adrenomedullin and Renal-Insufficiency

Heart failure is a major burden to the health care system in terms of not only cost, but also morbidity and mortality. Appropriate use of biomarkers is critically important to allow rapid identification and optimal risk stratification and management of patients with both acute and chronic heart failure. This review will discuss the biomarkers that have the most diagnostic, prognostic, and therapeutic value in patients with heart failure. We will discuss established biomarkers such as natriuretic peptides as well as emerging biomarkers reflective of myocyte stress, myocyte injury, extracellular matrix injury, and both neurohormonal and cardio-renal physiology.

Topics: Adrenomedullin; Biomarkers; Cost-Benefit Analysis; Cystatin C; Disease Progression; Early Diagnosis; Extracellular Matrix; Female; Galectin 3; Glycopeptides; Heart Failure; Hepatitis A Virus Cellular Receptor 1; Humans; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Interleukins; Male; Membrane Glycoproteins; Muscle Cells; Natriuretic Peptides; Neurotransmitter Agents; Peptide Fragments; Predictive Value of Tests; Prognosis; Protein Precursors; Receptors, Cell Surface; Receptors, Virus; Renal Insufficiency

Adrenomedullin (AM) is a vasodilator peptide that originally isolated from pheochromocytoma tissue. However, the mRNA is expressed in the normal adrenal gland, heart, kidney and blood vessels. The human AM gene is located in the short arm of chromosome 11 and is composed of 4 exons. There are 2 single nucleotide polymorphisms in introns 1 and 3, and the 3'-end of the AM gene is flanked by a microsatellite marker of cytosine-adenine repeats that is associated with an increased risk of developing hypertension and diabetic nephropathy. AM gene expression is promoted by various stimuli, including inflammation, hypoxia, oxidative stress, mechanical stress and activation of the renin-angiotensin and sympathetic nervous systems. The AM gene promoter region possessed binding site for several transcription factors, including nuclear factor for interleukin-6 expression (NF-IL6) and activator protein 2 (AP-2). Further, plasma AM levels are increased in patients with various cardiovascular diseases, including hypertension, heart failure and renal failure. These findings suggest that AM plays a role in the development of or response to cardiovascular disease. Indeed, experimental and clinical studies have demonstrated that systemic infusion of AM may have a therapeutic effect on myocardial infarction, heart failure and renal failure. Further, vasopeptidase inhibitors which augment the bioactivity of endogenous AM may benefit patients with hypertension and arteriosclerosis. Finally, the angiogenic and cytoprotective properties of AM may have utility in revascularization and infarcted myocardium and ischemic limbs. Because of the potential clinical benefits of AM, indications for use and optimal dosing strategies should be established.

Topics: Adrenomedullin; Amino Acid Sequence; Animals; Carcinogens; Cardiovascular Diseases; Cell Transplantation; Genetic Therapy; Heart Failure; Humans; Hypertension; Hypertension, Pulmonary; Molecular Sequence Data; Myocardial Infarction; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Renal Insufficiency; Renin-Angiotensin System; Signal Transduction

Doxorubicin (DOX) is an anticancer antibiotic which has various effects in human cancers. It is one of the commonly known causes of drug-induced nephrotoxicity, which results in acute renal injury. Adrenomedullin (ADM), a vasodilator peptide, is widely distributed in many tissues and has potent protective effects. Therefore, the current study aimed to examine the protective potential mechanisms of ADM against DOX-induced nephrotoxicity. A total of 28 male Wistar rats were randomized into four groups: control group, doxorubicin group (15 mg/kg single intraperitoneal injection of DOX), adrenomedullin + doxorubicin group (12 μg/kg/day intraperitoneal injection of ADM) 3 days prior to DOX injection and continuing for 14 days after the model was established, and adrenomedullin group. Kidney function biomarkers, oxidative stress markers, and inflammatory mediators (TNF-α, NLRP3, IL-1β, and IL-18) were assessed. The expressions of gasdermin D and ASC were assessed by real-time PCR. Furthermore, the abundances of caspase-1 (p20), Bcl-2, and Bax immunoreactivity were evaluated. ADM administration improved the biochemical parameters of DOX-induced nephrotoxicity, significantly reduced oxidative damage markers and inflammatory mediators, and suppressed both apoptosis and pyroptosis. These results were confirmed by the histopathological findings and revealed that ADM's antioxidant, anti-inflammatory, anti-apoptotic, and anti-pyroptotic properties may have prospective applications in the amelioration of DOX-induced nephrotoxicity.

Topics: Adrenomedullin; Animals; Apoptosis; Doxorubicin; Inflammation; Inflammation Mediators; Male; Oxidative Stress; Pyroptosis; Rats; Rats, Wistar; Renal Insufficiency

Following the SEPSIS-3 consensus, detection of organ failure as assessed by the SOFA (Sequential Organ Failure Assessment) score, is mandatory to detect sepsis. Calculating SOFA outside of the Intensive Care Unit (ICU) is challenging. The alternative in this scenario, the quick SOFA, is very specific but less sensible. Biomarkers could help to detect the presence of organ failure secondary to infection either in ICU and non-ICU settings.. We evaluated the ability of four biomarkers (C-Reactive protein (CRP), lactate, mid-regional proadrenomedullin (MR-proADM) and procalcitonin (PCT)) to detect each kind of organ failure considered in the SOFA in 213 patients with infection, sepsis or septic shock, by using multivariate regression analysis and calculation of the area under the receiver operating curve (AUROC).. In the multivariate analysis, MR-proADM was an independent predictor of five different failures (respiratory, coagulation, cardiovascular, neurological and renal). In turn, lactate predicted three (coagulation, cardiovascular and neurological) and PCT two (cardiovascular and renal). CRP did not predict any of the individual components of SOFA. The highest AUROCs were those of MR-proADM and PCT to detect cardiovascular (AUROC, CI95%): MR-proADM (0.82 [0.76-0.88]), PCT (0.81 [0.75-0.87] (P < .05) and renal failure: MR-proADM (0.87 [0.82-0.92]), PCT (0.81 [0.75-0.86]), (P < .05). None of the biomarkers tested was able to detect hepatic failure.. In patients with infection, MR-proADM was the biomarker detecting the largest number of SOFA score components, with the exception of hepatic failure.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Area Under Curve; Blood Coagulation Disorders; C-Reactive Protein; Cardiovascular Diseases; Female; Heart Failure; Humans; Infections; Intensive Care Units; Lactic Acid; Liver Failure; Male; Middle Aged; Multivariate Analysis; Nervous System Diseases; Organ Dysfunction Scores; Peptide Fragments; Procalcitonin; Protein Precursors; Renal Insufficiency; Respiratory Insufficiency; ROC Curve; Sepsis; Shock, Septic

Patients undergoing vascular surgery are prone to perioperative organ injury because of both higher prevalence of cardiovascular risk factors and the extent of surgery. Early detection of organ failure is essential to facilitate appropriate medical care. Midregional pro-adrenomedullin (MR-proADM) has been investigated in acute medical care settings to guide clinical decision-making regarding patient pathways and to identify patients prone to imminent cardiovascular or inflammatory complications. In this study, we evaluated the impact of perioperative MR-proADM levels as an early marker of perioperative cardiovascular and inflammatory stress reactions and kidney injury.. The study was conducted as a monocentric, prospective, noninterventional trial at Hannover Medical School, Germany. A total of 454 consecutive patients who underwent open vascular surgery were followed from the day prior to until 30 days after surgery. The composite primary end point was defined as the occurrence of major adverse cardiac events (MACEs), acute kidney injury (AKI), or systemic inflammatory response syndrome (SIRS). Measurements were correlated with both medical history and postoperative MACE, AKI, or SIRS using univariate and multivariate regression analysis.. One hundred thirty-nine (31%) of the patients reached the primary end point within the study interval. Midregional pro-adrenomedullin change was associated with the combined primary end point and with the intensity of surgical trauma. Midregional pro-adrenomedullin change was increased in patients reaching the secondary end points, SIRS (optimal cutoff: 0.2 nmol/L) and AKI (optimal cutoff: 0.7 nmol/L), but not in patients with MACEs.. Increased levels of MR-proADM within the perioperative setting (1) were linked to the invasiveness of surgery and (2) identified patients with ongoing loss of renal function. Increased MR-proADM levels may therefore identify a subgroup of patients prone to excessive cardiovascular stress but did not directly correlate with adverse cardiac events. Consistently low levels of MR-proADM may identify a subgroup of patients with acceptable low risk to guide discharge from high-density care units.

Topics: Adrenomedullin; Aged; Aged, 80 and over; Biomarkers; Critical Pathways; Female; Humans; Intraoperative Complications; Male; Middle Aged; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Protein Precursors; Renal Insufficiency; Systemic Inflammatory Response Syndrome; Vascular Surgical Procedures

Oliguria is a common symptom in critically ill patients and puts patients in a high risk category for further worsening renal function (WRF). We performed this study to explore the predictive value of biomarkers to predict WRF in oliguric intensive care unit (ICU) patients.. Single-center prospective observational study. ICU patients were included when they presented a first episode of oliguria. Plasma and urine biomarkers were measured: plasma and urine neutrophil gelatinase-associated lipocalin (pNGAL and uNGAL), urine α1-microglobulin, urine γ-glutamyl transferase, urine indices of tubular function, cystatin C, C terminal fragment of pro-arginine vasopressin (CT-ProAVP), and proadrenomedullin (MR-ProADM).. One hundred eleven patients formed the cohort, of whom 41 [corrected] had worsening renal function. Simplified Acute Physiology Score (SAPS) II was 41 (31-51). WRF was associated with increased mortality (hazard ratio 8.65 [95 % confidence interval (CI) 3.0-24.9], p = 0.0002). pNGAL, MR-ProADM, and cystatin C had the best odds ratio and area under the receiver-operating characteristic curve (AUC-ROC: 0.83 [0.75-0.9], 0.82 [0.71-0.91], and 0.83 [0.74-0.90]), but not different from serum creatinine (Screat, 0.80 [0.70-0.88]). A clinical model that included age, sepsis, SAPS II, and Screat had AUC-ROC of 0.79 [0.69-0.87]; inclusion of pNGAL increased the AUC-ROC to 0.86 (p = 0.03). The category-free net reclassification index improved with pNGAL (total net reclassification index for events to higher risk 61 % and nonevents to lower 82 %).. All episodes of oliguria do not carry the same risk. No biomarker further improved prediction of WRF compared with Screat in this selected cohort of patients at increased risk defined by oliguria.

Topics: Acute-Phase Proteins; Adrenomedullin; Aged; Alpha-Globulins; Biomarkers; Cystatin C; Disease Progression; Female; gamma-Glutamyltransferase; Glycopeptides; Humans; Intensive Care Units; Kidney Function Tests; Lipocalin-2; Lipocalins; Male; Middle Aged; Oliguria; Organ Dysfunction Scores; Predictive Value of Tests; Prospective Studies; Protein Precursors; Proto-Oncogene Proteins; Renal Insufficiency

We investigated the relationship between plasma mid-regional pro-adrenomedullin (MR-proADM)-like immunoreactive substance (IS) level and clinical characteristics associated with renal failure or resistance to antihypertensive therapy in stable kidney transplant recipients. Forty-six Japanese kidney transplant recipients who underwent transplantation more than 90 days prior to the study were included. To evaluate resistance to antihypertensive therapy, we calculated the treatment intensity score of the antihypertensive drugs in each recipient. Morning blood samples were collected and plasma MR-proADM-IS levels were measured using an enzyme immunoassay. A significant correlation was observed between plasma MR-proADM-IS level with creatinine clearance or treatment intensity score. Multiple regression analysis identified plasma MR-proADM level and body mass index as significant independent factors associated with treatment intensity score. Plasma MR-proADM level may be a useful biomarker indicating the degree of resistance to antihypertensive therapy.

Topics: Adolescent; Adrenomedullin; Adult; Aged; Antihypertensive Agents; Creatinine; Drug Resistance; Female; Humans; Kidney Transplantation; Male; Middle Aged; Peptide Fragments; Protein Precursors; Renal Insufficiency; Transplantation

We evaluated the effects of adrenomedullin (Peptide Institute, Minoh-shi, Osaka, Japan) on mediators, including nitric oxide and transforming growth factor-beta, and parameters of renal injury in a murine unilateral ureteral obstruction model.. Three study groups of control, adrenomedullin treated and adrenomedullin plus L-NAME treated BALB/C mice, respectively, underwent left unilateral ureteral obstruction. A 24-hour urine sample was collected to measure urinary NO(2)/NO(3) 1 day before unilateral ureteral obstruction and kidneys were harvested on postoperative day 14. Tubulointerstitial damage markers were evaluated by immunohistochemistry. Tissue transforming growth factor-beta was determined by enzyme-linked immunosorbent assay. Endothelial and inducible nitric oxide synthase immunolocalization was also determined.. Urinary NO(2)/NO(3) was significantly higher in the adrenomedullin group than in controls, confirming increased renal nitric oxide production. Immunohistochemistry showed increased endothelial nitric oxide synthase in vascular endothelial cells in the adrenomedullin group but tissue transforming growth factor-beta did not significantly differ in controls vs the adrenomedullin group. Interstitial collagen deposition and fibroblasts in the obstructed kidney were significantly decreased in the adrenomedullin group. The number of leukocytes and apoptotic cells in the obstructed kidney were significantly decreased by adrenomedullin. Renal injury amelioration resulting from adrenomedullin was blunted by the nitric oxide synthase inhibitor L-NAME.. Adrenomedullin increased renal nitric oxide, and suppressed tubular apoptosis, interstitial fibrosis and inflammatory cell infiltration in mice with unilateral ureteral obstruction. The renoprotective peptide adrenomedullin may be useful for that condition.

Topics: Adrenomedullin; Animals; Mice; Mice, Inbred BALB C; Nitric Oxide; Renal Insufficiency; Transforming Growth Factor alpha; Ureteral Obstruction

Adrenomedullin 2/intermedin (AM2/IMD) is a potent vasodilator peptide with organ-protective effects and is abundantly expressed in the kidney. We examined the expression of AM2/IMD in the kidneys of rats with hypertension or chronic renal impairment using quantitative RT-PCR, radioimmunoassay, and immunohistochemistry. Kidneys of 8-wk-old male spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were dissected into inner medulla, outer medulla, cortex, and glomerulus fractions. A rat renal impairment model was prepared by 5/6 nephrectomy in WKY rats. AM2/IMD mRNA levels were the highest in the cortex among four renal portions, and significantly lower in SHR than WKY rats in all renal portions. In the remnant kidneys of 5/6 nephrectomized rats, AM2/IMD mRNA levels were significantly decreased on days 3 and 56, whereas mRNA levels of calcitonin receptor-like receptor, receptor activity-modifying proteins-1 and -2, which form receptor for AM and AM2/IMD, were increased, compared with that in sham-operated rats. AM mRNA levels were decreased on day 3, but increased on day 56, after nephrectomy. Decreased immunoreactive AM2/IMD levels in the remnant kidneys of 5/6 nephrectomized rats on day 56 were confirmed by radioimmunoassay. The renal tubules were immunostained with anti-AM2/IMD antibody, with a decreased AM2/IMD immunostaining found in proximal tubular cells of 5/6 nephrectomized rats compared with sham-operated rats. In conclusion, intrarenal AM2/IMD expression is decreased in SHR and 5/6 nephrectomized rats. Given the organ-protective effects of AM2/IMD, the downregulation of AM2/IMD as an endogenous regulatory peptide may have a role in the progression of renal impairment.

Topics: Adrenomedullin; Animals; Calcitonin Receptor-Like Protein; Disease Models, Animal; Down-Regulation; Hypertension; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Kidney; Male; Membrane Proteins; Nephrectomy; Neuropeptides; Radioimmunoassay; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor Activity-Modifying Proteins; Receptors, Calcitonin; Renal Insufficiency; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors

Adrenomedullin (AM) is a hypotensive peptide widely produced in the cardiovascular organs and tissues such as the heart, kidney, and the vascular cells. We have previously cloned and sequenced the genomic DNA encoding human AM gene, and determined that the gene is located in the short arm of chromosome 11. The 3'-end of the gene is flanked by the microsatellite marker of cytosine adenine (CA) repeats. In this study, we investigated the association between DNA variations in AM gene and the predisposition to develop nephropathy in type 2 diabetes mellitus.. Genomic DNA was obtained from the peripheral leukocytes of 233 normal healthy subjects (NH), 139 type 2 diabetic patients on hemodialysis (DM-HD), 106 control patients with type 2 diabetes without nephropathy (DM-C) and 318 hemodialysis patients due to chronic glomerulonephritis (CGN-HD). The genomic DNA was subject to polymerase chain reaction (PCR) using a fluorescence-labeled primer, and the number of CA repeats were determined by polyacrylamide gel electrophoresis (PAGE).. In our Japanese subjects, there existed four types of alleles with different CA-repeat number; 11, 13, 14, and 19. The frequencies of these alleles were 11: 27.7%, 13: 32.8%, 14: 35.6%, and 19: 3.9% in NH. These allele frequencies were not significantly different in DM-C and CGN-HD. However, DM-HD showed significantly different distribution of allele frequency from other groups (chi 2 = 18.9, P = 0.026). Namely, the frequency of 19-repeat allele in DM-HD was higher (9.0%) than NH, DM-C, and CGN-HD (P = 0.005, 0.041, and 0.004, respectively).. The microsatellite DNA polymorphism of AM gene may be associated with the genetic predisposition to develop nephropathy in Japanese patients with type 2 diabetes mellitus.

Topics: Adrenomedullin; Adult; Aged; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Japan; Male; Microsatellite Repeats; Middle Aged; Peptides; Polymorphism, Genetic; Renal Insufficiency

Adrenomedullin (AM) is a potent vasodilating and natriuretic peptide that is thought to play important roles in cardiovascular function. Whether or not AM is involved in the development of cardiac hypertrophy and renal damage remains controversial. In the present study, using heterozygote knockout mice of the AM gene (AM +/-), we analyzed the physiological and pathological roles of the endogenous AM gene. There were no differences in body size or heart and kidney weight compared with wild-type (AM +/+) mice. However, angiotensin II (Ang II) infusion resulted in more severe cardiac hypertrophy in AM +/- mice. The increases in the heart weight-to-body weight ratio and wall thickness of the left ventricle were more prominent in the AM +/- mice. Renal dysfunction characterized by decreased creatinine clearance (C(cr)) was more severe in AM +/- after Ang II infusion. These results suggest that AM plays critical roles in the defense mechanism against cardiac hypertrophy and renal dysfunction. An improved understanding of these roles may pave the way to a novel pharmacological approach for the prevention of cardiovascular diseases.

Topics: Adrenomedullin; Angiotensin II; Animals; Cardiomegaly; Male; Mice; Mice, Knockout; Peptides; Renal Insufficiency; Time Factors; Vasoconstrictor Agents; Vasodilator Agents

The present study was designed to examine whether chronic adrenomedullin infusion has renoprotective effects in hypertensive renal failure and the mechanism by which chronic adrenomedullin infusion exerts its effects. Dahl salt-sensitive rats and Dahl salt-resistant rats were fed a high salt diet starting at 6 weeks of age. Recombinant human adrenomedullin or vehicle was infused for 7 weeks in 11-week-old Dahl salt-sensitive rats. Dahl salt-resistant rat was used as a control. After 7 weeks, untreated Dahl salt-sensitive rats were characterized by decreased kidney function, abnormal morphological findings, increased hormone levels, increased renal tissue angiotensin II levels, and altered mRNA expressions of transforming growth factor beta (TGF-beta) and components of the renin-angiotensin system compared with Dahl salt-resistant rats. Chronic adrenomedullin treatment significantly improved renal function (serum creatinine -87%, creatinine clearance +114%, urinary protein excretion -59%) and histological findings (glomerular injury score -54%) without changing mean arterial pressure compared with untreated Dahl salt-sensitive rats. Interestingly, long-term human adrenomedullin infusion decreased the endogenous rat adrenomedullin level (-97%) with a slight increase of human adrenomedullin level. Chronic adrenomedullin treatment also significantly inhibited the increase of plasma renin concentration (-269%), aldosterone level (-82%), and renal tissue angiotensin II levels (-60%). Furthermore, adrenomedullin infusion significantly decreased the increases of mRNA expressions of TGF-beta (- 63%), angiotensin-converting enzyme (-137%), renin (-230%), and angiotensinogen (-38%) in renal cortex. These results suggest that increased endogenous adrenomedullin plays a compensatory role in chronic hypertensive renal failure and that long-term adrenomedullin infusion has renoprotective effects in this type of hypertension model, partly via inhibition of the circulating and renal renin-angiotensin system.

Topics: Adrenomedullin; Angiotensin II; Animals; Creatinine; Drug Implants; Glomerulonephritis; Hormones; Hypertension; Kidney; Male; Peptides; Proteinuria; Rats; Rats, Inbred Dahl; Renal Insufficiency; Renin-Angiotensin System; RNA, Messenger; Sodium Chloride; Time Factors; Transforming Growth Factor beta

Adrenomedullin (AM) has vasodilator and diuretic actions, similarly to natriuretic peptides. AM receptor complexes are composed of calcitonin receptor-like receptor (CRLR) and receptor-activity modifying protein-2 (RAMP2), or CRLR and RAMP3. We aimed to know whether gene expression of AM and AM receptor complexes are regulated in kidneys under pathophysiological conditions. Expression of AM, RAMP2, RAMP3 and CRLR mRNA was studied in the remnant kidney of rats with renal mass ablation using competitive quantitative RT-PCR techniques. Partial cloning was performed to determine the rat RAMP3 nucleotide sequence. In normal rat kidneys, expression levels of RAMP2, RAMP3, CRLR and AM mRNAs were 26.5 +/- 1.9 mmol/mole of GAPDH, 7.7 +/- 0.9 mmol/mole of GAPDH, 3.6 +/- 0.2 mmol/mole of GAPDH and 0.57 +/- 0.03 mmol/mole of GAPDH (mean +/- SE, n = 6), respectively. RAMP3 mRNA levels decreased significantly to about 50% and about 70% of control (sham-operated rats) 4 days and 14 days after 5/6 nephrectomy, respectively. CRLR mRNA levels also decreased significantly to about 30% and about 43% of control. Sodium intake restriction had no significant effects on the RAMP3 and CRLR gene expression. On the other hand, RAMP2 mRNA expression in the kidney was suppressed by sodium intake restriction regardless of nephrectomy, while RAMP2 levels in the remnant kidney were not significantly changed by 5/6 nephrectomy. Neither 5/6 nephrectomy or sodium intake restriction had any significant effects on the AM gene expression in the kidney. The present study showed that expression of mRNAs encoding AM, RAMP2, RAMP3 and CRLR were differentially regulated in remnant kidneys of rats with renal mass ablation.

Topics: Adrenomedullin; Analysis of Variance; Animals; Calcitonin Receptor-Like Protein; Disease Models, Animal; Gene Expression; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Nephrectomy; Peptides; Rats; Rats, Wistar; Receptor Activity-Modifying Protein 2; Receptor Activity-Modifying Protein 3; Receptor Activity-Modifying Proteins; Receptors, Adrenomedullin; Receptors, Calcitonin; Receptors, Peptide; Renal Insufficiency; RNA, Messenger

Topics: Adrenomedullin; Aorta; Heart Failure; Humans; Hypertension; Myocardial Infarction; Myocardial Ischemia; Peptides; Pulmonary Artery; Reference Values; Renal Insufficiency; Renal Veins; Time Factors

Arterial vasodilation in cirrhosis may be related to increased circulating levels of vasodilators. This study was designed to assess the circulating levels of adrenomedullin, a recently described vasodilator peptide, in cirrhosis.. Plasma adrenomedullin levels were measured in 17 healthy subjects and 34 cirrhotic patients. Hemodynamic parameters, renal function, and levels of vasoactive substances were also assessed.. Patients with ascites had increased adrenomedullin levels (289 +/- 47 pg/mL) compared with healthy subjects and patients without ascites (135 +/- 17 and 142 +/- 32 pg/mL, respectively; P < 0.05). Adrenomedullin levels correlated inversely with arterial pressure, glomerular filtration rate, and renal plasma flow and correlated directly with pulse rate, endothelin levels, and aldosterone and plasma renin activity. In cirrhotic patients, no significant differences in adrenomedullin levels were found between samples obtained from hepatic vein, renal vein, pulmonary artery, and femoral artery. Plasma expansion with albumin suppressed the renin-angiotensin system but did not affect adrenomedullin levels.. Circulating levels of adrenomedullin are increased in patients with ascites and correlate with hemodynamic and renal abnormalities and activation of vasoconstrictor systems. These increased levels seem to result from a generalized increase in adrenomedullin production from vascular tissue and are not suppressed by plasma expansion. Adrenomedullin may participate in the pathogenesis of arterial vasodilation in cirrhosis.

Topics: Adrenomedullin; Ascites; Biomarkers; Female; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney; Liver Cirrhosis; Male; Middle Aged; Peptides; Renal Insufficiency; Vasoconstriction