natriuretic-peptide--c-type and Nephrotic-Syndrome

C-type natriuretic Peptide (CNP), the third natriuretic peptide (NP) identified, is mainly expressed in the nervous system and endothelial cells. In addition, CNP is believed to be produced locally in tubular cells and glomeruli of normal human kidneys. CNP exerts mainly vasodilatory and antimitogenetic effects rather than regulation of body fluid homeostasis via autocrine or paracrine pathway. Many factors, such as shear, pro-inflammatory cytokines and lipopolysaccharide, can regulate the production and excretion of CNP both in vivo and in vitro. However, little information about the renal action of CNP was obtained in the past from the model of isolated perfused rat kidney in which variables could be changed in a controlled manner and systemic influences could be eliminated. However, reviewing the data from the studies that used this model inspires us to conclude that such model can be a useful tool to probe the undiscovered aspects of the renal actions of CNP and should be advocated for future studies on it.

Topics: Animals; Humans; Kidney; Kidney Glomerulus; Natriuretic Peptide, C-Type; Nephrotic Syndrome; Perfusion; Rats; Renin-Angiotensin System; Vasodilation

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.

Topics: Adult; Diet, Protein-Restricted; Female; Glomerular Filtration Rate; Humans; Immunohistochemistry; In Situ Hybridization; Kidney; Lipids; Male; Middle Aged; Natriuretic Peptide, C-Type; Nephrotic Syndrome; Proteinuria; RNA, Messenger