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

Abstract

Background: Chronic kidney disease is a persistent disorder in kidney function. This is a progressive disorder characterized by arterial hypertension, glomerular hypertension, proteinuria and some other signs; controlling any of them can reduce the progression of chronic kidney disease. In chronic kidney disease, proteinuria is used as a measure for monitoring nephron injuries and its response to treatment. Angiotensin converting enzyme inhibitors and Angiotensin receptor blockers can reduce the progression of chronic kidney disease by inhibition of Renin-Angiotensin-Aldosterone system and reduction of glomerular pressure and controlling proteinuria. However, none of them can control plasma aldosterone level appropriately. Aldosterone produces Transforming growth factor-b (TGF-b), which induces proliferation of fibroblasts and glomerulosclerosis and accelerates chronic kidney disease. Aldosterone antagonist can increase useful effects of angiotensin-converting-enzyme inhibitor (ACEI) and Angiotensin receptor blockers (ARB) Drugs. Objectives: The study was designed to assess the effects of spironolactone as the aldosterone antagonist combined with ACEI or ARB 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 with ACEI or ARB with uncontrolled proteinuria above 0.9g/dL were treated with 25mg/d spironolactone for two months. 24-hour urine protein and some other variables were measured at the beginning of the study, after two months treatment and one month after discontinuing the treatment. Results: Administration of 25 mg/d spironolactone combined with ACEI or ARB for two months led to mean reduction of 24 h-urine protein from 2796.1 to 1857.4. No hyperkalemia or change in glomerular filtration rate occurred. One month after discontinuation of spironolactone, proteinuria returned to baseline level. Persistence of reduction in proteinuria in patients receiving ARBs was more than those taking ACEIs. Conclusions: Spironolactone combined with ACEIs or ARBs leads to reduction of proteinuria in chronic kidney disease and therefore reduction of progression of the disease.

Nicotinamide for photoprotection and skin cancer chemoprevention: A review of efficacy and safety

“…Also in ESRD patients, Takahashi et al reported that their 5 cases of diarrhoea (7.7%) occurred at dose of NAM >1500 mg/d. Shahbazian et al's study reported four patients (16.7%) with diarrhoea that occurred when their dose of NAM increased from 500 to 1000 mg/d. Their symptoms resolved with the reduction in NAM, as did Cheng et al's one patient with diarrhoea, suggesting a possible dose‐dependent relationship.…”

“…A number of recent studies have investigated NAM's action in reducing phosphate levels in patients with end‐stage renal disease (ESRD) requiring dialysis …”

“…In the adult studies, diarrhoea was reported to occur in patients with ESRD requiring haemodialysis, with an average dose of NAM of 1000 mg/d or more, and at an incidence between 3% and 23% …”

“…The paediatric population experienced additional gastrointestinal symptoms of nausea and vomiting at rates of 30% and 7%, respectively. All reports of diarrhoea with NAM ceased promptly with either spontaneous resolution, a dose reduction, or after ceasing the vitamin at the end of the study . Following its metabolism into one of three possible by‐products (methylation, oxidation or hydroxylation), NAM is excreted by the kidneys .…”

“…Thrombopenia from NAM was reported in three adult studies and one paediatric study. It was reported as having occurred in varying degrees and only in patients with ESRD on dialysis …”