Urodilatin (Ularitide, INN): A Renal Natriuretic Peptide

Forssmann, Wolf‐Georg

doi:10.1159/000188459

Cited by 27 publications

(18 citation statements)

References 49 publications

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“…The precise mechanism for the increased excretion of urodilatin in the urine is not clear. Generally the renal production of urodilatin is related to changes in prerenal arterial pressure/effective arterial volume [11]. A direct release of urodilatin from renal tubular cells triggered by hyperosmolality, which could have contributed to the radiocontrast-induced urodilatin excretion in the present study, is a possibility.…”

Section: Figmentioning

confidence: 69%

“…1). Urodilatin is exclusively found in urine and in the kidney suggesting that it participates in the intrarenal regulation of sodium homoeostasis in a paracrine manner, but its physiological function is still incompletely understood [10,11]. Since urodilatin appears to contribute to the sodium excretion during hypervolaemic states [12], we hypothesized that the radiocontrast-induced diuresis may be associated with an increased urodilatin excretion.…”

Section: Introductionmentioning

confidence: 99%

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Radiocontrast‐induced natriuresis associated with increased urinary urodilatin excretion

Haller

Meyer²,

Scheele

et al. 1998

Journal of Internal Medicine

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Abstract. Haller C, Meyer M, Scheele T, Koch A, Forssmann W-G and Kübler W (University of Heidelberg; and Lower Saxony Institute for Peptide Research, Hanover; Germany). Radiocontrastinduced natriuresis associated with increased urinary urodilatin excretion (original article). J Intern Med 1998; 243: 155-62.Objective. Intravascular radiocontrast agents induce a pronounced diuresis. The aim of the present study was to investigate the (patho-)physiological mechanisms of the radiocontrast-induced diuresis. Design. The fractional excretion of sodium, the urinary excretion of the renal natriuretic peptide urodilatin and the plasma concentration of atrial natriuretic peptide were measured in 42 unselected patients immediately before and after intravascular radiocontrast administration during coronary angiography. Setting. Cardiac catheterization laboratory of a university hospital. Results. After angiography both the plasma concentration of atrial natriuretic peptide (median post-pre difference: 3.9 pmol L Ϫ1 , quartiles Ϫ1.2; 7.0) and the urinary excretion of urodilatin (median post-pre difference: 67.0 nmol urodilatin/mol creatinine, quartiles 39.7; 152.1) were increased. The urinary urodilatin excretion was correlated with an increase in the fractional excretion of sodium (median post-pre difference: 1.7%, quartiles 0.6; 3.1). There was no correlation between the serum concentration of atrial natriuretic peptide and urinary sodium excretion. For the radiocontrast-induced increase in both urodilatin and sodium excretion there was no indication for differences between patients without (31) and with (11) intravenous saline infusion. Conclusion. The radiocontrast-induced diuresis is a natriuresis which is associated with an increased urinary excretion of urodilatin. The association between natriuresis and urinary urodilatin excretion irrespective of baseline volume status corroborates the hypothesis that urodilatin contributes to the sodium excretion after radiocontrast administration in a paracrine manner. This finding has pathophysiological and potentially therapeutic implications in radiocontrast-induced nephropathy.

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Section: Figmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Radiocontrast‐induced natriuresis associated with increased urinary urodilatin excretion

Haller

Meyer²,

Scheele

et al. 1998

Journal of Internal Medicine

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“…With the aid of a spe cific radioimmunoassay for URO, it was shown that circulating levels of URO in humans are below the detection limit . In contrast to the endocrine action of ANP, URO is therefore likely to act as a paracrine renal hor mone [Forssmann, 1995;Valentin and Humph reys, 1993].…”

Section: S Tru Ctu Re Synthesis and F Unction O F N A Triu Re Tic mentioning

confidence: 99%

“…Moreover, the fixed relationship between the vasorelaxant, hypotensive on one hand and the natriuretic properties on the other hand re strict their flexibility as pharmacological tools. Nevertheless, URO has been successfully used to prevent acute renal failure after liver and heart transplantation [Ccdidi et al, 1993;Forssmann, 1995]. The beneficial effects of URO as compared with those of ANP are attributed to its smaller hypotensive action at a similar natriuretic dose.…”

Section: P Hysiological Role O F Uromentioning

confidence: 99%

Urodilatin and the Control of Renal Microcirculation

Endlich

Steinhausen²

1997

Blood Purif

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“…Urodilatin is a natriuretic peptide produced by the kidney with structural similarity to A-type natriuretic peptide involved in the regulation of body fluid volume and electrolyte balance. Comparable to A-type natriuretic peptides, urodilatin binds to particulate guanylate cyclase-linked receptors leading to an increase in intracellular cyclic guanosine monophosphate (cGMP) levels leading to vasodilation and a decrease in renal sodium absorption [28,29] . Additionally, urodilatin has been shown to decrease plasma angiotensin II as well as aldosterone levels, acting as a functional antagonist of the RAAS.…”

Section: Introductionmentioning

confidence: 99%

Urodilatin and Pentoxifylline Prevent the Early Onset of <i>Escherichia coli</i>-Induced Acute Renal Failure in a Model of Isolated Perfused Rat Kidney

Groesdonk

Bauer²,

Kreft³

et al. 2009

Kidney Blood Press Res

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Background/Aims: Raised cytokine levels and a hypoperfusion-associated decrease in glomerular filtration rate (GFR) are hallmarks of the genesis of septic acute renal failure (ARF). Therefore, anti-inflammatory as well as renal vasodilating therapeutic strategies may afford renal protection during septic ARF. The present study was designed to determine the effects of administration of urodilatin, pentoxifylline and theophylline to improve renal function in an ex-vivo model of ‘septic renal injury’. Methods: Eight series of experiments were performed: no intervention, perfusion with a suspension containing Escherichia coli bacteria (strain 536/21); E. coli + 10 μg/l urodilatin, E. coli + 20 μg/l urodilatin, E. coli + 100 μM theophylline, E. coli + 100 μM pentoxifylline and E. coli + URO 20 μg/l given 90 min after start of perfusion. Renal vascular and glomerular functional parameters as well as TNF-α release were analyzed up to 180 min. Results: Perfusion with E. coli caused an acute deterioration of renal vascular and glomerular function. URO 20 μg/l and PTX decreased renal vascular resistance (RVR) from 83.7 ± 18.4 to 9.2 ± 1.1 and 8.6 ± 2.2 mm Hg/ml/min/g kidney and increased renal perfusion flow rate (PFR) from 8.2 ± 1.5 to 14.6 ± 0.8 and 14.1 ± 2.2 ml/min/g kidney. As a result, GFR improved from 102.1 ± 15.6 to 442 ± 48.3 and 525.8 ± 57 μl/min/g kidney during treatment with URO 20 μg/l and PTX, respectively. Renal TNF-α release was significantly reduced by URO 20 μg/l (from 178 ± 23 to 45.2 ± 2 and 47 ± 3 pg/ml) in the E. coli + URO 20 μg/l and by PTX in the E. coli + PTX group if added to the perfusion medium upon start of perfusion. Interestingly, URO 20 μg/l also decreased RVR significantly from 62.2 ± 6.1 to 35.9 ± 6.0 mm Hg/ml/min/g kidney, improved PFR from 5.4 ± 1.0 to 8.7 ± 1.0 ml/min/g kidney, increased GFR from 160 ± 43.3 to 280.7 ± 27.9 μl/min/g kidney, and decreased TNF-α release to 122 ± 18 pg/ml if applied 90 min after induction of septic ARF. In contrast, URO 10 μg/l did not significantly increase urine flow and did not appear to significantly improve renal perfusion. Theophylline showed no beneficial effects at all. Conclusion: This suggests that urodilatin and pentoxifylline might be useful to protect renal function if given before a septic renal insult. Additionally, treatment with urodilatin is capable of restoring renal function in early Gram-negative sepsis-induced ARF even if given after the septic insult.

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Urodilatin (Ularitide, INN): A Renal Natriuretic Peptide

Cited by 27 publications

References 49 publications

Radiocontrast‐induced natriuresis associated with increased urinary urodilatin excretion

Radiocontrast‐induced natriuresis associated with increased urinary urodilatin excretion

Urodilatin and the Control of Renal Microcirculation

Urodilatin and Pentoxifylline Prevent the Early Onset of <i>Escherichia coli</i>-Induced Acute Renal Failure in a Model of Isolated Perfused Rat Kidney

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