Detrimental effect of renin-angiotensin blockade on progression of chronic kidney disease at later stages: A matter of dosage adjustment?

Caravaca-Fontán, Fernando; Valladares, Julián; Díaz-Campillejo, Rosa; Barroso, Sérgio; Luna, Enrique; Caravaca, Francisco

doi:10.1016/j.nefroe.2019.02.009

Cited by 5 publications

(5 citation statements)

References 29 publications

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“…Our results suggest that dual ACEi/ARB therapy was associated with an increased risk of renal outcomes compared to ACEi alone in agreement with a smaller observational study by Caravaca-Fontán et al, which found dual therapy was associated with a faster decline of renal function in patients with CKD. 33 Fralick et al 34 used US insurance claims data to replicate ONTARGET results for the single therapy comparison and led to results closely comparable to the trial for 9330 patients but omitted the dual therapy analysis from their replication. Methodologically, although an increasing number of studies have used trial emulation methods across various therapeutic areas, few have looked at how to define dual therapy use in routine data.…”

Section: Discussionmentioning

confidence: 99%

Cardiorenal effects of dual blockade with Angiotensin-converting enzyme inhibitors and Angiotensin receptor blockers in people with CKD: analysis of routinely collected data with emulation of a reference trial (ONTARGET)

Baptiste,

Wong,

Schultze

et al. 2024

Preprint

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We aimed to explore whether the ONTARGET trial results, which led to an end of recommendations of dual angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) use, extended to patients with chronic kidney disease (CKD) who were underrepresented in the trial. We selected people prescribed an ACEi and/or an ARB in the UK Clinical Practice Research Datalink Aurum during 1/1/2001-31/7/2019. We specified an operational definition of dual users and applied ONTARGET eligibility criteria. We used propensity-score-weighted Cox-proportional hazards models to compare dual therapy to ACEi for the primary composite trial outcome (cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure), as well as a primary composite renal outcome (≥50% reduction in GFR or end-stage kidney disease), and other secondary outcomes, including hyperkalaemia. Conditional on successfully benchmarking results against the ONTARGET trial, we explored treatment effect heterogeneity by CKD at baseline. In the propensity-score-weighted trial-eligible analysis cohort (n=412 406), for dual therapy vs ACEi we observed hazard ratio (HR) 0.98 (95% CI: 0.93, 1.03), for the primary composite outcome, consistent with the trial results (ONTARGET HR 0.99, 95% CI: 0.92, 1.07). Dual therapy use was associated with an increased risk of the primary renal composite outcome, HR 1.25 (95% CI: 1.15, 1.36) vs ONTARGET HR 1.24 (1.01, 1.51) and hyperkalaemia, HR 1.15 (95% CI: 1.09, 1.22) in the trial eligible cohort, consistent with ONTARGET. The presence of CKD at baseline had minimal impact on results.

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Section: Discussionmentioning

confidence: 99%

Cardiorenal effects of dual blockade with Angiotensin-converting enzyme inhibitors and Angiotensin receptor blockers in people with CKD: analysis of routinely collected data with emulation of a reference trial (ONTARGET)

Baptiste,

Wong,

Schultze

et al. 2024

Preprint

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“…This finding is corroborated by earlier research in which RASI therapy in patients with CKD G4-G5 had a detrimental effect of eGFR decline, with improvement of eGFR after discontinuation of RASI therapy. 21 Small trials observed restoration of eGFR by 25-50% 12 months after cessation. 15 On a larger scale, an observational trial of 10,254 patients over 10 years on the SRR found a reduction of 8.6 RRT events per 100 patients with cessation of RASI therapy.…”

Section: Practice Pointsmentioning

confidence: 99%

Advanced chronic kidney disease: Considerations for renin-angiotensin system inhibitor use as disease processes

Morris¹,

Manickavasagam²

2023

Aust J Gen Pract

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“…In addition to anemia, the kidney's ability to receive enough oxygen decreases [58]. Interestingly, RAAS blockades are effective renoprotective drugs and individuals with CKD who have proteinuria respond to RAAS inhibition more favorably than those who do not [59]. According to many investigations, RAAS blockage improves tubulointerstitial hypoxia [60].…”

Section: Hypoxiamentioning

confidence: 99%

Anemia and Hypoxia Impact on Chronic Kidney Disease Onset and Progression: Review and Updates

Habas,

Al Adab,

Arryes

et al. 2023

Cureus

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Chronic kidney disease (CKD) is caused by hypoxia in the renal tissue, leading to inflammation and increased migration of pathogenic cells. Studies showed that leukocytes directly sense hypoxia and respond by initiating gene transcription, encoding the 2-integrin adhesion molecules. Moreover, other mechanisms participate in hypoxia, including anemia. CKD-associated anemia is common, which induces and worsens hypoxia, contributing to CKD progression. Anemia correction can slow CKD progression, but it should be cautiously approached.In this comprehensive review, the underlying pathophysiology mechanisms and the impact of renal tissue hypoxia and anemia in CKD onset and progression will be reviewed and discussed in detail. Searching for the latest updates in PubMed Central, Medline, PubMed database, Google Scholar, and Google search engines were conducted for original studies, including cross-sectional studies, cohort studies, clinical trials, and review articles using different keywords, phrases, and texts such as "CKD progression, anemia in CKD, CKD, anemia effect on CKD progression, anemia effect on CKD progression, and hypoxia and CKD progression". Kidney tissue hypoxia and anemia have an impact on CKD onset and progression. Hypoxia causes nephron cell death, enhancing fibrosis by increasing interstitium protein deposition, inflammatory cell activation, and apoptosis. Severe anemia correction improves life quality and may delay CKD progression. Detection and avoidance of the risk factors of hypoxia prevent recurrent acute kidney injury (AKI) and reduce the CKD rate. A better understanding of kidney hypoxia would prevent AKI and CKD and lead to new therapeutic strategies.

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Detrimental effect of renin-angiotensin blockade on progression of chronic kidney disease at later stages: A matter of dosage adjustment?

Cited by 5 publications

References 29 publications

Cardiorenal effects of dual blockade with Angiotensin-converting enzyme inhibitors and Angiotensin receptor blockers in people with CKD: analysis of routinely collected data with emulation of a reference trial (ONTARGET)

Cardiorenal effects of dual blockade with Angiotensin-converting enzyme inhibitors and Angiotensin receptor blockers in people with CKD: analysis of routinely collected data with emulation of a reference trial (ONTARGET)

Advanced chronic kidney disease: Considerations for renin-angiotensin system inhibitor use as disease processes

Anemia and Hypoxia Impact on Chronic Kidney Disease Onset and Progression: Review and Updates

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