Podocyte loss in human hypertensive nephrosclerosis.
BACKGROUND
Podocyte injury probably plays important roles in the pathogenesis of hypertensive nephropathy, but human data are limited. We studied glomerular podocyte count and intrarenal expression of podocyte-associated molecules in patients with hypertensive nephrosclerosis.


METHODS
We studied 41 consecutive patients with biopsy-proven hypertensive nephropathy, 10 cadaveric kidney donors, and 9 healthy subjects. Intrarenal and urinary mRNA expression of podocyte-associated molecules was quantified and podocyte number was determined by stereological method.


RESULTS
Intrarenal mRNA expression levels of nephrin, podocin, and synaptopodin were lower, and urinary mRNA expression levels were higher in patients with hypertensive nephropathy than controls. Glomerular podocyte number was significantly lower in patients with hypertensive nephrosclerosis than kidney donors (545 +/- 237 vs. 773 +/- 296 per glomeruli, P < 0.02). Podocyte density and intrarenal gene expression of podocyte-associated molecules significantly correlated with estimated glomerular filtration rate (GFR) and inversely correlated with blood pressure and the degree of renal fibrosis. Intrarenal gene expression of nephrin significantly correlated with change in renal function decline.


CONCLUSIONS
This study demonstrates a decrease in podocyte number and intrarenal gene expression of podocyte-associated molecules in patients with hypertensive nephrosclerosis. We observed correlations between glomerular podocyte density and intrarenal expression of podocyte-associated molecules with renal function and the degree of renal fibrosis, suggesting podocyte loss may play an important role in the pathogenesis of hypertensive nephrosclerosis.
Wang
Gang
G
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.
Lai
Fernand Mac-Moune
FM
Kwan
Bonnie Ching-Ha
BC
Lai
Ka-Bik
KB
Chow
Kai-Ming
KM
Li
Philip Kam-Tao
PK
Szeto
Cheuk-Chun
CC
D000368:Aged; D001706:Biopsy; D002452:Cell Count; D018797:Cell Cycle Proteins; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005919:Glomerular Filtration Rate; D006801:Humans; D006977:Hypertension, Renal / Q000235:genetics / Q000473:pathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000473:pathology; D008297:Male; D042282:Microdissection; D008875:Middle Aged; D009400:Nephrosclerosis / Q000235:genetics / Q000473:pathology*; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism; D050199:Podocytes / Q000473:pathology*; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000652:urine; D014019:Tissue Donors
D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; C419554:WTAP protein, human