Complement gene mutations in children with C3 glomerulopathy: do they affect the response to mycophenolate mofetil?

BACKGROUND: C3 glomerulopathy (C3G) is a complement-mediated disease. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to mycophenolate mofetil (MMF) treatment in pediatric C3G patients with and without mutations in complement-related genes. METHODS: Sixty pediatric C3G patients were included, divided into two groups based on complement-related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan-Meier analysis was performed for kidney survival. RESULTS: Out of the 60 patients, 17 had mutations. The most common mutation was in the CFH gene (47%). The mean age at diagnosis was higher in the group with mutation (12.9 ± 3.6 vs. 11.2 ± 4.1 years, p = 0.039). While the patients without mutation most frequently presented with nephritic syndrome (44.2%), the mutation group was most likely to have asymptomatic urinary abnormalities (47.1%, p = 0.043). Serum parameters and histopathological characteristics were similar, but hypoalbuminemia was more common in patients without mutation. During 45-month follow-up,10 patients progressed to chronic kidney disease stage 5 (CKD5), with 4 having genetic mutation. The time to develop CKD5 was longer in the mutation group but not significant. MMF treatment had no effect on progression in either group. CONCLUSIONS: This study is the largest pediatric C3G study examining the relationship between genotype and phenotype. We showed that the mutation group often presented with asymptomatic urinary abnormalities, was diagnosed relatively late but was not different from the without mutation group in terms of MMF treatment response and kidney survival.

Evaluation of endothelial dysfunction in hypertensive children and adolescents.

BACKGROUND: Atherosclerotic changes can be attributed to early endothelial damage in individuals with hypertension. We aimed to explore the relationship between endothelial dysfunction and hypertension in newly diagnosed children without end-organ damage, considering carotid intima-media thickness (CIMT), flow-mediated dilatation (FMD), and functional capillaroscopy parameters. We also analyzed the differences between dipper and non-dipper patients. METHODS: In this cross-sectional study, 20 patients diagnosed with essential hypertension with no target organ damage, and 20 age and sex-matched healthy volunteers were enrolled. The patient group comprised newly diagnosed individuals not receiving antihypertensive treatment. Hypertensive patients were divided into two groups (dipper and non-dipper patients). The measurements of CIMT, brachial FMD, and functional capillaroscopy were performed before starting treatment. RESULTS: Among the patients, 11 were boys, and 9 were girls, with a median age of 16.0 (2.13) years. Of 20 hypertensive patients, 10 were dipper and 10 were non-dipper. Significant differences were observed between the hypertensive patients and controls in terms of CIMT (p = 0.04), brachial artery FMD (p = 0.02), and functional capillary density (p < 0.001). Hypertensive patients exhibited increased CIMT, reduced brachial artery FMD, and lower capillary density. However, there were no differences between dippers and non-dippers regarding age, sex, height SDS, weight SDS, CIMT SDS, brachial artery FMD, and capillary density. CONCLUSIONS: Understanding the vascular consequences associated with essential hypertension emphasizes the importance of early detection and management of hypertension. Herein, we have effectively highlighted significant endothelial changes through the analysis of three parameters in newly diagnosed children without apparent target organ damage.

Evaluation of the Claria sharesource system from the perspectives of patient/caregiver, physician, and nurse in children undergoing automated peritoneal dialysis.

BACKGROUND: Automated peritoneal dialysis (APD) is increasingly preferred worldwide. By using a software application (Homechoice with Claria sharesource system (CSS)) with a mod-M added to the APD device, details of the home dialysis treatment become visible for PD nurses and physicians, allowing for close supervision. We aimed to evaluate the perceptions of patients/caregivers, PD nurses, and physicians about the advantages and disadvantages of CSS. METHODS: Three different web-based questionnaires for patients/caregivers, nurses, and physicians were sent to 15 pediatric nephrology centers with more than 1 year of experience with CSS. RESULTS: Respective questionnaires were answered by 30 patients/caregivers, 22 pediatric nephrologists, and 15 PD nurses. Most of the nurses and physicians (87% and 73%) reported that CSS improved patient monitoring. A total of 73% of nurses suggested that CCS is not well known by physicians, while half of them reported reviewing CSS data for all patients every morning. Sixty-eight percent of physicians thought that CSS helps save time for both patients/caregivers and healthcare providers by reducing visits. However, only 20% of patients/caregivers reported reduced hospital visits. A total of 90% of patients/caregivers reported that being under constant monitoring made them feel safe, and 83% stated that the patient's sleep quality improved. CONCLUSIONS: A remote monitoring APD system, CSS, can be successfully applied with children for increased adherence to dialysis prescription by giving shared responsibility and may help increase the patient's quality of life. This platform is more commonly used by nurses than physicians. Its potential benefits should be evaluated in further well-designed clinical studies with larger patient groups. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effect of high-dose oral cholecalciferol on cardiac mechanics in children with chronic kidney disease.

Cardiovascular factors are an important cause of mortality in chronic kidney disease, and vitamin-D deficiency is common in this patient population. Therefore, we aimed to investigate the effect of oral cholecalciferol on cardiac mechanics in children with chronic kidney disease. A total of 41 children with chronic kidney disease - the patient group - and 24 healthy subjects - the control group - free of any underlying cardiac or renal disease with low 25-hydroxyvitamin-D3 levels were evaluated by conventional tissue Doppler imaging and two-dimensional speckle-tracking echocardiography, both at baseline and following Stoss vitamin-D supplementation. Left ventricular strain and strain rate values were compared between the study groups. Initial longitudinal and radial strain as well as strain rate values of the left ventricle were significantly lower in patients. After vitamin-D supplementation, these improved significantly in patients, whereas no significant change was observed in the control group. Our study showed that, although conventional and tissue Doppler imaging methods could not determine any effect, two-dimensional speckle-tracking echocardiography revealed the favourable effects of high-dose cholecalciferol on cardiac mechanics, implying the importance of vitamin-D supplementation in children with chronic kidney disease.

Effect of cholecalciferol on local arterial stiffness and endothelial dysfunction in children with chronic kidney disease.

BACKGROUND: As cardiovascular factors are the leading cause of mortality in chronic kidney disease (CKD) and as vitamin D deficiency is prevalent in this population, we aimed to examine the effect of oral cholecalciferol on cardiac parameters and biomarkers for endothelial cell activation in children with CKD. METHODS: Forty-one children with CKD and 24 healthy subjects free of any underlying cardiac or renal disease with low 25-hydroxyvitamin D3 (25OHD) levels were evaluated using echocardiography basally and following Stoss vitamin D supplementation. The local vascular stiffness and endothelial dysfunction markers were compared among the groups. RESULTS: Initial flow-mediated dilatation (FMD) measurements were lower and local arterial stiffness was significantly higher in patients. After vitamin D supplementation, these improved significantly in patients, while no significant change was observed for the healthy group. Homocysteine showed inverse correlation with baseline vitamin D level in CKD children and von Willebrand factor emerged as an independent risk factor for FMD impairment. CONCLUSIONS: Our interventional study revealed the favorable effects of high-dose cholecalciferol on cardiovascular and endothelial parameters, implying the importance of vitamin D supplementation in children with CKD.

A case of SCNN1A splicing mutation presenting as mild systemic pseudohypoaldosteronism type 1.

Systemic pseudohypoaldosteronism type 1 (PHA1) is characterized by excessive salt loss from the renal tubulus, colon, sweat and salivary glands. Here we present a case of systemic PHA1 whose genetic analysis revealed a homozygous splicing mutation in intron 4 of SCNN1A (c.684+2 T>A) and discuss with the patient's phenotype. Previously described systemic PHA cases show varying degrees of severity dependent on the mutation. Most of the SCNN1A gene mutations present with a severe phenotype. The long-term follow-up and phenotype of the two reported cases with splicing mutation of the SCNN1A gene are unknown. Our case, with a new splicing mutation of SCNN1A, presented with a severe phenotype in the neonatal period. Since then she has been well without any hospitalization and respiratory illness. Her requirement for medication also decreased gradually. After early infancy she presented a mild systemic PHA1 phenotype up to the age of 39 months. In conclusion, the mutation in the patient is located at the splicing site and is definitely a new and pathogenic one, and the phenotype of the patient was milder as observed in a patient with missense mutation.

Hepatitis B vaccination in juvenile systemic lupus erythematosus.

OBJECTIVES: In this study, we examined the antibody responses after recombinant hepatitis B vaccine in juvenile SLE patients and whether antibody levels were affected by immunosuppressive therapy. METHODS: This study consisted of 64 juvenile SLE patients and 24 healthy controls. We evaluated HBsAg, Anti-HBs and Anti-HbcIgG titers in SLE patients. 24 patients (37%) were non-immunised, 39 patients were immunised (61%) and 1 patient (1.5%) was chronic hepatitis B carrier. Of the 24 non-immunised patients, 3 had active disease (SLEDAI>10) and 1 was being treated for tuberculosis infection so they were not included in the vaccination program. Twenty non-immunised SLE patients were given 3 dose recombinant hepatitis B vaccine doses at 0,1,6 months. AntiHBs antibody titer >10 IU/ml one month after the last dose of vaccine was accepted as seroconversion. RESULTS: After 3 doses of vaccination, 16 (80%) of SLE patients and all of the healthy controls had seroconversion. Since two patients had SLEDAI score >10 after the first 2 doses of vaccine and one patient had SLEDAI score >10 after the first dose, these patients were given only two doses of hepatitis B vaccine. These patients had already seroconverted. One patient had exacerbation of the disease one month after the third dose of the vaccine. Protective antibody responses were statistically insignificant between the two groups (p=0.49). Geometric mean antibody titers of SLE patients were lower than those of the healthy controls. Adequate antibody response was not affected by immunosuppressive treatment as prednisone, azathioprine, and hydroxychloroquine. CONCLUSIONS: Juvenile SLE patients could reach an adequate antibody response after recombinant hepatitis B vaccination and this response is not affected by immunosuppressive treatment.