Association of Urinary Inflammatory Markers and Renal Decline in Microalbuminuric Type 1 Diabetics

Abstract

Progressive renal function decline begins in one third of patients with microalbuminuria and type 1 diabetes. This study examined whether this decline is associated with elevated excretion of inflammatory markers in urine. Five inflammatory markers (IL-6, IL-8, monocyte chemoattractant protein-1, interferongamma-inducible protein (IP-10), and macrophage inflammatory protein-1␦) were measured in urine samples from the First Joslin Study of the Natural History of Microalbuminuria in Type 1 Diabetes, a cohort recruited in 1991. Samples were obtained from 43 participants with microalbuminuria and stable renal function (nondecliners), from 28 with microalbuminuria and early progressive renal function decline (decliners), and from 74 with normoalbuminuria and stable renal function (reference). Urinary concentrations of all five inflammatory markers were significantly higher in decliners than in nondecliners, who were similar to the reference group. Multivariate analysis revealed that those with more than two markers elevated were more than five times as likely to have early progressive decline of renal function. In contrast, serum concentrations of C-reactive protein, IL-8, and macrophage inflammatory protein-1␦ did not differ between decliners and nondecliners. These results support the hypothesis that inflammatory processes in the kidney contribute to the progression of nephropathy in patients with type 1 diabetes.

CRP Polymorphisms and Progression of Chronic Kidney Disease in African Americans

“…Alternatively, it is possible that rs3093058 is not a key pathogenic mediator for CKD in this population. Although epidemiologic data support the role of inflammation, including CRP in the pathogenic process (11,(13)(14)(15), CRP is a surrogate marker of the inflammatory process (33). CKD patients have a high burden of comorbidities, and reverse causation may explain the associations with CRP.…”

Diabetic Nephropathy: New Risk Factors and Improvements in Diagnosis

“…Elevated urinary levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a marker of oxidative stress, predict the progression of diabetic nephropathy in patients with T2D [47]. Patients with T1D or T2D and with higher levels of proinflammatory cytokines and chemokines (interleukin 6, interleukin 18, and monocyte chemoattractant protein-1), high-sensitivity Creactive protein (hsCRP, a marker of subclinical inflammation), or adhesion molecules (soluble vascular cellular adhesion molecule-1 and soluble Eselectin) are at higher risk for developing nephropathy and for advancing to more severe kidney disease [48][49][50][51]. In patients with T1D or T2D, elevated levels of tumor necrosis factor-α receptors are also independently associated with increased incidence of impaired kidney function [52,53].…”

Successes Achieved and Challenges Ahead in Translating Biomarkers into Clinical Applications

“…Resident kidney cells produce chemokines in response to stimulation by the diabetic milieu, which subsequently promotes the development of renal inflammation and tissue injury. Some of these chemokines (monocyte chemoattractant protein-1, interleukin (IL)-8, IP-10, and macrophage inflammatory protein-1δ) are elevated in the urine of diabetic patients and correlate with a decline in renal function (25). Urine chemokine levels appear to reflect the level of diabetic renal inflammation, which contributes to disease progression (26).…”