Predictive impact of elevated serum level of IL-18 for early renal dysfunction in type 2 diabetes: an observational follow-up study.
OBJECTIVE
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.


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 mug/min </= AER < 20 microg/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
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.
Araki
S
S
Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, 520-2192, Japan. araki@belle.shiga-med.ac.jp
Haneda
M
M
Koya
D
D
Sugimoto
T
T
Isshiki
K
K
Chin-Kanasaki
M
M
Uzu
T
T
Kashiwagi
A
A
D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D048909:Diabetes Complications / Q000175:diagnosis / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood* / Q000175:diagnosis*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation; D020382:Interleukin-18 / Q000097:blood* / Q000378:metabolism; D007564:Japan; D007674:Kidney Diseases / Q000097:blood* / Q000150:complications*; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D020382:Interleukin-18; D002097:C-Reactive Protein