Increased urine podocyte-associated messenger RNAs in severe obesity are evidence of podocyte injury

Abstract

Objective The aim of this study was to correlate different degrees of excess weight with the expression of podocyte-associated messenger RNAs (mRNAs) in urine. Methods The sample comprised 83 patients with overweight or obesity class I, II, or III and 18 healthy controls. The expression of nephrin, podocin, podocalyxin, α-actinin-4, α3β1integrin, vascular endothelial growth factor, and transforming growth factor-beta (TGF-β1) mRNA in urine was quantified with the real-time polymerase chain reaction. mRNA expression was correlated with body mass index, the metabolic syndrome, albuminuria, and inflammation. Results Adults with obesity class III had higher levels of serum lipids, glucose, HbA1C, insulin resistance, and C-reactive protein (P < 0.05), with 85% of the subjects meeting criteria for the metabolic syndrome (P < 0.001 vs. other groups). Urinary podocyte-associated mRNAs were higher in adults with obesity class III than in other groups (P < 0.05). Patients with overweight or obesity class I or II also had higher levels of podocyte mRNAs than controls: nephrin (P = 0.021), α-actinin-4 (P = 0.014), α3β1integrin (P = 0.036), and TGF-β1 (P = 0.005). Metabolic syndrome, hyperinsulinemia, and C-reactive protein were correlated with podocyturia, but only higher insulin levels were related regardless of obesity. Conclusions Severe obesity and hyperinsulinemia were associated with higher urinary expression of podocyte-associated mRNAs, even at normal urinary albumin excretion rates.