Adolescence-onset atypical hemolytic uremic syndrome: is it different from infant-onset?

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare, mostly complement-mediated thrombotic microangiopathy. The majority of patients are infants. In contrast to infantile-onset aHUS, the clinical and genetic characteristics of adolescence-onset aHUS have not been sufficiently addressed to date. METHODS: A total of 28 patients (21 girls, 7 boys) who were diagnosed as aHUS between the ages of ≥10 years and <18 years were included in this study. All available data in the Turkish Pediatric aHUS registry were collected and analyzed. RESULTS: The mean age at diagnosis was 12.8±2.3 years. Extra-renal involvement was noted in 13 patients (46.4%); neurological involvement was the most common (32%). A total of 21 patients (75%) required kidney replacement therapy. Five patients (17.8%) received only plasma therapy and 23 (82%) of the patients received eculizumab. Hematologic remission and renal remission were achieved in 25 (89.3%) and 17 (60.7%) of the patients, respectively. Compared with the infantile-onset aHUS patients, adolescent patients had a lower complete remission rate during the first episode (p = 0.002). Genetic analyses were performed in all and a genetic variant was detected in 39.3% of the patients. The mean follow-up duration was 4.9±2.6 years. At the last visit, adolescent patients had lower eGFR levels (p = 0.03) and higher rates of chronic kidney disease stage 5 when compared to infantile-onset aHUS patients (p = 0.04). CONCLUSIONS: Adolescence-onset aHUS is a rare disease but tends to cause more permanent renal dysfunction than infantile-onset aHUS. These results may modify the management approaches in these patients.

Variable phenotype and genotype of pediatric patients with HNF1B nephropathy.

AIMS: Hepatocyte nuclear factor 1ß (HNF1B) mutations are the most common monogenic cause of congenital anomalies of the kidney and urinary tract (CAKUT). We aimed to investigate clinical and genetic characteristics of patients with HNF1B nephropathy to expand its phenotypic and genetic spectrum. MATERIALS AND METHODS: This retrospective cohort study included 16 unrelated pediatric patients (6 females, 10 males) from 13 families with genetically confirmed HNF1B-related nephropathy. RESULTS: Abnormal prenatal kidney abnormalities were present in 13 patients (81.3%). The most common antenatal kidney abnormality was kidney cysts, which were observed in 8 patients (61.5%). Urinary system abnormalities (vesicoureteral reflux (VUR) and ureteropelvic junction obstruction (UPJO)) were present in 4 patients (25%). HNF1B analysis uncovered missense variants in 4 families (30.8%) as the most common genetic abnormality. In addition, 4 novel pathological variations have been defined. During follow-up, hypomagnesemia and hyperuricemia were observed in 7 (43.8%) and 5 patients (31.3%), respectively. None of the patients with a missense variant had hypomagnesemia. However, 7 out of 12 patients (58.3%) with a non-missense variant had hypomagnesemia (p = 0.09). None of the patients had an HNF1B score below 8, and the mean score was 15.3 ± 4.4. The mean follow-up period was 7.4 ± 5.0 years. While 100% of patients (n = 4) with missense variants were in various stages of CKD (CKD2: 2 patients, CKD3: 2 patients), 25% of those with non-missense variants had CKD (CKD2, 3, and 5; 1 patient, respectively) (p = 0.026). CONCLUSION: Patients with HNF1B-associated disease have concomitant urinary system abnormalities such as VUR or UPJO. Missense variants seem to be the most common pathological variations in HNF1B gene and have higher risk of CKD.

Pediatric kidney care experience after the 2023 Turkey/Syria earthquake.

BACKGROUND/AIMS: Two earthquakes on February 6th, 2023 destroyed ten cities in Türkiye. We report our experience with pediatric victims during these catastrophes, with a focus on crush syndrome related-acute kidney injury (Crush-AKI) and death. METHOD: A web-based software was prepared. Patient demographics, time under rubble (TUR), admission laboratory data, dialysis, and kidney and overall outcomes were asked. RESULTS: 903 injured children (median age: 11.62 years) were evaluated. Mean TUR was 13 h (Interquartile range-IQR: 32.5), max 240 h). 31 of 32 patients with a TUR of >120 h survived. The patient who rescued after ten days survived.Two-thirds of the patients were given 50 mEq/L sodium-bicarbonate in 0.45% sodium-chloride solution on admission day. 58% of patients were given intravenous fluid (IVF) at a volume of 2000-3000 mL/m2 body surface area (BSA), 40% of 3000-4000 mL/m2 BSA, and only 2% of >4000 mL/m2 BSA. 425 patients had surgeries, 48 suffered from major bleeding. Amputations were recorded in 96 patients. Eighty-two and 66 patients required ventilator and inotropic support, respectively.Crush-AKI developed in 314 patients (36% of all patients). 189 patients were dialyzed. Age > 15 years, creatine phosphokinase (CK)≥20 950 U/L, TUR≥10 h, and the first-day IVF volume < 3000-4000 mL/m2 BSA were associated with Crush-AKI development. 22 deaths were recorded, 20 of 22 occurred in patients with Crush-AKI and within the first 4 days of admission. All patients admitted after 7 days survived. CONCLUSIONS: This is the most extensive pediatric kidney disaster data after an earthquake. Serum CK level was significantly associated with Crush-AKI at the levels of >20 950 U/L, but not with death. Adolescent age and initial IVF of less than 3000-4000 mL/m2 BSA were also asscoiated with Crush-AKI. Given that mildly injured victims can survive longer periods in the disaster field, we suggest uninterrupted rescue activity for at least 10 days.

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 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.

Transplantation in pediatric aHUS within the era of eculizumab therapy.

aHUS is caused by the over-activation and dysregulation of the alternative complement pathway. Data regarding outcomes of pediatric aHUS patients after kidney transplantation are still very scarce. Accordingly, the aim of this study was to describe the clinical findings and outcomes of pediatric aHUS patients after renal transplantation. This is a retrospective, multicenter study including 12 patients from the national registry system. Among the 12 patients, eight had received prophylactic eculizumab and none of those patients (except one) had experienced aHUS recurrence during a median follow-up period of 58.5 (min-max, 4-94) months. Although eculizumab had been started on the day before transplantation in one of them, aHUS recurrence occurred during the transplantation procedure. Eculizumab had been stopped in only one patient who had no complement gene mutation after 35 months of therapy, and recurrence had not been observed during the 19 months of follow-up. In three patients, maintenance doses had been spaced out without any recurrence. One additional patient with anti-CFH antibody received only two doses of eculizumab for transplantation and had been followed for 46 months without aHUS recurrence. The remaining three patients had not received anti-C5 therapy and none of those patients experienced aHUS recurrence during a median follow-up period of 21 (min-max, 9-42) months. Prophylactic eculizumab is a safe and effective treatment for the prevention of aHUS recurrence. Eculizumab interval prolongation, discontinuation, and transplantation without eculizumab prophylaxis can be tried in selected patients with close follow-up.

Waist to height ratio as a screening tool for identifying childhood obesity and associated factors.

OBJECTIVE: To investigate the prevalence of obesity and associated factors during childhood in Southeastern Turkey. Another objective was to determine the cut-off points of Waist to Height Ratio (WHtR) values for defining obesity/abdominal obesity. METHODS: The community-based descriptive cross-sectional study was conducted in Gaziantep Turkey between November 2011 and December 2011 with 2718 primary school/high schools students aged 6-17 years. The SPSS 22.00 was used for the analysis of data. RESULTS: The prevalence of overweight, obesity, abdominal obesity, was 13.2%, 4.2% ,26.4%, respectively. There was a reverse relationship between BMI/WC values and sleep durations (p<0.05). The BMI/WC values were higher in students with computer usage time ≥1 hours in a day (p<0.05). Parental obesity status has an effective role on the WC/BMI values of children (p<0.05). The WHtR was a good predictor of diagnosis on obesity and abdominal obesity (AUC=0.928, p<0.0001; AUC=0.920, p<0.0001; respectively). The optimal cut-off values for obesity and abdominal obesity were detected as 0.5077, 0.4741, respectively. CONCLUSIONS: The WHtR can be used for diagnosis of obesity/abdominal obesity. Parental obesity, short sleep duration and computer use more than one hour per day are risk factors for the development of obesity in children and adolescents.

Pediatric post-streptococcal glomerulonephritis: Clinical and laboratory data.

BACKGROUND: Acute post-streptococcal glomerulonephritis (APSGN) is the most common post-infectious glomerulonephritis in childhood. The aim of this study was therefore to identify the possible risk factor(s) responsible for decreased glomerular filtration rate (GFR) in APSGN. METHODS: The data of patients followed up with a diagnosis of APSGN in the Pediatric Nephrology Clinic of Gaziantep University Hospital between October 2014 and October 2016 were retrospectively evaluated. RESULTS: The total number of subjects was 75 (male/female, 42/33) with a mean age of 8.20 ± 3.25 years. The most common presentations were edema (86.7%), macroscopic hematuria (82.7%) and hypertension (73.3%, n = 55). On laboratory examination, 28 children (37.3%) had hypoalbuminemia, 58 (77.3%) had proteinuria, 20 (26.7%) had increased C-reactive protein (CRP), while 74 (98.7%) and 12 (16%) had decreased complement (C)3 and C4, respectively. The number of children with GFR <90 mL/min/1.73 m2 was 22 (29.3%). The risk of decreased GFR was significantly higher in patients with increased CRP (P = 0.001; OR, 3.58), hypoalbuminemia (P = 0.006; OR, 4.83), and decreased C4 (P = 0.010; OR, 11.53). Additionally, white blood cell (WBC) count, neutrophil count, and neutrophil/lymphocyte ratio (NLR) were significantly higher (P = 0.02, P = 0.006, P = 0.004, respectively) in patients with low GFR. CONCLUSIONS: Although the prognosis of APSGN in children is good, severe systemic complications and renal failure may develop during the follow-up period. Decreased C4, presence of hypoalbuminemia, and increased inflammatory markers (WBC, CRP, neutrophil count and NLR) might be possible risk factors for severity of renal involvement. Decreased C4, in particular, may be a risk factor for decreased GFR in those children.

Determination of Risk Factors in Children Diagnosed With Henoch-Schönlein Purpura.

OBJECTIVES: This study aims to evaluate the frequency of skin, gastrointestinal, joint, and renal involvement in children with Henoch-Schönlein purpura and investigate the risk factors for organ/system involvement. PATIENTS AND METHODS: The data of 186 patients (97 boys, 89 girls; mean age 7.4±2.8 years; range 1.5 to 16.5 years) who were followed-up with the diagnosis of Henoch-Schönlein purpura in our clinic between October 2011 and December 2013 were evaluated retrospectively. RESULTS: Logistic regression analysis revealed that the risk of gastrointestinal system involvement was significantly higher in patients with skin lesions in the upper extremities (p=0.002, odds ratio [OR]=3.2). The risk of joint involvement was significantly higher in girls (p=0.024, OR=2.18), in patients with soft tissue swelling (p=0.005, OR=2.63), and with low mean platelet volume levels (p=0.008, OR=4.07). The risk of renal involvement was significantly higher in girls (p=0.047, OR=2.7), in patients >10 years (p=0.001, OR=1.4), and in patients with elevated C-reactive protein levels (p=0.007, OR=6.57). CONCLUSION: Having skin lesions in the upper extremities is a risk factor for gastrointestinal system involvement. Female sex, soft tissue swelling, and low mean platelet volume levels are risk factors for joint involvement. Female sex, >10 years of age, and high C-reactive protein levels are risk factors for renal involvement. Renal involvement in Henoch-Schönlein purpura is independent of gastrointestinal system or joint involvement and very close follow-up is required in the acute period particularly in girls >10 years with high C-reactive protein levels.

Uteroglobin gene polymorphism (G38A) may be a risk factor in childhood idiopathic nephrotic syndrome.

BACKGROUND: Uteroglobin (UG) is a multifunctional protein with anti-inflammatory properties. The aim of this study was to first evaluate the role of UG gene G38A polymorphism in childhood idiopathic nephrotic syndrome (INS), and determine whether this variation may be related to the occurrence of INS or a steroid response. METHODS: One hundred and thirty-six children diagnosed with INS in Gaziantep University, Department of Pediatric Nephrology, and 70 healthy volunteers were included. Children with INS were divided into two groups: steroid-sensitive (n = 84), and steroid-resistant (n = 52). Samples were examined using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) enzyme method. RESULTS: The distributions of AA, GG, and AG genotypes of UG gene G38A (G/A) were 16.9%, 44.9%, and 38.2% in the all-INS group, whereas they were 14.3%, 48.8%, and 36.9% in the steroid-sensitive INS (SSINS) group compared with 21.1%, 38.5%, and 40.4% in steroid-resistant INS (SRINS), and 5.7%, 41.4%, and 52.9% in controls. The risk of INS was increased almost 4-fold in children with the AA genotype (p = 0.016). The risk of having SSINS was increased 3.5-fold (p = 0.042) whereas the risk of SRINS was increased 4.8-fold in the same genotype (p = 0.014). CONCLUSIONS: The uteroglobin gene may play an important role in the development of INS, and the AA genotype of UG gene G38A polymorphism was found more frequently in those children. Further studies evaluating all polymorphisms in larger patient groups are needed to exactly determine the effect of UG gene on the development of INS and steroid response in children.

Adolescent obesity and the role of the fat mass and obesity-associated gene polymorphism.

PURPOSE: The association between fat mass and obesity-associated (FTO) gene and obesity is unclear in both adults and adolescents. The aim of this study was to examine the role of the FTO gene variant rs9939609 as a candidate gene for obesity and the relationship between insulin resistance (IR), metabolic syndrome (MetS), estimated glomerular filtration rate (eGFR) and neutrophil-to-lymphocyte ratio (NLR). METHODS: Obese adolescents (n=100) and healthy controls (n=100) were included. Rs9939609 polymorphism in the FTO gene was genotyped by PCR-SNaPshot. RESULTS: The prevalence of insulin resistance (IR), metabolic syndrome (MetS) and hyperfiltration were 47%, 60% and 27%, respectively. There were no significant differences in genotype and allele frequencies between obese adolescents and controls; however, prevalence of MetS in female patients with A allele carriers was more frequent and prevalence of hyperfiltration was less frequent with T allele carriers (P.

The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis.

BACKGROUND AND OBJECTIVES: Infantile nephropathic cystinosis is a severe disease that occurs due to mutations in the cystinosis gene, and it is characterized by progressive dysfunction of multiple organs; >100 cystinosis gene mutations have been identified in multiple populations. Our study aimed to identify the clinical characteristics and spectrum of cystinosis gene mutations in Turkish pediatric patients with cystinosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We identified the clinical characteristics and spectrum of cystinosis gene mutations in Turkish patients with cystinosis in a multicenter registry that was established for data collection. The data were extracted from this registry and analyzed. RESULTS: In total, 136 patients (75 men and 61 women) were enrolled in the study. The most common clinical findings were growth retardation, polyuria, and loss of appetite. None of the patients had the 57-kb deletion, but seven novel mutations were identified. The most common mutations identified were c.681G>A (p.Glu227Glu; 31%), c.1015G>A (p.Gly339Arg; 22%), and c.18_21 del (p.Thr7Phefs*7; 14%). These mutations were associated with earlier age of disease onset than the other mutations. To understand the effects of these allelic variants on clinical progression, the mutations were categorized into two major groups (missense versus deletion/duplication/splice site). Although patients with missense mutations had a better eGFR at the last follow-up visit, the difference was not significant. Patients in whom treatment began at age <2 years old had later onset of ESRD (P=0.02). Time to ESRD did not differ between the patients with group 1 and group 2 mutations. CONCLUSIONS: The most common cystinosis gene mutations identified in Turkey were c.681G>A (p.Glu227Glu), c.1015G>A (p.Gly339Arg), and c.18_21 del (p.Thr7Phefs*7). Patients with less severe cystinosis gene mutations tend to have better kidney outcome.

Kidney Disease Profile of Syrian Refugee Children.

INTRODUCTION: Although preventative nephrology is the effective management of childhood kidney diseases, it is hard to provide it in this undesirable conditions. In this study, we aimed to document the kidney disease profile of Syrian refugee children admitted to our hospital. MATERIALS AND METHODS: One hundred and thirty Syrian refugee children were admitted to the Pediatric Nephrology Department of the University of Gaziantep from September 2012 to January 2015. Demographic data, history, symptoms, physical examination findings, laboratory investigations, diagnosis, disease outcome, and therapeutic procedures such as peritoneal dialysis and hemodialysis were obtained from patient files. RESULTS: Of the 130 admitted children, 74 were girls (59.6%). The average age was 6.97 ± 4.2 years (range, 1 month to 17 years). Congenital abnormalities of the kidney and urinary tract were found in 34 children (26.2%). Other morbidities were chronic kidney disease in 30 (23.1%), nephrotic syndrome in 24 (18.5%), urolithiasis in 9 (6.9%), acute kidney injury in 4 (3.1%), glomerulonephritis in 5 (3.8%), enuresis in 12 (9.2%), and others in 12 (9.2%). CONCLUSIONS: Congenital abnormalities of the kidney and urinary tract and chronic kidney disease were highly prevalent in Syrian refugee children. Although free health care have been provided to all of these children, the continuation of political crisis and instability would increase the number of admissions and affect the quality of life of those children in a different environment from the home country.