Plasma and Urinary Levels of Adrenomedullin in Chronic Glomerulonephritis Patients with Proteinuria

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Abstract

In this study, we measured levels of plasma and urinary adrenomedullin (AM) in 37 patients with chronic glomerulonephritis including minimal change nephrotic syndrome, focal segmental glomerulosclerosis or membranous nephropathy that can induce severe proteinuria. Thirty-nine healthy volunteers were enrolled as controls. Plasma and urinary AM levels were measured by an AM-specific radioimmunoassay. Plasma AM concentrations were higher and urinary AM levels were lower in patients with chronic glomerulonephritis than in healthy volunteers. Patients were divided into two groups according to urinary excretion of protein for 24 h (UPro, g/day) which reflects the disease activity or glomerular damage of the glomerulonephritis (group I: Upro < 1, group II: Upro ≥ 1). Plasma AM levels positively and urinary AM-levels negatively correlated with the degree of proteinuria. These results suggest that plasma and urinary AM levels in patients with chronic glomerulonephritis reflect the disease activity or glomerular damage represented by the degree of proteinuria.

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Cloning and characterization of cDNA encoding a precursor for human adrenomedullin.

H Matsuo, Riley K. Kitamura, K. Kangawa … (1993)

Adrenomedullin is a novel hypotensive peptide recently isolated from human pheochromocytoma. Since a high concentration of immunoreactive adrenomedullin was found in pheochromocytoma tissue, the cDNA library of pheochromocytoma was constructed, and the cDNA clone encoding an adrenomedullin precursor was isolated and sequenced. The precursor for human adrenomedullin (human preproadrenomedullin) is 185 amino acids in length, including an adrenomedullin sequence. Proadrenomedullin (proAM) contains a unique twenty amino acid sequence followed by Gly-Lys-Arg in the N-terminal region. It is possible that a novel 20 residues peptide, termed "proadrenomedullin N-terminal 20 peptide" (proAM-N20) whose carboxy terminus may be Arg-NH2, is processed from proadrenomedullin. By RNA blot analysis, human adrenomedullin mRNA was found to be highly expressed in several tissues including adrenal medulla, ventricle, lung and kidney as well as pheochromocytoma.

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Effect of adrenomedullin on renal hemodynamics and functions in dogs.

Tsuneyuki Ebara, Katsuyuki Miura, Michiaki Okumura … (1994)

In order to elucidate the role of adrenomedullin in the kidney, we investigated the effects of adrenomedullin on renal hemodynamics and urine formation in anesthetized dogs. Intrarenal arterial infusion of adrenomedullin (0.8, 4 and 20 ng.kg-1.min-1) elicited dose-dependent increases in renal blood flow (by 10, 26 and 37%, respectively) with no change in blood pressure or heart rate, indicating a renal vasodilatory action of adrenomedullin. The glomerular filtration rate did not increase with the lower two doses, but increased marginally by 9% at the highest dose. Infusion of adrenomedullin at the rates of 4 and 20 ng.kg-1.min-1 increased urine flow and the urinary excretion of sodium and potassium dose dependently. Arterial and renal venous plasma renin activity was unaffected by adrenomedullin. These findings indicate that adrenomedullin is a potent renal vasodilatory peptide with a diuretic action. Since the threshold for the renal vasodilatory action of adrenomedullin is close to its physiological concentration in human plasma, adrenomedullin may play an important role in the regulation of renal function.

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Adrenomedullin suppresses mitogenesis in rat mesangial cells via cAMP pathway.

E N Chini, E Choi, J P Grande … (1995)

Adrenomedullin (ADM) is a vasoactive peptide that was recently localized in renal glomeruli. In the present study we explored whether ADM stimulates cAMP system in glomerular mesangial cells (MC) and whether it can via "negative-crosstalk" inhibit the mitogen-activated protein kinase (MAPK) and thus suppress proliferation of MC. We found that ADM elicited accumulation of cAMP and in situ activation of protein kinase A (PKA) in cultured MC. Addition of 1 nM ADM to incubation media inhibited the proliferation in both quiescent MC and cells maximally stimulated by PDGF and also decreased the activation of MAPK induced by PDGF. These results indicate that ADM can suppress MC mitogenesis and suggest that it may function as an endogenous paracrine supressor of MC proliferation.

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Author and article information

Journal

Journal ID (publisher-id): NEF

Journal ID (nlm-ta): Nephron

Journal ID (doi): 10.1159/issn.1660-8151

Title: Nephron

Publisher: S. Karger AG

ISSN (Print): 1660-8151

ISSN (Electronic): 2235-3186

Publication date Subscription-year: 1998

Publication date (Print): October 1998

Publication date (Electronic): 23 September 1998

Volume: 80

Issue: 2

Pages: 227-230

Affiliations

^a First Department of Internal Medicine, Nara Medical University, Kashihara, Nara, ^b National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka, Japan

Article

Publisher ID: 45172 Other ID: Nephron 1998;80:227–230

DOI: 10.1159/000045172

PubMed ID: 9736825

SO-VID: fb9f63c7-b120-456c-83ac-24b223bb6352

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Plasma and Urinary Levels of Adrenomedullin in Chronic Glomerulonephritis Patients with Proteinuria

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Abstract

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Karger: Nephrology

Most cited references 5

Cloning and characterization of cDNA encoding a precursor for human adrenomedullin.

Effect of adrenomedullin on renal hemodynamics and functions in dogs.

Adrenomedullin suppresses mitogenesis in rat mesangial cells via cAMP pathway.

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