Effects of urodilatin on natriuresis in cirrhosis patients with sodium retention

Jan Carstens, Henning Grønbaek, Helle K Larsen, Erling B Pedersen, Hendrik Vilstrup, Jan Carstens, Henning Grønbaek, Helle K Larsen, Erling B Pedersen, Hendrik Vilstrup

Abstract

Background: Sodium retention and ascites are serious clinical problems in cirrhosis. Urodilatin (URO) is a peptide with paracrine effects in decreasing sodium reabsorption in the distal nephron. Our aim was to investigate the renal potency of synthetic URO on urine sodium excretion in cirrhosis patients with sodium retention and ascites.

Methods: Seven cirrhosis patients with diuretics-resistant sodium retention received a short-term (90 min) infusion of URO in a single-blind, placebo-controlled cross-over study. In the basal state after rehydration the patients had urine sodium excretion < 50 mmol/24 h.

Results: URO transiently increased urine sodium excretion from 22 +/- 16 micromol/min (mean +/- SD) to 78 +/- 41 mumol/min (P < 0.05) and there was no effect of placebo (29 +/- 14 to 44 +/- 32). The increase of URO's second messenger after the receptor, cGMP, was normal. URO had no effect on urine flow or on blood pressure. Most of the patients had highly elevated plasma levels of renin, angiotensin II and aldosterone and URO did not change these.

Conclusion: The short-term low-dose URO infusion increased the sodium excretion of the patients. The increase was small but systematic and potentially clinically important for such patients. The small response contrasts the preserved responsiveness of the URO receptors. The markedly activated systemic pressor hormones in cirrhosis evidently antagonized the local tubular effects of URO.

Figures

Figure 1
Figure 1
Urine sodium excretion rate (UNa) at baseline (pre-infusion level) and after 90 min of infusion of URO and placebo in the 6 sodium retainers. P < 0.05 URO end of infusion period compared to baseline.
Figure 2
Figure 2
Relative changes (%) in urine sodium excretion rate (UNa) before (0 min), during (45 and 90 min), and after (135 and 180 min) infusion of URO and placebo in the 6 patients with severe sodium retention. Boxplots represent the interquartile range and whiskers represent highest and lowest values. * P = 0.05 URO end of infusion period compared to baseline.
Figure 3
Figure 3
Total urine sodium excretion during URO infusion and placebo is depicted for each patient.
Figure 4
Figure 4
Relative changes (%) in urine flow rate (U-Vol) before (0 min), during (45 and 90 min), and after (135 and 180 min) infusion of URO and placebo in the 6 patients with severe sodium retention. Boxplots represents the interquartile range and whiskers represent highest and lowest values.
Figure 5
Figure 5
Serum cGMP before before (0 min), during (45 and 90 min), and after (135 and 180 min) infusion of URO and placebo in the 6 patients with severe sodium retention. Results are given as means ± SD. * P

Figure 6

Corresponding values of serum cGMP…

Figure 6

Corresponding values of serum cGMP and total sodium excretion in urine after 90…

Figure 6
Corresponding values of serum cGMP and total sodium excretion in urine after 90 min of URO infusion. There was no significant correlation between the two variables.

Figure 7

Corresponding values of baseline serum…

Figure 7

Corresponding values of baseline serum renin and total sodium excretion in urine after…

Figure 7
Corresponding values of baseline serum renin and total sodium excretion in urine after 90 min of URO infusion. There was no significant inverse correlation between the two variables.

Figure 8

Corresponding values of baseline serum…

Figure 8

Corresponding values of baseline serum angiotensin II and total sodium excretion in urine…

Figure 8
Corresponding values of baseline serum angiotensin II and total sodium excretion in urine after 90 min of URO infusion. There was no significant inverse correlation between the two variables.

Figure 9

Corresponding values of baseline serum…

Figure 9

Corresponding values of baseline serum aldosterone and total sodium excretion in urine after…

Figure 9
Corresponding values of baseline serum aldosterone and total sodium excretion in urine after 90 min of URO infusion. There was no significant inverse correlation between the two variable.
All figures (9)
Figure 6
Figure 6
Corresponding values of serum cGMP and total sodium excretion in urine after 90 min of URO infusion. There was no significant correlation between the two variables.
Figure 7
Figure 7
Corresponding values of baseline serum renin and total sodium excretion in urine after 90 min of URO infusion. There was no significant inverse correlation between the two variables.
Figure 8
Figure 8
Corresponding values of baseline serum angiotensin II and total sodium excretion in urine after 90 min of URO infusion. There was no significant inverse correlation between the two variables.
Figure 9
Figure 9
Corresponding values of baseline serum aldosterone and total sodium excretion in urine after 90 min of URO infusion. There was no significant inverse correlation between the two variable.

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Source: PubMed

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