P0169DYSFUNCTION OF ABCG2, URATE TRANSPORTER, IS RELATED WITH UROLITHIASIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yuki Ohashi ◽  
Satoshi Yamaguchi ◽  
Hirotaka Matsuo ◽  
Makoto Hosoyamada ◽  
Kimiyoshi Ichida

Abstract 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.

2019 ◽  
Vol 48 (3) ◽  
pp. 030006051988726
Author(s):  
Xuebao Zhang ◽  
Jiajia Ma ◽  
Ning Wang ◽  
Chunhua Lin

Objective There has not been a study that analyzed the composition of urinary stones from patients in the eastern Shandong region of China. Thus, we explored the composition of urinary stones in the eastern Shandong region of China and discuss the clinical significance of the findings. Methods A total of 3684 urinary calculi from the eastern Shandong region were collected in our study. Compositions of the stones were analyzed using an Automatic Infrared Spectrum Analysis System (type LIIR-20). The results were verified through manual analysis of the spectrograms, which was accompanied by polarizing microscopy and chemical analysis if necessary. Results Among the 3684 specimens, there were 1767 single-component stones and 1917 mixed-component stones. According to the main components of the stones, the stones were divided into the following types: calcium oxalate monohydrate stones (1779, 48.3%), anhydrous uric acid stones (1105, 30.0%), carbonate apatite stones (590, 16.0%), ammonium magnesium phosphate hexahydrate stones (143, 3.9%), calcium oxalate dihydrate stones (36, 1.0%), and cystine stones (31, 0.8%). Conclusions There was a relatively high rate of uric acid stones in patients from the eastern Shandong region of China.


2013 ◽  
Vol 2 (4) ◽  
pp. 420 ◽  
Author(s):  
Blayne K. Welk ◽  
Joel M.H. Teichman

We report 2 patients who presented with uric acid renal calculi. Both patients had previously been treated unsuccessfully for their stones with shock wave lithotripsy and were referred to our centre for percutaneous nephrolithomy. We were able to avoid surgery in both cases owing to the recognition of uric acid stone composition despite the calculi being visible on CT scout films.


2010 ◽  
Vol 3 (2) ◽  
pp. 44-50 ◽  
Author(s):  
Konstantinos Tziomalos ◽  
Vasilios G. Athyros ◽  
Asterios Karagiannis ◽  
Dimitri P. Mikhailidis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daling Zhang ◽  
Songchao Li ◽  
Zhengguo Zhang ◽  
Ningyang Li ◽  
Xiang Yuan ◽  
...  

AbstractA total of 1520 patients with urinary stones from central China were collected and analysed by Fourier transform infrared spectroscopy between October 1, 2016 and December 31, 2019. For all patients, age, sex, comorbidities, stone location, laboratory examination and geographic region were collected. The most common stone component was calcium oxalate (77.5%), followed by calcium phosphate (8.7%), infection stone (7.6%), uric acid (UA) stone (5.3%)and cystine (0.9%). The males had more calcium oxalate stones (p < 0.001), while infection stone and cystine stones occurred more frequently in females (p < 0.001). The prevalence peak occurred at 41–60 years in both men and women. UA stones occurred frequently in patients with lower urinary pH (p < 0.001), while neutral urine or alkaline urine (p < 0.001) and urinary infection (p < 0.001) were more likely to be associated with infection stone stones. Patients with high levels of serum creatinine were more likely to develop UA stones (p < 0.001). The proportion of UA stones in diabetics was higher (p < 0.001), and the incidence of hypertension was higher in patients with UA stones (p < 0.001). Compared to the other types, more calcium oxalate stones were detected in the kidneys and ureters (p < 0.001), whereas struvite stones were more frequently observed in the lower urinary tract (p = 0.001). There was no significant difference in stone composition across the Qinling-Huaihe line in central China except UA stones, which were more frequently observed in patients south of the line (p < 0.001).


Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Inès Dufour ◽  
Alexis Werion ◽  
Leila Belkhir ◽  
Anastazja Wisniewska ◽  
Marie Perrot ◽  
...  

Abstract Background The severity of coronavirus disease 2019 (COVID-19) is highly variable between individuals, ranging from asymptomatic infection to critical disease with acute respiratory distress syndrome requiring mechanical ventilation. Such variability stresses the need for novel biomarkers associated with disease outcome. As SARS-CoV-2 infection causes a kidney proximal tubule dysfunction with urinary loss of uric acid, we hypothesized that low serum levels of uric acid (hypouricemia) may be associated with severity and outcome of COVID-19. Methods In a retrospective study using two independent cohorts, we investigated and validated the prevalence, kinetics and clinical correlates of hypouricemia among patients hospitalized with COVID-19 to a large academic hospital in Brussels, Belgium. Survival analyses using Cox regression and a competing risk approach assessed the time to mechanical ventilation and/or death. Confocal microscopy assessed the expression of urate transporter URAT1 in kidney proximal tubule cells from patients who died from COVID-19. Results The discovery and validation cohorts included 192 and 325 patients hospitalized with COVID-19, respectively. Out of the 517 patients, 274 (53%) had severe and 92 (18%) critical COVID-19. In both cohorts, the prevalence of hypouricemia increased from 6% upon admission to 20% within the first days of hospitalization for COVID-19, contrasting with a very rare occurrence (< 1%) before hospitalization for COVID-19. During a median (interquartile range) follow-up of 148 days (50–168), 61 (12%) patients required mechanical ventilation and 93 (18%) died. In both cohorts considered separately and in pooled analyses, low serum levels of uric acid were strongly associated with disease severity (linear trend, P < 0.001) and with progression to death and respiratory failure requiring mechanical ventilation in Cox (adjusted hazard ratio 5.3, 95% confidence interval 3.6–7.8, P < 0.001) or competing risks (adjusted hazard ratio 20.8, 95% confidence interval 10.4–41.4, P < 0.001) models. At the structural level, kidneys from patients with COVID-19 showed a major reduction in urate transporter URAT1 expression in the brush border of proximal tubules. Conclusions Among patients with COVID-19 requiring hospitalization, low serum levels of uric acid are common and associate with disease severity and with progression to respiratory failure requiring invasive mechanical ventilation.


2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Serhat Tanik ◽  
Savas Sarikaya ◽  
Kürşad Zengin ◽  
Sebahattin Albayrak ◽  
Yunus Keser Yilmaz ◽  
...  

Introduction. There is an increasing interest in the association between erectile dysfunction (ED) and cardiovascular risk factor. Epicardial adipose tissue (EAT) is associated with insulin resistance, increased cardiometabolic risk, and coronary artery disease. Our aim was to investigate relationships between epicardial fat thickness (EFT) as a cardiometabolic risk factor and erectile dysfunction.Method. We selected 30 erectile dysfunction patients without comorbidities and 30 healthy individuals. IIEF-5 score was applied to all patients, and IIEF-5 score below 22 was considered as erectile dysfunction. EFT was measured by echocardiography.Results. Body mass index (BMI) was higher in ED patients than those without ED (28.19 ± 4.45 kg/m2versus23.84±2.36 kg/m2,P = 0.001, resp.). Waist circumstance (WC) was higher in ED patients than those without ED (106.60±5.90versus87.86 ± 14.51,P = 0.001, resp.). EFT was higher in ED patients compared to non-ED patients (0.49 ± 0.09 cm versus0.45 ± 0.03 cm,P = 0.016, resp.). There was positive correlation among BMI, WC, and EFT. There was negative correlation between EFT and IIEF-5 score (r : -0.632,P = 0.001).Conclusion. EAT, BMI, and WC as cardiometabolic risk factors were higher in erectile dysfunction patients.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Sang-Ho Park ◽  
Seung Woon Rha ◽  
Ung Jun ◽  
Byoung Geol Choi ◽  
Se Yeon Choi ◽  
...  

Background: It has been reported that a major cause of vasospastic angina is endothelial dysfunction of the coronary artery. However, it is controversial whether the uric acid level is associated with vasospastic angina, and can be a prognostic factor for vasospastic angina. Methods: A total 3828 patients (pts) underwent coronary angiography with acetylcholine (Ach) provocation test from Mar 2004 to Sep 2012 were enrolled. The definition of positive coronary artery spasm (CAS) was defined as transient luminal narrowing more than 70%. The uric acid level was categorized into 4 quartile groups; less than 3.8, 3.9~4.7, 4.8~5.7, and more than 5.8 mg/dL. Major adverse cardiovascular events (MACEs) defined as the composite of recurrent chest pain, cardiac death, myocardial infarction, and cerebrovascular accident were valuated up to 3 years. Results: The follow-up rate was the 61.1% (2340/3828). There was no difference in uric acid level between negative and positive CAS groups in female gender but in male gender, uric acid level was higher in negative CAS group (Table 1). However, when adjusted by age, the difference was disappeared (OR, 0.965; 95% CI, 0.898-1.037; P-value, 0.335). The incidence of MACE was 11.1% in male gender and 8.6% in female gender. In male gender, the serum uric acid level between the groups with and without MACE was similar but in female gender, the uric acid level was higher in the group with MACE. However, when adjusted by age, uric acid was not associated with MACE (Table 2). Conclusions: In our study, uric acid was neither the risk factor nor prognostic factor for 3-year clinical events in CAS patients regardless of gender.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Masanari Kuwabara ◽  
Shigeko Hara ◽  
Koichiro Niwa ◽  
Minoru Ohno ◽  
Ichiro Hisatome

Objectives: Prehypertension frequently progresses to hypertension and is associated with cardiovascular diseases, stroke, excess morbidity and mortality. However, the identical risk factors for developing hypertension from prehypertension are not clarified. This study is conducted to clarify the risks. Methods: We conducted a retrospective 5-year cohort study using the data from 3,584 prehypertensive Japanese adults (52.1±11.0 years, 2,081 men) in 2004 and reevaluated it 5 years later. We calculated the cumulative incidences of hypertension over 5 years, then, we detected the risk factors and calculated odds ratios (ORs) for developing hypertension by crude analysis and after adjustments for age, sex, body mass index, smoking and drinking habits, baseline systolic and diastolic blood pressure, pulse rate, diabetes mellitus, dyslipidemia, chronic kidney disease, and serum uric acid. We also evaluated whether serum uric acid (hyperuricemia) provided an independent risk for developing hypertension. Results: The cumulative incidence of hypertension from prehypertension over 5 years was 25.3%, but there were no significant differences between women and men (24.4% vs 26.0%, p=0.28). The cumulative incidence of hypertension in subjects with hyperuricemia (n=726) was significantly higher than those without hyperuricemia (n=2,858) (30.7% vs 24.0%, p<0.001). After multivariable adjustments, the risk factors for developing hypertension from prehypertension were age (OR per 1 year increased: 1.023; 95% CI, 1.015-1.032), women (OR versus men: 1.595; 95% CI, 1.269-2.005), higher body mass index (OR per 1 kg/m 2 increased: 1.051; 95% CI 1.021-1.081), higher baseline systolic blood pressure (OR per 1 mmHg increased: 1.072; 95% CI, 1.055-1.089) and diastolic blood pressure (OR per 1 mmHg increased: 1.085; 95% CI, 1.065-1.106), and higher serum uric acid (OR pre 1 mg/dL increased: 1.149; 95% CI, 1.066-1.238), but not smoking and drinking habits, diabetes mellitus, dyslipidemia, and chronic kidney diseases. Conclusions: Increased serum uric acid is an independent risk factor for developing hypertension from prehypertension. Intervention studies are needed to clarify whether the treatments for hyperuricemia in prehypertensive subjects are useful.


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