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The dirty little secret of urate-lowering therapy: useless to stop chronic kidney disease progression and may increase mortality
Hyperuricaemia is frequent in chronic kidney disease (CKD). Observational studies have shown an association with adverse outcomes and acquired hyperuricaemia (meaning serum urate levels as low as 1.0 mg/dL) in animal models induces kidney injury. This evidence does not justify the widespread use of...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769546/ https://www.ncbi.nlm.nih.gov/pubmed/33391737 http://dx.doi.org/10.1093/ckj/sfaa236 |
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author | Gonzalez-Martin, Guillermo Cano, Jaime Carriazo, Sol Kanbay, Mehmet Perez-Gomez, Maria Vanessa Fernandez-Prado, Raul Ortiz, Alberto |
author_facet | Gonzalez-Martin, Guillermo Cano, Jaime Carriazo, Sol Kanbay, Mehmet Perez-Gomez, Maria Vanessa Fernandez-Prado, Raul Ortiz, Alberto |
author_sort | Gonzalez-Martin, Guillermo |
collection | PubMed |
description | Hyperuricaemia is frequent in chronic kidney disease (CKD). Observational studies have shown an association with adverse outcomes and acquired hyperuricaemia (meaning serum urate levels as low as 1.0 mg/dL) in animal models induces kidney injury. This evidence does not justify the widespread use of urate-lowering drugs for asymptomatic hyperuricaemia in CKD. However, promising results from small, open-label studies led some physicians to prescribe urate-lowering drugs to slow CKD progression. Two recent, large, placebo-controlled trials (CKD-FIX and PERL) showed no benefit from urate lowering with allopurinol on the primary endpoint of CKD progression, confirming prior negative results. Despite these negative findings, it was still argued that the study population could be optimized by enrolling younger non-proteinuric CKD patients with better preserved glomerular filtration rate (GFR). However, in these low-risk patients, GFR may be stable under placebo conditions. Additionally, the increased mortality trends already identified in gout trials of urate-lowering therapy were also observed in CKD-FIX and PERL, sending a strong safety signal: 21/449 (4.7%) and 10/444 (2.2%) patients died in the combined allopurinol and placebo groups, respectively [chi-squared P-value 0.048; relative risk 2.07 (95% CI 0.98–4.34); P = 0.06]. Given the absent evidence of benefit in multiple clinical trials and the potentially serious safety issues, the clear message should be that urate-lowering therapy should not be prescribed for the indication of slowing CKD progression. Additionally, regulatory agencies should urgently reassess the safety of chronic prescription of urate-lowering drugs for any indication. |
format | Online Article Text |
id | pubmed-7769546 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77695462020-12-31 The dirty little secret of urate-lowering therapy: useless to stop chronic kidney disease progression and may increase mortality Gonzalez-Martin, Guillermo Cano, Jaime Carriazo, Sol Kanbay, Mehmet Perez-Gomez, Maria Vanessa Fernandez-Prado, Raul Ortiz, Alberto Clin Kidney J Editorial Comments Hyperuricaemia is frequent in chronic kidney disease (CKD). Observational studies have shown an association with adverse outcomes and acquired hyperuricaemia (meaning serum urate levels as low as 1.0 mg/dL) in animal models induces kidney injury. This evidence does not justify the widespread use of urate-lowering drugs for asymptomatic hyperuricaemia in CKD. However, promising results from small, open-label studies led some physicians to prescribe urate-lowering drugs to slow CKD progression. Two recent, large, placebo-controlled trials (CKD-FIX and PERL) showed no benefit from urate lowering with allopurinol on the primary endpoint of CKD progression, confirming prior negative results. Despite these negative findings, it was still argued that the study population could be optimized by enrolling younger non-proteinuric CKD patients with better preserved glomerular filtration rate (GFR). However, in these low-risk patients, GFR may be stable under placebo conditions. Additionally, the increased mortality trends already identified in gout trials of urate-lowering therapy were also observed in CKD-FIX and PERL, sending a strong safety signal: 21/449 (4.7%) and 10/444 (2.2%) patients died in the combined allopurinol and placebo groups, respectively [chi-squared P-value 0.048; relative risk 2.07 (95% CI 0.98–4.34); P = 0.06]. Given the absent evidence of benefit in multiple clinical trials and the potentially serious safety issues, the clear message should be that urate-lowering therapy should not be prescribed for the indication of slowing CKD progression. Additionally, regulatory agencies should urgently reassess the safety of chronic prescription of urate-lowering drugs for any indication. Oxford University Press 2020-09-16 /pmc/articles/PMC7769546/ /pubmed/33391737 http://dx.doi.org/10.1093/ckj/sfaa236 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Editorial Comments Gonzalez-Martin, Guillermo Cano, Jaime Carriazo, Sol Kanbay, Mehmet Perez-Gomez, Maria Vanessa Fernandez-Prado, Raul Ortiz, Alberto The dirty little secret of urate-lowering therapy: useless to stop chronic kidney disease progression and may increase mortality |
title | The dirty little secret of urate-lowering therapy: useless to stop chronic kidney disease progression and may increase mortality |
title_full | The dirty little secret of urate-lowering therapy: useless to stop chronic kidney disease progression and may increase mortality |
title_fullStr | The dirty little secret of urate-lowering therapy: useless to stop chronic kidney disease progression and may increase mortality |
title_full_unstemmed | The dirty little secret of urate-lowering therapy: useless to stop chronic kidney disease progression and may increase mortality |
title_short | The dirty little secret of urate-lowering therapy: useless to stop chronic kidney disease progression and may increase mortality |
title_sort | dirty little secret of urate-lowering therapy: useless to stop chronic kidney disease progression and may increase mortality |
topic | Editorial Comments |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769546/ https://www.ncbi.nlm.nih.gov/pubmed/33391737 http://dx.doi.org/10.1093/ckj/sfaa236 |
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