Mugendi AG, BPharm, MPharm (Clin Pharm). Comparison of the effects of losartan and enalapril on renal function in adults with chronic kidney disease at.

Mugendi AG,

BPharm, MPharm (Clin Pharm)

Comparison of the effects of losartan and enalapril on renal function in adults with chronic

kidney disease at Kenyatta National Hospital

Introduction Chronic kidney disease (CKD) is a growing

health concern

Its prevalence is increasing at a rate of 8% per year worldwide

The renin angiotensin aldosterone system is strongly implicated in the progression of kidney failure

Introduction Angiotensin II converting enzyme inhibitors

and angiotensin II receptor blockers inhibit this system

They control blood pressure and retard the progression to end stage renal failure

Enalapril and losartan are commonly used at the renal and diabetic clinics in Kenyatta National Hospital

Study problemPrevious studies evaluated the adequacy of blood

pressure control in patients with CKD and hypertension

They did not investigate the state of renal function in patients who were on ACE inhibitors or ARBs

No comparisons were done between ACEi and ARBs

Paucity of local and regional data regarding the use of these drugs and renal outcomes

Objectives Broad objective To compare the effects of enalapril and

losartan on renal function in adults with chronic kidney disease at KNH

Specific objectives1. To compare the incidence of doubling of

baseline serum creatinine concentrations in patients using enalapril and losartan based regimens

Objectives Specific objectives 2. To compare the change in the level of

proteinuria in patients using enalapril and losartan based regimens

3. To compare the change in estimated glomerular filtration rate in patients using enalapril and losartan based regimens

Methodology Ethical approval was granted by the KNH UoN ERC

Retrospective analytic cohort at the Kenyatta National Hospital from January 2006-December 2012

Data collection was done between June and August 2013

Two arm study – enalapril and losartan

Male and female patients 18 years of age or older with hypertension and diabetic nephropathy were recruited

Results – doubling of serum creatinine Patients on losartan had a higher risk of doubling

of serum creatinine (Adjusted HR=1.572; 95% CI: (1.015-2.434); p=0.043) than those on enalapril

A significant difference in survival probabilities between the two arms – losartan 18 months, enalapril 36 month (p=0.046)- was noted

P=0.046Log Rank Test

Figure 1: Kaplan –Meir survival probability curve to first doubling of serum creatinine

Results – changes in eGFR Significant differences in the means of the

estimated glomerular filtration (eGFR) rates between the two arms were observed at months 3 (p=0.045) and month 6 (p=0.046) of follow up

Univariate analysis of variance revealed that increased length of therapy with either agent was protective (p=0.007)

Figure 4: Plot of the mean eGFR from baseline at different time points between the two arms.

Discussion Both drugs inhibit the renin angiotensin

aldosterone system

However, there is differential stimulation of the kallikrein kinin system (KKS)

KKS activation causes inhibition of the progression of diabetic nephropathy

Postulated to be the main reason for the difference of effect

Conclusion Patients on enalapril are less likely to

experience a doubling of baseline serum creatinine

Renal function is better preserved in patients on enalapril

Prolonged duration of therapy is also renoprotective

Recommendation Enalapril should be first line therapy in

hypertensive patients with diabetic nephropathy

RAAS blockers should be initiated as soon as possible after diagnosis

Larger studies- prospective cohort or randomised clinical studies- are required

Challenges 1. Incomplete records was the biggest

challenge