Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials

Elaine Ku; Lesley A. Inker; Hocine Tighiouart; Charles E. McCulloch; Ogechi M. Adingwupu; Tom Greene; Raymond O. Estacio; Mark Woodward; Dick de Zeeuw; Julia B. Lewis; Thierry Hannedouche; Tazeen H. Jafar; Enyu Imai; Giuseppe Remuzzi; Hiddo J.L. Heerspink; Fan Fan Hou; Robert D. Toto; Philip K. Li; Mark J. Sarnak

doi:10.7326/M23-3236

Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials

Elaine Ku^*, Lesley A. Inker, Hocine Tighiouart, Charles E. McCulloch, Ogechi M. Adingwupu, Tom Greene, Raymond O. Estacio, Mark Woodward, Dick de Zeeuw, Julia B. Lewis, Thierry Hannedouche, Tazeen H. Jafar, Enyu Imai, Giuseppe Remuzzi, Hiddo J.L. Heerspink, Fan Fan Hou, Robert D. Toto, Philip K. Li, Mark J. Sarnak

^*Corresponding author for this work

Groningen Kidney Center (GKC)

Research output: Contribution to journal › Review article › peer-review

1 Citation (Scopus)

Abstract

Background: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear.

Purpose: To examine the association of ACEi or ARB treatment initiation, relative to a non–ACEi or ARB comparator, with rates of KFRT and death.

Data Sources: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023.

Study Selection: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m².

Data Extraction: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m²), albuminuria (urine albumin–creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes.

Data Synthesis: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m², of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all).

Limitation: Individual participant–level data for hyperkalemia or acute kidney injury were not available.

Conclusion: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD.

Original language	English
Pages (from-to)	953-963
Number of pages	12
Journal	Annals of Internal Medicine
Volume	177
Issue number	7
DOIs	https://doi.org/10.7326/M23-3236
Publication status	Published - 2-Jul-2024

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Ku, E., Inker, L. A., Tighiouart, H., McCulloch, C. E., Adingwupu, O. M., Greene, T., Estacio, R. O., Woodward, M., de Zeeuw, D., Lewis, J. B., Hannedouche, T., Jafar, T. H., Imai, E., Remuzzi, G., Heerspink, H. J. L., Hou, F. F., Toto, R. D., Li, P. K., & Sarnak, M. J. (2024). Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials. Annals of Internal Medicine, 177(7), 953-963. https://doi.org/10.7326/M23-3236

@article{1e5b1cbf392b49148dc02b4c095a3431,

title = "Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials",

abstract = "Background: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear. Purpose: To examine the association of ACEi or ARB treatment initiation, relative to a non–ACEi or ARB comparator, with rates of KFRT and death. Data Sources: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023. Study Selection: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2. Data Extraction: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m2), albuminuria (urine albumin–creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes. Data Synthesis: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m2, of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all). Limitation: Individual participant–level data for hyperkalemia or acute kidney injury were not available. Conclusion: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD.",

author = "Elaine Ku and Inker, {Lesley A.} and Hocine Tighiouart and McCulloch, {Charles E.} and Adingwupu, {Ogechi M.} and Tom Greene and Estacio, {Raymond O.} and Mark Woodward and {de Zeeuw}, Dick and Lewis, {Julia B.} and Thierry Hannedouche and Jafar, {Tazeen H.} and Enyu Imai and Giuseppe Remuzzi and Heerspink, {Hiddo J.L.} and Hou, {Fan Fan} and Toto, {Robert D.} and Li, {Philip K.} and Sarnak, {Mark J.}",

note = "Publisher Copyright: {\textcopyright} 2024 American College of Physicians.",

year = "2024",

month = jul,

day = "2",

doi = "10.7326/M23-3236",

language = "English",

volume = "177",

pages = "953--963",

journal = "Annals of Internal Medicine",

issn = "0003-4819",

publisher = "AMER COLL PHYSICIANS",

number = "7",

}

Ku, E, Inker, LA, Tighiouart, H, McCulloch, CE, Adingwupu, OM, Greene, T, Estacio, RO, Woodward, M, de Zeeuw, D, Lewis, JB, Hannedouche, T, Jafar, TH, Imai, E, Remuzzi, G, Heerspink, HJL, Hou, FF, Toto, RD, Li, PK & Sarnak, MJ 2024, 'Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials', Annals of Internal Medicine, vol. 177, no. 7, pp. 953-963. https://doi.org/10.7326/M23-3236

Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials. / Ku, Elaine; Inker, Lesley A.; Tighiouart, Hocine et al.
In: Annals of Internal Medicine, Vol. 177, No. 7, 02.07.2024, p. 953-963.

Research output: Contribution to journal › Review article › peer-review

TY - JOUR

T1 - Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials

AU - Ku, Elaine

AU - Inker, Lesley A.

AU - Tighiouart, Hocine

AU - McCulloch, Charles E.

AU - Adingwupu, Ogechi M.

AU - Greene, Tom

AU - Estacio, Raymond O.

AU - Woodward, Mark

AU - de Zeeuw, Dick

AU - Lewis, Julia B.

AU - Hannedouche, Thierry

AU - Jafar, Tazeen H.

AU - Imai, Enyu

AU - Remuzzi, Giuseppe

AU - Heerspink, Hiddo J.L.

AU - Hou, Fan Fan

AU - Toto, Robert D.

AU - Li, Philip K.

AU - Sarnak, Mark J.

PY - 2024/7/2

Y1 - 2024/7/2

N2 - Background: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear. Purpose: To examine the association of ACEi or ARB treatment initiation, relative to a non–ACEi or ARB comparator, with rates of KFRT and death. Data Sources: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023. Study Selection: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2. Data Extraction: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m2), albuminuria (urine albumin–creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes. Data Synthesis: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m2, of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all). Limitation: Individual participant–level data for hyperkalemia or acute kidney injury were not available. Conclusion: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD.

AB - Background: In patients with advanced chronic kidney disease (CKD), the effects of initiating treatment with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) on the risk for kidney failure with replacement therapy (KFRT) and death remain unclear. Purpose: To examine the association of ACEi or ARB treatment initiation, relative to a non–ACEi or ARB comparator, with rates of KFRT and death. Data Sources: Ovid Medline and the Chronic Kidney Disease Epidemiology Collaboration Clinical Trials Consortium from 1946 through 31 December 2023. Study Selection: Completed randomized controlled trials testing either an ACEi or an ARB versus a comparator (placebo or antihypertensive drugs other than ACEi or ARB) that included patients with a baseline estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m2. Data Extraction: The primary outcome was KFRT, and the secondary outcome was death before KFRT. Analyses were done using Cox proportional hazards models according to the intention-to-treat principle. Prespecified subgroup analyses were done according to baseline age (<65 vs. ≥65 years), eGFR (<20 vs. ≥20 mL/min/1.73 m2), albuminuria (urine albumin–creatinine ratio <300 vs. ≥300 mg/g), and history of diabetes. Data Synthesis: A total of 1739 participants from 18 trials were included, with a mean age of 54.9 years and mean eGFR of 22.2 mL/min/1.73 m2, of whom 624 (35.9%) developed KFRT and 133 (7.6%) died during a median follow-up of 34 months (IQR, 19 to 40 months). Overall, ACEi or ARB treatment initiation led to lower risk for KFRT (adjusted hazard ratio, 0.66 [95% CI, 0.55 to 0.79]) but not death (hazard ratio, 0.86 [CI, 0.58 to 1.28]). There was no statistically significant interaction between ACEi or ARB treatment and age, eGFR, albuminuria, or diabetes (P for interaction > 0.05 for all). Limitation: Individual participant–level data for hyperkalemia or acute kidney injury were not available. Conclusion: Initiation of ACEi or ARB therapy protects against KFRT, but not death, in people with advanced CKD.

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U2 - 10.7326/M23-3236

DO - 10.7326/M23-3236

M3 - Review article

C2 - 38950402

AN - SCOPUS:85199124627

SN - 0003-4819

VL - 177

SP - 953

EP - 963

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

IS - 7

ER -

Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers for Advanced Chronic Kidney Disease A Systematic Review and Retrospective Individual Participant–Level Meta-analysis of Clinical Trials

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