ABCG2 Dysfunction May Increase Risk for Hyperuricemia, Chronic Kidney Disease

Asymptomatic hyperuricemia may be a risk factor for chronic kidney disease (CKD) in patients with reduced activity of a key urate transporter, investigators report.

The transporter, adenosine triphosphatase-binding cassette subfamily G member 2 (ABCG2), drives urate excretion in the kidney’s proximal tubule and in the small intestine, Yuki Ohashi, BPharm, of Tokyo University of Pharmacy and Life Sciences in Japan, and colleagues explained. ABCG2 also is involved in the excretion of the uremic toxin indoxyl sulfate. Two polymorphisms of ABCG2 are linked with reduced function.

A total of 1885 Japanese adults without moderate CKD at baseline were classified by their estimated ABCG2 function: 100%, 75%, or 50% or less. As ABCG2 function declined, the proportion of patients with hyperuricemia at baseline (defined as a serum uric acid level exceeding 7.0 mg/dL) increased: 12.6%, 17.8%, and 28.4%, respectively.

Of the 1885 adults, 311 had asymptomatic hyperuricemia. In propensity score-matched analyses, asymptomatic hyperuricemia was only significantly associated with a decline in estimated glomerular filtration rate (eGFR) in patients with a baseline eGFR of 60-89 mL/min/1.73 m² and 50% or less ABCG2 function. In this group with stage 2 CKD, patients with 50% or less ABCG2 function experienced significantly faster kidney function decline over 9-10 years than patients with higher ABCG2 function: eGFR slope -1.3 vs -1.0 mL/min/1.73 m² per year, respectively, Ohashi and colleagues reported in the American Journal of Kidney Diseases. When the investigators lowered the baseline serum uric acid criterion to 6.0 mg/dL or more, the rate of eGFR decline was -1.1 mL/min/1.73 m² per year in patients with 50% or less ABCG2 function.

“The results of the present study suggest that ABCG2 contributes to hyperuricemia-associated decreases in eGFR,” Ohashi’s team wrote.

Among the study’s limitations, the investigators were unable to measure urinary urate excretion or indoxyl sulfate. Further investigation is needed to determine which phenomenon spurs eGFR decline. The study results also need to be validated in non-Japanese populations.

In an accompanying editorial, Richard J. Johnson, MD, of the University of Colorado in Aurora, praised the study: “The study is significant, as it suggests that there may be subsets of individuals with hyperuricemia who may specifically benefit from urate-lowering therapy.”

References

Ohashi Y, Kuriyama S Nakano T, et al. Urate transporter ABCG2 function and asymptomatic hyperuricemia: A retrospective cohort study of CKD progression. Am J Kidney Dis. 2023 Feb;81(2):134-144. doi:10.1053/j.ajkd.2022.05.010

Johnson RJ. Intestinal hyperuricemia as a driving mechanism for CKD. Am J Kidney Dis. 2023 Feb;81(2):127-130. doi:10.1053/j.ajkd.2022.08.001

This article originally appeared on Renal and Urology News