Homoarginine in Patients With Primary Hyperparathyroidism

Tomaschitz, Andreas; Verheyen, Nicolas; Gaksch, Martin; Meinitzer, Andreas; Pieske, Burkert; Kraigher‐Krainer, Elisabeth; Colantonio, Caterina; März, Winfried; Schmidt, Albrecht; Belyavskiy, Evgeny; Rus-Machan, Jutta; Ballegooijen, Adriana J. van; Stiegler, Claudia; Amrein, Karin; Ritz, Eberhard; Fahrleitner‐Pammer, Astrid; Pilz, Stefan

doi:10.1097/maj.0000000000000419

Cited by 8 publications

(6 citation statements)

References 36 publications

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“…Normal range is 15–65 pg/ml (1.6–6.9 pmol/L), intra- and interassay CVs are 1.5% to 2.7% and 3.0% to 6.5%. Plasma calcium was adjusted for hypoalbuminemia as previously reported [19]. Other laboratory parameters were assessed using routine laboratory methods as previously described [17].…”

Section: Methodsmentioning

confidence: 99%

“…Echocardiographic examinations were performed with a Vivid 7 or Vivid 9 (GE Healthcare, Chalfont St Giles, UK), as previously reported [19]. All images and recorded loops were analyzed in a central core lab (Echocardiography CoreLab, Department of Cardiology, Medical University of Graz, Graz, Austria) by a single investigator who was blinded to individual participant data (EB).…”

Section: Methodsmentioning

confidence: 99%

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Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial

et al. 2017

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Observational studies suggested a link between bone disease and left ventricular (LV) dysfunction that may be pronounced in hyperparathyroid conditions. We therefore aimed to test the hypothesis that circulating markers of bone turnover correlate with LV function in a cohort of patients with primary hyperparathyroidism (pHPT). Cross-sectional data of 155 subjects with pHPT were analyzed who participated in the “Eplerenone in Primary Hyperparathyroidism” (EPATH) Trial. Multivariate linear regression analyses with LV ejection fraction (LVEF, systolic function) or peak early transmitral filling velocity (e’, diastolic function) as dependent variables and N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), or beta-crosslaps (CTX) as the respective independent variable were performed. Analyses were additionally adjusted for plasma parathyroid hormone, plasma calcium, age, sex, HbA1c, body mass index, mean 24-hours systolic blood pressure, smoking status, estimated glomerular filtration rate, antihypertensive treatment, osteoporosis treatment, 25-hydroxy vitamin D and N-terminal pro-brain B-type natriuretic peptide. Independent relationships were observed between P1NP and LVEF (adjusted β-coefficient = 0.201, P = 0.035) and e’ (β = 0.188, P = 0.042), respectively. OC (β = 0.192, P = 0.039) and BALP (β = 0.198, P = 0.030) were each independently related with e’. CTX showed no correlations with LVEF or e’. In conclusion, high bone formation markers were independently and paradoxically related with better LV diastolic and, partly, better systolic function, in the setting of pHPT. Potentially cardio-protective properties of stimulated bone formation in the context of hyperparathyroidism should be explored in future studies.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial

et al. 2017

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“…In view of a potential interplay between hArg and parathyroid hormone (PTH) (Tomaschitz et al 2015), we looked for an interaction between UhArg and PTH levels for predicting mortality risk and risk of graft failure. We found significant effect modification for the association between UhArg and mortality by PTH (P interaction = 0.02).…”

Section: Association Of Urinary Homoarginine With Mortality and Graftmentioning

confidence: 99%

High urinary homoarginine excretion is associated with low rates of all-cause mortality and graft failure in renal transplant recipients

et al. 2015

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Renal transplant recipients (RTR) have an increased cardiovascular risk profile. Low levels of circulating homoarginine (hArg) are a novel risk factor for mortality and the progression of atherosclerosis. The kidney is known as a major source of hArg, suggesting that urinary excretion of hArg (UhArg) might be associated with mortality and graft failure in RTR. hArg was quantified by mass spectrometry in 24-h urine samples of 704 RTR (functioning graft ≥1 year) and 103 healthy subjects. UhArg determinants were identified with multivariable linear regression models. Associations of UhArg with all-cause mortality and graft failure were assessed using multivariable Cox regression analyses. UhArg excretion was significantly lower in RTR compared to healthy controls [1.62 (1.09-2.61) vs. 2.46 (1.65-4.06) µmol/24 h, P < 0.001]. In multivariable linear regression models, body surface area, diastolic blood pressure, eGFR, pre-emptive transplantation, serum albumin, albuminuria, urinary excretion of urea and uric acid and use of sirolimus were positively associated with UhArg, while donor age and serum phosphate were inversely associated (model R (2) = 0.43). During follow-up for 3.1 (2.7-3.9) years, 83 (12 %) patients died and 45 (7 %) developed graft failure. UhArg was inversely associated with all-cause mortality [hazard risk (HR) 0.52 (95 % CI 0.40-0.66), P < 0.001] and graft failure [HR 0.58 (0.42-0.81), P = 0.001]. These associations remained independent of potential confounders. High UhArg levels are associated with reduced all-cause mortality and graft failure in RTR. Kidney-derived hArg is likely to be of particular importance for proper maintenance of cardiovascular and renal systems.

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“…The potential utility of hArg as a substrate for NOS has early led to the assumption that, if hArg would have a biological role, that would be due to its function as an NO precursor. Likely, this assumption has initiated many experimental and clinical studies, which eventually revealed hArg, specifically at concentrations lower than average concentrations measured in healthy humans, as a novel cardiovascular risk factor (März et al 2010;Pilz et al 2011a, b;Pilz et al 2014;Tomaschitz et al 2015). This is in contrast to the use of higher concentrations of ADMA, the asymmetrically guanidine (N G )-dimethylated Arg derivative, as a biomarker for risk of cardiovascular Proposed mechanisms for the biosynthesis of l-homoarginine and guanidinoacetate from l-arginine.…”

Section: Introductionmentioning

confidence: 99%

Homoarginine, arginine, and relatives: analysis, metabolism, transport, physiology, and pathology

Tsikas

2015

Amino Acids

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Homoarginine in Patients With Primary Hyperparathyroidism

Cited by 8 publications

References 36 publications

Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial

Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial

High urinary homoarginine excretion is associated with low rates of all-cause mortality and graft failure in renal transplant recipients

Homoarginine, arginine, and relatives: analysis, metabolism, transport, physiology, and pathology

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