Metabolic Syndrome: The Genesis of Nephrolithiasis in Gout Patients?

Abstract

Background/Purpose: Gout patients have a high frequency of metabolic syndrome (MS), a disorder known to be associated with hyperinsulinemia. The latter condition augments proximal tubular sodium reabsorption and leads to reduced renal urate excretion and hyperuricemia. There are no data, however, evaluating whether MS can influence gout-associated clinical characteristics. Thus, we aimed to determine the prevalence of MS in our population and to investigate if the presence of MS would characterize a particular clinical and laboratorial gout profile. Methods: This was a cross-sectional study of 158 gout patients (ACR criteria). MS was defined in accordance to the National Cholesterol Education Program ATP III (NCEP-ATP III) and the International Diabetes Federation (IDF) criteria. Demographic, anthropometric (body mass index - BMI) and clinical data were evaluated. Fasting serum levels of UA, glucose, triglycerides and cholesterol fractions were analyzed by routine laboratory tests. Nephrolithiasis was demonstrated by usual ultrasonography and urate under-excretion defined as UA clearance lower than 7.5 ml/min. Statistical comparisons were performed using Fisher’s exact, chi-square, students T and Spearman’s tests and P<0.05 was considered significant. Results: The frequency of MS in gout patients was 73% and 71% according to NCEP ATPIII and IDF criteria respectively. Further comparison of 125 patients with MS and those 33 without this condition revealed similar mean ages (63.0 ± 11.5 vs 62.5 ± 12.9; p>0,05) and male predominance (94% and 75%). As expected, those with MS had higher BMI (30.2 ± 5.5kg/m2 vs 27.0 5.8kg/m2; p=0.005) and higher prevalences of systemic arterial hypertension (93.3% vs 75% p=0.012) and diabetes (25.8% vs 0, p=0.001), though comparable frequency of coronary artery disease (22.5% vs 16.7%; p=0.469). With regard to gout clinical/laboratorial characteristic, patients with MS had more nephrolitiasis (37.1% vs 16.7%, p=0.026), but they did not differ from patients without MS concerning the presence of tophi (52.8% vs. 55.6%; p = 0.780) or uric acid underexcretion (83.1% vs 94.4%; p=0.148). Current alcohol consumption, mean estimated creatinine clearance and mean serum levels of uric acid, were alike in both groups (p>0.05). Conclusion: The novel demonstration that MS in gout is associated to nephrolithiasis suggests that this condition may underlie the genesis of uric acid stones. Whether insulin resistance may account for a renal alteration that may ultimately impair buffering and amplification of acidic urine remains to be determined. Moreover, the elevated prevalence of MS in gout patients from our country (almost 3⁄4) is higher than overall rates of 63% MS in gout worldwide, indicating possible influence of dietary, geographical and/or genetic background.