Acei in ckd
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The Role of ACE Inhibitors in Chronic Kidney Disease (CKD)
Introduction to ACE Inhibitors in CKD
Angiotensin-converting enzyme inhibitors (ACEi) are a cornerstone in the management of chronic kidney disease (CKD). They are primarily used to control blood pressure and reduce proteinuria, which are critical factors in slowing the progression of CKD and preventing cardiovascular events1 2. However, their efficacy and safety in different stages of CKD, particularly in advanced stages, remain subjects of ongoing research and debate.
ACE Inhibitors in Early-Stage CKD
Benefits in Early-Stage CKD
In early stages of CKD (stages 1 to 3), ACE inhibitors have shown beneficial effects in reducing proteinuria and controlling blood pressure, which are essential in slowing disease progression3. Studies have demonstrated that ACE inhibitors can significantly reduce the risk of kidney events, cardiovascular events, and all-cause mortality in non-dialysis CKD patients2 9.
Limitations and Uncertainties
Despite these benefits, the evidence for ACE inhibitors' effectiveness in early-stage CKD without diabetes is less conclusive. A review highlighted that there is insufficient evidence to definitively determine their impact on all-cause mortality and cardiovascular events in this subgroup3. This indicates a need for further research to establish clear guidelines for ACE inhibitor use in early CKD.
ACE Inhibitors in Advanced CKD
Potential Benefits and Risks
The use of ACE inhibitors in advanced CKD (stages 4 and 5) is more controversial. The STOP-ACEi trial aims to investigate whether discontinuing ACE inhibitors in patients with advanced CKD can stabilize or improve renal function without increasing cardiovascular risks1 6. Preliminary findings suggest that while ACE inhibitors are effective in reducing blood pressure and proteinuria, their benefits in advanced CKD are not as clear-cut, and there may be potential risks associated with their continued use6.
Comparative Efficacy
A network meta-analysis comparing ACE inhibitors with other antihypertensive drugs found that ACE inhibitors were superior in reducing kidney events, cardiovascular outcomes, and all-cause mortality in non-dialysis CKD stages 3-5 patients2. However, the combination of ACE inhibitors with angiotensin receptor blockers (ARBs) did not show additional benefits and was associated with higher risks of hyperkalemia and hypotension4.
ACE Inhibitors Post-Acute Kidney Injury (AKI)
Impact on Recovery and Outcomes
For patients who have experienced acute kidney injury (AKI), the use of ACE inhibitors has been associated with lower risks of all-cause mortality, recurrent AKI, and progression to CKD5. This suggests that ACE inhibitors may offer a survival benefit and aid in recovery post-AKI, although the risk of hyperkalemia remains a concern and requires careful monitoring5.
Conclusion
ACE inhibitors play a crucial role in managing CKD, particularly in early stages where they help reduce proteinuria and control blood pressure. However, their use in advanced CKD and post-AKI requires careful consideration of potential benefits and risks. Ongoing trials like STOP-ACEi will provide more insights into the optimal use of ACE inhibitors in advanced CKD. Clinicians must weigh the benefits of ACE inhibitors against the risks of adverse effects such as hyperkalemia and hypotension, especially in advanced stages of CKD.
Sources and full results
Most relevant research papers on this topic
Multicentre randomized controlled trial of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker withdrawal in advanced renal disease: the STOP-ACEi trial
Discontinuing ACEi/ARB treatment can stabilize or improve renal function in patients with advanced progressive chronic kidney disease without increasing cardiovascular events.
RCT
Large Human Trial
Highly CitedACE Inhibitor Benefit to Kidney and Cardiovascular Outcomes for Patients with Non-Dialysis Chronic Kidney Disease Stages 3–5: A Network Meta-Analysis of Randomised Clinical Trials
ACE inhibitors significantly decrease the odds of kidney events, cardiovascular events, and all-cause death in non-dialysis chronic kidney disease stages 3-5 patients, while ARBs show no significant advantage.
Meta-AnalysisHighly CitedAngiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease.
ACEi and ARB show potential benefits in managing early chronic kidney disease in adults without diabetes mellitus.
Systematic Review
Very Rigorous JournalHighly CitedEfficacy and Safety of Angiotensin-Converting Enzyme Inhibitor in Combination with Angiotensin-Receptor Blocker in Chronic Kidney Disease Based on Dose: A Systematic Review and Meta-Analysis
ACEI in combination with ARB is effective in reducing urine albumin and protein excretion in chronic kidney disease patients, but may cause decreased GFR and increased hyperkalemia rates.
Meta-AnalysisThe Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Receptor Blockers on Clinical Outcomes of Acute Kidney Disease Patients: A Systematic Review and Meta-Analysis
Exposure to ACEi/ARB after acute kidney injury is associated with lower risks of all-cause mortality, recurrent AKI, and progression to chronic kidney disease.
Meta-AnalysisShould We STOP Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers in Advanced Kidney Disease?
Stopping ACEi/ARB therapy in advanced kidney disease may not be beneficial due to potential adverse cardiovascular outcomes.
Literature ReviewAldosterone antagonists for preventing the progression of chronic kidney disease: a systematic review and meta-analysis.
Aldosterone antagonists reduce proteinuria in chronic kidney disease patients already on ACEis and ARBs but increase the risk of hyperkalemia.
Meta-AnalysisHighly CitedNo clear evidence of ACEi efficacy on the progression of chronic kidney disease in children with hypodysplastic nephropathy--report from the ItalKid Project database.
ACEi treatment does not significantly modify the naturally progressive course of hypodysplastic nephropathy in children, and further studies are needed before routinely proposing it for anti-progression purposes.
Observational StudyRenin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in Patients With CKD: A Bayesian Network Meta-analysis of Randomized Clinical Trials.
ACE inhibitors and ARBs reduce kidney failure and cardiovascular events in patients with chronic kidney disease, with ACE inhibitors potentially being the first choice for treatment.
Meta-AnalysisHighly Cited"Renalism" with Renin Angiotensin Aldosterone System Inhibitor use in Patients Enrolled in Trials for Heart Failure with Reduced Ejection Fraction and Advanced Chronic Kidney Disease: A Systematic Review.
In the past 10 years, CKD grades 4-5 patients have been increasingly included in heart failure with reduced ejection fraction clinical trials, while ACEI/ARB use has decreased.
Systematic Review