A sensitivity analysis was conducted by sequentially omitting each study to analyze the effect of individual research on the overall results of the meta-analysis. The omission of any single study had no significant impact on the comparison models of urolithiasis associated with NAFLD, suggesting a high level of integrity of our meta-analysis (Fig. 4).
Several studies have assessed the relationship between NAFLD and the risk of developing urolithiasis. A cross-sectional study which involved a total of 3719 Chinese men suggested that NAFLD was related to a higher prevalence of urinary calculi, independently of several traditional risk factors, such as physical activity, serum uric acid, and body mass index (BMI). Similarly, a retrospective study in Israel found a 3.24-fold increased risk of CT diagnosed renal colic among NAFLD patients than individuals without NAFLD. A cross-sectional study examining a total of 11245 ultrasonography reports revealed an increased prevalence of urolithiasis in NAFLD patients compared to subjects without NAFLD (OR: 2.4, 95% CI, 2.1–2.7). Again, a population-based retrospective study involving 1812 patients showed that the prevalence of renal stone disease in patients with NAFLD was markedly higher than those without NAFLD in multivariate analysis (OR: 5, 95% CI, 3–8.2) (P < .05). Also, a large cohort study involving 208,578 Korean adults who underwent a comprehensive health examination between January 2002 and December 2014 showed that the presence of NAFLD was significantly linked to an increased incidence of urolithiasis among in male subjects, independently of possible confounders. Collectively, an increasing number of studies have shown consistent evidence that the presence of NAFLD, defined as either ultrasonography or computed tomography, was closely linked to a higher risk of urolithiasis.
The plausible biologic mechanism by which NAFLD may contribute to increasing the risk for urolithiasis remains unclear. Reactive oxygen species (ROS) and oxidative stress (OS) have been implicated in the pathogenesis of NAFLD.[28,36,37] Furthermore, increased levels of γ-glutamyl transpeptidase and renal enzymes observed in the urine of idiopathic CaOx stone patients suggest the involvement of ROS in the pathogenesis of the idiopathic stone disease. A study involving adult participants of 1988 to 1994 NHANES III examined serum levels of antioxidants found that decreased antioxidant capacities, which indicated as lower levels of antioxidants, α-carotene, β-cryptoxanthin, β-carotene, predisposed to the development of kidney stones, furtherly supporting the role of ROS in nephrolithiasis. Collectively, clinical and experimental data provide evidence of the involvement of ROS production and OS development in the patients with NAFLD and urolithiasis, and OS may represent shared pathogenesis for both NAFLD and urolithiasis.[28,40,41] Again, accumulating evidence suggested that kidney stones are associated with metabolic syndrome (MetS) characterized by insulin resistance. A Japanese study examining the association between insulin resistance, adiponectin, and kidney stones showed that women with kidney stones had significantly higher HOMA-IR and insulin than in women without kidney stones, indicating a greater risk of kidney stones resulting from MetS components by insulin resistance or subclinical hyperinsulinemia.
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