Cardiovascular autonomic nervous system dysfunction in chronic kidney disease and end-stage kidney disease: disruption of the complementary forces

Abstract

Purpose of review Several nontraditional risk factors have been the focus of research in an attempt to understand the disproportionately high cardiovascular morbidity and mortality in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) populations. One such category of risk factors is cardiovascular autonomic dysfunction. Its true prevalence in the CKD/ESKD population is unknown but existing evidence suggests it is common. Due to lack of standardized diagnostic and treatment options, this condition remains undiagnosed and untreated in many patients. In this review, we discuss current evidence pointing toward the role of autonomic nervous system (ANS) dysfunction in CKD, building off of crucial historical evidence and thereby highlighting the areas in need for future research interest. Recent findings There are several key mediators and pathways leading to cardiovascular autonomic dysfunction in CKD and ESKD. We review studies exploring the mechanisms involved and discuss the current measurement tools and indices to evaluate the ANS and their pitfalls. There is a strong line of evidence establishing the temporal sequence of worsening autonomic function and kidney function and vice versa. Evidence linking ANS dysfunction and arrhythmia, sudden cardiac death, intradialytic hypotension, heart failure and hypertension are discussed. Summary There is a need for early recognition and referral of CKD and ESKD patients suspected of cardiovascular ANS dysfunction to prevent the downstream effects described in this review. There are many unknowns in this area and a clear need for further research.

Disparities in efficacy and safety of sodium-glucose cotransporter 2 inhibitor among patients with different extents of renal dysfunction: A systematic review and meta-analysis of randomized controlled trials

“…Meanwhile, since hypertension and edema are common comorbidities and complications in patients with CKD ( Kidney Disease: Improving Global Outcomes KDIGO Blood Pressure Work Group, 2021 ), concomitant antihypertensive medications, including diuretics, might also be applied in these patients, which might also be associated with the increased risk of hypovolemia. Moreover, cardiovascular autonomic dysfunction in patients with advanced CKD and end-stage kidney disease (ESKD) might also be associated with the increased incidence of hypovolemia and hypotension ( Soomro and Charytan, 2021 ; Shubrook et al, 2022 ). However, further analyses were limited due to insufficient information of baseline medications and cardiovascular profiles.…”

Dynamic Echocardiographic Assessments Reveal Septal E/e’ Ratio as Independent Predictor of Intradialytic Hypotension in Maintenance for Hemodialysis Patients with Preserved Ejection Fraction

“…Second, autonomic dysfunction, intradialytic electrolyte alteration and coronary arteries flow reserve were not assessed. Common investigations of autonomic functions include heart rate response to deep breathing, beat-to-beat cardiac variation (R-R interval ratio) with changes of position or respiration, decline of blood pressure on standing for three minutes and others [ 34 ]. All these maneuvers were difficult to perform during a 4 h HD.…”

Uremic toxins in chronic kidney disease highlight a fundamental gap in understanding their detrimental effects on cardiac electrophysiology and arrhythmogenesis

“…This is especially observed in ESRD patients 66 . While oxidative stress can be promoted by elevated UT levels, UTs are also presumed to directly increase sympathetic activity by inducing inflammation and NO deficiency in the central nervous system 59 . While further electrophysiological mechanisms are scarcely available in the setting of CKD, examples of increased NCX activity providing spontaneous calcium triggers are also observed 67 .…”

“…61 cGMP levels are mediated by NO, increasing cAMP breakdown via phosphodiesterases, resulting in negative inotropic effects. 62 During CKD, NO bioavailability is reduced, due to both increased oxidative stress and increasing asymmetric dimethylarginine (ADMA) levels, 59,63,64 which results in a sympathetic overdrive. 64,65 This is especially observed in ESRD patients.…”