Lutz T. Weber’s research while affiliated with University Hospital Cologne and other places

Chronic kidney disease (CKD) is characterised by a gradual loss of kidney function over time and is often linked to oral health issues. This case illustrates typical conditions in young CKD patients based on a 15-year-old girl with CKD stage 4 and methylmalonic aciduria, severe gingivitis and hyperplasia of the gingiva, and a need for orthodontic treatment. Oral hygiene interventions, homecare instructions and deep cleaning under antibiotic shielding were necessary to improve the patient’s oral health. The immediate worsening of oral health status after extending the interval between regular prophylaxis appointments highlights the need for intensive prevention in young CKD patients to control oral health disorders. This report aims to demonstrate burden-of-care-reducing oral prophylaxis options for patients suffering from severe CKD with oral manifestations. Trial Registration: German Registry of Clinical Trials: DRKS00010580

Background Chronic kidney disease (CKD) seriously affects the well-being and shortens the life expectancy of children and adolescents, but its progression is challenging to predict. Therefore, there is an urgent need for biomarkers that can identify children at risk of faster CKD progression. Alport syndrome (AS) is the most common monogenetic glomerular kidney disease. Urinary Dickkopf-related protein 3 ( DKK3) is associated with a decline in estimated glomerular filtration rate (eGFR) in adults and children with advanced CKD. However, its potential for early detection of CKD and its prognostic value in children with AS remain unknown. Methods Urine samples from 49 children enrolled in the EARLY PRO-TECT Alport trial were analyzed to evaluate whether DKK3 could identify children with AS to be at risk for faster CKD progression. Results DKK3 levels in patients with AS were higher than those of healthy individuals reported in the literature. DKK3 levels were more elevated in patients with later stages of AS. Furthermore, children who were not treated with renin angiotensin system inhibitors (RASi) had higher DKK3 levels than treated children. Children with above-average DKK3 levels were more likely to have increased albuminuria after 2 years of follow-up than children with below-average DKK3 levels. Conclusion Urinary DKK3 is significantly elevated in children at early stages of AS. There was a potential association between higher DKK3 levels, worsening albuminuria, and a decline in kidney function. These findings suggest that DKK3 may be a prognostic marker for predicting the risk of kidney damage in children with AS. Graphical Abstract

We investigated factors associated with post-transplant growth in pediatric kidney transplant (KTx) recipients with a focus on plasma bicarbonate (HCO3−) and estimated the effect of alkali treatment on growth. In this study of the CERTAIN Registry, data were collected up to 5 years post-transplant. Generalized Additive Mixed Models were applied to assess the association between post-transplant growth and covariates. A trial-emulation analysis was performed to estimate the causal effect of alkali supplementation on growth. We report on 2147 primary KTx recipients with a median age at KTx of 10.2 (IQR 5.1;14.3) years. No statistically significant association was found between growth and HCO3− (p = 0.21), but the shape of the estimated conditional association showed a decreasing estimated growth with increasing HCO3−. Glucocorticoid treatment and allograft rejection showed an inverse association with growth. Living donor KTx, glomerulopathy, recombinant growth hormone use, low height z-score at KTx, younger age, and higher eGFR were positively associated with growth. The trial-emulation analysis included patients at 30 days and 3, 6, and 9 months post-transplant with HCO3− < 22 mmol/L and no prior alkaline treatment. Alkaline treatment was initiated in 194, 93, 47, and 25 patients, respectively. After adjustment for confounders, there was no significant difference in growth at 1-year post-transplant in treated and untreated patients. We found no association between HCO3− and growth nor evidence of improved growth after treatment of metabolic acidosis. Living donor KTx was positively associated with post-transplant growth, while there was an inverse association with allograft rejection. A higher resolution version of the Graphical abstract is available as Supplementary information

The integrity of the filtration barrier of the kidney relies on the proper composition of podocyte interdigitating foot processes. Their architecture is supported by a complex actin-cytoskeleton. Following podocyte stress or injury, podocytes encounter structural changes, including rearrangement of the actin network and subsequent effacement of the foot processes. Immunosuppressive drugs, which are currently used as treatment in proteinuric kidney diseases, have been shown to exert not only immune-mediated effects. This review will focus on the direct effects of glucocorticoids, cyclosporine A, tacrolimus, mycophenolate mofetil, and rituximab on podocytes by regulation of Ca2+ ion channels and consecutive downstream signaling which prevent cytoskeletal rearrangements and ultimately proteinuria. In addition, the efficacy of these drugs in genetic nephrotic syndrome will be discussed. A higher resolution version of the Graphical abstract is available as Supplementary information

Background: Rare diseases affect fewer than 1 in 2,000 individuals, but approximately 150 rare kidney diseases account for about 10% of the chronic kidney disease (CKD) population, impacting millions across Europe and globally. The scarcity of medical experts for these conditions results in an unmet need for accurate and helpful patient information. Large language models like ChatGPT may offer a technological solution to assist medical professionals in educating patients and improving doctor-patient communication. We hypothesized that ChatGPT could provide accurate responses to frequently asked basic questions from patients with rare kidney diseases. Methods: Medical professionals and members of European Patient Advocacy Groups (ePAGs) affiliated with the European Rare Kidney Disease Reference Network (ERKNet) simulated patient-ChatGPT interactions using a Microsoft forms questionnaire and ChatGPT 3.5 and 4.0. Participants selected any rare kidney disease for a structured conversation with ChatGPT-3.5 or 4.0. Responses were evaluated for accuracy and helpfulness. Results: 46 ERKNet experts and 12 ePAGs from 13 European countries participated in this study. ChatGPT provided scientifically accurate and helpful information on 28 randomly selected rare kidney diseases, including prognostic information and genetic testing guidance. Participants expressed neutral positions regarding ChatGPT's recommendations on alternative treatments, second opinions, and other information sources. While ChatGPT generally was perceived as helpful and empathetic, concerns about patient safety persisted. Conclusions: ChatGPT exhibited substantial potential in addressing patient inquiries regarding rare kidney diseases in a real-world context. While it demonstrated resilience against misinformation in this application, careful human oversight remains essential and indispensable.

Our review summarizes and evaluates the current state of knowledge on lipid metabolism in relation to the pathomechanisms of kidney disease with a focus on common pediatric kidney diseases. In addition, we discuss how nutrition in early childhood can alter kidney development and permanently shape kidney lipid and protein metabolism, which in turn affects kidney health and disease throughout life. Comprehensive integrated lipidomics and proteomics network analyses are becoming increasingly available and offer exciting new insights into metabolic signatures. Lipid accumulation, lipid peroxidation, oxidative stress, and dysregulated pro-inflammatory lipid mediator signaling have been identified as important mechanisms influencing the progression of minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diabetic kidney disease, and acute kidney injury. We outline key features of metabolic homeostasis and lipid metabolic physiology in renal cells and discuss pathophysiological aspects in the pediatric context. On the one hand, special vulnerabilities such as reduced antioxidant capacity in neonates must be considered. On the other hand, there is a unique window of opportunity during kidney development, as nutrition in early life influences the composition of cellular phospholipid membranes in the growing kidney and thus affects local signaling pathways far beyond the growth phase. Graphical Abstract

Objectives: Children and young patients with chronic kidney disease (CKD) are at persistent risk of gingivitis despite usual preventive measures. This clinical study aimed to determine the efficacy of an intensive oral preventive programme (OPP) for young patients with CKD in treating plaque-induced gingivitis modified by systemic factors. Methods: Young patients with CKD (N = 30) were recruited/randomised to a need-related OPP (n = 15) or treatment as usual (TAU) including mainly motivation and instructions (controls, n = 15) followed by a single intensive prophylactic appointment after 3 months. For the OPP group, depending on the baseline degree of inflammation (PBI) professional mechanical plaque removal, local chlorhexidine gel application and mouth rinse were applied at need-related appointments focussing on local plaque control and reduction in inflammation. Results: After 3 months OPP, lower plaque indices were found (2.62–0.66, p < 0.05) in contrast to TAU (2.32–2.05, p > 0.05) with differences between study groups (p < 0.05). Regarding gingivitis, lower PBI values than baseline were observed in OPP (1.03– 0.05, p < 0.05) than TAU (1.15–1.00; p > 0.05); OPP reductions (effect size) were higher than after a single intensive appointment (1.00–0.36; p < 0.05). Degree of immunosuppressive therapy did not differ between groups throughout the study. Conclusions: Young patients with CKD suffer from generalised gingivitis with increased bleeding sites. This moderate degree of inflammation shows a normal distribution of high and low plaque responders, with no pattern of impact for the degree of immunosuppression. Effectiveness and duration of preventive measures follow a dose–response principle. Therefore, need-related preventive measures should be implemented and maintained in future regular care for CKD patients.

Background: Steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) significantly affect children’s quality of life. There are frequent relapses in SSNS and progression in SRNS. IPNA guidelines suggest that monoclonal antibodies like rituximab (RTX) are promising treatments. Objective: This study aims to evaluate the long-term efficacy and safety of rituximab administration in children with SSNS, encompassing FRNS and SDNS, and SRNS over a two-year follow-up period, facilitating individualized management. Methods: We conducted an open-label, multicenter, randomized, and patient-oriented study (RICHNESS), involving children aged 3–18 with SRNS (18) and SSNS (11) undergoing 2 years continuous RTX therapy. The primary outcome was complete/partial remission (CR/PR), as defined by IPNA/KDIGO guidelines, at 6, 12, 18, and 24 months on RTX; secondary outcomes included adverse events. Key endpoints included the estimated glomerular filtration rate (eGFR), the albumin-to-creatinine ratio (ACR), CD20 levels, IgG levels, and the incidence of infections. Kidney biopsies were performed in 94% of SRNS patients. RTX was administered every 6–9 months, depending on CD20 levels, IgG levels, and the presence of infections. The eGFR and ACR were assessed every 6 months. Results: Some 31 children were selected for RTX treatment. Overall, 2 experienced severe allergic reactions, leading to their exclusion from the final analysis of 29 children. In the SSNS group, all children achieved and maintained complete remission within 2 years. Remission rates in the SRNS group ranged from 39% (RR 0.78; 95% CI: 16.4–61.4%, NNT 9) at the 6th month to 72% (RR 1.44; 95% CI: 51.5–92.9%) over the 2-year follow-up period due to continuous RTX therapy. The median duration of RTX use was 26.1 months, with a median cumulative dose of 1820 mg/m². Adverse reactions and complications were presented by mild infusion-related reactions in 3 children (10.3%), severe allergic reactions in 2 children (6.2%), hypogammaglobulinemia in 7 children (24%), infections in 3 children (10.3%), severe destructive pneumonia in 1 child, recurrent respiratory infections in 2 children, and neutropenia in 1 child (3.44%). Conclusions: RTX was tolerated well, and proved highly effective as a steroid-sparing agent, offering potential in terms of stopping relapses and minimizing steroid-related side effects. It also demonstrated efficacy in slowing progression in SRNS, indicating potential for use in ACR reduction and renal function restoration, but requires careful use given potential severe allergic reactions and infectious complications. Further studies should focus on long-term cost-effectiveness and deferred side effects.