Blood pressure in chronic kidney disease stage 5D—report from a Kidney Disease: Improving Global Outcomes controversies conference
2009; Elsevier BV; Volume: 77; Issue: 4 Linguagem: Inglês
10.1038/ki.2009.469
ISSN1523-1755
AutoresNathan W. Levin, Peter Kotanko, Kai‐Uwe Eckardt, Bertram L. Kasiske, Charles Chazot, Alfred K. Cheung, Josep Redón, David C. Wheeler, Carmine Zoccali, Gérard M. London,
Tópico(s)Hemodynamic Monitoring and Therapy
ResumoManagement of blood pressure (BP) in patients with chronic kidney disease receiving dialysis (stage 5D) provides a significant challenge for healthcare professionals. The association between BP and cardiovascular disease risk has been well studied in the general population; however, in dialysis patients, physiological and dialysis-related mechanisms influencing BP are complex, and the associated risk is poorly understood. In stage 5D, BP is determined by the complex interplay of fluid volume and prescription of post-dialysis target weight, sodium load, the renin–angiotensin and sympathetic nervous systems, and diverse exogenous factors, such as administration of erythropoiesis-stimulating agents, the type and timing of administration of antihypertensive drugs, and dialysate composition. Management of BP in this population requires both generally applicable plans and individualization in order to determine the BP target and the treatment regimen. This report summarizes the deliberations and recommendations of a conference sponsored by the Kidney Disease: Improving Global Outcomes (KDIGO) to address the following questions: (1) what is the optimal BP treatment target in relation to end-organ damage and outcomes in dialysis patients; (2) how should antihypertensive drugs be used in dialysis patients; and (3) what nonpharmacological therapies can be considered in achieving BP targets? The conference report will augment the KDIGO clinical practice guideline on blood pressure in chronic kidney disease stages 1–5, which is currently under development. Management of blood pressure (BP) in patients with chronic kidney disease receiving dialysis (stage 5D) provides a significant challenge for healthcare professionals. The association between BP and cardiovascular disease risk has been well studied in the general population; however, in dialysis patients, physiological and dialysis-related mechanisms influencing BP are complex, and the associated risk is poorly understood. In stage 5D, BP is determined by the complex interplay of fluid volume and prescription of post-dialysis target weight, sodium load, the renin–angiotensin and sympathetic nervous systems, and diverse exogenous factors, such as administration of erythropoiesis-stimulating agents, the type and timing of administration of antihypertensive drugs, and dialysate composition. Management of BP in this population requires both generally applicable plans and individualization in order to determine the BP target and the treatment regimen. This report summarizes the deliberations and recommendations of a conference sponsored by the Kidney Disease: Improving Global Outcomes (KDIGO) to address the following questions: (1) what is the optimal BP treatment target in relation to end-organ damage and outcomes in dialysis patients; (2) how should antihypertensive drugs be used in dialysis patients; and (3) what nonpharmacological therapies can be considered in achieving BP targets? The conference report will augment the KDIGO clinical practice guideline on blood pressure in chronic kidney disease stages 1–5, which is currently under development. In March 2009, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Controversies Conference on Blood Pressure in chronic kidney disease (CKD) stage 5D. The conference, attended by 50 international experts, was designed to review the most current information available on the pathophysiology, epidemiology, and management of blood pressure (BP), particularly in this population. The plenary session presentations were followed by discussion in small breakout groups that were asked to address three specific issues, which the planning committee of the conference considered to be of central importance: (1) optimal BP in relation to end-organ damage in dialysis patients; (2) pharmacological therapy for cardioprotection and to achieve BP targets; and (3) nonpharmacological therapy to achieve BP targets—focus on volume and salt control. The breakout group deliberations were reported to the entire group and a consensus building process led to recommendations from the conference attendees. The following is a report on these deliberations and recommendations. The conference agenda, selected presentations, and abstracts of the meeting are posted on the KDIGO website: http://www.kdigo.org/meetings_events/BP_Controversies_Conference.php KDIGO is an independently incorporated non-profit organization governed by an international Board of Directors with the stated mission to 'improve the care and outcomes of kidney disease patients worldwide through promoting coordination, collaboration and integration of initiatives to develop and implement clinical practice guidelines.' One of the initiatives determined by the Board of Directors of KDIGO is a series of international conferences to examine what is known, what can be done with what is known and what needs to be known on controversial topics of clinical relevance in nephrology.1Eckardt K.U. Kasiske B.L. Kidney disease: improving global outcomes.Nat Rev Nephrol. 2009; 5: 650-657Crossref PubMed Scopus (67) Google Scholar Epidemiological studies in the general population have shown a close relationship between BP and the incidence of cardiovascular disease (CVD). In the past, the severity of hypertension (HTN) was classified principally on the basis of increased diastolic BP (DBP), which was considered to be the best predictor of CVD risk, with increased pulse pressure as an independent CVD risk factor in addition to DBP. DBP generally increases from birth to the fifth decade, followed by a decline starting at 50–60 years. The pulse pressure increases markedly in later life, and isolated systolic HTN becomes the predominant form of HTN after 60 years of age in the general population. In dialysis patients, increased systolic BP (SBP) and decreased DBP are both associated with CVD events. Presumably, this is related to increased arterial stiffness. In addition, decreased SBP following previous HTN is associated with adverse outcomes.2Li Z. Lacson Jr, E. Lowrie E.G. et al.The epidemiology of systolic blood pressure and death risk in hemodialysis patients.Am J Kidney Dis. 2006; 48: 606-615Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar Although BP is measured frequently in the dialysis treatment environment, the technical aspects are often unsatisfactory, with the use of poorly calibrated machines and poor BP cuff placement on the upper arm. Recently, quite different levels of BP in the same patients measured in the dialysis clinic before dialysis and at home using ambulatory BP measurements (ABPM) were shown, with ABPM being substantially lower than dialysis clinic measurements.3Alborzi P. Patel N. Agarwal R. Home blood pressures are of greater prognostic value than hemodialysis unit recordings.Clin J Am Soc Nephrol. 2007; 2: 1228-1234Crossref PubMed Scopus (165) Google Scholar A U-shaped curve relating BP to outcomes was apparent in both sets of BP measurements, but home BP measurements were significantly lower and more closely associated with CVD.3Alborzi P. Patel N. Agarwal R. Home blood pressures are of greater prognostic value than hemodialysis unit recordings.Clin J Am Soc Nephrol. 2007; 2: 1228-1234Crossref PubMed Scopus (165) Google Scholar The pathophysiology of these BP patterns is complex, implicating three principal factors: cardiac function (cardiac output), arterial stiffness (large arteries), and intensity of wave reflections (principally vasomotor tone of resistance arterioles). The complex pathogenesis of HTN explains the difficulty of its treatment. In addition, the effect of ultrafiltration (UF) and variable plasma volume refilling rates may frequently result in hypotensive episodes during dialysis. The relationship of low systolic pressure with CVD events is complex, as low SBP in some patients may represent ideal control, but in others, it may be associated with increased mortality.2Li Z. Lacson Jr, E. Lowrie E.G. et al.The epidemiology of systolic blood pressure and death risk in hemodialysis patients.Am J Kidney Dis. 2006; 48: 606-615Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar A practical quandary arises in the care of an individual patient when the BP measurements are in an apparently acceptable range, as this BP may be gradually falling over time because of associated cardiomyopathy. Clearly, management and outcomes are different in these instances. Cardiac studies, and especially echocardiography, are necessary to clarify the significance of apparently normal BP levels. Sound BP treatment requires information on cardiac structure and function.4K/DOQI Workgroup K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients.Am J Kidney Dis. 2005; 45: S1-S153Google Scholar,5Zoccali C. Mallamaci F. Tripepi G. Cardiovascular risk profile assessment and medication control should come first.Semin Dial. 2007; 20: 405-408Crossref PubMed Scopus (1) Google Scholar In addition to consideration of the effect of changes in extracellular fluid volume, the time of administration of antihypertensive drugs is also relevant, given drug clearance during dialysis and myocardial dysfunction. Studies of antihypertensive medication use in dialysis patients have been limited. In the randomized trials included in two recent meta-analyses, the study drugs were given for CVD management, rather than for HTN.6Agarwal R. Sinha A.D. Cardiovascular protection with antihypertensive drugs in dialysis patients: systematic review and meta-analysis.Hypertension. 2009; 53: 860-866Crossref PubMed Scopus (143) Google Scholar,7Heerspink H.J. Ninomiya T. Zoungas S. et al.Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systematic review and meta-analysis of randomised controlled trials.Lancet. 2009; 373: 1009-1015Abstract Full Text Full Text PDF PubMed Scopus (313) Google Scholar The relative merits of calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and β-adrenergic blockers alone and in combination with centrally acting sympatholytic agents are not satisfactorily established. A recent review points out the powerful relationship between aldosterone activation of aldosterone/mineralocorticoid receptors and inflammation, resulting in vessel wall fibrosis.8Brown N.J. Aldosterone and vascular inflammation.Hypertension. 2008; 51: 161-167Crossref PubMed Scopus (173) Google Scholar Blockade of these receptors may be useful, although hyperkalemia may limit their use. More needs to be learnt about the use of drugs in conjunction with salt restriction, volume control, and in the presence of specific cardiovascular (CV) comorbidities, especially those resulting in cardiac arrhythmias and sudden death. Quality-of-life considerations with regard to side effects are particularly relevant in dialysis patients. In patients with low BP associated with fluid overload and, by necessity, low UF rates, longer dialysis treatment times or more frequent dialysis could achieve normal hydration, but this is impractical in most instances. The patients at greatest risk are those who have low predialysis BP, as a result of severe cardiac dysfunction.2Li Z. Lacson Jr, E. Lowrie E.G. et al.The epidemiology of systolic blood pressure and death risk in hemodialysis patients.Am J Kidney Dis. 2006; 48: 606-615Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar The prognosis of these patients is poor, in part, because fluid can be removed only very slowly. To further aggravate this situation, diastolic dysfunction is often present. Even a small decrease in filling pressure after UF may result in decreased cardiac output and hypotension. As a result, fluid accumulates inexorably. In addition, autonomic neuropathy complicating uremia and diabetes, with inadequate peripheral arteriolar tone, further increases the risk of hypotension, with the patient remaining fluid overloaded. The recent finding that excess sodium is stored without osmotic activity at concentrations of 180–190 mEq/l in the skin, bound to glucosaminoglycans, could revolutionize current views of sodium balance.9Titze J. Ritz E. Salt – its effect on blood pressure and target organ damage: new pieces in an old puzzle.J Nephrol. 2009; 22: 177-189PubMed Google Scholar According to this work, the skin sodium system acts as a buffer to exogenous sodium loading, and this sodium store can be released into the circulation resulting in hypervolemia and oxidative stress. This problem may be accentuated by reduction in connective tissue mass during aging and catabolic processes, thus decreasing the capacity of the skin to serve as a sodium reservoir. Although it has been established that interdialytic salt restriction or intradialytic removal of salt and fluid volume is effective in reducing BP, absolute success over time has been very rare, with only the Tassin and Izmir groups consistently being able to virtually discard antihypertensive drugs.10Luik A.J. Vander Sande F.M. Weideman P. et al.The influence of increasing dialysis treatment time and reducing dry weight on blood pressure control in hemodialysis patients: a prospective study.Am J Nephrol. 2001; 21: 471-478Crossref PubMed Scopus (36) Google Scholar In the current three times per week dialysis regimen, each for 3–4 h, volume overload is common. Little consistent effort has been exerted in the United States to reduce exposure to excess sodium. Because the sodium concentration of dialysate is usually higher than that of the patient's serum, sodium concentration rises during hemodialysis (HD), with the consequence of increased thirst, extracellular volume (ECV) expansion, and interdialytic weight gain. In addition, salt balance is positive with habitual high dietary sodium intake and use of saline for 'sodium profiling' or to maintain plasma volume during UF. A further consequence of long-term hypervolemia and an activated renin–angiotensin system is hyperactivity of the sympathetic nervous system. Factors such as renal ischemia, chronic inflammation, oxidative stress, obesity, nocturnal hypoxia, and elevated plasma levels of asymmetric di-methyl-arginine may contribute to increased sympathetic activity. The sequelae are elevated arterial pressure, cardiac arrhythmias, increased myocardial oxygen demand, and, in concert with arterial HTN, reduced compliance of large arteries. In addition to its volume effects, sodium exerts direct pro-inflammatory, pro-fibrotic effects, with the potential for aggravating kidney disease and CVD. Salt directly increases oxidative stress and is associated with the secretion of endogenous ouabain-like substances, such as marinobufagenin and endogenous ouabain. These compounds inhibit Na/K ATPase, and may induce myocardial cell hypertrophy in vitro. The concentration of endogenous ouabain correlates with left ventricular mass in HD patients independent of arterial pressure.11Stella P. Manunta P. Mallamaci F. et al.Endogenous ouabain and cardiomyopathy in dialysis patients.J Intern Med. 2008; 263: 274-280Crossref PubMed Scopus (49) Google Scholar The attainment of normal body hydration ('dry weight (DW)'), expressed in practice by recognition and attainment of an appropriate post-dialysis weight, is difficult without adequate means of measurement; this is a subject of much current research.12Moissl U.M. Wabel P. Chamney P.W. et al.Body fluid volume determination via body composition spectroscopy in health and disease.Physiol Meas. 2006; 27: 921-933Crossref PubMed Scopus (412) Google Scholar, 13Wabel P. Moissl U. Chamney P. et al.Towards improved cardiovascular management: the necessity of combining blood pressure and fluid overload.Nephrol Dial Transplant. 2008; 23: 2965-2971Crossref PubMed Scopus (217) Google Scholar, 14Zhu F. Kuhlmann M.K. Kotanko P. et al.A method for the estimation of hydration state during hemodialysis using a calf bioimpedance technique.Physiol Meas. 2008; 29: S503-S516Crossref PubMed Scopus (64) Google Scholar In the absence of an absolute post-dialysis weight goal, salt restriction of all kinds is usually half-hearted. A confounding factor is a lag between achieving a normal extracellular fluid volume and reduction in BP. Current public policy and societal interest in reduction of salt intake combined with intradialytic technical solutions to prevent accumulation of sodium during dialysis may reduce the frequency of sodium-related HTN. Future effectiveness studies should determine whether this will occur. Other nonpharmacological methods to decrease BP include nephrectomy. Overall, the relative severity of CVD, fluctuations in BP with every dialysis treatment, association with inflammation, stimulation of vasoactive substances, activation of mineralocorticoid receptors, increased levels of sympathetic nervous activity, exposure to sodium loading combined with inadequate volume control, and other factors make management of HTN in the dialysis patient a difficult but fascinating problem. Guidelines on the complex problems of HTN in CKD are being written currently. Whether the special problems of a hypertensive dialysis patient can be addressed in clinical practice guidelines is a relevant question, but evidence is sparse and more clinical trials are needed. Several options exist, such as pre- or post-dialysis BP, ABPM, and interdialytic home BP. Interdialytic ABPM is considered the standard to define a patient's BP. In the general population, ABPM provided a more accurate prediction of CV outcomes than office BP.15Dolan E. Stanton A. Thijs L. et al.Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study.Hypertension. 2005; 46: 156-161Crossref PubMed Scopus (932) Google Scholar, 16Kikuya M. Ohkubo T. Asayama K. et al.Ambulatory blood pressure and 10-year risk of cardiovascular and noncardiovascular mortality: the Ohasama study.Hypertension. 2005; 45: 240-245Crossref PubMed Scopus (335) Google Scholar, 17Sega R. Facchetti R. Bombelli M. et al.Prognostic value of ambulatory and home blood pressures compared with office blood pressure in the general population: follow-up results from the Pressioni Arteriose Monitorate e Loro Associazioni (PAMELA) study.Circulation. 2005; 111: 1777-1783Crossref PubMed Scopus (771) Google Scholar In a single-center cross-sectional study, 1-week-averaged home SBP was similar to interdialytic ABPM and superior to pre- and post-HD BP in predicting left ventricular hypertrophy (LVH); DBP was not associated with LVH.18Agarwal R. Peixoto A.J. Santos S.F. et al.Out-of-office blood pressure monitoring in chronic kidney disease.Blood Press Monit. 2009; 14: 2-11Crossref PubMed Scopus (60) Google Scholar In an earlier study, ABPM added minimal information to the prediction of LVH, compared with the average of 12 routine pre-HD BP measurements.19Zoccali C. Mallamaci F. Tripepi G. et al.Prediction of left ventricular geometry by clinic, pre-dialysis and 24-h ambulatory BP monitoring in hemodialysis patients: CREED investigators.J Hypertens. 1999; 17: 1751-1758Crossref PubMed Scopus (90) Google Scholar Hemodialysis BP and ABPM correlation is poor. A recent meta-analysis showed that pre- and post-HD BP are imprecise estimates of interdialytic ambulatory BP.20Agarwal R. Peixoto A.J. Santos S.F. et al.Pre- and postdialysis blood pressures are imprecise estimates of interdialytic ambulatory blood pressure.Clin J Am Soc Nephrol. 2006; 1: 389-398Crossref PubMed Scopus (162) Google Scholar In this meta-analysis, median pre-HD SBP and DBP were 8.6 and 2.6 mm Hg higher than ABPM, respectively. A single-center cross-sectional study showed that home BP measured by the patients was better than pre-HD in predicting LVH. ABPM added only weak predictive information.18Agarwal R. Peixoto A.J. Santos S.F. et al.Out-of-office blood pressure monitoring in chronic kidney disease.Blood Press Monit. 2009; 14: 2-11Crossref PubMed Scopus (60) Google Scholar Although a worthy goal, neither measurement of APBM nor self-measured home BP may be feasible for most patients throughout the world, leaving pre-HD and post-HD BP measurements to be used, but with caution and with the knowledge that these are inferior. Systolic BP and DBP are associated with end-organ damage, including vascular stiffness. Both high and low levels of either SBP or DBP are associated with poor outcomes in dialysis patients. A high prevalence of isolated systolic HTN exists in the stage 5D CKD population. Clinical decisions in managing interdialytic BP should be based on SBP and DBP, but not on mean arterial BP. As referred to above, BP levels defining the presence or absence of HTN differ with the use of pre-HD, post-HD, self-measured home BP, and ABPM. The recent National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines suggest that pre-HD and post-HD BP should be <140/90 and 139 mm Hg or DBP>89 mm Hg, can only be decided by future research. Current data suggest that there is a 'U-shaped' association between pre-HD BP and mortality. An analysis based on the CREED study cohort adjusted for Framingham risk factors, background CV complication, and left ventricular mass and ejection fraction shows that the risk of death is lowest in dialysis patients with a pre-dialysis SBP between 100 and 125 mm Hg,22Zager P.G. Nikolic J. Brown R.H. et al.'U' curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc.Kidney Int. 1998; 54: 561-569Abstract Full Text Full Text PDF PubMed Scopus (560) Google Scholar whereas SBP>150 mm Hg was associated with increased mortality.23Zoccali C. Arterial pressure components and cardiovascular risk in end-stage renal disease.Nephrol Dial Transplant. 2003; 18: 249-252Crossref PubMed Scopus (23) Google Scholar Severe cardiomyopathy modifies the relationship between BP and mortality, and survival is very low in ESRD patients with SBP<115 mm Hg.2Li Z. Lacson Jr, E. Lowrie E.G. et al.The epidemiology of systolic blood pressure and death risk in hemodialysis patients.Am J Kidney Dis. 2006; 48: 606-615Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar,24Klassen P.S. Lowrie E.G. Reddan D.N. et al.Association between pulse pressure and mortality in patients undergoing maintenance hemodialysis.JAMA. 2002; 287: 1548-1555Crossref PubMed Scopus (341) Google Scholar On the other hand, both post-dialysis SBP≥180 mm Hg and DBP≥90 mm Hg were associated with a substantial increase in CV mortality.22Zager P.G. Nikolic J. Brown R.H. et al.'U' curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc.Kidney Int. 1998; 54: 561-569Abstract Full Text Full Text PDF PubMed Scopus (560) Google Scholar This should be interpreted in the light of a report of increased mortality with declining SBP.2Li Z. Lacson Jr, E. Lowrie E.G. et al.The epidemiology of systolic blood pressure and death risk in hemodialysis patients.Am J Kidney Dis. 2006; 48: 606-615Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar The difference in outcomes in patients with very low and very high BP may lie in the presence of severe cardiomyopathy in the former. In an observational study in incident HD patients pre-HD SBP≥200 mm Hg was associated with increased mortality or CV events.2Li Z. Lacson Jr, E. Lowrie E.G. et al.The epidemiology of systolic blood pressure and death risk in hemodialysis patients.Am J Kidney Dis. 2006; 48: 606-615Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar Therefore, pre-HD SBP above this level should be treated aggressively. The BP ranges associated with the minimal risk related to the use of self-measured home BP monitoring are currently not known in CKD stage 5D patients. In the only study published so far, the best outcome was observed with a self-measured home SBP range between 120 and 145 mm Hg.3Alborzi P. Patel N. Agarwal R. Home blood pressures are of greater prognostic value than hemodialysis unit recordings.Clin J Am Soc Nephrol. 2007; 2: 1228-1234Crossref PubMed Scopus (165) Google Scholar Research recommendations are listed in Table 1. Abbreviations: ABPM, ambulatory blood pressure measurement; BP, blood pressure; CKD, chronic kidney disease; HD, hemodialysis; PP, pulse pressure; RCT, randomized controlled trial. End-stage kidney disease is associated with a 10- to 20-fold increased risk of CV mortality, compared with age- and sex-matched controls without CKD,25Foley R.N. Collins A.J. End-stage renal disease in the United States: an update from the United States Renal Data System.J Am Soc Nephrol. 2007; 18: 2644-2648Crossref PubMed Scopus (339) Google Scholar and sudden death accounts for the majority of deaths. LVH in dialysis patients has been convincingly attributed to fluid overload, HTN, neuron–humoral activation, and severe anemia.26Remppis A. Ritz E. Cardiac problems in the dialysis patient: beyond coronary disease.Semin Dial. 2008; 21: 319-325Crossref PubMed Scopus (38) Google Scholar CV risk factors are accentuations of the risk factors observed in stage 4 and 5 CKD patients (for example, vascular medial calcification). In addition, dialysis patients have additional unique risk factors (for example, acute fluid and electrolyte shifts during HD).27Selby N.M. McIntyre C.W. The acute cardiac effects of dialysis.Semin Dial. 2007; 20: 220-228Crossref PubMed Scopus (130) Google Scholar Pharmacokinetics of antihypertensive and putative cardioprotective drugs are altered by both impaired kidney excretion of the drugs and by their dialyzability. The multitude of drugs that these patients usually take reduces compliance, because of tolerability, interactions with other drugs, side effects, and financial costs.28Schmid H. Hartmann B. Schiffl H. Adherence to prescribed oral medication in adult patients undergoing chronic hemodialysis: a critical review of the literature.Eur J Med Res. 2009; 14: 185-190Crossref PubMed Google Scholar Pharmacotherapy to lower BP may cause additional problems that are unique to dialysis patients, such as intradialytic hypotension and vascular access thrombosis.29Sulowicz W. Radziszewski A. Dialysis induced hypotension – a serious clinical problem in renal replacement therapy.Med Pregl. 2007; 60: 14-20PubMed Google Scholar These patients may be more prone to side effects of certain drugs than patients with earlier stages of CKD. The presence of and propensity to these side effects may be easily overlooked. For example, minoxidil may potentiate or be confused with uremic pericardial effusion. The evidence to guide practitioners in BP management, CV risk factors, and CV end-organ diseases is poor. Uncertainties in therapeutic indices of treatment strategies that have been proven in the nondialysis population, such as angiotensin-converting enzyme inhibitors, generate much controversy among nephrologists caring for the dialysis population. β-Blockers have been suggested to be cardioprotective in HD in a small randomized controlled trial.30Cice G. Ferrara L. D'Andrea A. et al.Carvedilol increases two-year survival in dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial.J Am Coll Cardiol. 2003; 41: 1438-1444Abstract Full Text Full Text PDF PubMed Scopus (439) Google Scholar Many practice guidelines are largely based on low-quality evidence and opinions. Cardiac deaths account for the majority of CV deaths in dialysis patients. The exact etiologies of these cardiac deaths are often unknown and likely include primary and secondary arrhythmias, cardiomyopathy, and coronary artery disease, and involve complex pathogeneses. Although fluid overload, increased afterload from HTN and vascular calcification, calcified valvular disease, and ischemia are probably important contributory factors, uremia per se seems to be an additional factor. To what extent hyperkalemia and hypokalemia, frequently present in these patients, contribute to the high incidence of sudden death in dialysis patients is not certain, but recent papers suggested the greater danger of hypokalemia.31Herzog C.A. Mangrum J.M. Passman R. Sudden cardiac death and dialysis patients.Semin Dial. 2008; 21: 300-307Crossref PubMed Scopus (236) Google Scholar,32Karnik J.A. Young B.S. Lew N.L. et al.Cardiac arrest and sudden death in dialysis units.Kidney Int. 2001; 60: 350-357Abstract Full Text Full Text PDF PubMed Scopus (261) Google Scholar In addition to their antihypertensive effects, some drugs are variably cardioprotective, which may be independent of their BP-lowering effects. Notable examples in this category are inhibitors of the renin–angiotensin–aldosterone system (RAAS), β-adrenergic blockers, CCBs, and aldosterone inhibitors (not in HD),33Sato A. Saruta T. Funder J.W. Combination therapy with aldosterone blockade and renin-angiotensin inhibitors confers organ protection.Hypertens Res. 2006; 29: 211-216Crossref PubMed Scopus (47) Google Scholar although the real impact beyond the BP-lowering effect of some of these agents is a matter of controversy and has been scrut
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