that could slow progression to ESRD.