Renin-Angiotensin System Dual Blockade Using Angiotensin Receptor Plus Aliskiren Decreases Severe Proteinuria in Kidney Transplant Recipients

López, Verónica; Martín, M.A.; Cobelo, Carmen; Aranda, Pedro J.; Cabello, Mercedes; Sola, E.; Gutiérrez, Cristina; Burgos, D.; Martínez, D. J. Clínica Universitaria Díez; Hernández, Domingo

doi:10.1016/j.transproceed.2010.07.053

Cited by 11 publications

(8 citation statements)

References 7 publications

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“…In addition, Lopez et al [26] found that dual blockade of the RAS with an Ang II type 1 receptor antagonist plus aliskiren has additive effects to decrease severe proteinuria and elevated blood pressure. Neither relevant adverse effects on renal function nor anemia or hyperkalemia were observed.…”

Section: Discussionmentioning

confidence: 99%

Circulating Angiotensin-Converting Enzyme 2 Activity in Kidney Transplantation: A Longitudinal Pilot Study

et al. 2012

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Background/Aims: Angiotensin-converting enzyme 2 (ACE2) is the only known active homologue of ACE, and degrades angiotensin (Ang) II and Ang I to Ang(1–7) and Ang(1–9), respectively. The role of ACE2 in kidney transplant (KT) is unknown. Our objective was to investigate circulating ACE2 activity in KT patients, and the relationship between serum ACE2 activity and age, gender, graft function and cardiovascular risk markers in KT patients. Methods: 113 KT patients with stable graft function were included in this cross-sectional study. Circulating ACE2 activity was assessed using a fluorescent assay. Results: Circulating ACE2 activity was detectable in KT patients and was increased in KT with ischemic heart disease as compared to KT without ischemic heart disease (105.9 ± 8.7 vs. 97.1 ± 7.05 relative fluorescence units (RFU)/µl/h, p < 0.05). ACE2 activity was increased in male KT as compared to females (105.2 ± 9.1 vs. 84.7 ± 6.9 RFU/µl/h, p = 0.05). ACE2 activity correlated positively with serum creatinine (r = 0.27), serum urea (r = 0.29), age (r = 0.24), aspartate transaminase (r = 0.39), alanine transaminase (r = 0.48), γ-glutamyl transferase (γ-GT) (r = 0.52), age (r = 0.24), and glycosylated hemoglobin (r = 0.19) (p < 0.05). By multiple regression analysis, age, serum creatinine, and serum γ-GT were independent predictors of serum ACE2 activity (r = 0.66, p < 0.001). Conclusions: Circulating ACE2 activity is measurable in KT patients and directly correlates with age, renal allograft and liver function parameters. These findings suggest that measurement of serum ACE2 may be used as a non-invasive marker to understand the role of the renin-angiotensin system in KT patients.

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Section: Discussionmentioning

confidence: 99%

Circulating Angiotensin-Converting Enzyme 2 Activity in Kidney Transplantation: A Longitudinal Pilot Study

et al. 2012

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“…Without a control group, Lopez et al and Tang et al demonstrated that add-on aliskiren reduced urinary protein in kidney transplant recipients (n = 12) and immunoglobulin A nephropathy patients (n = 25), respectively [30][31]. A prospective trial conducted by Tsukasa Nakamura et al found that combination therapy with aliskiren and ARBs decreased proteinuria in non-DM CKD patients more effectively than monotherapy alone, however their findings did not reach statistical significance due to the limited number of patients (n = 12 in each group) [32].…”

Section: Discussionmentioning

confidence: 99%

Effect of add-on direct renin inhibitor aliskiren in patients with non-diabetes related chronic kidney disease

Chen

et al. 2012

BMC Nephrol

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BackgroundThe renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney disease (CKD). Although dual RAAS inhibition results in worse renal outcomes than monotherapy in high risk type 2 diabetes patients, the effect of dual RAAS inhibition in patients with non-DM CKD is unclear. The aim of this study was to evaluate the potential renoprotective effect of add-on direct renin inhibitor in non-DM CKD patients.MethodsWe retrospectively enrolled 189 non-DM CKD patients who had been taking angiotensin II receptor blockers (ARBs) for more than six months. Patients were divided into an add-on aliskiren group and an ARB monotherapy group. The primary outcomes were a decline in glomerular filtration rate (GFR) and a reduction in urinary protein-to-creatinine ratio at six months.ResultsThe baseline characteristics of the two groups were similar. Aliskiren 150 mg daily reduced the urinary protein-to-creatinine ratio by 26% (95% confidence interval, 15 to 37%; p < 0.001). The decline in GFR was smaller in the add-on aliskiren group (−2.1 vs. -4.0 ml/min, p = 0.038). Add-on aliskiren had a neutral effect on serum potassium in the non-DM CKD patients. In subgroup analysis, the proteinuria-reducing effect of aliskiren was more prominent in patients with a GFR less than 60 ml/min, and in patients with a urinary protein-to-creatinine ratio greater than 1.8. The effect of aliskiren in retarding the decline in GFR was more prominent in patients with hypertensive nephropathy than in those with glomerulonephritis.ConclusionAdd-on direct renin inhibitor aliskiren (150 mg daily) safely reduced proteinuria and attenuated the decline in GFR in the non-DM CKD patients who were receiving ARBs.

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“…While ARBs and CCBs have a favorable effect on blood pressure and decrease the risk of several complications, these drugs have some adverse effects. Renin-angiotensin system inhibitors including ARBs are known to cause hyperkalemia [5] and anemia [6,7]. CCBs are known to cause edema [8].…”

Section: Introductionmentioning

confidence: 99%

Comparative effect of angiotensin II type I receptor blockers and calcium channel blockers on laboratory parameters in hypertensive patients with type 2 diabetes

Nishida

Takahashi

Nakayama

et al. 2012

Cardiovasc Diabetol

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BackgroundBoth angiotensin II type I receptor blockers (ARBs) and calcium channel blockers (CCBs) are widely used antihypertensive drugs. Many clinical studies have demonstrated and compared the organ-protection effects and adverse events of these drugs. However, few large-scale studies have focused on the effect of these drugs as monotherapy on laboratory parameters. We evaluated and compared the effects of ARB and CCB monotherapy on clinical laboratory parameters in patients with concomitant hypertension and type 2 diabetes mellitus.MethodsWe used data from the Clinical Data Warehouse of Nihon University School of Medicine obtained between Nov 1, 2004 and July 31, 2011, to identify cohorts of new ARB users (n = 601) and propensity-score matched new CCB users (n = 601), with concomitant mild to moderate hypertension and type 2 diabetes mellitus. We used a multivariate-adjusted regression model to adjust for differences between ARB and CCB users, and compared laboratory parameters including serum levels of triglyceride (TG), total cholesterol (TC), non-fasting blood glucose, hemoglobin A1c (HbA1c), sodium, potassium, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), hemoglobin and hematocrit, and white blood cell (WBC), red blood cell (RBC) and platelet (PLT) counts up to 12 months after the start of ARB or CCB monotherapy.ResultsWe found a significant reduction of serum TC, HbA1c, hemoglobin and hematocrit and RBC count and a significant increase of serum potassium in ARB users, and a reduction of serum TC and hemoglobin in CCB users, from the baseline period to the exposure period. The reductions of RBC count, hemoglobin and hematocrit in ARB users were significantly greater than those in CCB users. The increase of serum potassium in ARB users was significantly greater than that in CCB users.ConclusionsOur study suggested that hematological adverse effects and electrolyte imbalance are greater with ARB monotherapy than with CCB monotherapy.

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Renin-Angiotensin System Dual Blockade Using Angiotensin Receptor Plus Aliskiren Decreases Severe Proteinuria in Kidney Transplant Recipients

Cited by 11 publications

References 7 publications

Circulating Angiotensin-Converting Enzyme 2 Activity in Kidney Transplantation: A Longitudinal Pilot Study

Circulating Angiotensin-Converting Enzyme 2 Activity in Kidney Transplantation: A Longitudinal Pilot Study

Effect of add-on direct renin inhibitor aliskiren in patients with non-diabetes related chronic kidney disease

Comparative effect of angiotensin II type I receptor blockers and calcium channel blockers on laboratory parameters in hypertensive patients with type 2 diabetes

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