Urinary excretion of urodilatin in healthy children and children with renal disease
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Original article
Urinary excretion of urodilatin in healthy children and children with renal disease T. Seeman1, M. Meyer2, C. P. Schmitt1, T. Remer3, W.-G. Forssmann2, and K. SchaÈrer1 Division of Pediatric Nephrology, University Children's Hospital, Im Neuenheimer Feld 150, D-69120 Heidelberg, Germany Lower Saxony Institute for Peptide Research, D-30625 Hannover, Germany 3 Research Institute for Child Nutrition, D-44225 Dortmund, Germany 1 2
Received December 4, 1996; received in revised form and accepted June 13, 1997
Abstract. Urodilatin (URO) is a natriuretic peptide isolated from human urine which is thought to be produced by distal tubular cells. We measured urinary URO excretion in 50 healthy children and 23 children with acute (ARF), chronic renal failure (CRF), or hereditary tubular disorders, using a specific radioimmunoassay. The mean URO excreted in these four groups was 56, 45, 94, and 121 fmol/min per 1.73 m2, respectively (differences between first three groups not significant). The variation in URO excretion was larger in patients with kidney disease than in controls. There were significant correlations between urinary URO and sodium excretion in controls and CRF, but not in ARF. URO excretion also correlated with urine flow rate in CRF. Although no correlation was found between URO excretion and creatinine clearance, urinary URO was increased in some patients with advanced CRF, which suggests stimulated tubular production to compensate for reduced sodium excretion. In view of the therapeutic potential of URO in renal insufficiency, further study of the renal handling of URO is warranted. Key words: Urodilatin ± Acute renal failure ± Chronic renal failure ± Congential tubulopathies ± Sodium excretion
Introduction Urodilatin (CDD/ANP-95-126, URO) is a natriuretic peptide of the A-type which was isolated from human urine [1]. It has 4 additional N-terminal amino acids compared with the circulating atrial natriuretic peptide (CDD/ANP99-126, ANP). URO has not been detected in blood by current analytical methods, unlike ANP [2]. To measure URO in urine, a specific radioimmunoassay (RIA) with no cross-reaction with ANP was developed [3]. URO is thought to be synthesized in distal tubular cells and cleaved here from its precursor, a product of a common Correspondence to: K. SchaÈrer
single gene for URO and ANP [2, 4, 5]. It is secreted in the distal tubular lumen and acts in a paracrine fashion on luminal receptors of collecting duct cells, in which it inhibits water and sodium (Na) resorption [4]. URO excretion (UROe) is closely related to Na excretion and urine flow rate (UFR) [5, 6]. Intravenous URO infusion results in natriuresis and diuresis, which is modulated by Na balance and is more effective than an equimolar infusion of ANP [6, 7]. The diuretic and vasodilating effects of URO have been used successfully to prevent or revert incipient renal failure experimentally [8, 9], and in humans after liver transplantation [10] or cardiac surgery [10 ± 12], without appreciable side effects. Recently, UR
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