Effects of Renin-Angiotensin-Aldosterone System Blockade in Patients with End-Stage Renal Disease

Slomka, Teresa; Lennon, Emily S.; Akbar, Habibullah; Gosmanova, Elvira O.; Bhattacharya, Syamal K.; Oliphant, Carrie S.; Khouzam, Rami N.

doi:10.1016/j.amjms.2015.12.021

Cited by 10 publications

(5 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Angiotensin II (AngII) is the major bioactive peptide of the Renin-Angiotensin System (RAS) and influences a broad range of homeostatic and modulatory processes, including cardiovascular and renal physiology. Dysregulation of the RAS is associated with disease via actions on cardiac (1)(2)(3)(4), vascular (5,6) and renal (7,8) growth and remodeling, modulation of sympathetic nervous system activity (9)(10)(11), endothelial dysfunction (12), angiogenesis (13,14) and inflammation (15)(16)(17). AngII acts primarily through the type 1 AngII receptor (AT 1 R 1 ), a G protein-coupled receptor (GPCR), to mediate an array of intracellular signals, including calcium mobilization and generation of reactive oxygen species (ROS), modulation of receptor and non-receptor tyrosine kinases, mitogen-activated protein kinases (MAPK) (including the extracellular-regulated kinase 1/2 (ERK1/2)) and various ion channels (18,19).…”

Section: Introductionmentioning

confidence: 99%

BRET-based assay to monitor EGFR transactivation by the AT1R reveals Gq/11 protein-independent activation and AT1R-EGFR complexes

O’Brien

Johnstone

Devost

et al. 2018

Biochemical Pharmacology

View full text Add to dashboard Cite

The type 1 angiotensin II (AngII) receptor (AT 1 R) transactivates the epidermal growth factor receptor (EGFR), which leads to pathological remodeling of heart, blood vessels and kidney. End-point assays are used as surrogates of EGFR activation, however these downstream readouts are not applicable to live cells, in real-time. Herein, we report the use of a bioluminescence resonance energy transfer (BRET)-based assay to assess recruitment of the EGFR adaptor protein, growth factor receptor-bound protein 2 (Grb2), to the EGFR. In a variety of cell lines, both epidermal growth factor (EGF) and AngII stimulated Grb2 recruitment to EGFR. The BRET assay was used to screen a panel of 9 G protein-coupled receptors (GPCRs) and further developed for other EGFR family members (HER2 and HER3); the AT 1 R was able to transactivate HER2, but not HER3. Mechanistically, AT 1 R-mediated ERK1/2 activation was dependent on G q/11 and EGFR tyrosine kinase activity, whereas the recruitment of Grb2 to the EGFR was independent of G q/11 and only partially dependent on EGFR tyrosine kinase activity. This G q/11 independence of EGFR transactivation was confirmed using AT 1 R mutants and in CRISPR cell lines lacking G q/11. EGFR transactivation was also apparently independent of βarrestins. Finally, we used additional BRET-based assays and confocal microscopy to provide evidence that both AngII-and EGF-stimulation promoted AT 1 R-EGFR heteromerization. In summary, we report an alternative approach to monitoring AT 1 R-EGFR transactivation in live cells, which provides a more direct and proximal view of this process, including the potential for complexes between the AT 1 R and EGFR.

show abstract

Section: Introductionmentioning

confidence: 99%

BRET-based assay to monitor EGFR transactivation by the AT1R reveals Gq/11 protein-independent activation and AT1R-EGFR complexes

O’Brien

Johnstone

Devost

et al. 2018

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…Research has generally shown that the risk of a faster RRF decline increases in both diabetics and patients with heart failure 4,8,13 . RRF is better preserved in patients undergoing peritoneal dialysis than in those undergoing HD 13,19,20 , and, in particular, the risk of reduced RRF for peritoneal dialysis patients is smaller when a RAAS blockade is used, according to a meta-analysis 7 . In contrast, the effects of an RAAS blockade on RRF in HD patients are still uncertain.…”

Section: Discussionmentioning

confidence: 99%

Renin Angiotensin Aldosterone System Blockades Does Not Protect Residual Renal Function in Patients with Hemodialysis at 1 Year After Dialysis Initiation: A Prospective Observational Cohort Study

Yoo

Kim

Kwon

et al. 2019

Sci Rep

View full text Add to dashboard Cite

The beneficial effects of renin angiotensin aldosterone system (RAAS) blockade on residual renal function (RRF) in patients who have just initiated hemodialysis (HD) have been inconclusive. In this study, 935 patients with incident HD from a nationwide prospective observational cohort in Korea were included for analysis. The primary outcome showed that RRF as demonstrated by urine volume changes over 0, 3, and 12 months differed between the RAAS blockade and control groups. Mixed-effects linear regression was used to compare RRF between the groups. Patients in the RAAS group had a greater proportion of higher urine volume at study enrollment compared to the control group, but there was no difference in baseline characteristics, heart function, and dialysis-related indices. After adjusting for confounding factors, the RAAS group did not provide a significant benefit to RRF in a mixed-effects linear regression (p = 0.51). Male gender, high Charlson comorbidity index, diuretic use, and high weekly ultrafiltration volume were associated with faster decline in RRF. The RAAS group failed to provide a protective effect for the development of anuria 1 year after initiating dialysis based on the multivariate logistic regression (OR 0.73 95% CI 0.25–2.13, p = 0.57). In Korean patients with incident HD, RAAS blockade did not provide a protective effect for RRF after 1 year. Further research is needed to clarify the optimal treatment for preserving RRF in HD patients.

show abstract

“…The benefit of the renin-angiotensin-aldosterone system (RAAS) blockade for blood pressure control in patients with CKD and hemodialysis is controversial because most trials evaluating the renocardiovascular benefit of RAAS blockade exclude patients with ESRD (49) , (50) , (51) . In a review article, Slomka et al (51) recommend that RAAS blockade should be taken into consideration in patients with ESRD diagnosed as having heart failure and left ventricular hypertrophy, while paying attention to hyperpotassemia.…”

Section: Treatment With Renocardiovascular Protective Agents Immunosmentioning

confidence: 99%

Management of End-stage Renal Disease Associated with Systemic Rheumatic Diseases

Honda

Katsumata

Karasawa

et al. 2019

JMA J

View full text Add to dashboard Cite

The outcomes of rheumatic diseases (RDs) have improved over the past decades. However, a significant proportion of the patients still suffer from end-stage renal disease (ESRD) and have to bear the burden of hemodialysis. It is crucial to prevent patients with RDs from developing ESRD from viewpoints of medicine and medical economics. For those who already have ESRD, it is important to improve vial prognosis and quality of life through appropriate management of disease activity and comorbidities related to ESRD. Thus, rheumatologists and nephrologists need to recognize risk factors associated with progression to ESRD along with their appropriate management. Although the activity of most RDs tends to decrease after initiation of hemodialysis, disease activity may still increase, and recognizing how to appropriately use immunosuppressive agents even after the development of ESRD is crucial. The treatment of RDs needs extra attention as hydroxychloroquine requires more frequent monitoring for adverse drug reactions; therapeutic drug monitoring is necessary for mycophenolate mofetil, cyclosporine A, and tacrolimus; cyclophosphamide and azathioprine need dose adjustments; methotrexate and bucillamine are contraindicated in patients with ESRD; leflunomide and sulfasalazine do not require significant dose reduction and iguratimod should be carefully administered. The pharmacokinetics of biological agents such as rituximab or belimumab are not affected by ESRD, and dose adjustments are not necessary. Collaboration between rheumatologists and nephrologists is needed more than ever and is expected to produce a complementary effect and achieve better outcomes in clinical settings, although this cooperation has not always been conducted appropriately.

show abstract

Effects of Renin-Angiotensin-Aldosterone System Blockade in Patients with End-Stage Renal Disease

Cited by 10 publications

References 66 publications

BRET-based assay to monitor EGFR transactivation by the AT1R reveals Gq/11 protein-independent activation and AT1R-EGFR complexes

BRET-based assay to monitor EGFR transactivation by the AT1R reveals Gq/11 protein-independent activation and AT1R-EGFR complexes

Renin Angiotensin Aldosterone System Blockades Does Not Protect Residual Renal Function in Patients with Hemodialysis at 1 Year After Dialysis Initiation: A Prospective Observational Cohort Study

Management of End-stage Renal Disease Associated with Systemic Rheumatic Diseases

Contact Info

Product

Resources

About