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Burnier M.,Service of Nephrology and Hypertension
Current Opinion in Nephrology and Hypertension | Year: 2014

PURPOSE OF REVIEW: Adherence to preventive measures and prescribed medications is the cornerstone of the successful management of hypertension. The role of adherence is particularly important when treatments are not providing the expected clinical results, for example, in patients with resistant hypertension. The goal of this article is to review the recent observations regarding drug adherence in resistant hypertension. RECENT FINDINGS: Today, the role of drug adherence as a potential cause of resistant hypertension is largely underestimated. Most studies suggest that a low adherence to the prescribed medications can affect up to 50% of patients with resistant hypertension.A good adherence to therapy is generally associated with an improved prognosis. Nonetheless, adherence should probably not be a target for treatment per se because data on adherence should always be interpreted in the view of clinical results. In our opinion, the availability of reliable data on drug adherence would be a major help for physicians to manage patients apparently resistant to therapy. SUMMARY: The actual development of new drugs for hypertension is slow. Thus, focusing on drug adherence to the drugs available is an important way to improve blood pressure control in the population. More emphasis should be put on measuring drug adherence in patients with resistant hypertension to avoid costly investigations and treatments. Copyright © Lippincott Williams & Wilkins. Source

Mordasini D.,University of Bern | Loffing-Cueni D.,University of Zurich | Loffing J.,University of Zurich | Beatrice R.,University of Bern | And 5 more authors.
Pflugers Archiv European Journal of Physiology | Year: 2015

Cirrhosis is a frequent and severe disease, complicated by renal sodium retention leading to ascites and oedema. A better understanding of the complex mechanisms responsible for renal sodium handling could improve clinical management of sodium retention. Our aim was to determine the importance of the amiloride-sensitive epithelial sodium channel (ENaC) in collecting ducts in compensate and decompensate cirrhosis. Bile duct ligation was performed in control mice (CTL) and collecting duct-specific αENaC knockout (KO) mice, and ascites development, aldosterone plasma concentration, urinary sodium/potassium ratio and sodium transporter expression were compared. Disruption of ENaC in collecting ducts (CDs) did not alter ascites development, urinary sodium/potassium ratio, plasma aldosterone concentrations or Na,K-ATPase abundance in CCDs. Total αENaC abundance in whole kidney increased in cirrhotic mice of both genotypes and cleaved forms of α and γ ENaC increased only in ascitic mice of both genotypes. The sodium chloride cotransporter (NCC) abundance was lower in non-ascitic KO, compared to non-ascitic CTL, and increased when ascites appeared. In ascitic mice, the lack of αENaC in CDs induced an upregulation of total ENaC and NCC and correlated with the cleavage of ENaC subunits. This revealed compensatory mechanisms which could also take place when treating the patients with diuretics. These compensatory mechanisms should be considered for future development of therapeutic strategies. © 2015, Springer-Verlag Berlin Heidelberg. Source

Meier P.,Service of Nephrology and Hypertension | Meier P.,University of Lausanne | Maillard M.P.,Service of Nephrology and Hypertension | Meier J.R.,Service of Nephrology and Hypertension | And 4 more authors.
Journal of Hypertension | Year: 2011

Objective: The goal of this study was to investigate whether increasing the dose of an angiotensin II receptor blocker (ARB) provides as much benefits as combining the ARB with an angiotensin-converting enzyme inhibitor (ACEI) in terms of blood pressure (BP) control and urinary albumin excretion (UAE) in hypertensive patients with a proteinuria. Methods: We enrolled 20 hypertensive patients with proteinuric nephropathies and a reduced renal function in a randomized, 12-month, triple-crossover, prospective, open-label study to compare the effects of a regular dose of losartan (Los 100 mg q.d., LOS100) vs. a high dose of losartan (Los 100 mg b.i.d., LOS200) vs. losartan 100 mg q.d. associated with lisinopril 20 mg q.d. (LOS100 + LIS20). Each treatment was given for 8 weeks with a 4-week initial run-in period and 2 weeks of washout between each treatment phases. 24 h UAE and ambulatory BP were measured during the running phase and at the end of each treatment period. Results: Compared to pretreatment, 24 h SBP and DBP were reduced by 10/5 ± 7/4 mmHg with LOS100 (P = 0.023 vs. baseline) and, respectively, 13/6 ± 12/5 mmHg with LOS200 (P = 0.011) and 19/9 ± 15/8 mmHg with LOS100 + LIS20 (P < 0.01). UAE decreased significantly with LOS100 and to an even greater degree with LOS200 and LOS100 + LIS20 (P < 0.01 vs. baseline for both and P = 0.032, LOS100 + LIS20 vs. LOS200). The combination had a greater impact in patients with a high baseline proteinuria as suggested by a nonparallel leftward shift of the relationship between the changes in UAE induced by the combination and those induced by LOS200. The high dose of losartan was better tolerated than the combination. Conclusion: Increasing the dose of losartan from 100 mg once daily to 100 mg twice a day enables to obtain a greater decrease in BP and proteinuria and is better tolerated than combining the ARB with lisinopril, though the high dose appears to be slightly less effective than the combination in patients with a marked proteinuria. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

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