Urinary Adrenomedullin Levels Research Articles

Combined evaluation of plasma B-type natriuretic peptide and urinary liver-type fatty acid-binding protein/creatinine ratio is related to worsening renal function in patients undergoing elective percutaneous coronary intervention.

There are few reports on the significance for the combined evaluation of blood humoral factors and urinary biomarkers in terms of worsening renal function (WRF) after coronary angiography (CAG)/percutaneous coronary arterial intervention (PCI). Urinary liver type-fatty acid-binding protein (L-FABP), neutrophil gelatinase associated lipocalin (NGAL), and adrenomedullin (AM) were measured less than 24h before and 3h, 6h, 1day, and 2days after CAG/PCI. WRF was defined as a > 20% decrease in the estimated GFR. WRF occurred in seven of 100 patients and the increase in L-FABP/creatinine (Cr) at 1day after CAG/PCI was significantly higher in the WRF group than in the non-WRF group. Plasma B-type natriuretic peptide (BNP) before CAG/PCI and L-FABP/Cr at 1day after CAG/PCI were independent predictors for WRF. The areas under the receiver-operating characteristic curves were as follows: 0.760 for BNP before CAG/PCI, 0.731 for L-FABP/Cr at 1day after CAG/PCI, and 0.892 for BNP and L-FABP/Cr. Urinary AM levels after PCI/CAG were negatively correlated only to serum potassium levels. Gene expressions of AM and AM-receptor were detectable in renal tubule epithelial cells. AM increased intracellular second messenger levels in a dose-dependent manner. Our results suggest that combined evaluation of plasma BNP and urinary L-FABP/Cr is useful as a predictor of renal dysfunction in CAG/PCI patients.

Plasma and urinary adrenomedullin levels in children with acute pyelonephritis

Adrenomedullin (AM), a novel peptide recently isolated from pheochromocytoma, eliciting vasorelaxing activity, is the strongest among all known peptides. AM has been detected in the adrenal medulla, cardiac tissue, lung and kidney. Immunohistochemical studies have demonstrated the localization of AM in glomeruli, tubules and collecting cells of the kidney. Clinically, plasma and urinary AM levels are altered in patients with different renal disease. The present study aims to determine plasma and urinary AM levels in children with acute pyelonephritis (APN) and compare the results with a control group. The study group was comprised of 19 patients with APN aged 11.6 +/- 3.7 months (range, 6-18 months) and the control group consisted of 16 cases aged 11.5 +/- 3.2 months (range, 7-16 months). Acute pyelonephritis was diagnosed by clinical, laboratory and imaging methods. Plasma and urinary AM levels were measured by high performance liquid chromotography (HPLC). The plasma AM levels were lower in APN patients (33.40 +/- 2.27 pmol/mL) than in the control group (43.76 +/- 4.27 pmol/mL) (P < 0.001), whereas the urinary AM levels were higher in APN patients (248.58 +/- 140.63 pmol/mg urinary creatinine) than in the control group (49.42 +/- 45.23 pmol/mg) (P < 0.001). Coefficients of correlation between urinary AM levels and C-reactive protein and white blood cells were statistically significant (r = 0.472, P = 0.041; r = 0.555, P = 0.014, respectively). Adrenomedullin, a smooth muscle relaxant peptide that is synthesized in urinary tract tissue might have a role in acute pyelonephritis. However, the importance of AM in the pathogenesis of acute pyelonephritis remains to be determined by further detailed studies.

Plasma and urinary adrenomedullin levels in children with renal parenchymal scar and vesicoureteral reflux

Adrenomedullin (AM) is a strong vasodilator peptide with proven antimitogenic and antiproliferative effects in renal mesangial cells, as well as diuretic and natriuretic actions. Its gene expression is stimulated by endotoxins (lipopolysacharides) and cytokines. Consequently, its plasma and urinary levels are known to deviate from normal levels in many renal diseases. The purpose of this study is to determine plasma and urinary AM levels in children with renal parenchymal scar (RPS) and vesicoureteral reflux (VUR). The study was carried out on 74 children with recurrent urinary tract infections, arranged in groups: 25 patients with RPS with VUR (group I), 16 patients with RPS without VUR (group II), 12 patients with VUR without RPS (group III) and 21 healthy children as the control group. Plasma and urinary AM concentrations were both determined by high performance liquid chromotography (HPLC). Plasma AM was measured as picomoles per milliliter (pM/ml) and urinary AM as pM/mg urinary creatinine. In addition, serum creatinine, creatinine clearance and fractional sodium excretion (FE(Na)) were measured. All cases with RPS and VUR had normal blood pressure levels. The plasma AM levels were higher, although not significantly, in the control group (56.2+/-14.0 pM/ml) than in group I (50.6+/-4.2 pM/ml), group II (49.6+/-3.7 pM/ml) and group III (50.6+/-3.6 pM/ml) ( P =0.162). The urinary AM levels were higher in the control group (80.1+/-33.9 pM/mg) than in the three study groups (52+/-7.6 pM/mg, 58.6+/-7.5 pM/mg and 44.2+/-6.4 pM/mg; P =0.003, P =0.002 and P =0.002, respectively). There were no differences among the 4 groups (group I, group II, group III and the control group) in terms of FE(Na) and creatinine clearance ( P >0.05 and P >0.05, respectively). The finding that diminished urinary AM levels in patients with RPS and VUR implies that AM can be a prognostic factor in the long-term follow-up of cases with these diseases.

Adrenomedullin and total nitrite levels in children with acute rheumatic fever

Objective: To investigate the levels of adrenomedullin (AM) and total nitrite, a stable product of nitric oxide (NO), in children with acute rheumatic fever (ARF). Design and methods: Eleven children with ARF were investigated in comparison with 14 healthy controls. Adrenomedullin was detected by HPLC, while total nitrite was quantitated by the Griess reaction. Results: Plasma urinary AM and total nitrite levels were significantly higher in children with ARF, irrespective of whether they were in the acute or convalescent phase of disease. Plasma AM (pmol/mL) levels were 49.19 ± 3.23 in the acute phase, 44.52 ± 4.26 in the convalescent phase, 35.49 ± 3.43 in controls, and urinary AM excretion (pmol/mg creatinine) was 43.45 ± 18.40 in the acute phase, 32.38 ± 15.37 in the convalescent phase, and 24.84 ± 11.38 in controls. Plasma total nitrite levels (μmol/L) were 75.37 ± 13.13 in the acute phase, 59.81 ± 12.78 in the convalescent phase, and 41.09 ± 10.27 in controls. Urinary total nitrite excretion (μmol/mg creatinine) was 3.82 ± 1.56 in the acute phase, 2.15 ± 0.58 in the convalescent phase, and 1.33 ± 0.61 in controls. The differences were statistically significant for all ( P < 0.05). Conclusion: This study considered that AM and NO may have a role in the immunoinflammatory process of ARF.

Adrenomedullin and nitrite levels in children with Bartter syndrome.

Children with Bartter syndrome have lower than normal vascular reactivity with normotension in spite of biochemical and hormonal abnormalities which are typical of hypertension. Nitric oxide (NO) is a potent endogenous vasodilator, and plays an important role in the control of vascular tone. Adrenomedullin (AM) is a novel hypotensive peptide originally isolated from human pheochromocytoma. The possible role of NO and AM in maintaining this reduced vascular reactivity was examined by studying plasma and urinary nitrite, a stable metabolite of NO, and AM levels in ten children with Bartter syndrome, ten healthy controls, and five children with hypokalemia of causes other than Bartter syndrome (pseudo-Bartter). Urinary excretion of nitrite (mumol/mg urinary creatinine) was 8.9 +/- 1.2 in children with Bartter syndrome, 4.7 +/- 0.9 in healthy controls, and 2.9 +/- 0.8 in pseudo-Bartter (P < 0.05). Plasma nitrite levels (mumol/l) were 101.9 +/- 23.4, 59.9 +/- 14.7, and 65.0 +/- 29.7, respectively (P < 0.05), in the three groups. Urinary excretion of AM (pmol/mg urinary creatinine) was 187 +/- 40, 65 +/- 10, and 160 +/- 50, respectively (P < 0.05), in the three groups. Plasma AM levels were 47.4 +/- 1.8, 39.9 +/- 5.9, and 42.4 +/- 3.9, respectively (P > 0.05), in the three groups. The same parameters were repeated in the two groups of controls and in the Bartter patients in the 6th month of therapy. Urinary nitrite and AM levels were still higher in the Bartter patients than in the other groups. We conclude that in Bartter syndrome the increased NO production may be responsible for the reduced vascular response of the disease. Initially, increased levels of AM in Bartter syndrome and pseudo-Bartter may be a compensatory response to acute hypokalemia; however, continuation of a high level of urinary excretion of AM in children with Bartter syndrome may suggest also the possible role of AM in the reduced vascular response of the disease.

Adrenomedullin and nitrite levels in children with minimal change nephrotic syndrome.

Nitric oxide (NO) serves many functions within the kidney, and recent evidence suggests that NO contributes to glomerular injury. Adrenomedullin (AM) is a novel hypotensive peptide originally isolated from human pheochromocytoma. Recent studies showed that plasma AM concentrations correlated with the extent of proteinuria. We have examined the possible role of these two agents by studying plasma and urinary total nitrite (NO-2 + NO-3) and AM levels in children with minimal change nephrotic syndrome (MCNS). In comparison with healthy controls, children with MCNS had increased urinary nitrite excretion (micromol/mg urinary creatinine), irrespective of whether the disease was in relapse or remission (3.2+/-0.2 in relapse, n=13; 1.9+/-0.3 in remission, n=12; 1.0+/-0.2 in controls, n=10, P<0.05). Plasma nitrite levels (micromol/l) were high in relapse compared with controls (53.2+/-8.7 vs. 32+/-4.0, P<0.05). Plasma AM levels (pmol/ml) were decreased in relapse (27.6+/-1.4 in relapse, 43.3+/-1.2 in remission, 41.5+/-1.6 in controls, P<0.05). Urinary AM levels (pmol/mg urinary creatinine) were significantly higher in relapse than in remission and in controls (156+/-43 in relapse, 56+/-18 in remission, 36+/-16 in controls, P<0.05). Our data indicate that NO may play a role in mediating the clinical manifestations of MCNS in children. However, changes in AM levels may be the result of heavy proteinuria.

Increased urinary levels of adrenomedullin in patients with cystitis.

In this study, we examined urinary levels of adrenomedullin (AM) in 18 healthy volunteers and 18 patients with cystitis. We also compared urinary levels of AM in 11 patients with cystitis before and after antibiotic treatment. Urinary AM concentrations were measured by a radioimmunoassay specific for human AM. Urinary AM levels in patients with cystitis were significantly elevated compared with those of healthy volunteers and correlated positively with the number of urine leukocytes. By antibiotic treatment, urinary AM levels significantly decreased as compared with before the treatment. By RNA blot analysis of AM transcript, we detected significant levels of AM mRNA in canine urinary bladder and ureter. Intravenous administration of lipopolysaccharide elevated the AM mRNA level in the urinary bladder. These data suggest that infection and inflammation stimulate AM production in the urinary tract, which results in increased urinary AM levels in patients with cystitis. Based on these results, it is deduced that AM participates in the pathophysiology of cystitis, and its urinary level could be used as an index of the degree of cystitis.

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

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.

Measurement of Plasma and Urinary Adrenomedullin in Patients with IgA Nephropathy

In this study, we measured plasma and urinary adrenomedullin (AM) concentrations in 47 patients with IgA nephropathy. Controls were 39 healthy volunteers. Plasma and urinary AM values were measured by specific radioimmunoassay. The plasma AM concentrations were higher, and the urinary AM levels were lower in patients with IgA nephropathy than in healthy volunteers. Plasma AM concentrations showed a positive correlation with serum creatinine and blood urea nitrogen, whereas urinary AM levels correlated negatively with serum creatinine and blood urea nitrogen. The plasma AM concentrations showed a positive correlation with fractional excretions of sodium and potassium. Renal biopsy specimens of patients without renal failure were scored for activity (percentage of glomeruli demonstrating cellular crescent formation, degree of mesangial proliferation and interstitial infiltration; total score = 9). Urinary AM levels were shown to be lower in the group with a high activity (score 3–9) as compared with the group with a low activity (score 0–2) based on renal biopsy. Thus, urinary levels of AM are affected by the degree of the activity in IgA nephropathy, and AM may participate in the pathophysiology of IgA nephropathy.

Decrease in circulating and urine adrenomedullin concentrations in stroke-prone spontaneously hypertensive rats.

Adrenomedullin (AM) is a peptide with potent vasodilatory and hypotensive properties. Plasma AM levels in rats with experimentally induced hypertension, such as Dahl salt-sensitive rats and two-kidney, one-clip hypertensive rats, are higher than those in normotensive rats. We previously noted, however, that plasma AM levels in spontaneously hypertensive rats (SHR) are similar to those in Wistar-Kyoto rats. To define the role of AM in rats with severe hypertension, we investigated changes in circulating and tissue AM levels in stroke-prone spontaneously hypertensive rats (SHRSP/Izm). The immunoreactive rat AM levels in plasma, urine, and tissue measured with a sensitive radioimmunoassay, and the AM mRNA levels in various tissues in 15-wk-old SHRSP/Izm were compared with those in age-matched Wistar-Kyoto rats (WKY/Izm). The plasma and urinary AM levels in SHRSP/Izm were significantly lower than those in WKY/Izm [plasma AM, 2.14+/-0.06 (SE) vs. 3.24+/-0.16 fmol/ml, p< 0.001; urinary AM, 16.36+/-3.21 vs. 36.12+/-6.09 fmol/ml, p< 0.01]. A negative correlation was found between the plasma AM level and the systolic blood pressure in both SHRSP/Izm and WKY/Izm. Reverse-phase high-performance liquid chromatography showed that the molecular components of plasma immunoreactive AM in SHRSP/Izm were similar to those in WKY/Izm. Furthermore, tissue AM levels in various organs in SHRSP/Izm were not lower than those in WKY/Izm. In conclusion, low levels of circulating AM may contribute to the maintenance of high blood pressure in 15-wk-old SHRSP/Izm. These low plasma AM levels may be caused by accelerated metabolism of circulating AM in SHRSP/Izm.