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Sphingosine-1-phosphate (S1P) lyase is a vitamin B6-dependent enzyme that degrades sphingosine-1-phosphate in the final step of sphingolipid metabolism. In 2017, a new inherited disorder was described caused by mutations in SGPL1, which encodes sphingosine phosphate lyase (SPL). This condition is referred to as SPL insufficiency syndrome (SPLIS) or alternatively as nephrotic syndrome type 14 (NPHS14). Patients with SPLIS exhibit lymphopenia, nephrosis, adrenal insufficiency, and/or neurological defects. No targeted therapy for SPLIS has been reported. Vitamin B6 supplementation has therapeutic activity in some genetic diseases involving B6-dependent enzymes, a finding ascribed largely to the vitamins chaperone function. We investigated whether B6 supplementation might have activity in SPLIS patients. We retrospectively monitored responses of disease biomarkers in patients supplemented with B6 and measured SPL activity and sphingolipids in B6-treated patient-derived fibroblasts. In two patients, disease biomarkers responded to B6 supplementation. S1P abundance and activity levels increased and sphingolipids decreased in response to B6. One responsive patient is homozygous for an SPL R222Q variant present in almost 30% of SPLIS patients. Molecular modeling suggests the variant distorts the dimer interface which could be overcome by cofactor supplementation. We demonstrate the first potential targeted therapy for SPLIS and suggest that 30% of SPLIS patients might respond to cofactor supplementation.

Clinical practice guidelines (CPGs) are systematically developed statements backed by scientific evidence to assist practitioners in management in clinical practice. An international cross-sectional survey was conducted by the IPNA to examine the perceptions of pediatric nephrologists on guidelines and their usage and to identify important diseases for future clinical practice guidelines (CPGs). The survey found that the majority of pediatric nephrologists find CPGs useful in clinical practice and admitted to using them most of the time. Developing CPGs is challenging and there are standards available to develop trustworthy guidelines. While evidence-based global guidelines are ideal, pediatric nephrologists expressed the desire that they address regional differences. Most respondents (89.2%) to the survey agreed that adult guidelines did not cover the pediatric perspective adequately and 71.4% opined that consensus-based pediatric guidelines can be developed when evidence for the pediatric population is lacking. The development of high-quality practice guidelines requires substantial resources and may not be feasible in resource-poor countries. Adaptation of an existing guideline has been suggested as an alternative and the ADAPTE collaboration provides a systematic approach to adapting guidelines. Several diseases where pediatric guidelines are needed as a priority including IgA and C3 glomerulopathy were identified in the survey. Implementation of guideline-based care is challenging and the survey found that lack of availability of guidelines (43%) and resources (22.8%) are important reasons for poor implementation in lower-middle and low-income countries. Perceived complexity of guidelines, physician attitudes, and lack of training also contribute to non-adherence to guidelines., Author(s): Pankaj Hari [sup.1] , Khalid Alhasan [sup.2] , Arvind Bagga [sup.1] , Melvin Bonilla-Felix [sup.3] , Paula Alejandra Coccia [sup.4] , Ali Duzova [sup.5] , Ill-So Ha [sup.6] , [...]

Background: Dialysis disequilibrium syndrome (DDS) is a rare but significant concern in adult and pediatric patients undergoing dialysis initiation with advanced uremia or if done after an interval. It is imperative to gain insights into the epidemiological patterns, pathophysiological mechanisms, and preventive strategies aimed at averting the onset of this ailment. Design: Prospective observational quality improvement initiative cohort study. Setting and Participants: A prospective single‐center study involving 50 pediatric patients under 18 years recently diagnosed with chronic kidney disease stage V with blood urea ≥200 mg/dL, admitted to our tertiary care center for dialysis initiation from January 2017 to October 2023. Quality Improvement Plan: A standardized protocol was developed and followed for hemodialysis in pediatric patients with advanced uremia. This protocol included measures such as lower urea reduction ratios (targeted at 20%–30%) with shorter dialysis sessions and linear dialysate sodium profiling. Prophylactic administration of mannitol and 25% dextrose was also done to prevent the incidence of dialysis disequilibrium syndrome. Measures: Incidence of dialysis disequilibrium syndrome and severe dialysis disequilibrium syndrome, mortality, urea reduction ratios (URRs), neurological outcome at discharge, and development of complications such as infection and hypotension. Long‐term outcomes were assessed at the 1‐year follow‐up including adherence to dialysis, renal transplantation, death, and loss to follow‐up. Results: The median serum creatinine and urea levels at presentation were 7.93 and 224 mg/dL, respectively. A total of 20% of patients had neurological symptoms attributable to advanced uremia at the time of presentation. The incidence of dialysis disequilibrium syndrome was 4% (n = 2) with severe dialysis disequilibrium syndrome only 2% (n = 1). Overall mortality was 8% (n = 4) but none of the deaths were attributed to dialysis disequilibrium syndrome. The mean urea reduction ratios for the first, second, and third dialysis sessions were 23.45%, 34.56%, and 33.50%, respectively. The patients with dialysis disequilibrium syndrome were discharged with normal neurological status. Long‐term outcomes showed 88% adherence to dialysis and 38% renal transplantation. Limitations: This study is characterized by a single‐center design, nonrandomized approach, and limited sample size. Conclusions: Our structured protocol served as a framework for standardizing procedures contributing to low incidence rates of dialysis disequilibrium syndrome. [ABSTRACT FROM AUTHOR]

Background Approximately 50% of children with steroid-sensitive nephrotic syndrome (SSNS) will suffer from frequent relapses or steroid dependency, prompting the use of so-called steroid-sparing drugs. In this pilot study, we compare the efficacy and safety of rituximab to oral cyclophosphamide as first-line steroid-sparing medications. Methods A prospective open-label non-randomized study of children with frequent relapsing or steroid-dependant SSNS. Exclusion criteria were steroid-resistant disease, prescription of immunosuppressive agents other than prednisolone or levamisole, evidence of impaired kidney function, leucopenia, or active infection. The recruited children were allocated either to the oral cyclophosphamide (3 mg/kg/day for 8 weeks) or intravenous rituximab treatment (two doses of 375 mg/m.sup.2/dose, 2 weeks apart) and were monitored for relapses and side effects for 12 months. Results Forty-six subjects were included from two centers; 27 received cyclophosphamide and 19 received rituximab. One-year relapse-free survival was reached in 17 (58.6%) patients treated with cyclophosphamide compared to 16 (84.2%) with rituximab (adjusted HR 0.36; 95% CI 0.09-1.45; p = 0.151). The mean interval to relapse was 6.9 months in the cyclophosphamide group (N = 10) and 6.3 months in the rituximab group (N = 3). Both treatments were associated with a significant (p < 0.001) reduction in prescribed dose of oral alternate-day steroid from 1.02 to 0.36 mg/kg (cyclophosphamide) and 0.86 to 0.08 mg/kg (rituximab). Importantly, a significantly (p = 0.003) higher percentage of patients achieved complete withdrawal of steroid within 3 months of commencing study treatment in the rituximab (73.7%) versus cyclophosphamide (29.6%) group. Transient leucopenia was the most frequent adverse effect observed in the cyclophosphamide group (18.5%) and one patient (3.4%) had acute hepatotoxicity besides severe leucopenia and neutropenia in the 7th week of treatment with complete recovery with the withdrawal of cyclophosphamide and maintenance of remission. A minor infusion-related reaction in the form of a generalized macular skin rash was observed in one patient (5%) in the rituximab group. Conclusions Rituximab is non-inferior to cyclophosphamide and safe as a first-line steroid-sparing agent in children with SSNS. A larger multicenter study is required to assess superiority over cyclophosphamide., Author(s): Jameela A. Kari [sup.1] [sup.2] , Khalid A. Alhasan [sup.3] , Amr S. Albanna [sup.4] , Osama Y. Safdar [sup.1] [sup.2] , Mohamed A. Shalaby [sup.1] [sup.2] , Detlef [...]

Background: Organ transplantation is inherently dependent on the availability of organ donors. There is a noticeable paucity of literature addressing the rates of organ donation registration and the awareness of Islamic regulations (Fatwa) regarding organ donation within Saudi Arabia. Our study aimed to evaluate the level of organ donation registration, awareness of Islamic regulations, and knowledge of the Saudi Center for Organ Transplantation (SCOT) within the Saudi society. Methods: We conducted a cross-sectional survey from 30 March to 9 April 2023. This survey aimed to assess the awareness of Islamic (Fatwa) guidance on organ donation, the role of SCOT, and the rate of organ donation registration facilitated through the Tawakkalna app, the official health passport application in Saudi Arabia. Results: Out of 2329 respondents, 21% had registered as potential deceased organ donors, despite 87% acknowledging the importance of organ donation. Awareness of the Islamic Fatwa regarding organ donation was reported by 54.7% of respondents, and 37% recognized the Fatwa's acceptance of brain death criteria. The likelihood of registration as organ donors was higher among Saudi citizens under 45 years of age, females, healthcare workers (HCWs), individuals with higher education, relatives of patients awaiting organ donations, those informed about the Islamic Fatwas, and those willing to donate organs to friends. Conversely, being over the age of 25, Saudi nationality, employment as an HCW, awareness of SCOT, and prior organ donation registration were predictive of a heightened awareness of Islamic Fatwas. However, perceiving the importance of organ donation correlated with a lower awareness of the Fatwas. Significant positive correlations were found between awareness of SCOT, awareness of Fatwas, and registration for organ donation. Conclusions: While the Saudi population exhibits a high regard for the importance of organ donation, this recognition is not adequately translated into registration rates. The discrepancy may be attributable to limited awareness of SCOT and the relevant Islamic Fatwas. It is imperative to initiate organ donation awareness campaigns that focus on religious authorization to boost organ donation rates and rectify prevalent misconceptions. [ABSTRACT FROM AUTHOR]

AI algorithms can help identify patients at risk of kidney disease, predict the progression of kidney disease and personalise treatment plans based on individual patient data. ChatGPT answer 2: Artificial intelligence (AI) has the potential to revolutionise kidney care by helping clinicians better predict, diagnose and treat kidney diseases. AI and kidney care ChatGPT answer 1: Artificial intelligence (AI) has the potential to revolutionise kidney care by providing more accurate and timely diagnosis, treatment, and monitoring of kidney diseases. Keywords: AI; ChatGPT EN AI ChatGPT 1844 1848 5 08/10/23 20230901 NES 230901 Abbreviations AI artificial intelligence Rapid advances have been made in artificial intelligence (AI) and researchers are constantly increasing their use of this technology. [Extracted from the article]

Background Acute kidney injury (AKI) is a common problem encountered in critically ill children with an increasing incidence and evolving epidemiology. AKI carries a serious morbidity and mortality in patients requiring admission to a pediatric intensive care unit (PICU). Methods We undertook a prospective cohort study of PICU admissions at three tertiary care hospitals in the Kingdom of Saudi Arabia over 2 years. The Kidney Disease Improving Global Outcomes (KDIGO) definition was used to diagnose AKI. Results A total of 1367 pediatrics PICU admissions were included in the study. AKI affected 511 children (37.4%), with 243 children (17.8%) classified as stage I (mild), 168 patients (12.3%) stage II (moderate), and 100 children (7.3%) were classified as stage III (severe). After adjustment for age, sex, and underlying diagnosis, in-hospital mortality was six times more likely among patients with AKI as compared to patients with normal renal function (adjusted OR: 6.5, 95% CI: 4.2-10). AKI was also a risk factor for hypertension (adjusted OR: 4.1, 95% CI: 2.8-5.9) and prolonged stay in the PICU and hospital, as it increased the average number of admission days by 10 (95% CI: 8.6-11) days in the PICU and 12 (95% CI: 10-14) days in the hospital. Conclusions One-third of PICU admissions were complicated with AKI. AKI was associated with increased hospital mortality and the length of stay in both PICU and hospital., Author(s): Jameela A. Kari [sup.1] , Khalid A. Alhasan [sup.2] , Mohamed A. Shalaby [sup.1] , Norah Khathlan [sup.3] , Osama Y. Safdar [sup.1] , Suleman A. Al Rezgan [sup.4] [...]