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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
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
0741-238X
193–220
Garcia Sanchez, Juan Jose
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Thompson, Juliette
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Scott, David A
19b5fd34-9974-4ae4-8be0-27a693639e20
Evans, Rachel
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Rao, Naveen
40a953c4-7cef-4f2b-930d-f85cb7c6e136
Sörstadius, Elisabeth
a2628980-457d-40e7-ad00-72dec012a9a8
James, Glen
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Nolan, Stephen
0a6c4794-6d1f-4f58-b8be-1977776f921e
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
6db24e9a-24bb-4f34-8d32-a97352af4e09
Garcia Sanchez, Juan Jose
724b6c0c-4d4d-495b-a0e6-1ef4d56a5c14
Thompson, Juliette
28a24d4b-8b21-436c-85db-0b6608c46a09
Scott, David A
19b5fd34-9974-4ae4-8be0-27a693639e20
Evans, Rachel
a61a4bac-e744-45c2-aca2-59a1fbedb37b
Rao, Naveen
40a953c4-7cef-4f2b-930d-f85cb7c6e136
Sörstadius, Elisabeth
a2628980-457d-40e7-ad00-72dec012a9a8
James, Glen
525fa6f0-dbb6-440c-bcf4-3c6d8a04135c
Nolan, Stephen
0a6c4794-6d1f-4f58-b8be-1977776f921e
Wittbrodt, Eric T
67872e06-b316-4238-b1de-95c36cae044a
Abdul Sultan, Alyshah
fafdc8a4-3aa3-4b13-8e16-15e24e132ef3
Stefansson, Bergur V
3f93f16f-42d4-4574-afc9-17876a08f1f2
Jackson, Dan
2b09afba-b3b5-4282-8b61-b6adcb9b43d6
Abrams, Keith R
6db24e9a-24bb-4f34-8d32-a97352af4e09

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), 193–220. (doi:10.1007/s12325-021-02006-z).

Record type: Article

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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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

Identifiers

Local EPrints ID: 454933
URI: http://eprints.soton.ac.uk/id/eprint/454933
ISSN: 0741-238X
PURE UUID: 4e115ffe-8a2d-41ae-a544-5ef71e976382
ORCID for David A Scott: ORCID iD orcid.org/0000-0001-6475-8046

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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 ORCID iD
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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