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PubMed | Service of Nephrology and Hypertension, Medical University of Gdańsk, University of Bern and Biomedical Imaging Center
Type: | Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | Year: 2016

Determinations of renal oxygenation by blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) in chronic kidney disease (CKD) patients have given heterogeneous results, possibly due to the lack of a reproducible method to analyse BOLD-MRI. It therefore remains uncertain whether patients with CKD have a reduced renal tissue oxygenation. We developed a new method to analyse BOLD-MRI signals and applied it to CKD patients and controls.MRI was performed under standardized conditions before and 15 min after IV furosemide in 104 CKD patients, 61 hypertensives and 42 controls. MR images were analysed with the new twelve-layer concentric objects method (TLCO) that divides renal parenchyma in 12 layers of equal thickness. The mean R2* value of each layer was reported, along with the change in R2* between successive layers, as measured by the slope steepness of the relevant curve.Inter-observer variability was 2.3 0.9%, 1.9 0.8% and 3.0 2.3% in, respectively, controls, moderate and severe CKD. The mean R2* of the outer (more cortical) layers was significantly higher in CKD, suggesting lower cortical oxygenation as compared with controls. In CKD patients, the response to furosemide was blunted in the inner (more medullary) layers, and the R2* slope was flatter. In multivariable regression analysis, the R2* slope correlated positively with estimated glomerular filtration rate (eGFR) in patients with an eGFR <90 mL/min/1.73 mUsing the new TLCO method, we confirm the hypothesis that renal cortical oxygenation is reduced in CKD in humans, and that the level of cortical oxygenation correlates with CKD severity.


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.


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.


Mordasini D.,University of Bern | Loffing-Cueni D.,University of Zürich | Loffing J.,University of Zürich | 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.


PubMed | Service of Nephrology and Hypertension, University of Zürich, University of Bern and University of Lausanne
Type: Journal Article | Journal: 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 ENaC 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 ENaC abundance in whole kidney increased in cirrhotic mice of both genotypes and cleaved forms of and 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 ENaC 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.


PubMed | Service of Nephrology and Hypertension
Type: Journal Article | Journal: Current opinion in nephrology and hypertension | Year: 2014

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.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.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.


PubMed | Service of Nephrology and Hypertension
Type: | Journal: Journal of hypertension | Year: 2015

Renal tissue oxygenation may play an important role in the progression of renal diseases. Today, blockers of the renin-angiotensin system and diuretics are two major drug classes used to treat hypertension in patients with or without chronic kidney diseases. The purpose of the present study was to compare the direct renin inhibitor aliskiren to the diuretic hydrochlorothiazide (HCTZ) in their ability to modulate renal tissue oxygenation in hypertensive patients.(Figure is included in full-text article.): Twenty four patients were enrolled in this randomized prospective study and 20 completed the protocol. Patients were randomly assigned to receive either aliskiren 150 titrated to 300mg/d or HCTZ 12.5mg titrated to 25mg/d for 8 weeks. Renal oxygenation was measured by BOLD-MRI at weeks 0 and 8, 30hours after the last dose. BOLD-MRI data were analyzed using the onion peel technique, a newly developed method which measures mean R2* levels in 12 computed layers of equal thickness in the kidney enabling to asses renal oxygenation according to the depth within the kidney, a higher R2* value corresponding to lower oxygenation.Our results show that aliskiren tended to increase oxygenation in the outer (more cortical) layers and decreased oxygenation in the inner (more medullary) layers whereas HCTZ induced a significant overall decrease in renal tissue oxygenation (Figure 1). This latter finding may be due to the increased sodium reabsorption 30h after the last dose of HCTZ (FELi: 21.29% at W0 and 16.46.0% at W8), p=0.01). Patients responding to treatment by a fall in systolic blood pressure of >10 mmHg also increased renal tissue oxygenation when compared to non-responders.Taken together these results show that blockade of the renin-angiotensin system with aliskiren has a more favorable impact on renal tissue oxygenation in hypertensive patients than HCTZ. This finding may contribute to explain the renal protective effect of blockers of the renin-angiotensin system.

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