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

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, α3ß1integrin, vascular endothelial growth factor, and transforming growth factor-beta (TGF-ß1 ) 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), α3ß1integrin (P = 0.036), and TGF-ß1 (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.

Expression patterns of podocyte-associated mRNAs in patients with proliferative or non-proliferative glomerulopathies.

AIM: It is not clear how the podocyte damage manifests in different glomerulopathies. This study evaluated the podocyte-associated mRNA profiles in renal tissue and urine of patients with proliferative (PGs) or non-proliferative (NPGs) glomerulopathies. METHODS: Messenger RNA levels of nephrin, podocin, podocalyxin, synaptopodin, and alpha-actinin-4 were measured in the kidney tissue and urinary cells by real-time polymerase chain reaction. Podocyte-associated mRNAs were correlated with proteinuria and renal function, and the effect of immunosuppressive treatment of PGs and NPGs on urine mRNAs was assessed up to one year of follow up. RESULTS: Podocyte-associated mRNAs were expressed consistently less in kidney tissue from patients with NPGs, and urinary podocyte mRNA levels were significantly higher in the PG group. After six months of immunosuppressive therapy, patients with PGs showed a significant reduction in the expression of podocin, podocalyxin, and alpha-actinin-4 compared with baseline (p<0.001). In the NPG group, alpha-actinin-4 levels decreased (p=0.008), and there was also a trend toward reduced podocalyxin mRNA (p=0.08). Urine podocyte-associated mRNAs correlated with the level of proteinuria at baseline and at six months, and there was a trend toward an inverse correlation between urinary mRNAs and kidney function at one year of follow up. CONCLUSIONS: Podocyte-associated mRNAs were inhibited in kidney tissue concomitantly with their increase in urine in these patients with glomerulopathies. Different profiles of mRNA expression were seen, pointing to a higher degree of intra-renal podocytopenia in the NPGs and of podocyturia in the PGs. The immunosuppressive therapy effectively reduced the urinary levels of podocyte-associated mRNAs.