Aims/hypothesis  

The early identification of type 2 diabetic patients at risk of developing microalbuminuria—an independent risk factor for renal and cardiovascular diseases—is important to improve the patients’ outcomes. We investigated whether serum levels of IL-18, a proinflammatory cytokine, were a predictor of early renal dysfunction.

Materials and methods  

A total of 249 Japanese type 2 diabetic patients without overt proteinuria were enrolled in an observational follow-up study (median follow-up 7 years), and their stage of diabetic nephropathy was classified and their estimated glomerular filtration rate (eGFR) was calculated annually.

Results  

At baseline, serum levels of IL-18 were higher in subjects with microalbuminuria (n = 76) than in those with normoalbuminuria (n = 173). Elevated serum levels of IL-18 were associated with the progression of nephropathy to a higher stage in normoalbuminuric subjects (118 [interquartile range 91–159] ng/l vs 155 [interquartile range 121–205] ng/l, p = 0.003), but not in microalbuminuric subjects (154 [interquartile range 113–200] ng/l vs 160 [interquartile range 101–190] ng/l, p = 0.50). The adjusted risk for developing microalbuminuria was 3.6 (95% CI 1.2–10.4) in normoalbuminuric subjects with serum IL-18 levels above the median (≥134.6 ng/l), and was significantly enhanced in those urinary AERs at the upper end of the normal range (7.5 μg/min ≤ AER < 20 μg/min). Furthermore, the annual rate of decline in eGFR, when examined in the study population as a whole, was significantly greater in subjects with serum IL-18 levels above the median than in other subjects.

Conclusions/interpretation  

The results of our observational follow-up study indicate that elevated serum levels of IL-18 may be a predictor of future renal dysfunction in type 2 diabetic patients with normoalbuminuria.