Cardiac Arrhythmias in Patients with Chronic Kidney Disease: Implications of Renal Failure for Antiarrhythmic Drug Therapy

Abstract

The kidney has numerous complex interactions with the heart, including shared risk factors (e.g., hypertension, dyslipidemia, etc.) and mutual amplification of morbidity and mortality. Both cardiovascular diseases and chronic kidney disease (CKD) may cause various alterations in cardiovascular system, metabolic homeostasis and autonomic nervous system that may facilitate the occurrence of cardiac arrhythmias. Also, pre-existent or incident cardiac arrhythmias such as atrial fibrillation (AF) may accelerate the progression of CKD. Patients with CKD may experience various cardiac rhythm disturbances including sudden cardiac death. Contemporary management of cardiac arrhythmias includes the use of antiarrhythmic drugs (AADs), catheter ablation and cardiac implantable electronic devices (CIEDs). Importantly, AADs are not used only as the principal treatment strategy, but also as an adjunct therapy in combination with CIEDs, to facilitate their effects or to minimize inappropriate device activation in selected patients. Along with their principal antiarrhythmic effect, AADs may also induce cardiac arrhythmias and the risk for such proarrhythmic effect(s) is particularly increased in patients with reduced left ventricular systolic function or in the setting of electrolyte imbalance. Moreover, CKD itself can induce profound alterations in the pharmacokinetics and pharmacodynamics of many drugs including AADs, thus facilitating the drug accumulation and increased exposure. Hence, the use of AADs in patients with CKD may be challenging. In this review article, we provide an overview of the characteristics of arrhythmogenesis in patients with CKD with special emphasis on the complexity of pharmacokinetics and risk for proarrhythmias when using AADs in patients with cardiac arrhythmias and CKD.

Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

“… Modified from Potpara et al 101 and Weir et al 102 Metoprolol elimination data from Hoffman et al 103 Labetalol protein binding data from Drugbank.ca 104 and dialyzability data from in vitro data by Daheb et al 105 All other dialyzability data from Frishman. 106 CKD, chronic kidney disease; CrCl, creatinine clearance; GFR, glomerular filtration rate.…”

“… CHF, congestive heart failure; CKD, chronic kidney disease; CrCl, creatinine clearance; EF, ejection fraction; eGFR, estimated glomerular filtration rate; HD, haemodialysis. Modified from Potpara et al 101 Propafenone elimination data from Drugbank.ca. 110 Dialyzability data from Frishman.…”

Metformin with insulin relieves oxidative stress and confers renoprotection in type 1 diabetes in vivo

“…Oxidative stress causes direct damage to the glomerulus and affects tubule-interstitial structures and functions, leading to diabetic nephropathy (15). Reduction in renal function may lead to electrolytes retention and imbalance hence accelerating the development of cardiovascular disease complications (16,17). Metformin is commonly administered as a firstline drug in the treatment of type 2 diabetes as it suppresses hepatic gluconeogenesis, decreases fatty acid oxidation and increases peripheral insulin sensitivity, leading to improved glucose uptake in the skeletal muscles and adipose tissues (7,(18)(19)(20).…”

Atrial fibrillation in patients with chronic kidney disease

“…Особенности использования основных медикаментов для контроля частоты сокращения желудочков или антиаритмических препаратов представлены в табл. 3 [6,26,27].…”