Treatments for chronic kidney disease: a systematic literature review of randomized controlled trials
Treatments for chronic kidney disease: a systematic literature review of randomized controlled trials
Delaying disease progression and reducing the risk of mortality are key goals in the treatment of chronic kidney disease (CKD). New drug classes to augment renin-angiotensin-aldosterone system (RAAS) inhibitors as the standard of care have scarcely met their primary endpoints until recently. This systematic literature review explored treatments evaluated in patients with CKD since 1990 to understand what contemporary data add to the treatment landscape. Eighty-nine clinical trials were identified that had enrolled patients with estimated glomerular filtration rate 13.9-102.8 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 29.9-2911.0 mg/g, with (75.5%) and without (20.6%) type 2 diabetes (T2D). Clinically objective outcomes of kidney failure and all-cause mortality (ACM) were reported in 32 and 64 trials, respectively. Significant reductions (P < 0.05) in the risk of kidney failure were observed in seven trials: five small trials published before 2008 had evaluated the RAAS inhibitors losartan, benazepril, or ramipril in patients with (n = 751) or without (n = 84-436) T2D; two larger trials (n = 2152-2202) published onwards of 2019 had evaluated the sodium-glucose co-transporter 2 (SGLT2) inhibitors canagliflozin (in patients with T2D and UACR > 300-5000 mg/g) and dapagliflozin (in patients with or without T2D and UACR 200-5000 mg/g) added to a background of RAAS inhibition. Significant reductions in ACM were observed with dapagliflozin in the DAPA-CKD trial. Contemporary data therefore suggest that augmenting RAAS inhibitors with new drug classes has the potential to improve clinical outcomes in a broad range of patients with CKD.
Albuminuria, All-cause mortality, Chronic kidney disease, Diabetes, Estimated glomerular filtration rate, Kidney failure
193–220
Garcia Sanchez, Juan Jose
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Thompson, Juliette
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Scott, David A
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Evans, Rachel
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Rao, Naveen
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Sörstadius, Elisabeth
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James, Glen
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Nolan, Stephen
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Wittbrodt, Eric T
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Abdul Sultan, Alyshah
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Stefansson, Bergur V
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Jackson, Dan
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Abrams, Keith R
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8 December 2021
Garcia Sanchez, Juan Jose
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Thompson, Juliette
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Scott, David A
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Evans, Rachel
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Rao, Naveen
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Sörstadius, Elisabeth
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James, Glen
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Nolan, Stephen
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Wittbrodt, Eric T
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Abdul Sultan, Alyshah
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Stefansson, Bergur V
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Jackson, Dan
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Abrams, Keith R
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Garcia Sanchez, Juan Jose, Thompson, Juliette, Scott, David A, Evans, Rachel, Rao, Naveen, Sörstadius, Elisabeth, James, Glen, Nolan, Stephen, Wittbrodt, Eric T, Abdul Sultan, Alyshah, Stefansson, Bergur V, Jackson, Dan and Abrams, Keith R
(2021)
Treatments for chronic kidney disease: a systematic literature review of randomized controlled trials.
Advances in Therapy, 39 (1), .
(doi:10.1007/s12325-021-02006-z).
Abstract
Delaying disease progression and reducing the risk of mortality are key goals in the treatment of chronic kidney disease (CKD). New drug classes to augment renin-angiotensin-aldosterone system (RAAS) inhibitors as the standard of care have scarcely met their primary endpoints until recently. This systematic literature review explored treatments evaluated in patients with CKD since 1990 to understand what contemporary data add to the treatment landscape. Eighty-nine clinical trials were identified that had enrolled patients with estimated glomerular filtration rate 13.9-102.8 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 29.9-2911.0 mg/g, with (75.5%) and without (20.6%) type 2 diabetes (T2D). Clinically objective outcomes of kidney failure and all-cause mortality (ACM) were reported in 32 and 64 trials, respectively. Significant reductions (P < 0.05) in the risk of kidney failure were observed in seven trials: five small trials published before 2008 had evaluated the RAAS inhibitors losartan, benazepril, or ramipril in patients with (n = 751) or without (n = 84-436) T2D; two larger trials (n = 2152-2202) published onwards of 2019 had evaluated the sodium-glucose co-transporter 2 (SGLT2) inhibitors canagliflozin (in patients with T2D and UACR > 300-5000 mg/g) and dapagliflozin (in patients with or without T2D and UACR 200-5000 mg/g) added to a background of RAAS inhibition. Significant reductions in ACM were observed with dapagliflozin in the DAPA-CKD trial. Contemporary data therefore suggest that augmenting RAAS inhibitors with new drug classes has the potential to improve clinical outcomes in a broad range of patients with CKD.
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GarciaSanchez2022_Article_TreatmentsForChronicKidneyDise
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Accepted/In Press date: 26 November 2021
Published date: 8 December 2021
Keywords:
Albuminuria, All-cause mortality, Chronic kidney disease, Diabetes, Estimated glomerular filtration rate, Kidney failure
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Local EPrints ID: 454933
URI: http://eprints.soton.ac.uk/id/eprint/454933
ISSN: 0741-238X
PURE UUID: 4e115ffe-8a2d-41ae-a544-5ef71e976382
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Date deposited: 01 Mar 2022 17:52
Last modified: 17 Mar 2024 04:02
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Contributors
Author:
Juan Jose Garcia Sanchez
Author:
Juliette Thompson
Author:
David A Scott
Author:
Rachel Evans
Author:
Naveen Rao
Author:
Elisabeth Sörstadius
Author:
Glen James
Author:
Stephen Nolan
Author:
Eric T Wittbrodt
Author:
Alyshah Abdul Sultan
Author:
Bergur V Stefansson
Author:
Dan Jackson
Author:
Keith R Abrams
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