Abstract

Chronic kidney disease is the most common complication of diabetes. Without interventions, diabetic kidney disease (DKD) progresses to end stage renal disease (ESRD). In the United States, minority ethnic groups (e.g. African Americans) are disproportionately burdened by DKD. While genetic factors contribute to the disparities in DKD, little is known about the underlying cellular and molecular mechanisms. Several studies have shown that inflammation plays a role in the pathophysiology of DKD and the fibrosis observed in diabetic nephropathy. The goal of the current study was to determine the association between specific inflammation markers and diabetic kidney injury in diabetic African American men, an underrepresented sub‐population with high risk for diabetes and DKD. To this end, diabetic patients with (n=21) and without (n=88) diagnosed kidney disease were recruited at the Cone Health Community Health and Wellness Center in Greensboro, NC. Age‐matched, non‐diabetic subjects (n=81) served as controls. Assays for albumin and creatinine were used for biochemical assessment of kidney function. The diabetic patients were then stratified into three groups based on their albumin to creatinine ratios (ACR); normoalbuminuria (ACR<30 mg/g), microalbuminuria (30 mg/g<ACR<300 mg/g), and macroalbuminuria (ACR>300 mg/g). Enzyme‐linked immunosorbent assays were used to measure the plasma and urinary levels of five inflammatory markers; two markers of system‐wide markers (adiponectin and C‐reactive protein (CRP)); and three markers involved in renal inflammation (tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6), intercellular cell adhesion molecule‐1 (ICAM‐1)). Plasma levels of the pro‐inflammatory cytokines TNF‐α and IL‐6 were significantly higher in diabetic patients with micro‐ and macroalbuminuria when compared to non‐diabetic controls and diabetic patients with normoalbuminuria. Urinary levels for ICAM‐1 and the anti‐inflammatory cytokine, adiponectin, were higher in diabetic patients with macroalbuminuria than the other three groups. Plasma CRP was elevated in diabetic subjects compared to non‐diabetic controls, but did not correlate with the extent of diabetic kidney injury. In contrast, urinary ICAM‐1, plasma TNF‐α, and plasma adiponectin had moderate positive correlations with ACR. The plasma levels for ICAM‐1, IL‐6, and CRP were not significantly correlated with the ACR. The data suggest that certain inflammation pathways play a role in the pathogenesis of DKD in African American men.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‐Awards # HU140400 (to RHN and EMO) and HU150006 (to EMO and SHH); and the NIH/NIGMS Award Number SC3GM102049 to EMO.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Highlights

  • The prevalence of diabetes mellitus has reached epidemic proportions in the United States and worldwide

  • Participants were divided into three groups based on clinical diagnosis of diabetes and diabetic kidney disease (DKD)

  • No significant differences in estimated glomerular filtration rates (eGFR) were observed among diabetic patients with normo, micro, or macroalbuminuria, suggesting that Urinary albumin-to-creatinine ratios (UACRs) may be more reliable for predicting early onset of diabetic kidney injury in this subset of patients

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Summary

Introduction

The prevalence of diabetes mellitus has reached epidemic proportions in the United States and worldwide. This is largely driven by the obesity epidemic, the primary cause of type 2 diabetes (T2D). The most recent data from the U.S Center for Disease Control (CDC) suggest that 40% of adults and 18% of youth in the U.S are obese [1]. A common complication of diabetes is chronic kidney disease (CKD). Diabetic kidney disease (DKD), which is a leading cause of CKD and end-stage renal disease (ESRD), is estimated to affect nearly 40 percent of all diabetic patients [4]

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