THE RENAL PARACRINE PEPTIDE SYSTEM - POSSIBLE UROLOGIC IMPLICATIONS OF URODILATIN

Cardiodilatin/atrial natriuretic peptide (CDD/ANP) is a hormone system of great clinical importance. The prohormone CDD/ANP-1-126 is a pepti de synthesized in the heart and cleaved during exocytosis into the cir culating form CDD/ANP-99-126. Urodilatin (CDD/ANP-95-126) is a homolog ue natriuretic peptide that differs from CDD/ANP-99-126 by four amino acids. Whereas CDD/ANP-99-126 circulates in blood plasma and is not ex creted into the urine, urodilatin is detected only in urine. Urodilati n exerts its renal effects in a paracrine fashion. After its secretion from cells in the distal tubule, it interacts with luminally located receptors in the collecting duct, resulting in increased diuresis and natriuresis. Results suggest that urodilatin plays an important role i n the physiologic regulation of fluid balance and sodium homeostasis. Pharmacology studies reveal significant differences when urodilatin an d CDD/ANP-99-126 are given intravenously, showing that stronger diures is and natriuresis are induced by urodilatin as compared with those in duced by CDD/ANP-99-126. Clinical studies indicate the prophylactic an d therapeutic effect of urodilatin in patients suffering from acute re nal failure following heart and liver transplantation. A significant r eduction in requirements for hemodialysis/hemofiltration can be achiev ed using urodilatin. Postobstructive diuresis and natriuresis is proba bly due to a defective urinary concentrating mechanism and is usually resistant to treatment with antidiuretic hormone. The distal tubule an d collecting duct have often been considered to be the site of altered sodium and water excretion following relief of obstruction. Since cir culating CDD/ANP-99-126 levels are markedly elevated during obstructio n and decrease upon relief of the obstruction, natriuretic peptides ma y play an important role in this clinical feature. On the basis of rec ent findings attributing an important role in sodium homeostasis to ur odilatin in contrast to CDD/ANP-99-126, future studies have to clarify whether urodilatin, not CDD/ANP-99-126, might be responsible for the altered renal sodium excretion observed in postobstructive diuresis.