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Published ahead of print on March 2, 2005
J Am Soc Nephrol 16: 1091-1098, 2005
© 2005 American Society of Nephrology
doi: 10.1681/ASN.2004090742
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Epidemiology and Outcomes

Renal Insulin Resistance Syndrome, Adiponectin and Cardiovascular Events in Patients with Kidney Disease: The Mild and Moderate Kidney Disease Study

Bjoern Becker*, Florian Kronenberg{dagger}, Jan T. Kielstein*, Hermann Haller*, Christian Morath{ddagger}, Eberhard Ritz{ddagger}, Danilo Fliser* for the MMKD Study Group

* Department of Internal Medicine, Hannover Medical School, Hannover, Germany; {dagger} Division of Genetic Epidemiology, Department of Medical Genetics, Molecular Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria; and {ddagger} Department of Internal Medicine, Ruperto-Carola University, Heidelberg, Germany

Address correspondence to: Dr. Danilo Fliser, Division of Nephrology, Department of Internal Medicine, Medical School Hannover, Carl Neuberg Strasse 1, 30625 Hannover, Germany. Phone: 49-511-532-6319; Fax: 49-511-55-2366; E-mail: fliser.danilo{at}mh-hannover.de

Received for publication September 8, 2004. Accepted for publication January 24, 2005.

The relationship among insulin resistance, adiponectin, and cardiovascular (CV) morbidity in patients with mild and moderate kidney disease was investigated. Insulin sensitivity (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]) and adiponectin plasma levels were assessed in 227 nondiabetic renal patients at different degrees of renal dysfunction and in 76 healthy subjects of similar age and gender distribution and body mass index. In renal patients, association with prevalent CV events was evaluated, and incident CV events were evaluated in a prospective study. HOMA-IR was markedly higher in patients than in healthy subjects (3.59 ± 3.55 versus 1.39 ± 0.51; P < 0.01). In renal patients, HOMA-IR was significantly correlated with body mass index (r = 0.477; P < 0.01), triglycerides (r = 0.384; P < 0.01), adiponectin plasma levels (r = –0.253; P < 0.01), and age (r = 0.164; P < 0.05), but not with renal function (GFR by iod-thalamate clearance). Patients with previous CV events were significantly older, had higher HOMA-IR and serum triglycerides, and had lower adiponectin plasma levels (all P < 0.05). Logistic regression analysis revealed age (P < 0.001) and adiponectin (P < 0.002) as independent variables related to prevalent CV events. In the prospective study, median follow-up was 54 mo. Patients who experienced CV events had significantly higher serum glucose and lower adiponectin plasma levels (both P < 0.05). In patients with chronic kidney diseases, a syndrome of insulin resistance is present even in the earliest stage of renal dysfunction, and several components of this syndrome are associated with CV events. Moreover, hypoadiponectinemia is a novel putative CV risk factor in patients with mild and moderate renal failure.




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