Messenger RNA expression of glomerular podocyte markers in the urinary sediment of acquired proteinuric diseases.
BACKGROUND
Podocyte slit diaphragm plays an important role in the control of glomerular permeability. We hypothesize that studying the gene expression profile of podocyte in urinary sediment may provide diagnostic and prognostic information on acquired proteinuric diseases.


METHODS
We studied 28 patients who required kidney biopsy for acquired proteinuric diseases (diabetic glomerulosclerosis, 9 cases; IgA nephropathy, 10 cases; minimal change disease, 5 cases; membranous nephropathy, 5 cases). We also studied 10 cases of diabetic microalbuminuria and 9 healthy controls. The mRNA expressions of nephrin (NephRNA), podocin (PodRNA) and synaptopodin (SynRNA) in urinary sediment were measured by real time quantitative PCR. After recruitment, all patients were followed for at least 12 months.


RESULTS
There were significant differences in the NephRNA and PodRNA in the urinary sediment between diagnosis groups (p<0.005). On the other hand, SynRNA was only marginally significant between diagnosis groups (p<0.05). Although statistically significant, the degree of proteinuria had only modest correlations with the urinary expression of nephrin. After a median follow up for 23 months, there was a significant correlation between the rate of decline in renal function and NephRNA (r=0.559, p=0.001) and PodRNA (r=0.530, p=0.002), but not SynRNA (r=0.054, p=NS). The correlation remained statistically significant after multivariate analysis to adjust for the degree of proteinuria and initial renal function.


CONCLUSIONS
Urinary mRNA expression of podocyte markers, such as nephrin and podocin, are significantly different between proteinuric disease categories. Further, NephRNA and PodRNA correlated with the rate of decline in renal function. Our results suggest that urinary podocyte gene expression may be a useful non-invasive tool which provides additional information for the management of proteinuric diseases.
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China. ccszeto@cuhk.edu.hk
Cheuk-Chun
CC
Szeto
Ka-Bik
KB
Lai
Kai-Ming
KM
Chow
Carol Yi-Ki
CY
Szeto
Thomas Wai-Cheong
TW
Yip
Kam-Sang
KS
Woo
Philip Kam-Tao
PK
Li
Fernand Mac-Moune
FM
Lai
D000328:Adult; D015415:Biomarkers / Q000652:urine; D005260:Female; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007677:Kidney Function Tests; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D050199:Podocytes / Q000378:metabolism*; D011507:Proteinuria / Q000175:diagnosis / Q000235:genetics* / Q000652:urine*; D012333:RNA, Messenger / Q000235:genetics / Q000652:urine*
D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D012333:RNA, Messenger; C113267:nephrin