Assessment of Spironolactone Effects on the Prevention of Progression of Proteinuria in Chronic Kidney Diseases

Abstract

AbstractBackground: Chronic kidney disease is a persistent disorder in kidney function. This is a progressive disorder characterized byarterial hypertension, glomerular hypertension, proteinuria and some other signs; controlling any of them can reduce the progressionof chronic kidney disease. In chronic kidney disease, proteinuria is used as a measure for monitoring nephron injuries andits response to treatment. Angiotensin converting enzyme inhibitors and Angiotensin receptor blockers can reduce the progressionof chronic kidney disease by inhibition of Renin-Angiotensin-Aldosterone system and reduction of glomerular pressure andcontrolling proteinuria. However, none of them can control plasma aldosterone level appropriately. Aldosterone produces Transforminggrowth factor-b (TGF-b), which induces proliferation of fibroblasts and glomerulosclerosis and accelerates chronic kidneydisease. Aldosterone antagonist can increase useful effects of angiotensin-converting-enzyme inhibitor (ACEI) and Angiotensin receptorblockers (ARB) Drugs.Objectives: The study was designed to assess the effects of spironolactone as the aldosterone antagonist combined with ACEI orARB drugs to reduce proteinuria in chronic kidney disease to prevent its progression.Patients and Methods: This was a semi-experimental without control study. Eighty patients treated for at least two months withACEI or ARB with uncontrolled proteinuria above 0.9g/dL were treated with 25mg/d spironolactone for two months. 24-hour urineprotein and some other variables were measured at the beginning of the study, after two months treatment and one month afterdiscontinuing the treatment.Results: Administration of 25 mg/d spironolactone combined with ACEI or ARB for two months led to mean reduction of 24 h-urineprotein from 2796.1 to 1857.4. No hyperkalemia or change in glomerular filtration rate occurred. One month after discontinuationof spironolactone, proteinuria returned to baseline level. Persistence of reduction in proteinuria in patients receiving ARBs wasmore than those taking ACEIs.Conclusions: Spironolactone combined with ACEIs or ARBs leads to reduction of proteinuria in chronic kidney disease and thereforereduction of progression of the disease.Keywords: Spironolactone, Proteinuria, Angiotensins, Aldosterone, Chronic Kidney Disease1. BackgroundChronic kidney disease (CKD) is a persistent disorder inthe kidney function so that the kidney cannot maintain thenormal values of protein metabolic products such as urea,blood pressure, hematocrit and acid-base equilibrium. Atlast, it leads to end stage renal disease (ESRD), which needskidney replacement treatment such as dialysis or kidneytransplantation (1). These patients are often symptom-freeuntil the final stages of disease, but have numerous laboratorychanges such as proteinuria (1). Risk factors of chronickidney disease