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Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes.

Abstract

Initiation of blockade of the renin-angiotensin system may cause an acute decrease in glomerular filtration rate (GFR): the prognostic significance of this is unknown. We did a post hoc analysis of patients with, or at risk for, vascular disease, in two randomized controlled trials: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease (TRANSCEND), whose median follow-up was 56 months. In 9340 patients new to renin-angiotensin system blockade, who were then randomized to renin-angiotensin system blockade, a fall in GFR of 15% or more at 2 weeks after starting renin-angiotensin system blockade was seen in 1480 participants (16%), with persistence at 8 weeks in 700 (7%). Both acute increases and decreases in GFR after initiation of renin-angiotensin system blockade were associated with tendencies, mostly not statistically significant, to increased risk of cardiovascular outcomes, which occurred in 1280 participants, and of microalbuminuria, which occurred in 864. Analyses of creatinine-based outcomes were suggestive of regression to the mean. In more than 3000 patients randomized in TRANSCEND to telmisartan or placebo, there was no interaction between acute change in GFR and renal or cardiovascular benefit from telmisartan. Thus, both increases and decreases in GFR on initiation of renin-angiotensin system blockade are common, and may be weakly associated with increased risk of cardiovascular and renal outcomes. Changes do not predict increased benefit from therapy.

Authors+Show Affiliations

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Department of Medicine and Clinical Epidemiology, McMaster University, Hamilton, Ontario, Canada. Electronic address: clase@mcmaster.ca.

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Kaiser Permanente of Georgia, Atlanta, Georgia, USA.

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Population Heart Research Institute, Hamilton, Ontario, Canada.

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Department of Nephrology, Galway University Hospitals, Gaillimh, Connacht, Ireland.

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Department of Medicine, University Hospital Erlangen, Erlangen, Bavaria, Germany.

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Department of Medicine, Sunnybrook HSC, Toronto, Ontario, Canada.

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Department of Medicine and Clinical Epidemiology, McMaster University, Hamilton, Ontario, Canada; Population Heart Research Institute, Hamilton, Ontario, Canada.

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Department of Medicine and Clinical Epidemiology, McMaster University, Hamilton, Ontario, Canada; Population Heart Research Institute, Hamilton, Ontario, Canada.

Departments of Nephrology and Hypertension, Friedrich Alexander University, Erlangen, Bavaria, Germany.

Source

Kidney international 91:3 2017 03 pg 683-690

MeSH

Angiotensin II Type 1 Receptor Blockers
Angiotensin-Converting Enzyme Inhibitors
Benzimidazoles
Benzoates
Cardiovascular Diseases
Disease Progression
Drug Therapy, Combination
Female
Glomerular Filtration Rate
Hemodynamics
Humans
Kidney
Kidney Diseases
Male
Middle Aged
Odds Ratio
Ramipril
Renin-Angiotensin System
Risk Factors
Telmisartan
Time Factors
Treatment Outcome

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

27927602

Citation

Clase, Catherine M., et al. "Acute Change in Glomerular Filtration Rate With inhibition of the Renin-angiotensin System does Not predict Subsequent Renal And cardiovascular outcomes." Kidney International, vol. 91, no. 3, 2017, pp. 683-690.
Clase CM, Barzilay J, Gao P, et al. Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes. Kidney Int. 2017;91(3):683-690.
Clase, C. M., Barzilay, J., Gao, P., Smyth, A., Schmieder, R. E., Tobe, S., ... Mann, J. F. (2017). Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes. Kidney International, 91(3), pp. 683-690. doi:10.1016/j.kint.2016.09.038.
Clase CM, et al. Acute Change in Glomerular Filtration Rate With inhibition of the Renin-angiotensin System does Not predict Subsequent Renal And cardiovascular outcomes. Kidney Int. 2017;91(3):683-690. PubMed PMID: 27927602.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acute change in glomerular filtration rate with inhibition of the renin-angiotensin system does not predict subsequent renal and cardiovascular outcomes. AU - Clase,Catherine M, AU - Barzilay,Joshua, AU - Gao,Peggy, AU - Smyth,Andrew, AU - Schmieder,Roland E, AU - Tobe,Sheldon, AU - Teo,Koon K, AU - Yusuf,Salim, AU - Mann,Johannes F E, Y1 - 2016/12/04/ PY - 2016/04/20/received PY - 2016/09/12/revised PY - 2016/09/22/accepted PY - 2016/12/9/pubmed PY - 2017/11/3/medline PY - 2016/12/9/entrez KW - GFR KW - chronic kidney disease KW - renin–angiotensin system blockade SP - 683 EP - 690 JF - Kidney international JO - Kidney Int. VL - 91 IS - 3 N2 - Initiation of blockade of the renin-angiotensin system may cause an acute decrease in glomerular filtration rate (GFR): the prognostic significance of this is unknown. We did a post hoc analysis of patients with, or at risk for, vascular disease, in two randomized controlled trials: Ongoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease (TRANSCEND), whose median follow-up was 56 months. In 9340 patients new to renin-angiotensin system blockade, who were then randomized to renin-angiotensin system blockade, a fall in GFR of 15% or more at 2 weeks after starting renin-angiotensin system blockade was seen in 1480 participants (16%), with persistence at 8 weeks in 700 (7%). Both acute increases and decreases in GFR after initiation of renin-angiotensin system blockade were associated with tendencies, mostly not statistically significant, to increased risk of cardiovascular outcomes, which occurred in 1280 participants, and of microalbuminuria, which occurred in 864. Analyses of creatinine-based outcomes were suggestive of regression to the mean. In more than 3000 patients randomized in TRANSCEND to telmisartan or placebo, there was no interaction between acute change in GFR and renal or cardiovascular benefit from telmisartan. Thus, both increases and decreases in GFR on initiation of renin-angiotensin system blockade are common, and may be weakly associated with increased risk of cardiovascular and renal outcomes. Changes do not predict increased benefit from therapy. SN - 1523-1755 UR - https://www.unboundmedicine.com/medline/citation/27927602/Acute_change_in_glomerular_filtration_rate_with inhibition_of_the_renin_angiotensin_system does_not predict_subsequent_renal_and cardiovascular outcomes_ L2 - https://medlineplus.gov/kidneydiseases.html DB - PRIME DP - Unbound Medicine ER -