Antihypertensive drug use
Despite the controversies regarding BP measurement and optimal BP targets for HD patients, the use of antihypertensive medications in these patients does seem to confer benefits. A meta-analysis of eight randomized clinical trials in 1,679 patients on dialysis (including some patients on peritoneal dialysis) demonstrated that active antihypertensive treatment significantly reduced the risk of cardiovascular events, all-cause mortality, and cardiovascular mortality by 29%, 20%, and 29%, respectively, compared with controls.19
The eight trials included in the meta-analysis used a variety of antihypertensive medication classes, including beta-blockers, ACE inhibitors, angiotensin receptor blockers and calcium channel blockers, but none was compared head-to-head. Thus, recommendations regarding the preferential use of specific drug classes remain largely based on extrapolation from non-dialysis populations (e.g., beta-blockers following a myocardial infarction).
Of note, in the recent Hypertension in Hemodialysis Patients Treated with Atenolol or Lisinopril (HDPAL) study,20 HD patients with left ventricular hypertrophy and hypertension randomized to an atenolol-based regimen had lower rates of heart failure and other cardiovascular events compared with patients receiving a lisinopril-based regimen. However, this was a relatively small study (200 patients) with predominately African-American patients (86%), necessitating replication of this trial in larger, more diverse dialysis populations.
In summary, there are a number of controversies regarding BP management in HD patients, including the optimal method of measurement, appropriate and safe BP targets, and whether certain classes of antihypertensive medications are preferred over others.
Despite these ongoing uncertainties, controlling BP to a level of less than 140/90 mm Hg pre-dialysis using a combination of pharmacologic and non-pharmacologic therapies (e.g., maximizing ultrafiltration, reducing sodium exposure in the diet and dialysate, and extending the duration and frequency of HD), without precipitating intradialytic hypotension, is a reasonable goal. Future studies that will put these controversies to rest are clearly needed.
Dr. Chang is an instructor in medicine (nephrology) at the Stanford University School of Medicine in Palo Alto, Calif.
- U.S. Renal Data System, USRDS 2013 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health, Editor 2013: Bethesda, MD.
- Agarwal R, Lewis RR. Prediction of hypertension in chronic hemodialysis patients. Kidney Int 2001;60:1982-1989.
- Agarwal R, Peixoto AJ, Santos SF, Zoccali C. Pre- and postdialysis blood pressures are imprecise estimates of interdialytic ambulatory blood pressure. Clin J Am Soc Nephrol 2006;1:389-398.
- Fagugli RM, Ricciardi D, Rossi D, et al. Blood pressure assessment in haemodialysis patients: comparison between pre-dialysis blood pressure and ambulatory blood pressure measurement. Nephrology 2009;14::283-290.
- Agarwal R, Brim NJ, Mahenthiran J, et al. Out-of-hemodialysis-unit blood pressure is a superior determinant of left ventricular hypertrophy. Hypertension 2006;47:62-68.
- Khangura J, Culleton BF, Manns BJ, et al. Association between routine and standardized blood pressure measurements and left ventricular hypertrophy among patients on hemodialysis. BMC Nephrol 2010;11:13.
- Agarwal R. Blood pressure and mortality among hemodialysis patients. Hypertension 2010;55:762-768.
- Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903-1913.
- Li Z, Lacson E Jr, Lowrie EG, et al. The epidemiology of systolic blood pressure and death risk in hemodialysis patients. Am J Kidney Dis 2006;48:606-615.
- Robinson BM, Tong L, Zhang J, et al. Blood pressure levels and mortality risk among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2012;82::570-580.
- National Kidney Foundation. Clinical practice guidelines and clinical practice recommendations 2006 Update. Am J Kidney Dis 2006;48:S1-S322 (suppl 1).
- Levin NW, Kotanko P, Eckardt KU, et al. Blood pressure in chronic kidney disease stage 5D-report from a Kidney Diseaes: Improving Global Outcomes controversies conference. Kidney Int 2009;77:273-284..
- Davenport A, Cox C, Thuraisingham R. Achieving blood pressure targets during dialysis improves control but increases intradialytic hypotension. Kidney Int 2008;73:759-764.
- Burton JO, Jefferies HJ, Selby NM, McIntyre CW. Hemodialysis-induced cardiac injury: determinants and associated outcomes. Clin J Am Soc Nephrol 2009;4:914-920.
- Chang TI, Paik J, Greene T, et al. Intradialytic hypotension and vascular access thrombosis. J Am Soc Nephrol 2011l;22:1526-1533.
- Shoji T, Tsubakihara Y, Fujii M, Imai E. Hemodialysis-associated hypotension as an independent risk factor for two-year mortalty in hemodialysis patients. Kidney Int 2004;66:1212-1220.
- Tislér A, Akócsi K, Borbás B, et al. The effect of frequent or occasional dialysis-associated hypotension on survival of patients on maintenance haemodialysis. Nephrol. Dial. Transplant 2003;18:2601-2605.
- Tislér A, Akócsi K, Hárshegyi I, et al. Comparison of dialysis and clinical characteristics of patients with frequent and occasional hemodialysis-associated hypotension. Kidney Blood Press Res 2002;25:97-102.
- Heerspink HJ, Ninomiya T, Zoungas S, et al. Effect of lowering blood pressure on cardiovascular events and mortality in patients on dialysis: a systemic review and meta-analysis of randomised controlled trials. Lancet 2009;373:1009-1015.
- Agarwal R, Sinha AD, Pappas MK, et al. Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized controlled trial. Nephrol Dial Transplant 2014 (Epub ahead of print).