QT Interval and QT Dispersion in Patients Undergoing Hemodialysis: Revisiting the Old Theory

Al-Abd, Mohamed; El-Hammady, Walid; Shawky, Ahmed M.; Nammas, Wail; Eltayeb, Mohamed

doi:10.1159/000328930

Cited by 22 publications

(26 citation statements)

References 29 publications

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“…Electrocardiogram, QTcB intervals and ionized calcium levels were extensively evaluated throughout this study and showed no safety issues associated with treatment with the study drug in the HD patient population. Moreover, disturbance of QT prolongations are frequent findings among patients with chronic kidney disease, especially in ESRD patients on HD . A negative correlation has been established between Ca, P and K and QT/QTc interval increase in dialysis .…”

Section: Discussionmentioning

confidence: 99%

A phase 1b randomized, placebo‐controlled clinical trial with SNF472 in haemodialysis patients

Salcedo

Joubert

Ferrer

et al. 2019

Brit J Clinical Pharma

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Aims: SNF472 is a calcification inhibitor that is being studied as a novel treatment for calciphylaxis and cardiovascular calcification (CVC). A first study showed acceptable safety and tolerability in a single ascending dose administration in healthy volunteers and a single dose administration in haemodialysis (HD) patients. This study aimed to assess the safety, tolerability, and pharmacokinetics/pharmacodynamics relationship of intravenous SNF472 in HD patients in a multiple ascending dose administration trial with 5 doses tested for 1 week (3 administrations) and 1 dose tested for 4 weeks (12 administrations).Methods: This double blind, randomized, placebo-controlled Phase 1b study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of SNF472 after repeated administrations to HD patients for up to 28 days. A pharmacodynamic assessment was performed to evaluate the potential for SNF472 to inhibit hydroxyapatite (HAP) formation. Patients were grouped into 2 cohorts, receiving multiple ascending doses for 1 week (1 to 20 mg/kg, Cohort 1) and 1 dose of 10 mg/kg for 4 weeks (Cohort 2) of intravenous SNF472.Results: Physical status, body weight, cardiorespiratory function, body temperature and laboratory parameters were in the normal range. No clinically relevant effects on heart rate or blood pressure were observed. No abnormal electrocardiogram or QTcB period were reported. The peak plasma concentration (7.6, 16.1, 46.0 and 66.9 μg/mL for 3, 5, 12.5 and 20 mg/kg, respectively) was observed at the end of the 4-hour infusion and thereafter concentrations declined rapidly with half-life between 32 and 65 min. SNF472 at 10 mg/kg inhibited dose dependently HAP crystallization in plasma samples after 28 days of treatment (78% inhibition, P < .001).Conclusions: SNF472 is safe and well tolerated in HD patients after 2 schemes: multiple ascending doses for 1 week and after repeated dosing of 10 mg/kg for 4 weeks. In both schemes, SNF472 inhibits the induction of HAP crystallization.These results provide support for the use of SNF472 as a novel treatment for CVC in end-stage renal disease.The authors confirm that the PI for this paper is Francesc Maduell and that he had direct clinical responsibility for patients.

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Section: Discussionmentioning

confidence: 99%

A phase 1b randomized, placebo‐controlled clinical trial with SNF472 in haemodialysis patients

Salcedo

Joubert

Ferrer

et al. 2019

Brit J Clinical Pharma

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“…Decreased serum Mg levels induced by a low Mg dialysate enhanced susceptibility to intradialytic hypotension, possibly because of impaired cardiac contractility. Limited information is currently available on the effects of Mg on arrhythmia, but Alabd et al reported that the post-dialysis QTc interval duration inversely correlated with a decrease in serum Mg levels during the HD session [61]. Table 1 shows observational studies that examined the relationship between serum Mg levels and cardiovascular calcification/atherosclerosis in CKD/ESRD patients [32,[62][63][64][65][66][67][68].…”

Section: Mg and Dialysis Therapymentioning

confidence: 99%

Cardiovascular disease, mortality, and magnesium in chronic kidney disease: growing interest in magnesium-related interventions

Ikee¹

2018

Ren Replace Ther

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Magnesium (Mg) is an essential element that plays pivotal roles in a number of biological processes in the human body. Hypomagnesemia is involved in the pathophysiology of hypertension, vascular calcification, and metabolic derangements including diabetes mellitus and dyslipidemia, which are all risk factors for cardiovascular disease, the leading cause of mortality and morbidity in patients with chronic kidney disease (CKD). Hypomagnesemia is also associated with the development and progression of CKD. As CKD advances, renal Mg excretion decreases and hypermagnesemia emerges in end-stage renal disease (ESRD). In addition, dialysates with high Mg concentrations, which were used in the early era of dialysis therapy, increased the risk of hypermagnesemia, and thus, the dialysate Mg composition has since been reduced. Accordingly, dialysis patients in the modern era commonly have normomagnesemia or even hypomagnesemia. The relationships between hypomagnesemia and cardiovascular disease and mortality have been increasingly reported in observational studies in CKD/ESRD. However, these relationships may be attenuated by a patient's race or region. Although dialysates with higher Mg concentrations or Mg-containing phosphate binders appear to be promising in this setting, only a few interventional studies have examined the effects of Mg supplementation on cardiovascular lesions. Furthermore, the effects of Mg supplementation on mortality have not yet been investigated as a primary end-point in randomized controlled trials. Further studies are required in order to establish the efficacy and safety of Mg in CKD patients.

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“…90 Mg deficiency has been implicated in the pathogenesis of ventricular arrhythmias and torsades de points which is associated with the presence of QT prolongation. 91 Alabd et al 92 reported that postdialysis QTc interval duration is inversely correlated with the decrease of Mg levels after HD. Lower serum Mg levels in the general population predict a higher risk of atrial fibrillation.…”

Section: Cardiac Arrhythmiasmentioning

confidence: 99%

Hypomagnesemia, chronic kidney disease and cardiovascular mortality: Pronounced association but unproven causation

Dousdampanis

Trigka

Fourtounas

2014

Hemodialysis International

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Magnesium is as an essential metal implicated in numerous physiological functions of human cells. The kidney plays a crucial role in magnesium homeostasis. In advanced chronic kidney disease, serum magnesium levels are increased. Data from experimental and observational studies suggest that low levels of magnesium are associated with several factors, such as insulin resistance, diabetes, oxidative stress, hypertension, atherosclerosis, and inflammation which are implicated in the progression of chronic kidney disease. Moreover, low levels of magnesium have been correlated with cardiovascular disease and all-cause mortality in end-stage renal disease patients. Hypomagnesemia has also been associated with poorer renal allograft and transplant recipients' outcomes. The causality of these relationships has not been completely elucidated. A thorough review of the current literature indicates that low magnesium levels in dialysis patients may reflect a poorer nutritional status and/or are the result of systemic inflammation. Further studies in chronic kidney disease and dialysis patients are needed in order to clarify the causality of these associations.

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QT Interval and QT Dispersion in Patients Undergoing Hemodialysis: Revisiting the Old Theory

Cited by 22 publications

References 29 publications

A phase 1b randomized, placebo‐controlled clinical trial with SNF472 in haemodialysis patients

A phase 1b randomized, placebo‐controlled clinical trial with SNF472 in haemodialysis patients

Cardiovascular disease, mortality, and magnesium in chronic kidney disease: growing interest in magnesium-related interventions

Hypomagnesemia, chronic kidney disease and cardiovascular mortality: Pronounced association but unproven causation

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