Objective To investigate the cardiac structure and function within one year after kidney transplantation in children. Methods A total of 50 children with normal renal function within one year after allogeneic kidney transplantation hospitalized in the Department of Pediatric Cardiology, the First Affiliated Hospital of Sun Yat-sen University from February 2021 to December 2024 were retrospectively enrolled as the kidney transplantation group. Another 50 healthy children matched for age and gender were recruited as the control group. Echocardiography was performed in all subjects. General clinical characteristics and echocardiographic parameters were compared between the two groups, and left ventricular structure was analyzed in children of the kidney transplantation group. Results The duration after kidney transplantation was 3 (2, 6) months. Forty-six patients received pre-transplant dialysis with a dialysis duration of 9 (5, 13) months. Echocardiographic findings revealed statistically significant intergroup differences in cardiac structure, systolic function and diastolic function (all P<0.05), while left ventricular ejection fraction (LVEF) remained within normal limits in both groups. In the kidney transplantation group, left ventricular hypertrophy was detected in 42% of patients, and concentric left ventricular remodeling was observed in 52% of patients. Conclusions Most children still present abnormalities in cardiac structure as well as systolic and diastolic dysfunction after kidney transplantation. Compared with conventional echocardiographic indices, two-dimensional speckle-tracking echocardiography is more sensitive for evaluating cardiac function in pediatric kidney transplant recipients. Regular echocardiographic surveillance for children with kidney transplantation facilitates early identification of alterations in cardiac structure and function, enabling timely intervention and improvement of quality of life.

Objective To establish the HPLC analysis method for ketoconazole related substances,and to provide technical support for the improvement of the quality standard and the purity of ketoconazole.Methods Gradient elution conditions were optimized based on the chromatographic parameters outlined in the 2024"British Pharmacopoeia"for ketoconazole cream.A C18 column(4.6 mm×150 mm,3 μm)was used to facilitate the elution process using a gradient of acetonitrile and acetate buffer,and detection performed at a wavelength of 230 nm.Results The known impurities and potentially genotoxic impurities in the material drugs of ketoconazole can be more effectively separated using the established methods,which are both robust and highly sensitive.The content of the two potentially geno toxic impurities,six known impurities and unknown impurities in the 21 batches of ketoconazole sourced from five raw material pharmaceutical companies is below the specified limit requirements.Conclusion This method contributes to improving the quality of ketoconazole ingredients,ensuring the safety of ketoconazole preparations,and better supporting the regulatory supervision.

Objective To establish the HPLC analysis method for ketoconazole related substances,and to provide technical support for the improvement of the quality standard and the purity of ketoconazole.Methods Gradient elution conditions were optimized based on the chromatographic parameters outlined in the 2024"British Pharmacopoeia"for ketoconazole cream.A C18 column(4.6 mm×150 mm,3 μm)was used to facilitate the elution process using a gradient of acetonitrile and acetate buffer,and detection performed at a wavelength of 230 nm.Results The known impurities and potentially genotoxic impurities in the material drugs of ketoconazole can be more effectively separated using the established methods,which are both robust and highly sensitive.The content of the two potentially geno toxic impurities,six known impurities and unknown impurities in the 21 batches of ketoconazole sourced from five raw material pharmaceutical companies is below the specified limit requirements.Conclusion This method contributes to improving the quality of ketoconazole ingredients,ensuring the safety of ketoconazole preparations,and better supporting the regulatory supervision.

Objective:To explore the impact of early and late antibody-mediated rejection (AMR) on treatment options and allograft outcomes after kidney transplantation (KT).Methods:From January 2013 to December 2022, the study retrospectively enrolled 141 KT allograft recipients receiving allograft biopsy and diagnosed as AMR according to the Banff 2019 criteria. Recipients with a diagnosis of AMR within 30 days post-KT were classified into early AMR group (n=19) while the remainders assigned as late AMR group (n=122). The outcome endpoints included recipient survival rate, death-censored graft survival rate, follow-up estimated glomerular filtration rate (eGFR) and immunodominant donor-specific antibody (DSA) intensity. Wilcoxon's test was utilized for assessing the differences in eGFR and DSA intensity while Kaplan-Meier curve and Log-rank test were employed for evaluating graft survival impact. Treatment regimens for AMR were collected and categorized.Results:The median follow-up duration was 2.6(1.2, 5.2) year. No graft failure was noted in early AMR group while 44 recipients in late AMR group experienced graft failure, with 34 cases (77.2%) due to AMR progression. The 5-year death-censored graft survival rate was significantly better in early AMR group than that in late AMR group [100% vs 60.1%(50.5%, 71.6%), P=0.002]. The one-year change in eGFR for early AMR group was significantly superior to that of late AMR group [19.3(-2.6, 38.1) vs -3.3(-14.0, 5.4), P=0.001]. One-year mean fluorescent intensity (MFI) of early AMR group was 1 158(401.5, 3 126.5). It was significantly lower than that when diagnosed with early AMR [3 120.5(2 392.8, 9 340.0)] and one-year MFI of late AMR group [8 094(2 251.5, 13 560.5)] ( P=0.005, P<0.001). Early AMR group primarily received standard treatment (3/19, 15.8%) and regimens centered on rituximab and/or bortezomib (7/19, 43.8%). Late AMR group mainly received standard (16/122, 13.1%) or intensified regimens (9/122, 7.4%) and regimens focused upon rituximab and/or bortezomib (32/122, 26.2%) and MP monotherapy (21/122, 17.2%). Conclusion:The outcome for early AMR is significantly better than that for late AMR. For early AMR, early and robust immunosuppression is recommended. For late AMR, early detection and timely treatment are crucial and individualized strategies should be implemented.

This report described one patient of giant polycystic liver and polycystic kidney involving iliac fossa. Preoperative computed tomography (CT) revealed a large polycystic kidney occupying partially iliac fossa space. A decompression of lower pole of original kidney was planned for placing transplanted kidney. During total liver resection plus orthotopic liver transplantation, right polycystic kidney could move up on its own and iliac fossa space was released for placing transplanted kidney smoothly. Polycystic kidney shrunk markedly post-operation. It provided references for surgical planning of combined liver-kidney transplantation for this type of disease.

Based upon the underlying mechanism and pathological evidence of tissue injury of antibody-mediated rejection (AMR) , four etiological and symptomatic therapies were proposed for managing AMR, including etiological treatment of AMR including antibody-targeting, B cell or plasma cell-targeting therapies; strategies for preventing antibody-mediated endothelial damage: an inhibition of complement/antibody dependent cell-mediated pathways; anticoagulant & thrombolytic therapies for thrombotic microangiopathy secondary to endothelial damage ; anti-inflammatory therapies for acute/chronic vascular inflammation secondary to endothelial damage. Etiological treatment is essential for preventing and treating AMR while symptomatic measures, such as anticoagulant, thrombolytic and antiinflammatory therapies, are stressed. Finally the authors devised therapeutic strategies for AMR in 4 different patient groups of non-sensitized allograft recipients, sensitized allograft recipients, individuals with active AMR and those with chronic active AMR.

Objective:To explore the morbidity features and therapeutic outcomes of rejections in pediatric kidney transplantation (KT) recipients.Methods:Between January 2013 and June 2022, 360 children undergoing KT were recruited.The relevant clinical data were collected for examining the morbidity features and therapeutic outcomes of rejections.The serum levels of creatinine were compared among groups by non-parametric rank test.And Kaplan-Meier and Log-rank methods were employed for examining the incidence of rejection and comparing mortality-censored graft survival rates among patients with different times of rejection.Results:A total of 58 recipients had 82 incidents of rejection with a cumulative incidence of 6.3%, 9.2% and 11.3% at 3/6/12 months respectively.Among 50 incidents of biopsy-proved rejections, the types were T cell-mediated rejection [TCMR, 42.0%(21/50)], antibody-mediated rejection [20.0%(10/50), ABMR] and mixed rejection [38.0%(19/50)].Among 58 incidents of initial rejection, 69% had maintained graft function (MGF) and 31% impaired graft function (IGF) after anti-rejection regimens.Among 80.8%, 85.7% and 75% of recipients with clinical rejection, ABMR or borderline rejection while 36.4% in TCMR patients had MGF.Fifteen kidney allografts lost function in 58 recipients with rejection.Five-year death-censored graft survival was significantly lower in patients with two or more incidents of rejection (30.5%, 95% CI: 12.3%-75.4%) than in those without rejection (92.9%, 95% CI: 89.3%-96.6%) ( P<0.000 1) or with only one rejection (82.9%, 95% CI: 65.9%-100%)( P<0.001). Conclusions:The rejection rate remains high in KT children and it affects graft survival.And TCMR is more likely to cause impaired graft function.Recurrent rejections have a more pronounced impact upon graft survival.

OBJECTIVE: To explore the genetic etiology and clinical outcome of a child with steroid-resistant nephrotic syndrome and diffuse mesangial sclerosis. METHODS: Genomic DNA was extracted from peripheral blood leukocytes of the proband and his parents. Targeted capture - next generation sequencing and Sanger sequencing were carried out. Candidate variant was verified by segregation analysis in his family. RESULTS: A heterozygous missense variant of the TRPC6 gene, namely c.325G>A (p.Gly109Ser), was detected in the proband. The same variant was not detected in either parent. According to the guidelines for the interpretation of sequence variants developed by American College of Medical Genetics and Genomics, the variant was predicted as pathogenic. CONCLUSION The missense variant of the TRPC6 gene probably underlay the diffuse mesangial sclerosis in this patient. Above finding has expanded the phenotypic spectrum of the TRPC6 gene.
Child ; Genomics ; Humans ; Mutation, Missense ; Nephrotic Syndrome/genetics* ; Sclerosis ; TRPC6 Cation Channel/genetics*

Objective:To explore the diagnosis and treatment of transplanted renal artery stenosis(TRAS)in children.Methods:From January 2016 to August 2021, clinical data of 7 TRAS patients were collected.A definite diagnosis was confirmed by Doppler ultrasound and computed tomography angiography.Results:Patient age was significantly higher than donor age(11.9±3.7 vs 1.0±0.5 years, P<0.001); 5 patients had a widened diameter at stenotic grafted renal artery after intervention(1.98±0.47 vs 4.64±1.19 mm, P=0.002). A reduction in peak systolic flow velocity in stenotic segment of artery(463.3±90.6 vs 183.6±58.9 cm/s, P<0.001)and lower systolic blood pressure(137.2±15.5 vs 129.7±12.3 mmHg, P=0.029)were observed.Resistance index rose(0.38±0.22 vs 0.60±0.03, P=0.063). Significant difference of estimated glomerular filtration rate was observed at Week 4 post-operation as compared with pre-intervention.Two patients developed complications after intervention, including perirenal hematoma and stent-attached thrombus.Two patients were treated conservatively with a gradual increase in blood pressure and three antihypertensive drugs prescribed. Conclusions:Doppler ultrasound should be performed regularly after renal transplantation for detecting TRAS at an early stage in children.Interventional treatment is ideal for severe TRAS to improve perfusion and renal function.Clinicians should pay more attention to complications.