Clinical significance of urinary cyclic guanosine monophosphate in diagnosis of heart failure

Jakob, G.; Mair, Johannes; Vorderwinkler, Karl-Paul; Judmaier, G; König, Paul; Zwierzina, Heinz; Pichler, Max; Puschendorf, Bernd

doi:10.1093/clinchem/40.1.96

Cited by 27 publications

(15 citation statements)

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“…NA, not assessed. healthy individuals was 12.1 Ϯ 1.6 pg/ml, which is consistent with the levels previously observed in healthy control individuals (20,25,27,32).…”

Section: H542supporting

confidence: 90%

Increased urinary excretion of uroguanylin in patients with congestive heart failure

Carrithers

Eber

Forte

et al. 2000

American Journal of Physiology-Heart and Circulatory Physiology

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Uroguanylin is a small-molecular-weight peptide that activates membrane-bound receptor-guanylate cyclases in the intestine, kidney, and other epithelia. Uroguanylin has been shown to participate in the regulation of salt and water homeostasis in mammals via cGMP-mediated processes, bearing a distinct similarity to the action of the atriopeptins, which play a defined role in natriuresis and act as prognostic indicators of severe congestive heart failure (CHF). The objectives of this study were to measure the urinary levels of uroguanylin and the circulating plasma levels of atrial natriuretic peptide (ANP) in healthy individuals (n = 53) and patients with CHF (n = 16). Urinary excretion of uroguanylin was assessed by a cGMP accumulation bioassay employing human T84 intestinal cells. In individuals without CHF, the concentration of uroguanylin bioactivity was 1.31 +/- 0.27 nmol cGMP/ml urine and 1.73 +/- 0.25 micromol cGMP/24-h urine collection. The urinary bioactivity of uroguanylin in males (1.74 +/- 0.55 nmol cGMP/ml urine; n = 27) tended to be higher than the excretion levels in females (0.94 +/- 0.16 nmol cGMP/ml urine; n = 26) over a 24-h period but did not achieve statistical significance. Both male and female groups showed 24-h temporal diurnal variations with the highest uroguanylin levels observed between the hours of 8:00 AM and 2:00 PM. The circulating level of ANP was 12.1 +/- 1.6 pg/ml plasma and did not significantly vary with respect to male/female population or diurnal variation. In patients with CHF, the concentration of plasma ANP and urinary uroguanylin bioactivity increased substantially (7.5-fold and 70-fold, respectively, both P

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“…NA, not assessed. healthy individuals was 12.1 Ϯ 1.6 pg/ml, which is consistent with the levels previously observed in healthy control individuals (20,25,27,32).…”

Section: H542supporting

confidence: 90%

Increased urinary excretion of uroguanylin in patients with congestive heart failure

Carrithers

Eber

Forte

et al. 2000

American Journal of Physiology-Heart and Circulatory Physiology

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“…5,6 Furthermore, while both sGC and pGC activation results in the accumulation of cGMP within cells, pGC activation (in contrast to sGC) also results in significant release of cGMP into the extracellular space and circulation. [7][8][9][10][11] Therefore, while both sGC and pGC increase intracellular cGMP, the resulting biological actions are quite different. 4,12,13 Cyclic GMP therapies are currently employed in the treatment of heart failure (HF).…”

mentioning

confidence: 99%

M‐Atrial Natriuretic Peptide and Nitroglycerin in a Canine Model of Experimental Acute Hypertensive Heart Failure: Differential Actions of 2 cGMP Activating Therapeutics

McKie

Cataliotti

Ichiki

et al. 2014

JAHA

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BackgroundSystemic hypertension is a common characteristic in acute heart failure (HF). This increasingly recognized phenotype is commonly associated with renal dysfunction and there is an unmet need for renal enhancing therapies. In a canine model of HF and acute vasoconstrictive hypertension we characterized and compared the cardiorenal actions of M‐atrial natriuretic peptide (M‐ANP), a novel particulate guanylyl cyclase (pGC) activator, and nitroglycerin, a soluble guanylyl cyclase (sGC) activator.Methods and ResultsHF was induced by rapid RV pacing (180 beats per minute) for 10 days. On day 11, hypertension was induced by continuous angiotensin II infusion. We characterized the cardiorenal and humoral actions prior to, during, and following intravenous M‐ANP (n=7), nitroglycerin (n=7), and vehicle (n=7) infusion. Mean arterial pressure (MAP) was reduced by M‐ANP (139±4 to 118±3 mm Hg, P<0.05) and nitroglycerin (137±3 to 116±4 mm Hg, P<0.05); similar findings were recorded for pulmonary wedge pressure (PCWP) with M‐ANP (12±2 to 6±2 mm Hg, P<0.05) and nitroglycerin (12±1 to 6±1 mm Hg, P<0.05). M‐ANP enhanced renal function with significant increases (P<0.05) in glomerular filtration rate (38±4 to 53±5 mL/min), renal blood flow (132±18 to 236±23 mL/min), and natriuresis (11±4 to 689±37 mEq/min) and also inhibited aldosterone activation (32±3 to 23±2 ng/dL, P<0.05), whereas nitroglycerin had no significant (P>0.05) effects on these renal parameters or aldosterone activation.ConclusionsOur results advance the differential cardiorenal actions of pGC (M‐ANP) and sGC (nitroglycerin) mediated cGMP activation. These distinct renal and aldosterone modulating actions make M‐ANP an attractive therapeutic for HF with concomitant hypertension, where renal protection is a key therapeutic goal.

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“…cGMP is produced by particulate (pGC) and soluble (sGC) guanylyl cyclases, as a result of natriuretic peptide and NO activation [ 14 ]. Although both sGC and pGC activation increase cGMP intracellular concentration, pGC activation (unlike sGC) results also in significant release of cGMP into the extracellular space and blood circulation [ 15 – 19 ]. Therefore, while both sGC and pGC increase cGMP within cells, the resulting biological actions are quite different.…”

Section: Introductionmentioning

confidence: 99%

“…Due to in part different localizations of sGC and pGC receptors, and timing of their signaling in the kidney, the NP/pGC/cGMP pathway predominantly regulates GFR and sodium excretion whereas the NO/sGC/cGMP pathway mostly controls renal vascular tone[ 20 , 21 ]. Urinary and plasma cGMP concentrations are influenced by renal function [ 19 , 22 ]. Urinary cGMP is primarily of renal cellular origin [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…A positive correlation between increased cGMP in plasma and cGMP in urine was shown previously [ 23 ], therefore it was suggested as biomarker candidate for kidney injury. Furthermore, in contrast to plasma cGMP, urinary cGMP is not related to the severity of heart failure as assessed clinically according to the NYHA classification[ 19 ]. Thus, the goal of our study was to evaluate the predictive value of urinary cGMP clearance 24 hrs prior to contrast medium application for the development of adverse events in patients at risk for contrast-induced kidney injury.…”

Section: Introductionmentioning

confidence: 99%

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Urinary cGMP predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus before exposure to contrast medium

et al. 2018

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BackgroundThe use of iodine-based contrast agents entails the risk of contrast induced nephropathy (CIN). Radiocontrast agents elicit the third most common cause of nephropathy among hospitalized patients, accounting for 11–12% of cases. CIN is connected with clinically significant consequences, including increased morbidity, prolonged hospitalization, increased risk of complications, potential need for dialysis, and increased mortality rate. The number of in-hospital examinations using iodine-based contrast media has been significantly increasing over the last decade. In order to protect patients from possible complications of such examinations, new biomarkers are needed that are able to predict a risk of contrast-induced nephropathy. Urinary and plasma cyclic guanosine monophosphate (cGMP) concentrations are influenced by renal function. Urinary cGMP is primarily of renal cellular origin. Therefore, we assessed if urinary cGMP concentration may predict major adverse renal events (MARE) after contrast media exposure during coronary angiography.MethodsUrine samples were prospectively collected from non-randomized consecutive patients with either diabetes or preexisting impaired kidney function receiving intra-arterial contrast medium (CM) for emergent or elective coronary angiography at the Charité Campus Mitte, University Hospital Berlin. Urinary cGMP concentration in spot urine was analyzed 24 hours after CM exposure. Patients were followed up over 90 days for occurrence of death, initiation of dialysis, doubling of plasma creatinine concentration or MARE.ResultsIn total, 289 consecutive patients were included into the study. Urine cGMP/creatinine ratio 24 hours before CM exposure expressed as mean±SD was predictive for the need of dialysis (no dialysis: 89.77±92.85 μM/mM, n = 277; need for dialysis: 140.3±82.90 μM/mM, n = 12, p = 0.008), death (no death during follow-up: 90.60±92.50 μM/mM, n = 280; death during follow-up: 169.88±81.52 μM/mM, n = 9; p = 0.002), and the composite endpoint MARE (no MARE: 86.02±93.17 μM/mM, n = 271; MARE: 146.64±74.68 μM/mM, n = 18, p<0.001) during the follow-up of 90 days after contrast media application. cGMP/creatinine ratio stayed significantly increased at values exceeding 120 μM/mM in patients who developed MARE, required dialysis or died.ConclusionsUrinary cGMP/creatinine ratio ≥ 120 μM/mM before CM exposure is a promising biomarker for the need of dialysis and all-cause mortality 90 days after CM exposure in patients with preexisting renal impairment or diabetes.

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Clinical significance of urinary cyclic guanosine monophosphate in diagnosis of heart failure

Cited by 27 publications

References 0 publications

Increased urinary excretion of uroguanylin in patients with congestive heart failure

Increased urinary excretion of uroguanylin in patients with congestive heart failure

M‐Atrial Natriuretic Peptide and Nitroglycerin in a Canine Model of Experimental Acute Hypertensive Heart Failure: Differential Actions of 2 cGMP Activating Therapeutics

Urinary cGMP predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus before exposure to contrast medium

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