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Background The phenotypic and genotypic spectrum and kidney outcome of PLC[epsilon]1-related kidney disease are not well known. We attempted to study 25 genetically confirmed cases of PLC[epsilon]1-related kidney disease from 11 centers to expand the clinical spectrum and to determine the relationship between phenotypic and genotypic features, kidney outcome, and the impact of treatment on outcome. Methods Data regarding demographics, clinical and laboratory characteristics, histopathological and genetic test results, and treatments were evaluated retrospectively. Results Of 25 patients, 36% presented with isolated proteinuria, 28% with nephrotic syndrome, and 36% with chronic kidney disease stage 5. Twenty patients underwent kidney biopsy, 13 (65%) showed focal segmental glomerulosclerosis (FSGS), and 7 (35%) showed diffuse mesangial sclerosis (DMS). Of the mutations identified, 80% had non-missense, and 20% had missense; ten were novel. No clear genotype-phenotype correlation was observed; however, significant intrafamilial variations were observed in three families. Patients with isolated proteinuria had significantly better kidney survival than patients with nephrotic syndrome at onset (p = 0.0004). Patients with FSGS had significantly better kidney survival than patients with DMS (p = 0.007). Patients who presented with nephrotic syndrome did not respond to any immunosuppressive therapy; however, 4/9 children who presented with isolated proteinuria showed a decrease in proteinuria with steroids and/or calcineurin inhibitors. Conclusion PLC[epsilon]1-related kidney disease may occur in a wide clinical spectrum, and genetic variations are not associated with clinical presentation or disease course. However, clinical presentation and histopathology appear to be important determinants for prognosis. Immunosuppressive medications in addition to angiotensin-converting enzyme inhibitors may be beneficial for selected patients. Graphical abstract 'A higher resolution version of the Graphical abstract is available as Supplementary information'., Author(s): Esra Karabag Yilmaz [sup.1] , Seha Saygili [sup.1] , Bora Gulhan [sup.2] , Nur Canpolat [sup.1] , Aysun Karabay Bayazit [sup.3] , Beltinge Demircioglu Kilic [sup.4] , Nurver Akinci [...]

Background: Complement 3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are ultra-rare chronic kidney diseases with an overall poor prognosis, with approximately 40–50% of patients progressing to kidney failure within 10 years of diagnosis. C3G is characterized by a high rate of disease recurrence in the transplanted kidney. However, there is a lack of published data on clinical outcomes in the pediatric population following transplantation. Methods: In this multicenter longitudinal cohort study of the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, we compared the post-transplant outcomes of pediatric patients with C3G (n = 17) or IC-MPGN (n = 3) with a matched case–control group (n = 20). Results: Eleven of 20 children (55%) with C3G or IC-MPGN experienced a recurrence within 5 years post-transplant. Patients with C3G or IC-MPGN had a 5-year graft survival of 61.4%, which was significantly (P = 0.029) lower than the 5-year graft survival of 90% in controls; five patients with C3G or IC-MPGN lost their graft due to recurrence during this observation period. Both the 1-year (20%) and the 5-year (42%) rates of biopsy-proven acute rejection episodes were comparable between patients and controls. Complement-targeted therapy with eculizumab, either as prophylaxis or treatment, did not appear to be effective. Conclusions: These data in pediatric patients with C3G or IC-MPGN show a high risk of post-transplant disease recurrence (55%) and a significantly lower 5-year graft survival compared to matched controls with other primary kidney diseases. These data underscore the need for post-transplant patients for effective and specific therapies that target the underlying disease mechanism. [ABSTRACT FROM AUTHOR]

Background Alport syndrome (AS) is an inherited glomerular disease caused by mutations in COL4A3, COL4A4, or COL4A5. Associations between clinical manifestations and genotype are not yet well defined. Our study aimed to define clinical and genetic characteristics, establish genotype-phenotype correlations, and determine prognosis of AS in children. Methods A total of 87 children with AS from 10 pediatric nephrology centers, whom had genetic analyses performed at the Hacettepe University Nephrogenetics Laboratory between February 2017 and February 2019, were included. Data regarding demographics, family history, clinical and laboratory characteristics, histopathological and genetic test results, treatments, and yearly follow-up results were retrospectively analyzed. Results Of 87 patients, 16% presented with nephrotic syndrome. In patients with nephrotic syndrome, kidney biopsy findings showed focal segmental glomerulosclerosis (FSGS) in 79%, and COL4A3 mutations were the leading genetic abnormality (50%). Twenty-four percent of all patients progressed to chronic kidney disease (CKD). The rate of progression to CKD and the decline in the glomerular filtration rate of the patients with COL4A3 mutation were higher than other mutation groups (p < 0.001 and p = 0.04, respectively). In kidney survival analysis, nephrotic syndrome presentation, histopathology of FSGS, COL4A3 mutations, and autosomal recessive inheritance were found as independent risk factors for earlier progression to CKD. Cyclosporin A treatment did not improve kidney survival. Conclusions We emphasize that genetic testing is important for patients suspected as having AS. Furthermore, COL4A mutations should be considered in patients with FSGS and steroid-resistant nephrotic syndrome. This approach will shed light on the prognosis of patients and help with definitive diagnosis, preventing unnecessary and potentially harmful medications., Author(s): Gulsah Ozdemir [sup.1] , Bora Gulhan [sup.1] , Emine Atayar [sup.2] , Seha Saygili [sup.3] , Oguz Soylemezoglu [sup.4] , Zeynep Birsin Ozcakar [sup.5] , Fehime Kara Eroglu [sup.6] [...]

Author(s): Tugba Tastemel Ozturk [sup.1] , Demet Baltu [sup.1] , Eda Didem Kurt Sukur [sup.1] , Yasemin Ozsurekci [sup.2] , Safak Gucer [sup.3] , Ozge Basaran [sup.4] , Bora Gulhan [...]

Background: Data on the characteristics of acute kidney injury (AKI) in pediatric COVID-19 and MIS-C are limited. We aimed to define the frequency, associated factors and early outcome of AKI in moderate, severe or critical COVID-19 and MIS-C; and to present a tertiary referral center experience from Türkiye. Methods: Hospitalized patients ≤ 18 years of age with confirmed COVID-19 or MIS-C at İhsan Doğramacı Children's Hospital, Hacettepe University, between March 2020—December 2021 were enrolled. The characteristics of AKI in the COVID-19 group were investigated in moderate, severe and critically ill patients; patients with mild COVID-19 were excluded. Results: The median (Q1-Q3) age in the COVID-19 (n = 66) and MIS-C (n = 111) groups was 10.7 years (3.9–15.2) and 8.7 years (4.5–12.7), respectively. The frequency of AKI was 22.7% (15/66) in COVID-19 and 15.3% (17/111) in MIS-C; all MIS-C patients with AKI and 73.3% (11/15) of COVID-19 patients with AKI had AKI at the time of admission. Multivariate analyses revealed need for vasoactive/inotropic agents [Odds ratio (OR) 19.233, p = 0.002] and presence of vomiting and/or diarrhea (OR 4.465, p = 0.036) as independent risk factors of AKI in COVID-19 patients; and need for vasoactive/inotropic agents (OR 22.542, p = 0.020), procalcitonin and ferritin levels as independent risk factors of AKI in the MIS-C group. Age was correlated with lymphocyte count (r = -0.513, p < 0.001) and troponin level (r = 0.518, p < 0.001) in MIS-C patients. Length of hospital stay was significantly longer in both groups with AKI, compared to those without AKI. Mortality was 9.1% in the COVID-19 group; and was associated with AKI (p = 0.021). There was no mortality in MIS-C patients. AKI recovery at discharge was 63.6% in COVID-19 survivors and 100% in MIS-C patients. Conclusions: Independent risk factors for AKI were need for vasoactive/inotropic agents and vomiting/diarrhea in moderate, severe or critical COVID-19 patients; and need for vasoactive/inotropic agents and severe inflammation in MIS-C patients. Our findings suggest that inflammation and cardiac dysfunction are associated with AKI in MIS-C patients; and the association with age in this group merits further studies in larger groups. Early outcome is favorable; long-term follow-up for kidney functions is needed. [ABSTRACT FROM AUTHOR]

Background ADCK4-related glomerulopathy is an important differential diagnosis in adolescents with steroid-resistant nephrotic syndrome (SRNS) and/or chronic kidney disease (CKD) of unknown origin. We screened adolescent patients to determine the frequency of ADCK4 mutation and the efficacy of early CoQ10 administration. Methods A total of 146 index patients aged 10-18 years, with newly diagnosed non-nephrotic proteinuria, nephrotic syndrome, or chronic renal failure and end-stage kidney disease (ESKD) of unknown etiology were screened for ADCK4 mutation. Results Twenty-eight individuals with bi-allelic mutation from 11 families were identified. Median age at diagnosis was 12.4 (interquartile range [IQR] 8.04-19.7) years. Upon first admission, all patients had albuminuria and 18 had CKD (6 ESKD). Eight were diagnosed either through the screening of family members following index case identification or during genetic investigation of proteinuria in an individual with a history of a transplanted sibling. Median age of these 8 patients was 21.5 (range 4.4-39) years. CoQ10 supplementation was administered following genetic diagnosis. Median estimated glomerular filtration rate (eGFR) just before CoQ10 administration was 140 (IQR 117-155) ml/min/1.73m.sup.2, proteinuria was 1,008 (IQR 281-1,567) mg/m.sup.2/day. After a median follow-up of 11.5 (range 4-21) months following CoQ10 administration, proteinuria was significantly decreased (median 363 [IQR 175-561] mg/m.sup.2/day, P=0.025), whereas eGFR was preserved (median 137 [IQR 113-158] ml/min/1.73m.sup.2, P=0.61). Conclusions ADCK4 mutations are one of the most common causes of adolescent-onset albuminuria and/or CKD of unknown etiology in Turkey. CoQ10 supplementation appears efficacious at reducing proteinuria, and may thereby be renoprotective., Author(s): Mustafa Atmaca [sup.1] , Bora Gulhan [sup.2] , Emine Korkmaz [sup.3] , Mihriban Inozu [sup.2] , Oguz Soylemezoglu [sup.4] , Cengiz Candan [sup.5] , Aysun Karabay Bayazit [sup.6] , [...]

Author(s): Tugba Tastemel Ozturk [sup.1] , Demet Baltu [sup.1] , Eda Didem Kurt Sukur [sup.1] , Yasemin Ozsurekci [sup.2] , Safak Gucer [sup.3] , Ozge Basaran [sup.4] , Bora Gulhan [...]

Background The aim of the study was to investigate the prevalence of post-transplant hypertension (HT) and to assess the blood pressure (BP) of transplanted children with possible risk factors. Methods Office and ambulatory blood pressure measurements were performed for each patient. Results Twenty-nine patients were included in the study, including 13 patients with newly diagnosed untreated HT according to the results of ambulatory blood pressure monitoring (ABPM). Fourteen patients were on antihypertensive medication, but only in five of these patients was the HT under control; nine patients receiving antihypertensive drugs had uncontrolled HT. Of the 29 patients, two had normotension without any antihypertensive drug(s). Standard deviation scores (SDS) of the nocturnal diastolic BP of the ABPM were positively correlated with the prednisolone dosage per kilogram (p = 0.013, r = 0.45) and negatively correlated with the time period after transplantation (p = 0.024, r = -0.41). Similarly, the SDS of the 24-h diastolic BP was positively correlated with the prednisolone dosage per kilogram (p = 0.006, r = 0.50) and negatively correlated with the time period after transplantation (p = 0.016, r = -0.44). Patients with alternate-day steroid treatment had lower nocturnal systolic (p = 0.016), nocturnal diastolic (p = 0.001) and 24-h diastolic (p = 0.008) SDS when compared to those receiving daily steroid medication. Conclusion The prevalence of HT among children after renal transplantation was high among our patient cohort, and steroids had direct impact on nocturnal and diastolic BP. Keywords Renal transplant * Children * Hypertension * Ambulatory blood pressure monitoring * Steroid, Introduction Recent studies have shown that pediatric patients with end stage renal disease (ESRD) suffer from significant cardiovascular morbidity and mortality [1]. The United States Renal Data System study demonstrated [...]

Background Atypical hemolytic uremic syndrome (aHUS) is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Neonatal cases are extremely uncommon. Plasma therapy is the first choice therapy in patients with aHUS based on the belief of an underlying complement dysregulation. Alternatively, eculizumab, which targets complement 5, is used to block complement activation. Case-diagnosis/treatment Sudden onset macroscopic hematuria, hypertension, and bruises over the entire body were noted in a 5 day-old newborn. Investigations revealed hemolytic anemia, thrombocytopenia, renal impairment, and a low serum C3, leading to the diagnosis of aHUS. Fresh frozen plasma (FFP) infusions and peritoneal dialysis for acute kidney injury were initiated. This approach yielded full renal and hematological remission. The patient was discharged with FFP infusions, but subsequently developed three life-threatening disease recurrences at 1, 3, and 6 months of age. The last relapse presented with uncontrolled hypertension and impaired renal function while the patient was receiving FFP infusions. After the first dose of eculizumab, his renal and hematological parameters returned to normal and his blood pressure normalized. Genetic screening of the CFH gene revealed a novel homozygous p. Tyr1177Cys mutation. Conclusion Eculizumab can be considered as an alternative to plasma therapy in the treatment of specific patients with aHUS, even in infants. Keywords Atypical hemolytic uremic syndrome * Complement factor H mutation * Eculizumab * Newborn, Introduction Atypical hemolytic uremic syndrome (HUS) is a rare disease and is characterized by the triad of microangiopathic hemolytic anemia [hemoglobin (Hb) upper limit of normal age) [1, 2]. Atypical [...]