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Introduction: We investigated the relationship between metabolic acidosis over time and allograft outcome in pediatric kidney transplantation (KTx)., Methods: This registry study collected data up to 10 years posttransplant. Survival analysis for a composite end point of graft loss or estimated glomerular filtration rate (eGFR) ≤ 30 ml/min per 1.73 m 2 or ≥50% decline from eGFR at month 3 posttransplant was performed. The association of serum bicarbonate concentration (HCO 3 - ) < 22 mmol/l (metabolic acidosis) and HCO 3 -  < 18 mmol/l (severe metabolic acidosis) with allograft outcome was investigated using stratified Cox models and marginal structural models. Secondary analyses included the identification of risk factors for metabolic acidosis and the relationship between alkali supplementation and allograft outcome., Results: We report on 1911 patients, of whom 347 reached the composite end point. The prevalence of metabolic acidosis over time ranged from 20.4% to 38.9%. In the adjusted Cox models, metabolic acidosis (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.54-2.60) and severe metabolic acidosis (HR, 2.49; 95% CI, 1.56-3.99) were associated with allograft dysfunction. Marginal structural models showed similar results (HR, 1.75; 95% CI, 1.32-2.31 and HR, 2.09; 95% CI, 1.23-3.55, respectively). Older age was associated with a lower risk of metabolic acidosis (odds ratio [OR] 0.93/yr older; 95% CI, 0.91-0.96) and severe metabolic acidosis (OR, 0.89; 95% CI, 0.84-0.95). Patients with uncontrolled metabolic acidosis had the worst outcome compared to those without metabolic acidosis and without alkali (HR, 3.70; 95% CI, 2.54-5.40)., Conclusion: The degree of metabolic acidosis is associated with allograft dysfunction., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Background: Therapeutic apheresis (TA) is based on the principles of either removing dissolved pathogenic substances (e.g., antibodies) from the blood plasma or replacing plasma factors. It expands the therapeutic scope for a variety of diseases. Safety analysis in the pediatric field are scant. The aim of this analysis was to analyze specific complications of TA modalities - plasma exchange (PE) and immunoadsorption (IA) - in children and adolescents., Methods: Children and adolescents ( n = 298) who had received TA from 2008 to 2018 in five pediatric nephrology centers were analyzed retrospectively. In total, 4.004 treatments (2.287 PE and 1.717 IA) were evaluated., Results: Indications for TA were mainly nephrological and neurological diseases. The three main indications were antibody-mediated graft rejection (13.4%), hemolytic uremic syndrome mainly with neurological involvement (12.8%), and AB0-incompatible transplantation (11.7%). Complications developed in 440 of the 4004 sessions (11%), of which one third were non-specific (nausea, headache). IA was better tolerated than PE. Complications were reported in 9.5% ( n = 163) of the IA versus 12.1% (277) of the PE sessions ( p < 0.001). When considering different types of complications, significantly more non-specific/non-allergic events ( p = 0.02) and allergic reactions occurred in PE sessions ( p < 0.001). More complications occurred with PE, when using fresh frozen plasma (16.2%; n = 145) in comparison to human albumin (14.5%; n = 115) ( p < 0.001)., Conclusions: Therapeutic apheresis in childhood and adolescence is a safe treatment procedure. IA showed a lower complication rate than PE. Therefore, IA may be preferably provided if the underlying disease pathomechanisms do not require PE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Taylan, Schaaf, Dorn, Schmitt, Loos, Kanzelmeyer, Pape, Müller, Weber and Thumfart.)

Background: In untreated patients, phenylketonuria (PKU) results in severe encephalopathy with mental retardation. A protein-restricted diet is recommended which can be relaxed in adolescence/adulthood., Methods: We contacted all 72 adult/adolescent PKU patients who had been treated in our center during early childhood. Some still regularly attended our outpatient clinics, while others were lost for follow-up, giving 51 patients in our study. We asked all patients to complete a dietary protocol as well as a questionnaire on quality of life. Blood and urine were analyzed and body impedance plethysmography and cerebral MRI were performed., Results: 42 % of the patients followed protein restriction supplemented with amino acid mixtures (AAM), others had a vegan diet with (8 %) or without (14 %) AAM; 36 % said they were eating normally and did not need any AAM. However, based on dietary protocols and blood urea levels, protein intake was restricted in this patient group. None of the patients examined had serious nutritional deficits. Phenylalanine levels were higher in patients not taking AAM. MRI of the brain was not different from those following protein restriction and taking AAM. The lesions score and mood correlated best with the cumulative phenylalanine values during the first 10 years of life., Conclusion: In summary, 50 % of adult/adolescent patients from our center did not take AAM at the start of our survey although they unknowingly followed self-imposed protein restriction. They had no overt nutritional deficits; however, long-term brain function may be compromised. Our study emphasizes the need for specialized metabolic care in PKU during adulthood.

Background: Steroid-resistant nephrotic syndromes (NS) with focal and segmental glomerulosclerosis (FSGS) can be differentiated into sporadic and syndromic forms. In sporadic NS, a circulating FSGS-factor is discussed in the pathogenesis and is thought to inhibit the synthesis of nitric oxide (NO) from L-arginine by blocking the NO synthase (NOS). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of all types of NOS. In a previous study we did not find an elevation of ADMA in a syndromic form of FSGS, the Schimke-immuno-osseous dysplasia. Here we report for the first time data on the L-arginine/NO pathway in sporadic FSGS of childhood., Methods: Nine children (5 to 18 years of age) suffering from sporadic FSGS and age-matched healthy controls were investigated. ADMA in plasma and urine as well as L-arginine in plasma were determined by gas chromatography-tandem mass spectrometry. The NO metabolites nitrate and nitrite were measured in plasma and urine by gas chromatography-mass spectrometry (GC-MS). The ADMA metabolite dimethylamine (DMA) was measured in urine by GC-MS., Results: We found elevated plasma levels of ADMA in children suffering from sporadic FSGS compared to healthy controls (851 nmol/L versus 684 nmol/L, P = 0.008). An inverse correlation between ADMA and glomerular filtration rate (GFR) was found in sporadic FSGS (Pearson's correlation coefficient -0.784, P = 0.012)., Conclusion: Our study suggests that ADMA synthesis is elevated in sporadic FSGS. This finding argues for the involvement of ADMA in the pathogenesis of this disease in childhood.