Use of Readily Accessible Inflammatory Markers to Predict Diabetic Kidney Disease

Abstract

Diabetic kidney disease is a common complication of type 1 and type 2 diabetes and is the primary cause of end-stage renal disease in developed countries. Early detection of diabetic kidney disease will facilitate early intervention aimed at reducing the rate of progression to end-stage renal disease. Diabetic kidney disease has been traditionally classified based on the presence of albuminuria. More recently estimated glomerular filtration rate has also been incorporated into the staging of diabetic kidney disease. While albuminuric diabetic kidney disease is well described, the phenotype of non-albuminuric diabetic kidney disease is now widely accepted. An association between markers of inflammation and diabetic kidney disease has previously been demonstrated. Effector molecules of the innate immune system including C-reactive protein, interleukin-6, and tumor necrosis factor-α are increased in patients with diabetic kidney disease. Furthermore, renal infiltration of neutrophils, macrophages, and lymphocytes are observed in renal biopsies of patients with diabetic kidney disease. Similarly high serum neutrophil and low serum lymphocyte counts have been shown to be associated with diabetic kidney disease. The neutrophil–lymphocyte ratio is considered a robust measure of systemic inflammation and is associated with the presence of inflammatory conditions including the metabolic syndrome and insulin resistance. Cross-sectional studies have demonstrated a link between high levels of the above inflammatory biomarkers and diabetic kidney disease. Further longitudinal studies will be required to determine if these readily available inflammatory biomarkers can accurately predict the presence and prognosis of diabetic kidney disease, above and beyond albuminuria, and estimated glomerular filtration rate.

Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as novel risk markers for diabetic nephropathy in patients with type 2 diabetes

“…An increase in urinary albumin excretion is a clinical manifestation for DN, starting from microalbuminuria to macroalbuminuria and eventually ESRD [8,9]. Current diagnosis of DN is depended on albuminuria as a biomarker [11]. However, its diagnostic value in early-stage DN is limited because renal injury commonly precedes urinary albumin secretion [6].…”

Global diabetic kidney disease research from 2000 to 2017

“…[20,21] Some other biomarkers, such as α1-microglobulin (α1-MG), β2-microglobulin (β2-MG), inflammatory markers (e.g., C-reactive protein, interleukin-6, and tumor necrosis factor-α), as well as several angiogenic and anti-angiogenic factors (e.g., vascular endothelial growth factor (VEGF), VEGF receptors, angiopoietins and endostatin) were reported to play important roles in early detection, therapeutic prevention and implementation of DKD. [36–38] Plasma tumor necrosis factor receptor-1 (TNFR-1), TNFR-2, and kidney injury molecule-1 (KIM-1) were independently associated with higher risk of eGFR decline in patients with early or advanced DKD. [39,40] The research in “biomarker” should still be a direction in the future.…”

Longitudinal Associations between Obesity, Inflammation, and the Incidence of Type 2 Diabetes Mellitus among US Black and White Adults in the CARDIA Study

“…Although studies have shown a positive relationship between CRP and diabetes, this association is often reduced or attenuated completely when anthropometric body measures, such as body mass index and hip-waist ratio, are accounted for in the analyses [ 25 ]. In our study, however, we found that the association between CRP and T2DM was robust for both Blacks and Whites ( Table 3 ], and notably stronger among Whites than Blacks even when waist circumference was added to the models.…”