FP083TREATMENT OF HYPERURICEMIA WITH ALLOPURINOL IN RESISTANT HYPERTENSIVE PREDIALYSIS CHRONIC KIDNEY DISEASE PATIENTS HAVE ADDITIONAL POSITIVE EFFECTS ON BLOOD PRESSURE AND RENAL FUNCTION

Abstract

Introduction and Aims: Elevated levels of serum uric acid have been associated with an increased risk of cardiovascular disease (CVD). Small studies have observed an antihypertensive effect of urate-lowering therapy with Allopurinol (A) in hyperuricemic patients and in obese adolescent males with hypertension. The aim of this study was to investigate effects of A therapy on blood pressure (BP) and renal function parameters in predialysis chronic kidney disease patients (CKDND) with resistant hypertension (RHp). Methods: A total of 50 RHp patients with CKDND were divided in two groups: 25 RHp who had BP readings taken before and after being prescribed A for 6 weeks (Group 1) and 25 RHp who had not taken A (Group 2), both groups (12M/13F, age 68 ±7 years in Group 1, and 67±8 years in Group 2, duration of RH 11±6 years), from RHp registar in our hospital. RH was defined as BP remaining above goal, despite the use of optimal doses of 3 or more than three medicines of different classes (including a diuretic). Patients with a history of gout were excluded, and levels of serum uric acid were from 333-605 umol/L. No patients received a higher dose than 200 mg A daily. We investigated the incidence of worsening of chronic kidney disease (CKD) in Group 1 and 2 using the Modification of Diet in Renal Disease Study (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in estimating glomerular filtration rate (eGFR). Level of statistical significance was chosen to be p<0.05. Statistical analysis was performed by statistical package STATA/IC ver.11.1. Results: Treatment with A (Group 1) caused an additional significant reduction in BP: systolic BP fell 9.8 mmHg and diastolic 8.0 mmHg compared with Group 2. Reduction of BP was not related to the primary uric acid level or to other drugs the patients were taking. Number of antihypertensive medication was for 3-8 and most used drug classes were: diuretic in 100% (including thiazides which can raise uric acid levels and indapamide), angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in 100%, calcium antagonists in 94%, beta blockers (nebivolol or carvedilol) in 82%, central acting drugs in 64%, alfa-blockers in 26%, vasodilatators in 8%, mineralocorticoid receptor antagonists: spironolactone in 24% and eplerenone in 4%. Worsening of renal function in CKDND patients with RHp in Group 1 was not observed: MDRD ≥ 60 mL/min per 1.73m2 (stages 1 and 2) have 62% patients in Group 1 and 60% in Group 2 , 22% of patients in Group 1 have CKD stage 3, 14% stage 4 and 2% stage 5. In Group 2 23% of patients have CKD stage 3, 15% stage 4, and 2% stage 5. There were no significant differences between the eGFR values derived by MDRD and CKD-EPI in both groups ( p>0.05). Conclusions: The results of our study suggest that therapy with A lowered BP in RHp with CKDND without worsening of kidney function. Blocking the xanthine oxidase-mediated conversion of molecular oxygen to produce mediators of oxidative stres can partially explane additional BP lowering and safety of A in RHp with CKDND.