Our case analysis is of a 44 year old Hispanic female Patient who has been noted to have an uncontrolled blood pressure of 191/115 mmHg. To manage her blood pressure, the patient has been under home medication. The home medication is 20mg doxazosin and 25mg tablets that she takes twice a day. She also undergoes dialysis three times a week. The patient smokes and has diabetes and ESRD. The mentioned conditions are probably the reasons why her blood pressure is greatly affected. With such a compromised blood pressure, she stands a great chance of developing cardiovascular diseases (CVD). The patient is not responding to the mentioned medication and thus there is a consideration to switch her to ACEI and ARBs therapies.
Hypertension is common among patients on dialysis. It is a major risk factor of CVD related death. Thus, management of blood pressure is critical in reducing morbidity and mortality. The recommended pre-dialysis blood pressure is <140/90 mm Hg and post-dialysis blood pressure is <130/80 mm Hg. These are clinical guidelines provided by K/DOQI for cardiovascular disease in dialysis patients. K/DOQI notes the use of either ACEI or ARBs as the preferred medication in ESRD patients. ACEI and ARBs have been associated with lowering mortality in ESRD patients. However, K/DOQI Clinical Practice Guidelines on hypertension and antihypertensive Agents in Chronic Kidney Disease recommended the use of the combination therapy of ACEI and ARBs in CVD patients with diabetes. It proves to be beneficial in lowering blood pressure, slowing the progression of kidney disease and reduce proteinuria.
Efrati, Zaidenstein and Dishy conducted a study to investigate the efficacy of ACEI on mortality of ESRD patients undergoing long-term hemo-dialysis. The study included 177 hemo-dialysis patients’ records between the years 1994 and 1999. The study though is retrospective. There is no specified inclusion criterion and it excluded any patient that was on dialysis for less than a year or those who had received a kidney transplant. The study also excluded patients who had left the dialysis unit and those with Kt/V <1 or any record with inadequate clinical information. A study sample population of 126 patients (n=66 ACEI, n=60 none) were followed for an average of 59 months. Statistical tests done were in RR and at 95% CI. The study used control group and a treatment group. The control group comprised of 64 patients were less than 65 years old and 62 patients who were more than 65 years old. The study revealed that LVH was significantly higher in the treated group at 60 percent compared with the control group at 33 percent. The mean diastolic blood pressure was also significantly higher in the treated group 84.5 _ 10.6 at relative to the control group at 78.7 _ 11.4 mm Hg; P _ 0.015. Similarly, the proportion of patients in the treatment group who received alpha-blockers was 48%, which was significantly higher than that of the control group at 23%. A follow up revealed that the mean systolic blood pressure of the treatment group was 143 _ 18.9 mm Hg that is significantly higher than the control group at 132.5 _ 21.4 mm Hg. Similarly, the follow up also revealed that the mean systolic blood pressure of the treatment group was 77.9 _ 9.0 mm Hg that is significantly higher than the control group at 72.6 _ 8.4 mm Hg. Therefore, it can be concluded that there is a potential negative relationship between ACE inhibitor and death rates.
Another review article by Cravedi, Remuzzi and Ruggenent explored whether renin–angiotensin system (RAS) inhibitors had cardio-protective effects in patients on dialysis. It also investigated possible effects of these drugs on residual renal function (RRF), vascular access survival, and filtration properties of the peritoneal membrane. The included tests on the efficacy of Ramipril in Nephrology (REIN) and the effects of Angiotensin II Antagonist Losar- tan (RENAAL) in reducing the endpoints in NIDDM. These trials consistently indicated that ACE inhibitors and ARBs may preserve the integrity of RRF in patients with severe (stage 4–5 CKD) renal insufficiency. An analysis of ACE inhibitor or ARB therapies in 837 patients some of who were on hemodialysis displayed a huge loss in LV mass compared to therapies that do not inhibit the renin–angiotensin system (RAS). The significance of the loss of LV mass can prolong life. In addition, it is more important that this loss was the result of the use of ACE inhibitor or ARB therapies. Evidence shows that a combination of both ARBs and ACE inhibitor offers better results. This is in comparison with when ACE inhibitor is singly used. A randomized study on 332 patients showed that the addition of ACE inhibitor to a telmisartan therapy or placebo could reduce deaths by up to 49% than when ACE inhibitor is singly used. Other beneficial outcomes noted because of using ACE inhibitor in combination therapies included: improved NYHA functions and left ventricular reverse remodeling. A small, randomized open-label controlled trial of 60 continuous ambulatory peritoneal dialysis (CAPD) patients comparing ramipril to a control group reveals that the risk of anuria and decline rate in GFR over a period of one year was significantly lower in the treatment group
Several limitations noted in the two separate review study articles done by Efrati, Zaidenstein and Dishy and that done by Cravedi, Remuzzi and Ruggenent. Both studies base their consideration on the findings carried out on patients with patients with ESRD. The effectiveness of both angiotensin-converting enzyme (ACE) inhibitors and the angiotensin II receptor blockers (ARBs) is assumed on persons who have been diagnosed with end-stage renal disease and not those who ESRD free. The inconsideration of persons free from ESRD from such conclusion renders such assumption invalid. These are the shortcomings associated with these two studies. Because these reviews are only based on assumptions that do no clarify whether ARB and ACEI have a renal protective effect, they simply do not grant conclusive answer to our question. Efrati, Zaidenstein and Dishy admit to the limitation of their study in that their population sample use was not sufficiently representative, their design seemed somehow outdated and that their procedures were not standard . The length of time required to carry out monitoring of progressive conditions are normally longer than the scope of these reviews could allow. The review by Efrati, Zaidenstein and Dishy did not reveal whether there is a relationship between the action of angiotensin-converting enzyme (ACE) inhibitors and the control of blood pressure thus it is hard to tell if at all, any relationship does exist . The review by Cravedi, Remuzzi and Ruggenenti also admits to the fact that the authors cannot confirm that there is a proved curing effect of the renin–angiotensin system inhibiting drugs such as angiotensin-converting enzyme (ACE) inhibitors and the angiotensin II receptor blockers (ARBs) on the population of persons with dialysis problems . The review also agrees that the specific protective effects of these renin–angiotensin system inhibiting medication on the cardiovascular system of persons with end-stage renal disease ( ESRD) remains largely unknown and thus cannot be explained and that their application cannot be verified . The publication goes ahead to claim that for the most part, the assumption of the cure of cardiovascular diseases by angiotensin-converting enzyme (ACE) inhibitors and the angiotensin II receptor blockers (ARBs) is largely based on a partial and non-representative population and not the whole population of persons with end-stage renal disease ( ESRD) and those without . This is similar to the claim admitted by the article publication reviewed by Efrati, Zaidenstein and Dishy. The authors also base their arguments on the findings of small-randomized control trial to prove that ACEI/ARBs preserve renal functions. There is no evidence from large randomized trials that can allow conclusive findings from which generalizations can be drawn.
It is important to avoid making conclusive assumption on whether angiotensin-converting enzyme (ACE) inhibitors and the angiotensin II receptor blockers (ARBs) are effective in acting as protective agents in impaired renal system. Efrati, Zaidenstein and Dishy reveal that the mean blood pressure was higher despite the use of ACEI. Further investigation that incorporates the review of populations not suffering from end-stage renal disease could be carried out as control samples so that thorough and valid assumption can be drawn on the effectiveness of these medications. Similarly engaging a large population as a sample and in a more randomized way will ensure that conclusions and assumptions made from such studies are sufficiently representative. It will also be vital to allocate sufficient time to ensure progressive conditions within the test populations are sufficiently monitored. The two studies provided an insight of the direction in which further studies and research can take. The good thing is that the studies proved that RAS inhibition could contribute to reduction of CVD related deaths in patients on hemodialysis.
Works Cited
Cravedi, Paolo, Giuseppe Remuzzi and Piero Ruggenenti. "Targeting the Renin Angiotensin System in Dialysis Patients." Seminars in Dialysis 24.3 (2011): 290–297.
Efrati, Shai, et al. "ACE Inhibitors and Survival of Hemodialysis Patients." American Journal of Kidney Diseases 40.5 (2002): 1023-1029.
