Messenger RNA Expression of Podocyte-Associated Molecules in the Urinary Sediment of Patients with Diabetic Nephropathy

Abstract

Background: Podocyte loss plays an important role in the pathogenesis of diabetic nephropathy. We hypothesize that messenger RNA expression of podocyte-associated molecules in urinary sediment may provide important clinical information in patients with diabetic nephropathy. Method: We studied 21 patients with biopsy-proven diabetic nephropathy and 9 healthy controls. The mRNA expression of nephrin, podocin, synaptopodin, Wilms’ tumor-1 (WT-1) and α-actinin-4 in urinary sediment were measured by real-time quantitative polymerase chain reaction. The degree of histological damage was quantified by morphometric analysis. Patients were then followed for an average of 25.63 ± 10.76 months. The rate of glomerular filtration rate (GFR) decline was calculated by the least-square regression. Results: There were significant differences in nephrin, podocin, synaptopodin, α-actinin-4 (p < 0.01 for all comparisons) and WT-1 (p = 0.028) expression between patients and normal controls. Urinary nephrin expression was significantly correlated with proteinuria (r = 0.502, p = 0.020); urinary synaptopodin was significantly correlated with proteinuria (r = 0.585, p = 0.005), serum creatinine (r = 0.516, p = 0.017) and estimated GFR (r = –0.560, p = 0.008), and urinary WT-1 expression was significantly correlated with the degree of tubulointerstitial fibrosis (r = 0.558, p = 0.009). There was no significant correlation between GFR decline and urinary expression of target genes. Conclusion: Urinary mRNA expressions of nephrin, podocin, synaptopodin, WT-1 and α-actinin-4 are higher in patients with diabetic nephropathy than in normal controls. Urinary nephrin and synaptopodin expressions are correlated with baseline clinical parameters such as proteinuria or renal function, while WT-1 expression is related to the degree of histological damage. Our results suggest that urinary mRNA expression of podocyte-associated molecules may be used for risk stratification of diabetic nephropathy.

Urinary messenger RNA expression of podocyte-associated molecules in patients with diabetic nephropathy treated by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker

“…In the present study, we examined the urinary mRNA expression of podocyteassociated molecule, namely nephrin, podocin, and synaptopodin, in diabetic nephropathy patients treated with ACEI and ARB. We have previously demonstrated an increase of nephrin, podocin, and synaptopodin mRNA expression in the urinary sediment of patients with chronic kidney diseases and diabetic nephropathy (12). In the present study, we found that the urinary expression of podocyteassociated molecules correlated with baseline renal function.…”

“…In the last few years, with the development of reliable RNA extraction techniques from urinary sediment and RT real-time quantitative PCR (RT-QPCR), measurement of mRNA expression in urinary sediment has become an emerging tool for the study of kidney diseases (11). Our previous crosssectional study has showed that the mRNA expression of podocyte markers, such as nephrin, podocin, and synaptopodin, in urinary sediment is increased in patients with diabetic nephropathy (12). The objective of the present study was to examine the change in gene expression of podocyte-associated molecules in the urinary sediment of patients with diabetic nephropathy after treatment with ACEI and ARB.…”

Biomarkers of Fabry Disease Nephropathy

“…Podocyte count in urine sediments is a time-consuming procedure and it may be technically challenging to obtain reliable data because the reading is observer-dependent. However, recent studies have shown the feasibility of measuring mRNA of podocyte origin through quantitative reverse transcription-PCR of urine sediments (28,29). Currently, the evaluation of podocytes in the urine, although promising, cannot be considered a substitute for renal biopsy but could possibly constitute a tool for follow-up of an outpatient after biopsy-proven diagnosis.…”

Is there a role for urinary podocyte excretion assessment in lupus nephritis?

“…Podocyturia assessment has recently emerged as an interesting alternative biomarker. [1][2][3] Podocyturia has been identified before the onset of proteinuria in diseases such as diabetes, focal segmental glomerulosclerosis, IgA nephropathy and lupus nephritis. [4][5][6][7] Under certain conditions, apoptosis of the podocytes has been observed along with consequent detachment into the urinary space, thus leading to podocyturia and podocytopenia.…”