Intra-renal and urinary mRNA expression of podocyte-associated molecules for the estimation of glomerular podocyte loss

BACKGROUND: Podocyte loss plays an important role in the pathogenesis of diabetic nephropathy, but counting the number of glomerular podocyte in renal biopsy specimen is a labor-intensive task. We study whether intra-renal and urinary messenger RNA expression of podocyte-associated molecules could be used to estimate glomerular podocyte number in patients with diabetic nephropathy. METHOD: We studied 21 consecutive patients with biopsy-proven diabetic nephropathy. The intra-renal and urinary mRNA expression of nephrin, podocin, and synaptopodin were measured by real-time quantitative polymerase chain reaction. Podocyte number was determined in micro-dissected glomerulus. The degree of histological scarring was quantified by morphometric analysis. RESULTS: Glomerular podocyte number correlated with intra-renal expression of nephrin (r=0.510, p=0.044), podocin (r=0.605, p=0.013), and synaptopodin (r=0.480, p=0.060). Glomerular podocyte number also significantly correlated with urinary expression of synaptopodin (r=0.595, p=0.019) but not other targets. Baseline renal function correlated with intra-renal expression of nephrin (r=0.617, p=0.005), synaptopodin (r=0.474, p=0.040), and podocin (r=0.443, p=0.057). The degree of tubulointerstitial scarring also inversely correlated with intra-renal expression of nephrin (r=-0.462, p=0.047), podocin (r=-0.458, p=0.049), and synaptopodin (r=-0.500, p=0.029) but not with urinary gene expression. CONCLUSION: Intra-renal expression of podocyte-associated molecules correlated with glomerular podocyte number, renal function, and tubulointerstitial scarring. The results suggest that intra-renal, but not urinary expression of podocyte-associated molecules, might be used to assess the degree of podocyte loss in diabetic nephropathy.