Linking adiponectin to proteinuria

Abstract

Obesity predisposes toward renal disease independently of diabetes and hypertension. In this issue of the JCI, Sharma and colleagues assessed the role of adiponectin, an adipose-derived hormone, in the pathogenesis of albuminuria (see the related article beginning on page 1645). Obese African Americans had reduced adiponectin levels associated with albuminuria. Adiponectin deficiency in mice induced oxidative stress, fusion of podocyte foot processes in the kidney glomerulus, and urinary albumin excretion. Adiponectin treatment reversed these abnormalities, likely through activation of AMPK. The benefits of adiponectin were observed in diabetic and nondiabetic mice. These findings suggest that adiponectin is a biomarker for kidney disease and may be targeted for prevention and treatment.

Figure 1. Schematic demonstrating the interdigitation of podocyte foot processes that surround glomerular capillaries.

Figure 2. Schematic illustration of the effects of adiponectin on podocytes.

(A) In lean individuals, high levels of adiponectin phosphorylate and activate AMPK, presumably via AdipoR1, which prevents oxidative stress and the fusion of podocyte foot processes as well as limits albumin excretion. (B) As Sharma et al. demonstrate in this issue of the JCI (7), total adiponectin deficiency in Ad^–/– mice or partial deficiency in obesity diminishes AMPK activity, increases oxidative stress, promotes the fusion of podocyte foot processes, and leads to higher urinary albumin excretion.