Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Oct-Dec;43(4):572-579.
doi: 10.1590/2175-8239-JBN-2020-U002.

Hyperuricemia and chronic kidney disease: to treat or not to treat

[Article in English, Portuguese]
Federica Piani  1   2 , Fumihiko Sasai  1 , Petter Bjornstad  1 , Claudio Borghi  2 , Ashio Yoshimura  3 , Laura G Sanchez-Lozada  1 , Carlos Roncal-Jimenez  1 , Gabriela E Garcia  1 , Ana Andres Hernando  1 , Gabriel Cara Fuentes  1 , Bernardo Rodriguez-Iturbe  4 , Miguel A Lanaspa  1 , Richard J Johnson  1   5
Affiliations

Hyperuricemia and chronic kidney disease: to treat or not to treat

[Article in English, Portuguese]
Federica Piani et al. J Bras Nefrol. 2021 Oct-Dec.

Abstract
in English, Portuguese

Hyperuricemia is common in chronic kidney disease (CKD) and may be present in 50% of patients presenting for dialysis. Hyperuricemia can be secondary to impaired glomerular filtration rate (GFR) that occurs in CKD. However, hyperuricemia can also precede the development of kidney disease and predict incident CKD. Experimental studies of hyperuricemic models have found that both soluble and crystalline uric acid can cause significant kidney damage, characterized by ischemia, tubulointerstitial fibrosis, and inflammation. However, most Mendelian randomization studies failed to demonstrate a causal relationship between uric acid and CKD, and clinical trials have had variable results. Here we suggest potential explanations for the negative clinical and genetic findings, including the role of crystalline uric acid, intracellular uric acid, and xanthine oxidase activity in uric acid-mediated kidney injury. We propose future clinical trials as well as an algorithm for treatment of hyperuricemia in patients with CKD.

A hiperuricemia é comum na doença renal crônica (DRC) e pode estar presente em até 50% dos pacientes que se apresentam para diálise. A hiperuricemia pode ser secundária ao comprometimento da taxa de filtração glomerular (TFG) que ocorre na DRC. No entanto, ela também pode preceder o desenvolvimento da doença renal e mesmo prever uma DRC incidente. Estudos experimentais de modelos hiperuricêmicos descobriram que tanto o ácido úrico solúvel quanto o cristalino podem causar danos renais significativos, caracterizados por isquemia, fibrose tubulointersticial e inflamação. Entretanto, a maioria dos estudos de randomização Mendeliana falhou em demonstrar uma relação causal entre o ácido úrico e a DRC, e os ensaios clínicos têm apresentado resultados variáveis. Aqui sugerimos explicações potenciais para os achados clínicos e genéticos negativos, incluindo o papel do ácido úrico cristalino, do ácido úrico intracelular e da atividade da xantina oxidase na lesão renal mediada por ácido úrico. Propomos ensaios clínicos futuros, bem como um algoritmo para o tratamento de hiperuricemia em pacientes com DRC.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

RJJ has equity with XORTX therapeutics that is developing novel xanthine oxidase inhibitors, and he has also consulted for Horizon Pharma. No other individuals have any conflicts of interest.

Figures

Figure 1
Figure 1. Mechanisms of uric acid-induced kidney injury.
See this image and copyright information in PMC

References

    1. Bardin T, Richette P. Impact of comorbidities on gout and hyperuricaemia: an update on prevalence and treatment options. BMC Med. 2017;15(1):123–123. - PMC - PubMed
    1. Davis NS., Junior The cardio-vascular and renal relations and manifestations of gout. JAMA. 1897 Aug;29(6):261–262.
    1. Johnson G. On the diseases of the kidney. London: John W Parker and Son; 1852.
    1. Krishnan E, Akhras KS, Sharma H, Marynchenko M, Wu E, Tawk RH. Serum urate and incidence of kidney disease among veterans with gout. J Rheumatol. 2013 May;40(7):1166–1172. - PubMed
    1. Fuldeore MJ, Riedel AA, Zarotsky V, Pandya BJ, Dabbous O, Krishnan E. Chronic kidney disease in gout in a managed care setting. BMC Nephrol. 2011 Aug;12:36–36. - PMC - PubMed