A retrospective study on sex difference in patients with urolithiasis: who is more vulnerable to chronic kidney disease?

Background Urolithiasis is considered a vital public health issue with a substantial burden on kidney function. Additionally, only few reports focused on the gender difference in patients with urolithiasis. Therefore, this study aimed to compare the clinical characteristics of sex difference and their potential risk for chronic kidney disease (CKD) in patients with urolithiasis. Methods Patients diagnosed with stone disease from 2013 to 2018 were retrospectively reviewed and divided into two groups by gender. Clinical demographic characteristics, stone location, stone composition, urine chemistries, and renal function were investigated. Univariate and multivariate analyses were used to assess the relationship and potential risk of CKD between sex groups. Results A total of 1802 patients were included: 1312 from men and 490 from women. Female patients had a higher rate of hypertension, diabetes, and dyslipidemia. Male patients predominantly had calcium-containing stones, especially calcium oxalate stone, uric acid stone, and struvite stone. Carbonate apatite stone was more frequently found in women. Complex surgeries such as percutaneous nephrolithotomy (PCNL) and ureteroscopic lithotripsy (URSL) were more frequently performed in women than that in men. Multivariate analysis confirmed that age > 60 years (odds ratios [ORs] = 6.36; 95% confidence interval [CI], 3.8–10.8), female sex (ORs = 5.31; 95% CI 3.3–8.4), uric acid stone (ORs = 3.55; 95% CI 2.0–6.4), hypertension (OR = 7.20; 95% CI 3.8–13.7), and diabetes (OR = 7.06; 95% CI 3.1–16.2) were independent predictors of poor prognoses in CKD. Conclusions The female gender is significantly associated with a higher prevalence of CKD among patients with urolithiasis. Therefore, women with stone disease may need close renal function monitoring during follow-up.

A Retrospective Study on Sex Difference in Patients With Urolithiasis: Who Is More Vulnerable to Chronic Kidney Disease?

Background: Urolithiasis is considered a vital public health issue with a substantial burden on kidney function. Additionally, only few reports focused on the gender difference in patients with urolithiasis. Therefore, this study aimed to compare the clinical characteristics of sex difference and their potential risk for chronic kidney disease (CKD) in patients with urolithiasis.Methods: Patients diagnosed with stone disease from 2013 to 2018 were retrospectively reviewed and divided into two groups by gender. Clinical demographic characteristics, stone location, stone composition, urine chemistries, and renal function were investigated. Univariate and multivariate analyses were used to assess the relationship and potential risk of CKD between sex groups.Results: A total of 1,802 stones were included: 1,312 from men and 490 from women. Female patients had higher rate of hypertension, diabetes, and dyslipidemia. Male patients predominantly had calcium-containing stones, especially calcium oxalate stone, uric acid stone, and struvite stone. Carbonate apatite stone was more frequently found in women. Complex surgeries such as percutaneous nephrolithotomy (PCNL) and ureteroscopic lithotripsy (URSL) were more frequently performed in women than that in men. Multivariate analysis confirmed that age >60 years (odds ratios [ORs] = 6.36; 95% confidence interval [CI], 3.8–10.8), female sex (ORs = 5.31; 95% CI 3.3–8.4), uric acid stone (ORs = 3.55; 95% CI 2.0–6.4), hypertension (OR = 7.20; 95% CI 3.8–13.7), and diabetes (OR = 7.06; 95% CI 3.1–16.2) were independent predictors of poor prognoses in CKD.Conclusions: Gender is significantly associated with higher prevalence of CKD among patients with urolithiasis. Therefore, women with stone disease may need close renal function monitoring during follow-up.

P0169DYSFUNCTION OF ABCG2, URATE TRANSPORTER, IS RELATED WITH UROLITHIASIS

Background and Aims Urolithiasis is one of the rapidly increasing diseases in developed countries. It has been reported that urolithiasis is related with lifestyles, diet, obesity, climate and chronic diseases including hyperuricemia, diabetes mellitus, metabolic syndrome, chronic kidney disease et cetera. Among them, hyperuricemia is the leading cause of urolithiasis. ATP–binding cassette subfamily G member 2 (ABCG2), urate transporter, excretes uric acid in the kidney and the intestinal tract and ABCG2 dysfunction increases a risk of hyperuricemia. In this study, we investigated the estimated ABCG2 function by common two dysfunctional variants, Q126X (rs72552713) and Q141K (rs2231142), in patients with urolithiasis, and we evaluated the relation between urolithiasis and ABCG2 dysfunction. Method One hundred and ninety-seven urolithiasis patients without gout (150 males and 47 females) were enrolled. Q126X totally abolishes ABCG2 function, while Q141K reduces its function by about 50%. Since these two SNPs do not link each other and two SNPs do not exist on same chromosome, these two are regarded as independent risks. Namely, based on the genotype of Q126X and Q141K, it can be divided into three categories: a full functional group, a 75% functional group and a ≦50% functional group. Serum uric acid levels and amount of urinary uric acid were measured. Renal uric acid handling of the patients was classified into renal uric acid underexcretion type or renal uric acid overload type based on uric acid clearance and amount of urinary uric acid. Stone composition was analysed, if it had been possible. Results ABCG2 function of the patients was evaluated as follows: 82 patients, ABCG2 full function (41.6%); 78 patients, 75% function (39.6%); 37 patients, ≦50% function (18.8%). 155 patients were classified into renal uric acid underexcretion type, 13 patients were classified into renal uric acid overload type and 2 patients were classified into normal type (27 patients have not had 24-hour urine biochemical test). Stone composition analysis was performed for 136 patients; calcium oxalate stone was identified in 107 patients and uric acid stone in 29 patients. In this study, 58.4 % of the patients with urolithiasis had some ABCG2 dysfunction as against 49.8 % of the healthy individuals previously reported (p=0.0246). In addition, the ratio of subjects with urolithiasis having 50% or less of ABCG2 function was higher than healthy individuals significantly (OR=1.773, p=0.007). The high ratio of ABCG2 dysfunctional patients with urolithiasis suggested that ABCG2 dysfunction is a risk factor for urolithiasis. In the patients with urolithiasis, renal uric acid underexcretion type accounted for about 90% of the patients. This means that this type accelerated urolithiasis as well as hyperuricosuria. Conclusion ABCG2 dysfunction and renal uric acid underexcretion type were suggested to be a risk factor for urolithiasis.

Targeted renal knockdown of Na+/H+ exchanger regulatory factor Sip1 produces uric acid nephrolithiasis in Drosophila

Nephrolithiasis is one of the most common kidney diseases, with poorly understood pathophysiology, but experimental study has been hindered by lack of experimentally tractable models. Drosophila melanogaster is a useful model organism for renal diseases because of genetic and functional similarities of Malpighian (renal) tubules with the human kidney. Here, we demonstrated function of the sex-determining region Y protein-interacting protein-1 ( Sip1) gene, an ortholog of human Na+/H+ exchanger regulatory factor ( NHERF1), in Drosophila Malpighian tubules and its impact on nephrolithiasis. Abundant birefringent calculi were observed in Sip1 mutant flies, and the phenotype was also observed in renal stellate cell-specific RNA interference Sip1 knockdown in otherwise normal flies, confirming a renal etiology. This phenotype was abolished in rosy mutant flies (which model human xanthinuria) and by the xanthine oxidase inhibitor allopurinol, suggesting that the calculi were of uric acid. This was confirmed by direct biochemical assay for urate. Stones rapidly dissolved when the tubule was bathed in alkaline media, suggesting that Sip1 knockdown was acidifying the tubule. SIP1 was shown to collocate with Na+/H+ exchanger isoform 2 (NHE2) and with moesin in stellate cells. Knockdown of NHE2 specifically to the stellate cells also increased renal uric acid stone formation, and so a model was developed in which SIP1 normally regulates NHE2 activity and luminal pH, ultimately leading to uric acid stone formation. Drosophila renal tubules may thus offer a useful model for urate nephrolithiasis.