Messenger RNA expression of podocyte-associated molecules in the urinary sediment of patients with diabetic nephropathy.
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.


METHODS
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 alpha-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, alpha-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.


CONCLUSIONS
Urinary mRNA expressions of nephrin, podocin, synaptopodin, WT-1 and alpha-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.
Wang
Gang
G
Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, SAR, China.
Lai
Fernand Mac-Moune
FM
Lai
Ka-Bik
KB
Chow
Kai-Ming
KM
Li
Kam-Tao Philip
KT
Szeto
Cheuk-Chun
CC
D000328:Adult; D003928:Diabetic Nephropathies / Q000652:urine*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000652:urine*
D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger