CNP production in the kidney and effects of protein intake restriction in nephrotic syndrome.
C-type natriuretic peptide (CNP) possesses well-established cardiovascular properties. Although present in the mammalian kidney, CNP production in human kidney and its modulation in human renal disease remain less defined. We investigated the presence of CNP in normal human kidney and in patients with nephrotic syndrome (NS). We also addressed whether or not a low-protein diet (LPD) alters plasma CNP and urinary CNP excretion in NS. In situ hybridization studies demonstrated CNP mRNA expression in tubular cells and glomeruli of normal human kidneys. CNP immunoreactivity was positive in proximal, distal, and medullary collecting duct tubular cells in both controls and patients with NS. The ratios of plasma CNP and urinary CNP to creatinine were significantly higher in patients with NS compared with controls. Urinary CNP, but not plasma CNP, was significantly lowered in patients with NS after an LPD. Similarly, the ratios of urinary protein to creatinine and urinary albumin to creatinine, but not urinary guanosine 3',5'-cyclic monophosphate to creatinine, decreased significantly with an LPD. These data confirm and extend previous reports and demonstrate for the first time the presence of CNP in human kidney with NS. We also report increased plasma CNP concentration and urinary CNP excretion in NS patients and a significant reduction of CNP excretion with an LPD. Our findings demonstrate that CNP metabolism is altered in patients with NS and support the hypothesis that activation of renal CNP can be partially offset by an LPD. These results underscore that the beneficial effect of an LPD on protein excretion is paralleled by a substantial reduction in intrarenal CNP release.
Cataliotti
Alessandro
A
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases and Nephrology, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. cataliotti.alessandro@mayo.edu
Giordano
Mauro
M
De Pascale
Emanuela
E
Giordano
Gelsomina
G
Castellino
Pietro
P
Jougasaki
Michihisa
M
Costello
Lisa C
LC
Boerrigter
Guido
G
Tsuruda
Toshihiro
T
Belluardo
Paola
P
Lee
Shang-Chiun
SC
Huntley
Brenda
B
Sandberg
Sharon
S
Malatino
Lorenzo S
LS
Burnett
John C
JC
D000328:Adult; D018753:Diet, Protein-Restricted; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D020098:Natriuretic Peptide, C-Type / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009404:Nephrotic Syndrome / Q000178:diet therapy / Q000378:metabolism*; D011507:Proteinuria; D012333:RNA, Messenger / Q000032:analysis
D008055:Lipids; D012333:RNA, Messenger; D020098:Natriuretic Peptide, C-Type