Assessment of the Effects of the Combination of Spironolactone to Conventional Pharmacotherapy in Dialysis Patients

Materials and Methods: will be conducted an interventional, randomized, double-blind, placebo-controlled study. The series will consist of patients with at least 18 years old, suffering from chronic kidney disease stage V on dialysis and mean residential blood pressure superior to 135 x 85 mm Hg with left ventricular mass indexed for height to the 2.7 power greater than 51 g/m2,7. This protocol follows the guidelines of resolution 196/96 of the Brazilian National Health Council and is approved by the Ethics Committee of the Faculty of Medicine of Botucatu - UNESP Protocol (CEP 3439-2010).

All patients will give informed consent in writing. Exclusion criteria will be thew following: history or evidence of angina or myocardial infarction, heart failure, peripheral vascular disease, Hyperkalemia, valvular disease, atrial fibrillation, anemia (hemoglobin <10 g / dl) doses of parathyroid hormone (PTH) greater than 300 pg / mL, patients in treatment with spironolactone and Patients who have suspended or initiated the use of inhibitors of angiotensin converting enzyme inhibitors, angiotensin receptor blockers and renin blockers in the last six months. Patients will be assessed at baseline (before the run-in phase), weekly in the first month and monthly thereafter until one year, or 52 weeks. Will be include clinical examination at each visit and laboratory tests. In the visits of weeks zero, 26 and 52 will be held monitoring home blood pressure, echocardiography, determining the of pulse wave velocity, central arterial pressure and augmentation index. Aldosterone an ouabaín will be monitored immediately before run-in fase and at 52 weeks.

Groups: Patients will be randomly divided into two groups: active drug and placebo groups. One group will receive spironolactone and the other placebo spironolactone. It is important to note that placebo therapy is only of spironolactone and not other anti-hypertensive drugs, so patients will not in any way deprived of the benefit established in the literature which is the reduction of blood pressure. Physicians' assistants enrolled will be free to prescribe any antihypertensive medication except the study drug. In the active treatment group, the dose employed will be 25 mg each other day and titrated to 25 mg daily according to the potassium. Patients with potassium between 5.5 and 5.9 mmol/L will have reduced spironolactone to 25 mg each other day if they are in use 25 mg daily or will not increase the dose. These patients receive pharmaceutical care and nutritional guidance according the routine of the unit.

The placebo group will receive placebo with the same protocol. These patients also receive pharmaceutical care and nutritional guidance, beyond any conventional antihypertensive treatment. The pharmaceutical form of placebo will consist of colloidal silicon dioxide, cornstarch, lactose monohydrate, microcrystalline cellulose and magnesium stearate, inert excipients according to reference literature. The pharmaceutical form of the active drug will consist of spironolactone 25 mg and the other components of the placebo.

The laboratory tests will be performed as routine in our dialysis unit, which follow the rules of operation of hemodialysis established by the Brazilian Ministry of Health, as follows: blood samples are collected immediately before the start of hemodialysis for routine hematology (red blood cells, platelets white blood cell count) and biochemical (urea, creatinine, potassium, calcium, phosphorus, glutamic-pyruvic transaminase and venous blood gas) monthly. Will be held quarterly glycosylated hemoglobin for diabetics, total proteins and fractions, alkaline phosphatase, transferrin, serum iron, ferritin, C-reactive protein, parathyroid hormone and lipid levels, the dosage of uric acid is each six months and aluminum will be annual. Measurement of plasma renin, aldosterone, angiotensin II and ouabaín will be held at time zero and after 52 weeks. Urine collections in 24 hours will be obtained for measurement of residual urea clearance and calculation of protein nitrogen appearance in weeks zero, 26 and 52. Will be collected monthly samples of urine after dialysis for determination of fractional clearance of urea (dialysis dose) that will be determined by the Daugirdas's formula (1995). Prior to collecting samples for measurement of plasma renin, the patient should be 2 h in the supine position (stabilization of serum and standardization of interpretation of results).