الفهرس 
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Abstract
Summary
Diabetes mellitus (DM) is one of the commonest chronic disorders which is characterized by chronic hyperglycemia and impaired metabolism of fats and proteins. It is a disease of the most important diseases worldwide and is increasing in prevalence.
The microvascular complications of DM include diabetic nephropathy (DN), which is the most common cause of end stage renal disease. The presence of kidney disease is associated with markedly increased cardiovascular morbidity and mortality in people with diabetes.
Diabetic nephropathy (DN) is associated with increased urine protein excretion. A minimal increase in albumin excretion in urine (microalbuminuria) or (incipient DN) characterizes the early stage of DN. Further progression of the disease is associated with macroalbuminuria or (overt DN).
The earlier diabetic nephropathy abnormalities involve locally occurring damages of the kidneys facilitated by uncontrolled blood glucose level in both types of diabetes mellitus. The hemodynamic impacts of enhanced RAAS and deficient autoregulation of afferent arterioles compound this. Over time, this local renal damage results in decreased glomerular filtration rate (GFR) and albuminuria.
The inhibition of RAAS at several levels provides the current cornerstone for antihypertensive, cardioprotective and renoprotevtive therapies, such as angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), renin inhibitors or mineralocorticoid receptor antagonists (MRAs).
When aldosterone is incompletely blocked the anti-albuminuric benefit is also incomplete in patients with diabetic nephropathy and diabetic kidney disease continues its progression and this may occur when ACEIs or ARBs are used as monotherapy without adding another aldosterone antagonist. This inadequate blockade was demonstrated by several studies to be a result of aldosterone escape or rebound which occurs in many of patients with DN during long-term blockade of the renin-angiotensin-aldosterone system by ACEIs or ARBs alone and is associated with an accelerated rate of decline of GFR.
Therefore, aldosterone antagonists are essential for inhibiting the progression of diabetic kidney disease in diabetic hypertensive patients. This may be fulfilled by the use of the nonselective aldosterone blocker spironolactone or by using the selective aldosterone blocker eplerenone. Both drugs are effective in reduction of blood pressure and renal protection but eplerenone is superior to spironolactone as eplerenone lacks the antiandrogenic or progestational side effects which frequently happen with spironolactone therapy.
In our study we compared the antiproteinuric efficacy of ramipril (ACEI), eplerenone (selective MRA) and their combination among patients with type 2 DM, mild hypertension and microalbuminuria. Also we compared their antihypertensive efficacy and their effects on serum creatinine, eGFR and serum potassium levels.
75 patients were collected and subjected to full history taking, clinical evaluation, electrocardiogram (ECG) and laboratory investigations.
Patients were randomized to receive ramipril 10 mg monotherapy (25 patients), eplerenone 50 mg (25 patients) and eplerenone/ramipril 50/10 mg combination (25 patients). All doses were reached by forced titration over 4 weeks and patients were followed up monthly till the end of the study after 24 weeks.
Data were coded and analyzed using STATA version (14.2). When P value was less than 0.05, it was considered statistically significant.
Ramipril and eplerenone monotherapy showed significant reduction of urinary albumin: creatinine ratio (UACR) after 24 weeks (-39% and -37% respectively) and significant reduction in both systolic and diastolic blood pressure (BP). Both drugs showed insignificant changes in serum creatinine and eGFR. Also there was insignificant increase in serum potassium levels with both drugs after 24 weeks.
The combination group (eplerenone/ramipril) showed significant higher reduction of UACR (-74%) and higher reduction of systolic BP than monotherapy groups without significant changes in serum creatinine and eGFR. There was slight higher but insignificant incidence of sustained hyperkalemia in combination group (eplerenone/ramipril) compared with monotherapy groups.
There was higher incidence in sustained hyperkalemia among patients with eGFR <60 ml/min/m² in all groups.
We conclude that the use of an angiotensin-converting enzyme inhibitor (ACEI) monotherapy or selective MRA monotherapy is an effective way of reducing microalbuminuria and their combination is a more potent treatment option with higher reduction of proteinuria and systolic BP than monotherapy and was well tolerated in patients with eGFR > 60 ml/min/m².