Abstract The principal organs involved in the control of mineral homeostasis are the kidneys, parathyroid glands, intestine and bone, which interact in a finely coordinated manner to maintain calcium and phosphorus levels. Mineral balance is disrupted in the context of chronic kidney disease (CKD), triggering compensatory mechanisms that paradoxically lead to a cascade of systemic complications that affect numerous organs. Among these organs, bone has increasingly been recognized as an endocrine organ, highlighting the role of bone-derived hormones in CKD complications beyond mineral metabolism. Osteocytes play a key role in the regulation of phosphorus metabolism, mediated by Fibroblast Growth Factor 23 (FGF23), which also demonstrates pleiotropic effects. Furthermore, bone cells produce a wide range of proteins that participate in the regulation of diverse systemic functions, such as glucose metabolism, male fertility, cognitive function, inflammation, appetite and hematopoiesis, which are processes commonly impaired in patients with CKD. So far, the systemic impact of dysregulated bone homeostasis in CKD has not been addressed in detail beyond its role in calcium-phosphate metabolism. This review aims to provide an overview of the role of bone as a main endocrine organ and its potential roles in organ dysfunction in CKD.
Abstract Background Native polycystic kidneys often regress after kidney transplantation in patients with autosomal-dominant polycystic kidney disease (ADPKD), but the degree of regression varies widely, and no externally validated preoperative prediction model is available. Therefore, we aimed to develop and externally validate a preoperative model to predict post-transplant native kidney volume changes. Methods This multicentre, retrospective study included 224 patients with ADPKD who underwent kidney transplantation at 11 Japanese centres. Patients were divided by centre into non-overlapping development (four centres, n = 164) and validation (seven centres, n = 60) sets. Total kidney volume (TKV) was measured before and one year after transplantation. The TKV change ratio (TKVCR) was calculated as post-transplantation TKV divided by baseline TKV. Multivariable linear regression was used to identify preoperative predictors. Results The final model included five preoperative predictors: body mass index, age², log₁₀(TKV), systolic blood pressure, and log₁₀(dialysis duration + 1) (R²=0.168). On external validation, the R² was 0.255, mean absolute error was 0.122, and root mean squared error was 0.154; however, individual-level prediction was limited. In an exploratory binary classification using the overall cohort mean TKVCR (0.62) as the cutoff, accuracy was 0.783, negative predictive value was 0.862, and the area under the receiver operating characteristic curve was 0.850 (95% confidence interval, 0.743–0.947). Conclusions Preoperative factors were associated with post-transplant native kidney volume change, but accuracy for individual patients was limited. These findings provide preliminary evidence that volume changes may be partly predictable.
Abstract Background Conventional diagnostic markers, such as eGFR or albuminuria, often detect established late stages of kidney disease missing early adaptive changes. Acylcarnitines (ACs), intermediates of mitochondrial fatty acid oxidation, have been suggested as markers of metabolic dysfunction and impaired energy metabolism, which are important processes in early kidney injury. However, their role as prognostic biomarkers for early kidney disease remains unclear. Aim To analyse ACs as an early prognostic biomarker for progression to kidney disease in an apparently healthy European population-based sample. Methods Data from 1 960 apparently healthy adults in a population-based cohort in Lausanne, Switzerland. Incident chronic kidney disease (CKD) was defined as progression to eGFR<60 mL/min/1.73 m² and eGFR trajectory as progression from eGFR >90 mL/min/1.73 m² to eGFR 60-90 mL/min/1.73 m² during the follow-up period. Results Over a median follow-up of 8.5 years, 53 participants (2.7%) developed CKD, and 365 participants (18.4%) developed eGFR trajectory. In multivariate analyses, long-chain ACs (Arachidonyl-) remained positively associated with incident CKD and their baseline standardized log-transformed concentrations AC levels were higher. Baseline levels of short-chain ACs (Butyryl- and Hydroxybutyryl-), long-chain ACs (Tetradecanedienoyl-, Hexadecenoyl-, Stearoyl- and Oleoyl-) were significantly higher in the participants who later developed eGFR trajectory. Conclusion ACs were independently associated with both incident CKD and eGFR trajectory in healthy adults free from diabetes, obesity or cardiovascular disease. However, the findings of the current study cannot establish the clinical utility of ACs profiling as a prognostic marker for prognostic CKD and require confirmation in studies with sufficient events.
Abstract Targeted-release budesonide (Nefecon) is the first gut–kidney axis–directed therapy for high-risk Immunoglobulin A Nephropathy (IgAN) and relies on intact hepatic first-pass metabolism to limit systemic exposure. We report a 63-year-old man who developed acute portal vein thrombosis within three days of treatment initiation. Imaging demonstrated near-complete thrombosis of the portal venous system. Subsequent evaluation revealed previously unrecognized chronic liver disease, including hereditary hemochromatosis, alcohol use, and early hepatocellular carcinoma without vascular invasion. In conjunction with three previously reported cases of splanchnic vein thrombosis in patients receiving budesonide to treat advanced autoimmune hepatobiliary disease and published pharmacokinetic data, this observation suggests that hepatic dysfunction and disease may lower the thrombotic threshold for budesonide. These findings support careful assessment of hepatic function when initiating targeted-release budesonide in IgAN.
Abstract Background Chronic kidney disease is a leading cause of death and disability globally, with the greatest burden and most limited access to kidney therapies in low- and middle-income countries. Environmentally sustainable kidney care is increasingly recognized as essential. Structured, patient-informed collaboration between academia and the kidney medical device industry holds potential toward solving these problems. Methods We conducted a narrative review of partnerships between academia and industry in environmentally sustainable kidney care. A scoping search of PubMed, Google Scholar, CINAHL and the Cochrane Library was combined with targeted grey-literature searches of key organizations. Eligible sources describe partnership structures, governance, financing, environmental or social outcomes, or lessons learned. Findings were synthesized thematically, informed by patient perspective, then interpreted using a United Nations sustainable development partnership framework. Results Existing initiatives and consortia such as the International Society of Nephrology’s GREEN-K, the Kidney Health Initiative and KitNewCare illustrate the potential of multi-stakeholder collaboration to advance sustainable kidney care. Patient organizations, notably the European Kidney Patients’ Federation, emphasise that environmental initiatives must align with treatment quality, patient autonomy and equity. Industry-led innovations include water- and energy-efficient technologies, life-cycle assessment of processes and/or consumables, lower-impact concentrates and operational optimizations. Key barriers include heterogeneous regulatory requirements, limited materials circularity, public procurement that prioritizes cost over sustainability, and financial investments associated with device innovation. We envision partnering opportunities to both improve access to, and environmental sustainability of, kidney therapies. Conclusions Achieving low-carbon, resilient and equitable kidney care requires academia–industry partnerships that embed meaningful patient involvement, position industry as co-creator, and align incentives around shared clinical and environmental goals. Structured partnering frameworks can support transparent governance, harmonised metrics and scalable green innovation across the kidney medical device sector.
