1. Mugendi AG, BPharm, MPharm (Clin Pharm)

2. Comparison of the effects of losartan and enalapril on renal function in adults with chronic kidney disease at Kenyatta National Hospital

3. 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

4. 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

5. Study problem Previous 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

6. Objectives Broad objective  To compare the effects of enalapril and losartan on renal function in adults with chronic kidney disease at KNH Specific objectives 1. To compare the incidence of doubling of baseline serum creatinine concentrations in patients using enalapril and losartan based regimens

7. 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

8. 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

9. 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

10. Results – doubling of serum creatinine P=0.046 Log Rank Test Figure 1: Kaplan –Meir survival probability curve to first doubling of serum creatinine

11. 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)

12. Results – changes in eGFR Figure 4: Plot of the mean eGFR from baseline at different time points between the two arms.

13. 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

14. 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

15. 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

16. Challenges 1. Incomplete records was the biggest challenge