Feasibility of combined treatment with enalapril and candesartan in advanced chronic kidney disease

BACKGROUND: Dual blockade of the renin-angiotensin system (RAS) has been claimed to have a specific renal protective effect in chronic kidney disease (CKD). The present short-term study reports on the feasibility of dual blockade in a consecutive group of patients with CKD stage 3-5. METHODS: Forty-seven CKD patients, mean age 59 years, with mean estimated glomerular filtration rate (GFR) 26 ml/min/1.73 m(2) (range 13-49) and blood pressure (BP) 133/78 mmHg, were block randomized in an open study to 16 weeks of monotherapy with increasing doses of RAS blockade aiming at enalapril 20 mg o.d. or candesartan 16 mg o.d. Thereafter, the complementary drug was added in incremental doses over a period of 5 weeks aiming at combined enalapril 20 mg and candesartan 16 mg for 3 weeks. Seventy-five percent of the patients were known to be RAS blockade tolerant. Blood samples and BP were measured every 2-3 weeks. Doses of study medication were reduced in case of hyperkalemia >5.5 mmol/l, a sustained rise in p-creatinine >30% or symptomatic hypotension. RESULTS: Twenty-one patients (45%) did not tolerate dual blockade in aimed dosages due to unacceptable p-creatinine increase (n = 12, including two study withdrawals), hypotension (n = 6), general discomfort (n = 2) or unmanageable hyperkalemia (n = 1). Hyperkalemia >5.5 mmol/l was seen in seven patients (15%). The reduced-dose group had baseline lower eGFR and diastolic BP. CONCLUSIONS: Forty-five percent of CKD stage 3-5 patients did not tolerate dual RAS blockade with 20 mg enalapril and 16 mg candesartan daily, primarily due to loss of renal function or hypotension. Hyperkalemia could be managed in most patients. Caution is recommended when giving this treatment to patients with advanced CKD.