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. 2000 Dec;47(6):852–857. doi: 10.1136/gut.47.6.852

Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure

V Gulberg 1, S Moller 1, J Henriksen 1, A Gerbes 1
PMCID: PMC1728134  PMID: 11076886

Abstract

BACKGROUND/AIMS—C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is considered to be involved in the regulation of vascular tone. Furthermore, the recent demonstration of CNP in human kidney and urine may indicate a role for CNP in fluid and electrolyte homeostasis. Therefore, the aim of the present study was to investigate the possible role of CNP in renal function disturbances in patients with cirrhosis of the liver.
METHODS—Peripheral venous and urinary concentrations of CNP were determined in samples from 11 healthy controls, 20 cirrhotic patients with normal renal function (creatinine clearance 117 (8) ml/min), and 20 cirrhotic patients with impaired renal function (creatinine clearance 35 (4) ml/min). In a second protocol, arterial and renal venous plasma concentrations of CNP were determined in 37 patients with cirrhosis of the liver to estimate renal extraction ratios of CNP. A sensitive and specific radioimmunoassay was applied after solid phase extraction of samples.
RESULTS—Plasma CNP was lower in cirrhotic patients with normal and impaired renal function than in controls (3.0 (0.4) and 2.7 (0.2) v 4.2 (0.4) pg/ml, respectively; p< 0.05; mean (SEM)). In contrast, urinary CNP was higher in patients with impaired renal function compared with those with normal renal function and healthy controls (47.2 (7.4) v 20.8 (1.9) and 17.0 (3.0) ng CNP/g creatinine, respectively; p<0.05). Urinary CNP was found to be inversely related to urinary sodium excretion in cirrhotic patients (r=−0.56; p<0.01). No differences were observed between arterial and renal venous concentrations of CNP in cirrhosis (2.4 (0.2) v 2.4 (0.2) pg/ml). In cirrhotic patients with hepatorenal syndrome or refractory ascites (n=5), urinary CNP decreased from 132 (59) to 38 (7) ng/g creatinine (p<0.05) one week after either ornipressin infusion or insertion of a transjugular intrahepatic portosystemic shunt together with an increase in urinary sodium excretion from 27 (17) to 90 (34) mmol/24 hours.
CONCLUSIONS—Increased urinary CNP in cirrhotic patients in the absence of renal arteriovenous concentration gradients suggests enhanced renal CNP production in cirrhosis. Furthermore, an inverse relation between urinary CNP and urinary sodium excretion suggests a role for this peptide in renal sodium handling in patients with cirrhosis.


Keywords: C-type natriuretic peptide; renal function; natriuresis; cirrhosis

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Figure 1  .

Figure 1  

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Circulating plasma concentrations of C-type natriuretic peptide (CNP) in control subjects (n=11) and in cirrhotic patients with normal (n=20) or impaired renal function (n=20). Data are mean (SEM).

Figure 2  .

Figure 2  

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Circulating plasma concentrations of C-type natriuretic peptide (CNP) were inversely correlated with circulating atrial natriuretic peptide (ANP) plasma concentrations in healthy controls (r=−0.80; p=0.005; ANP plasma concentration only available in 10 subjects; A). No such relationship was observed in cirrhotic patients with normal or impaired renal function (B).

Figure 3  .

Figure 3  

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Urinary excretion of C-type natriuretic peptide (CNP) was significantly increased in cirrhotic patients with impaired renal function (n=20) compared with those with normal renal function (n=20) or healthy controls (n=11). Data are mean (SEM).

Figure 4  .

Figure 4  

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Urinary excretion of C-type natriuretic peptide (CNP) was inversely correlated with urinary sodium excretion in cirrhotic patients (r=−0.56; p<0.01; B), but not in control subjects (A).

Figure 5  .

Figure 5  

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Changes in urinary C-type natriuretic peptide (CNP) and natriuresis in five patients following therapeutic interventions. Due to the skewed distribution of the values, both variables are presented on a logarithmic scale.

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