Targher G et al. (2008) Increased risk of CKD among type 2 diabetics with nonalcoholic fatty liver disease. J Am Soc Nephrol 19: 1564–1570

The proportion of patients with type 2 diabetes who are on dialysis is steadily increasing. Early treatment of chronic kidney disease (CKD) delays the onset of end-stage renal disease in these individuals; therefore, the identification of risk factors for CKD is imperative. Targher et al. investigated whether nonalcoholic fatty liver disease (NAFLD), which is thought to affect 70–75% of patients with type 2 diabetes, is a risk factor for CKD in this population.

The authors enrolled 1,827 outpatients from the Valpolicella Heart Diabetes Study who had type 2 diabetes, normal or near-normal kidney function and no overt proteinuria at baseline. During 6.5 years of follow-up, 547 of the 1,760 participants who attended routine medical examinations developed incident CKD. Patients with NAFLD, as diagnosed by patient history and liver ultrasonography, were at increased risk of developing CKD (hazard ratio 1.69; P <0.001). Adjustments for confounders such as sex, age, BMI, waist circumference, blood pressure, smoking, glycosylated hemoglobin level, blood lipids, baseline estimated glomerular filtration rate, microalbuminuria and medication use did not substantially modify the correlation (hazard ratio 1.49; P <0.01).

CKD and NAFLD share many risk factors; however, the data suggest that NAFLD confers an additional risk of CKD, beyond that which would be expected from the common risk factors alone. Systemic release of proinflammatory mediators from the liver (e.g. C-reactive protein, fibrinogen and plasminogen activator inhibitor 1) and worsening of insulin resistance could be among the major underlying mechanisms by which NAFLD, especially in its necro-inflammatory form, increases the risk of CKD.