Children's Memorial Health Institute

The dynamic growth in the use of artificial intelligence (AI) in medicine is driven by advances in computer processing power, memory, and data storage capabilities. The digital progress, combined with continuously growing datasets, enables the development of modern tools that support oncological, neurological, and genetic diagnostics. Achievements in the application of AI in medicine make it possible to analyze genotype–phenotype correlations, and rare diseases, which include more than 6,000 distinct conditions characterized by unique phenotypes and complex pathomechanisms, present a particular challenge in this context. This article presents the basic issues related to machine learning and describes the mechanisms of the most commonly used algorithms. In addition, a review was conducted of modern tools that enable the analysis of genotype–phenotype correlations and the prediction of symptoms of the rare disease neurofibromatosis type 1 (NF1). Tools developed so far to support therapeutic decision-making related to NF1 were collected and described. The tools were classified according to their functionality, and their usefulness in the diagnostic process was discussed in detail, emphasizing how advanced algorithms can support precise phenotypic assessment and patient health evaluation and contribute to the optimization of their treatment. Despite its great potential, the use of AI in the diagnosis of rare diseases is associated with challenges such as the need to standardize small patient groups and the necessity of interdisciplinary collaboration between experts in genetics, bioinformatics, laboratory medicine, and clinical medicine.

Introduction Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies ( N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria. Objective FIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria. Design FIONA (NCT05196035; Eudra-CT: 2021–002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months’ duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m 2 if ≥ 1 to < 18 years or a serum creatinine level ≤ 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria despite ACEi or ARB usage. The primary objective is to demonstrate that finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021–002905-89) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data. FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥ 30% from baseline to day 180 and percent change in UPCR from baseline to day 180. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints. Conclusion FIONA is evaluating the use of finerenone in children with CKD and proteinuria. Should safety, tolerability, and efficacy be demonstrated, finerenone could become a useful additional therapeutic agent in managing proteinuria and improving kidney outcomes in children with CKD. Trial registration ClinicalTrials.gov NCT05196035. Registered on 19 January 2022.

BACKGROUND:Hyperuricemia has traditionally been viewed primarily as a cause of gout; however, accumulating evidence indicates that elevated serum uric acid (sUA) is also associated with increased cardiovascular and renal risk. Recent epidemiological studies suggest that adverse outcomes may occur at sUA levels well below the classic crystal-based thresholds, particularly in patients with high cardiovascular risk. METHODS:This expert consensus document was developed by a multidisciplinary European panel of cardiology, internal medicine, nephrology, and hypertension specialists. The recommendations are based on a critical narrative review of the literature published, including large cohort studies, meta-analyses, randomized controlled trials, and contemporary European guidelines (ESC, ESH, KDIGO, EULAR). Particular emphasis was placed on outcome-driven serum urate thresholds and clinically applicable risk stratification. RESULTS:Hyperuricemia is common and increasingly prevalent, especially among individuals with hypertension, chronic kidney disease, obesity, diabetes, and established cardiovascular disease. Elevated sUA is independently associated with cardiovascular mortality, heart failure, stroke, and faster progression of chronic kidney disease. However, randomized trials have not shown clear cardiovascular or renal benefit from routine urate-lowering therapy in patients with asymptomatic hyperuricemia. Based on current evidence, this consensus proposes a risk-based, individualized approach to hyperuricemia management and presents a pragmatic six-rung therapeutic ladder integrating lifestyle measures, optimization of comorbidities, and pharmacological urate-lowering therapy when clinically indicated. CONCLUSIONS:Hyperuricemia should be recognized as a relevant cardiovascular and renal risk factor rather than a benign biochemical finding. Serum urate measurement can improve risk stratification in selected high-risk populations. While routine treatment of asymptomatic hyperuricemia cannot be universally recommended, targeted urate-lowering strategies may be appropriate in patients with high cardiovascular risk, symptomatic disease, or very high sUA levels. Future randomized trials are needed to define whether urate-lowering therapy can improve hard cardiovascular and renal outcomes in these populations.

CONTEXT:Accurately assessing dietary intake in children and adolescents is challenging due to the limitations of traditional self-reported methods. Metabolomics has emerged as a valuable tool for assessing the body's biochemical response to specific foods, food groups, or dietary patterns, thereby improving the evaluation of diet-health relationships. However, evidence on how diet influences metabolomic profiles in pediatric populations remains limited. OBJECTIVE:To evaluate the evidence on the relationship between nutritional interventions or habitual dietary intake and metabolites measured in blood or urine among children and adolescents. DATA SOURCES:A systematic search was conducted in PubMed, Cochrane, and Embase databases up to September 2024. DATA EXTRACTION:This systematic review was conducted in accordance with the principles of the Cochrane Collaboration, and PRISMA guidelines were followed. Randomized clinical trials and observational studies in children and adolescents were included. DATA ANALYSIS:From 659 records, 8 studies met the inclusion criteria, involving 5992 participants across 12 countries. The included studies reported associations across 3 dietary categories: dietary patterns, food groups, and specific food ingredients. Both targeted and untargeted metabolomic analyses were used to identify diet-related biomarkers in blood and urine. Positive associations were observed between higher adherence to the Mediterranean diet and greater fruit and vegetable consumption with metabolites such as hippurate, trigonelline, and proline betaine. In contrast, higher intake of ultra-processed foods and adherence to vegan diets were inversely associated with branched-chain amino acids and aromatic amino acids such as tyrosine and docosahexaenoic acid. CONCLUSION:This review identifies several metabolites consistently associated with specific dietary components across different studies in children and adolescents. These findings support the potential of metabolomics for validating dietary biomarkers and improving the accuracy of dietary assessment in pediatric populations. Although metabolomic markers reflect actual dietary intake, their implications for health outcomes remain to be explored. SYSTEMATIC REVIEW REGISTRATION:PROSPERO registration no. CRD42024506437.

Background. There is a lack of robust evidence regarding immunosuppressive therapy in children and adolescents after kidney transplantation (KTx), and as such, international practice is highly variable. Recent clinical practice recommendations advocating individualized immunosuppressive strategies that incorporate newer agents are often not implemented. This can potentially contribute to reduced patient and renal allograft survival. Methods. The guideline was developed between January 1, 2024, and December 12, 2025, according to the Guidance Manual of the German Association of Scientific Medical Societies by the German Societies for Pediatric Nephrology, Nephrology, Transplantation, and Pediatrics, the German Kidney Association, the International Pediatric Transplant Association, the European Society for Pediatric Nephrology and the Members of the Cooperative European Pediatric Renal Transplant Initiative. Results. This evidence- and consensus-based guideline provides up-to-date, state-of-the-art recommendations for immunosuppressive therapy after KTx in pediatric kidney transplant recipients. It is based on the best available evidence and the consensus of the relevant German Medical Societies, Members of the Cooperative European Paediatric Renal Transplant Initiative, and the working group on transplantation of the European Society for Paediatric Nephrology, and the International Pediatric Transplant Association. Conclusions. The formal consensus reached is particularly significant in cases of weak or inconclusive evidence and where recommendations are based solely on expert opinion.