Safety of enhanced renin-angiotensin-aldosterone system inhibition with aliskiren in nondiabetic patients with chronic kidney disease.

INTRODUCTION: Various methods of combination renin-angiotensin-aldosterone system blockade help achieve more potent antiproteinuric effects, but may be associated with higher risk of side effects. Therapies involving direct renin inhibitor, aliskiren, may promote renal fibrosis by stimulating (pro)renin receptor due to increased renin levels. OBJECTIVES: The aim of the study was to compare the effects of combination treatment with angiotensin receptor blockers, telmisartan (80 mg/d) and aliskiren (300 mg/d) with those of combination treatment with 80 mg/d telmisartan and mineralocorticoid receptor blocker (50 mg/d eplerenone) and telmisartan (160 mg/d) alone on the urinary excretion of transforming growth factor ß1 (TGF­ß1), renal function, and serum potassium levels. PATIENTS AND METHODS: A randomized open-label controlled cross-over study was performed in 18 white patients (7 women and 11 men; mean age, 42.4 ±1.9 years) with proteinuric nondiabetic chronic kidney disease and estimated glomerular filtration rate of 85.2 ±4.6 ml/min. RESULTS: The urinary excretion of TGF­ß1 was stable despite a significant increase in plasma renin levels after treatment with telmisartan and aliskiren. There were no differences in renal function and serum potassium levels between the compared treatments. Moreover, there were no episodes of hypotension or acute renal impairment. CONCLUSIONS: Combination therapy with telmisartan and aliskiren may be safe in young nondiabetic patients with normal renal function at low vascular risk. This treatment may be an alternative for a subset of patients in whom standard RAA system blockade is ineffective.

The enhanced renin-angiotensin-aldosteron system pharmacological blockade--which is the best?.

BACKGROUND/AIMS: Pharmacological inhibition of renin-angiotensin-aldosteron system (RAAS) may reduce proteinuria and the rate of chronic kidney disease progression. The aim was to compare the effects on albuminuria of the therapy with either: (i) telmisartan 80 mg and aliskiren 300 mg, (ii) telmisartan 80 mg and eplerenone 50 mg, (iii) telmisartan 160 mg as monotherapy. DESIGN AND PATIENTS: Randomized, double-center, double-blind, cross-over, three treatments-three periods of 8 weeks each study. 18 patients with non-diabetic proteinuric CKD stage 1-3 completed the protocol. RESULTS: There was significant difference in albuminuria between studied therapies (ANOVA; p<0.01). The combination therapy with telmisartan plus aliskiren decreased albuminuria more effectively than the treatment with telmisartan plus eplerenone and monotherapy with telmisartan 160 mg OD [376 mg/g creatinine (286-686) vs. 707 (502-1204) vs. 525 (318-763); post-hoc p<0.01 and p<0.05, respectively]. CONCLUSIONS: The study demonstrated that the combination therapy with angiotensin receptor blocker (ARB) and renin inhibitor was more effective in albuminuria lowering than the concomitant usage of ARB and mineralocorticoid receptor antagonist as well as than ARB in doses two-fold higher than usually used in treatment of hypertension in patients with non-diabetic CKD and that this higher antiproteinuric efficacy was independent on changes in blood pressure.

[Role of vitamin D3 in arterial blood pressure control]. / Rola witaminy D3 w patogenezie nadcisnienia tetniczego.

The basic function of vitamin D3 in human body is to maintain the calcium-phosphate homeostasis. Its metabolic function is mediated by the nuclear VDR receptor. The existance of vitamin D3 receptors outside tissues and organs which take part in calcium-phosphate metabolism has resulted in not treating it as an anti rickets agent only. Lower arterial blood pressure observed in people living in sunny areas and decrease of arterial blood pressure values after exposure to UVB radiation could confirm the relationship between vitamin D3 and hypertension. Perhaps through its influence on calcium-phosphate metabolism, RAA system, immune system, control of endocrine glands and endothelium function the vitamin D3 contributes to lowering arterial blood pressure and lessening the risk of cardiovascular disease.