Hyperuricemia Linked to Increased Risk of Nephrolithiasis

A hyperuricemia diagnosis was independently associated with an increased risk of developing nephrolithiasis, according to a study published in BMC Public Health.¹ Prior to obtaining the diagnostic criteria for hyperuricemia, the most important risk factor for gout, nephrolithiasis risk raised with the increase of serum uric acid. Therefore, controlling SUA levels may be a critical factor in preventing nephrolithiasis, even in an asymptomatic gout-free population.

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Nephrolithiasis, a highly prevalent and often recurrent condition, continues to increase in incidence and prevalence worldwide. The disease is linked to an increase in the likelihood of chronic kidney disease, end-stage renal disease, and hypertension, among other adverse renal outcomes. Additionally, it is associated with metabolic syndrome, type 2 diabetes, coronary artery disease, ischemic stroke, and bone loss.²

“It is very reasonable to believe that SUA levels play an important role in the independent association between nephrolithiasis and gout,” wrote a group of Chinese investigators. “However, hyperuricemia is often used as an accompanying symptom of gout to explore its association with nephrolithiasis. There are limited studies to explore whether hyperuricemia itself or SUA levels are related to the risk of nephrolithiasis.”

Adult patients aged 30 – 79 years who participated in the China Multi-Ethnic Cohort (CMEC) study, a prospective cohort study designed to consider China's ethnic characteristics, population size, and non-communicable disease patterns, in Yunnan Province from May 2018 to September 2019 were included in the study. All 22,303 patients received standardized face-to-face interviews using electronic questionnaires, biochemical examinations, and medical examinations. Demographics, disease history, lifestyle behaviors, and other information were collected. Nephrolithiasis was defined as a diagnosis by abdominal ultrasonography or a diagnosis by a doctor in a hospital at the township/district level or above.

A restricted cubic spline (RCS) model analyzed the dose-response relationship between SUA and nephrolithiasis, while logistic regression determined the link between hyperuricemia and nephrolithiasis.

Most (67.69%) patients were female, from rural areas (92.96%), and the mean age of participants was 52.9 years. In total, 14.5% of participants were diagnosed with hyperuricemia and 12.1% (n = 2678) were diagnosed with nephrolithiasis. The prevalence of nephrolithiasis was higher in men (15.71%) when compared with women (10.40%). Additionally, those with a nephrolithiasis diagnosis were more likely to be current or ex-smokers, have hypertension, diabetes, high body fat, a fatty liver, or hyperlipidemia.

After making adjustments for confounders, the odds ratio (OR; 95% confidence interval [CI]) for developing nephrolithiasis in patients with hyperuricemia when compared with those without hyperuricemia was 1.464 (1.312,1.633; P < .001). After stratifying for gender, age, and ethnicity, hyperuricemia remained positively associated with nephrolithiasis.

The RCS analysis showed the risk of nephrolithiasis increased with increases in SUA. Further, when SUA levels were higher than 356 μmol/L in male patients and higher than 265 μmol/L in female patients, there was a dose-response relationship between increases in SUA and the risk of developing nephrolithiasis (P for nonlinearity = .1668; P for nonlinearity = .0667).

Investigators noted limitations including the cross-sectional study design, which hindered the assessment of the causal relationship between asymptomatic hyperuricemia and nephrolithiasis. Additionally, the type of nephrolithiasis could not be determined due to using ultrasonography as the diagnostic method of choice. However, the study was strengthened by including a large sample size encompassing a wide age range of patients, as well as adjusting for lifestyle and diet.

References

1. ^{Deng H, Zhang X, Cheng N, et al. Asymptomatic hyperuricemia associated with increased risk of nephrolithiasis: a cross-sectional study. BMC Public Health. 2023;23(1):1525. Published 2023 Aug 10. doi:10.1186/s12889-023-16469-y}
2. ^{Sakhaee K, Maalouf NM, Sinnott B. Clinical review. Kidney stones 2012: pathogenesis, diagnosis, and management. J Clin Endocrinol Metab. 2012;97(6):1847–60. https://doi.org/10.1210/jc.2011-3492}