Elevated uric acid levels in premenopausal female systemic lupus erythematosus patients: Association with potential or existing renal damage

Abstract

Do premenopausal female systemic lupus erythematosus (SLE) patients have a low incidence of hyperuricaemia (HU) as healthy premenopausal females? As of yet, there have been few studies. This study aims to investigate the serum uric acid (UA) levels of premenopausal female SLE patients and the associated clinical risk factors. 107 premenopausal female SLE patients were divided into two groups: the high UA SLE group (n = 45) and the normal UA SLE group (n = 62). In total, 50 age-matched healthy premenopausal females served as the control group. Serum UA concentration, kidney damage index, lupus index, disease activity score of lupus and serum lipid index were collected and compared between the SLE subgroups. Binary logistic regression and multiple linear regression analyses were used to analyse the association of high UA levels with clinical features. The mean UA level of the SLE group was significantly higher than that of the control group (509.73 ± 150.28 μmol/L vs 296.78 ± 69.87 μmol/L, P < 0.001), as was the incidence of HU (42.06% vs 14.00%, P = 0.01). The UA levels of the high UA SLE group and the normal UA SLE group were 515.91 ± 120.64 μmol/L and 245.71 ± 63.18 μmol/L, respectively, which was statistically significant (P < 0.001). None of the patients with HU had current or previous gout attacks. The frequency of patients with renal manifestations in the high UA SLE group was significantly higher than that in the normal UA SLE group (χ 2 = 26.278, P < 0.001). In the SLE group, the medications azathioprine and cyclosporine were not associated with HU (P = 0.689), as analysed by binary linear regression. Using multiple linear regression analysis, it was found that urinary blood (P = 0.048), creatinine (P = 0.016), triglycerides (P = 0.029), peripheral white blood cells (P = 0.007) and renal manifestation (P < 0.001) were associated with HU in the SLE group. Our results demonstrate that premenopausal SLE patients had higher levels of UA than healthy premenopausal females, which may be associated with potential or existing renal damage.

A Systematic Review on Exploring the Role of Uric Acid in Predicting New-Onset Renal Damage in Lupus Nephritis

“…Elevated uric acid has been linked to the development of new-onset renal damage in SLE [14It predominantly causes renal injury, which causes glomerular blood vessel hypertension, which eventually progresses to systemic hypertension [18]. Several studies have established hyperuricemia as a risk factor for renal damage and persistent injury.…”

“…Ryom Oh et al found a connection between uric acid and C3 levels, indicating that elevated uric acid activates the complement system, leading to C3 consumption via both classical and alternative pathways (P value <0.001) [13]. Furthermore, several studies have supported a significantly negative correlation between C3 and uric acid [16,18,23]. However, some studies reported no significant relationship between uric acid and C3 [4,5,17].…”

“…Several factors influence uric acid levels, including gender and age. Females tend to have higher uric acid levels due to multiple hypotheses, one of which suggests the estrogen effect on urate excretion, leading to higher uric acid levels in premenopausal SLE patients compared to healthy premenopausal individuals [18,19].…”

“…A significant association was found between uric acid levels and LN progression in females, with a hazard ratio (HR) of 1.158 (95% confidence interval [CI] = 1.018-1.317, p < 0.028). However, no association was found in males [18]. One study reported no association between gender and poor renal outcomes [13].…”

Low expression of estrogen receptor β in renal tubular epithelial cells may cause hyperuricemia in premenopausal patients with systemic lupus erythematosus

“…Our initial study showed that the incidence of hyperuricemia in premenopausal SLE patients was 42.06%, compared to an incidence of 14% in healthy young females. 11 Although hyperuricemia was closely related to kidney damage, it did not depend on renal failure, neither was it associated with the use of cyclosporin or azathioprine. These results suggested that premenopausal female SLE patients did not maintain normal levels of UA even though they were hyperestrogenic.…”