ESPU Meeting on Saturday 11, June 2022, 10:55 - 11:35
10:55 - 10:58
Yukun LIU, Wenying WANG, Yucheng GE, Chen NING, Lei WANG, Jun LI and Ye TIAN
Beijing Friendship Hospital, Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, CHINA
To analyze the genotypic characteristics of Chinese patients with primary hyperoxaluria (PH) and provide the putative mutation hotspot regions.
PATIENTS AND METHODS
This study admitted 41 patients, who underwent whole-exome sequencing and were diagnosed with PH. The results were confirmed by Sanger sequencing, and the clinical data and gene reports of pediatric PH patients were analyzed.
Among the 41 pediatric patients, including 18 cases of PH1, 7 cases of PH2 and 16 cases of PH3 were found. In PH1 cohort, seventeen mutations of the AGXT gene were detected, including one novel mutations, c.824G>A. The most prevalent AGXT gene mutation was c.33dupC (8/36), followed by c.815_816insGA (6/36). Furthermore, for PH1 patients, the most common type of mutation was a frameshift mutation (18/36), which could result in the production of truncated AGT proteins. In PH2 cohort, four mutations of GRHPR gene were detected, including one novel mutations, c.83+1G>C. The most common GRHPR gene mutation was c.864_865delTG (10/14), which was a frameshift mutation and may be associated with translational difficulty. In PH3 cohort, ten mutations of the HOGA1 gene were detected. Two recurrent variants originated from a mutational hotspot (c.834_834+1), accounting for about 56.3% of all the variant alleles.
PH1 was the most prevalent, accounting for 43.9%, followed by PH3 (39%) and PH2 (17.1%). The results of this investigation showed that 2 novel gene mutations were identified in Chinese patients with primary hyperoxaluria. Moreover, the hotspot mutation or hotspot region were c.33dupC and c.815-816insGA mutations in AGXT, c.864_865delTG mutation in GRHPR and c.834-834+1 mutation region in HOGA1 gene respectively, which differ from patients with PH in other nationalities.
10:58 - 11:01
Yucheng GE, Wenying WANG, Ruichao ZHAN, Yukun LIU, Chen NING, Jun LI and Ye TIAN
Beijing Friendship Hospital, Capital Medical University, Urology, Beijing, CHINA
To analyze the genotype and phenotype correlations of primary hyperoxaluria (PH) in children in China, and determine the long-term prognosis of PH patients with different genotypes.
MATERIAL AND METHODS
The data of PH patients from 2012 to 2021 were retrospectively analyzed, including basal condition, symptom, genotype, diagnosis and therapy, changes in renal function and oxalic acid metabolism indicators before and after diagnosis.
Of the 41 PH patients, PH1 was the most common, followed by PH3 and PH2. Three types had hotspot mutations respectively in mainland China, which were c.815-816 insGA and c.33dupC mutation, c.864-865delTG mutation and c.834-834+1 mutation regions, and three novel mutations were found. Of the type 1 patients, there was no significant difference in age of onset, mean oxalic acid, and mean urinary calcium among patients with hotspot mutations and non-hotspot mutations but eGFR values correlated with genotypes significantly, with patients with c.33dupC mutations having the highest mean eGFR, followed by patients in the c.815-816 insGA and non-hotspot mutation group. In type 2 patients, there was no significant difference in various indicators between hotspot mutations and non-hotspot mutations. In type 3 patients, there was no statistically significant difference, as in PH2 patients, but some patients with hotspot mutation had stone recurrence.In addition, there was a negative relationship between urinary oxalate levels and urinary calcium in PH3 patients.
Among Chinese PH patients, the clinical phenotype of PH may be correlated with genotype. Patients with hotspot mutation may lead to more severe symptoms, mainly manifested as worse renal function, higher eGFR value and stone recurrence in patients with hotspot mutation. In addition, there was a significant negative relationship between urinary oxalate levels and urinary calcium in PH3 patients.
11:01 - 11:04
Zhan RUICHAO, Wenying WANG and Yucheng GE
Beijing Friendship Hospital, Department of Urology, Beijing, CHINA
To investigate the genotype characteristics of cystinuria in Chinese population and its correlation with phenotype.
MATERIAL AND METHODS
We evaluated 14 pediatric patients with cystine stones who visited our clinic from 2016 to 2020. We performed whole-exome sequencing and predicted the pathogenicity of the mutations.
he age of first stone onset varied from 4 months to 9 years in 14 unrelated patients with cystinuria. The stone size varied from 0.5 to 2.6 cm. We detected a total of 13 SLC3A1 gene mutations as well as 9 SLC7A9 gene mutations, of which 10 mutations were novel mutations. In silico analysis was performed to predict pathogenicity and they were all disease-causing mutations. No clear correlation between genotype and phenotype was found in our study.
We analyzed the genotype and phenotype of cystinuria in 14 children and found 10 novel mutations. There is a large genetic heterogeneity of cystinuria gene mutations, and we did not find a significant correlation between genotype and phenotype in the Chinese population. The clinical and genotypic characteristics of cystinuria in the Chinese population still need further multicenter studies.
11:04 - 11:07
Mehmet BULUT 1, Erdinç DINÇER 1, Cengiz ÇANAKÇI 1, Utku CAN 1, Alper COŞKUN 1, Berkan ŞIMŞEK 1 and Onur TELLI 2
1) Kartal Dr. Lütfi Kırdar Training and Research Hospital, Urology, Istanbul, TURKEY - 2) Kartal Dr. Lütfi Kırdar Training and Research Hospital, Pediatric Urology, Istanbul, TURKEY
Triple D score was developed using skin-to-stone distance, stone density, and stone volume for prediction of extracorporeal shockwave lithotripsy (SWL) outcomes in adults. Shock wave lithotripsy (SWL) is the first-line treatment method for kidney stones smaller than 2 cm in children however it was not validated in pediatric population. The present paper aims to validate Triple D score in pediatric patients.
MATERIAL AND METHODS
Of the 269 children treated with SWL between 2007 and 2021, a total of 147 children who had adequate follow-up data and evaluated with non-contrast computed tomography before SWL, were included in the study. Parameters were calculated for each of the stone volume (SV), skin-to-stone distance (SSD), and stone density (SD) variables. Receiver operator characteristic analysis was used to set cut-off values. Triple D scores were calculated, and success rates were determined for each score. Stone-free status was determined as complete clearance after three months of final SWL.
The median age of the study group was 7 (range 1 to 16). Ninety-three of the 147 (63%) children had stone-free status. Mean SV, SSD and SD values were significantly higher in SWL failed group than stone-free group after detecting cutoff values of 155 mm3, 6.5 cm, and 550 HU, respectively. Stone-free rates were detected as 23.8%, 35.1%, 74.0%, and 92.0% with the Triple D scores of 0, 1, 2, and 3 points.
Our study confirms that Triple D scores supports the SWL outcomes in pediatric population. We believe that our research will serve as a base for future studies on Triple D score validation in children that various factors may affect to predict the success of SWL.
11:07 - 11:10
Bashir AHMED 1, Sajid SULTAN 2, Sadaf ABA UMER KODWAVWALA 2 and Adeeb-Ul-Hassan RIZVI 2
1) Sindh Institute of Urology & transplantation, Philips G Rensley Department of Paediatric Urology, Karachi, PAKISTAN - 2) Sindh Institute of Urology & transplantation, Philip G Ransley Department of Paediatric Urology, Karachi, PAKISTAN
To compare the safety, efficacy, and outcome (stone clearance, number of ESWL sessions, and complications) between the different locations of renal stone by ESWL.
MATERIAL AND METHODS
Records of 562 children (603 renal units) with single renal stone in a different location (pelvis, upper, middle, and lower calyces) managed by Extracorporeal Shock Wave Lithotripter(StorzModulith®SLX-F2) between January 2014 to December 2020 were reviewed. Clinical records were reviewed for age, gender, stone laterality, location, size, stenting, number of ESWL sessions, stone clearance, and complications. ANOVA, Independent samples t-test, and chi-square tests were used for statistical analysis.
Patients were divided according to stone location into four groups. The male to female ratio was 2:1. Out of 603 renal units 243(40%), 299(38%), 103(17%), 28(5%) had pelvic, lower, middle, and upper calyceal stones. The mean age between the group was comparable 4.7+3.2 VS 5.8+3.7 VS 5.8+3.7 VS 6.4+3.9(p=0.17). The mean stone size (mm) was statistically significant between pelvic, and lower calyceal stone 10+2.6 VS 8.7+2.5(p=0.00). The mean session of ESWL was statistically significant between Pelvic and lower calyceal stone 1.2+0.44 VS 1.1+0.37(p=0.03). Stone-free rates between the groups were upper calyceal 89%, pelvic stone 86%, middle and lower calyx 84%(p=0.61). If we combined stone-free rate and CIRF, the overall success rate were upper 27(96.4%) VS middle 100(97%), VS lower calyceal stone 20(87.7%) VS pelvic stone 220(90.5%) but not statistically significant(p=0.11). Overall complication(clavian I) 108(17.8%) however 32(5.3%) renal unit required ancillary procedure due to Stenstrasse(Clavian III).
This study showed excellent stone clearance between the groups with acceptable complication rates. Lower calyx has a statistically smaller stone size as compared to pelvic stone and the overall success rate among the groups was low in lower calyceal stone.