Chronic kidney disease-mineral and bone disorder (CKD-MBD) presents with extra-skeletal calcification and renal osteodystrophy (ROD). However, the pathophysiology of ROD remains unclear. Here we examine the hypothesis that stalled mitophagy within osteocytes of CKD-MBD mouse models contributes to bone loss. RNA-seq analysis revealed an altered expression of genes associated with mitophagy and mitochondrial function in tibia of CKD-MBD mice. The expression of mitophagy regulators, p62/SQSTM1, ATG7 and LC3, was inconsistent with functional mitophagy, and in mito-QC reporter mice with ROD, there was a two- to three-fold increase in osteocyte mitolysosomes. To determine if uremic toxins were potentially responsible for these observations, treatment of cultured osteoblasts with uremic toxins revealed increased mitolysosome number and mitochondria with distorted morphology. Membrane potential and oxidative phosphorylation were also decreased, and oxygen-free radical production increased. The altered p62/SQSTM1 and LC3-II expression was consistent with impaired mitophagy machinery, and the effects of uremic toxins were reversible by rapamycin. A causal link between uremic toxins and the development of mitochondrial abnormalities and ROD was established by showing that a mitochondria-targeted antioxidant (MitoQ) and the charcoal adsorbent AST-120 were able to mitigate the uremic toxin-induced mitochondrial changes and improve bone health. Overall, our study shows that impaired clearance of damaged mitochondria may contribute to the ROD phenotype. Targeting uremic toxins, oxygen-free radical production and the mitophagy process may offer novel routes for intervention to preserve bone health in patients with CKD-MBD. This would be timely as our current armamentarium of anti-fracture medications for patients with severe CKD-MBD is limited.

Hyperphosphatemia is common in chronic kidney disease (CKD) patients, especially patients on hemodialysis. Tenapanor is a novel drug with fewer side effects and high compliance compared to traditional phosphate binders. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of tenapanor.

A comprehensive search was conducted on PubMed, Scopus, Web of Science, and Cochrane Library, from inception to June 25, 2024. Nine randomized controlled trials (RCTs) and three single-arm studies comparing tenapanor to placebo were included. By adopting a random-effect empirical Bayes model, STATA and RevMan were used to pool dichotomous and continuous data. The primary outcome assessed was serum phosphate. Secondary outcomes included intact parathyroid hormone (iPTH), serum calcium, potassium, and sodium, bowel movement frequency, stool consistency using BSFS score and safety outcomes.

Twelve studies with a total of 2,251 patients were included. Tenapanor was superior to placebo in reducing phosphate at all assessed end points, week 1 (MD = -1.28 mg/dL, P < 0.001), week 2 (MD = -1.07 mg/dL, P < 0.001), week 3 (MD = -1.22 mg/dL, P < 0.001), and week 4 (MD = -0.91 mg/dL, P < 0.001). In addition, iPTH was almost statistically significantly lower in the tenapanor group (MD = -36.53 ng/L, P = 0.07). Moreover, it led to a statistically significant reduction in sodium level (MD = -0.7 mmol/L, P = 0.0003). On the contrary, tenapanor had no statistically significant effect on calcium or potassium levels. Bowel movement frequency and stool consistency were significantly higher in the tenapanor group at all assessed end points. Regarding safety analysis, diarrhea and nausea were statistically significantly higher in the tenapanor group, (RR = 3.71, P < 0.001) and (RR = 1.97, P < 0.001), respectively. There were no significant differences in other adverse events.

Based on our meta-analysis, tenapanor can effectively reduce serum phosphate, iPTH, and sodium. Additionally, it improves bowel movement frequency and stool consistency. However, it is associated with a higher risk of GIT symptoms that should be considered and managed during treatment. We recommend conducting further RCTs to perform head-to-head comparisons against other active comparators such as phosphate binders.

Fracture risk is significantly elevated in patients with chronic kidney disease (CKD), yet the diagnosis and treatment of CKD-associated osteoporosis remain complex. This review addresses the current gaps in managing bone health in CKD and highlights emerging strategies in this high-risk population.

Diagnosis of CKD-associated osteoporosis requires integration of imaging, bone turnover markers, and occasionally bone biopsy. Correction of mineral metabolism disturbances is foundational, while bone-targeted therapies must be carefully selected. Treatment strategies are informed by bone turnover status. Antiresorptives such as bisphosphonates and denosumab are used in high-turnover disease, and osteoanabolic agents such as teriparatide and romosozumab are promising for low-turnover disease.

Management of osteoporosis in CKD requires individualized approaches based on bone turnover and mineral metabolism status. While several pharmacologic options exist, evidence from randomized trials in CKD populations is limited. Further research is needed to guide treatment selection, define well tolerated therapeutic targets, and improve skeletal outcomes in this vulnerable group.

Growing evidence indicates an interesting interplay between kidney and bone. The pathophysiological condition of the skeletal system is intricately associated with the normal functioning of the kidneys. This relationship is modulated by various factors, including calcium and phosphate, 1-α-hydroxylase, erythropoietin (EPO), klotho, fibroblast growth factor 23 (FGF23), bone morphogenetic protein-7 (BMP-7), and extracellular vesicles (EVs). These interactions are notably evident in conditions such as chronic kidney disease with bone mineral density (CKD-BMD), renal osteodystrophy (ROD), and osteoporosis (OP). Furthermore, innovative methodologies such as cell co-culture, organ-on-a-chip, single-cell sequencing, and spatial transcriptomics are highlighted as instrumental in advancing the study of inter-organ interactions. This review, grounded in the pathogenesis, diagnostic and therapeutic modalities, and pharmacological treatments of OP, synthesizes evidence from molecular biology to clinical perspectives. It aims to establish a foundation for the development of more complex and physiologically relevant in vitro models and to propose potential therapeutic strategies.

Fracture is an under-recognized but common complication of diabetes mellitus, with an incidence approaching twofold in type 2 diabetes mellitus (T2DM) and up to sevenfold in type 1 diabetes mellitus (T1DM) compared with that in the general population. Both T1DM and T2DM induce chronic hyperglycaemia, leading to the accumulation of advanced glycosylation end products that affect osteoblast function, increased collagen crosslinking and a senescence phenotype promoting inflammation. Together with an increased incidence of microvascular disease and an increased risk of vitamin D deficiency, these factors reduce bone quality, thereby increasing bone fragility. In T1DM, reduced anabolic stimuli as well as the presence of autoimmune conditions might also contribute to reduced bone mass and increased fragility. Diabetes mellitus is the most common cause of kidney failure, and fracture risk is exacerbated when chronic kidney disease (CKD)-related mineral and bone disorders are superimposed on diabetic changes. Microvascular pathology, cortical thinning and trabecular deterioration are particularly prominent in patients with T1DM and CKD, who suffer more fragility fractures than do other patients with CKD. This Review explores the pathophysiology of bone fragility in patients with diabetes mellitus and CKD and discusses techniques to predict fracture and pharmacotherapy that might reduce fracture risk.

A man with hyperparathyroidism secondary to kidney failure on peritoneal dialysis underwent a parathyroidectomy with half-gland reimplantation complicated by severe hungry bone syndrome resulting in severe hypocalcaemia, hypotension and QT prolongation on ECG. He was initially managed with oral calcium and intravenous (IV) calcium chloride. Despite standard supportive treatment, attempts to wean IV therapy were unsuccessful. We report the novel use of intraperitoneal calcium to facilitate the weaning of IV calcium and discharge from hospital. A subsequent peritoneal membrane adequacy study did not demonstrate loss of peritoneal membrane adequacy.

Patients with kidney failure have elevated fracture risk that remains high following kidney transplantation. This study aimed to assess whether dual-energy x-ray absorptiometry-derived advanced hip analysis (AHA) and the trabecular bone score (TBS) improve bone mineral density (BMD)-based post-transplant fracture prediction.

Patients receiving kidney-only or simultaneous pancreas-kidney (SPK) transplants underwent immediate post-transplant dual-energy x-ray absorptiometry to provide BMD, the TBS, and AHA parameters; femoral neck, calcar, and shaft cortical thickness (CTh), and femoral neck buckling ratio (BR), an index of structural instability. Patients received treatment to reduce post-transplant BMD loss, using an established risk algorithm. Hazard ratios were determined using Kaplan-Meier and Cox proportional hazard models.

Of 357 transplant recipients, 289 (83%) received a kidney-only transplant. There were 83 incident fractures over a median of 4.4 years (IQR: 2.5-5.5). Fracture was associated with type 1 diabetes mellitus (p < 0.001), former smoking (p = 0.006), lower 25-hydroxyvitamin D (p = 0.003), BMD at total proximal femur and neck of femur (p < 0.001) and spine (p = 0.008), lower CTh at the calcar (p = 0.005) and shaft (p = 0.023), higher BR (p = 0.016) and lower TBS (p = 0.047). Following multivariable adjustment, type 1 diabetes mellitus, 25-hydroxyvitamin D, smoking, and femoral neck BMD remained significant. Using the BMD-based risk algorithm, inclusion of the BR improved the model fit.

BMD, the TBS, and AHA parameters are associated with incident fracture in kidney-only and SPK transplant recipients. Pre-transplant smoking, lower 25-hydroxyvitamin D and BMD are potentially modifiable factors that could reduce post-transplant fracture risk.

Calcimimetics are a mainstay of treatment for secondary hyperparathyroidism (sHPT), a ubiquitous condition in end-stage kidney disease (ESKD) associated with fractures, cardiovascular events, and mortality. In 2018, Medicare implemented the Transitional Drug Add-On Payment Adjustment (TDAPA), which shifted calcimimetic coverage from Part D prescription drug plans to Part B. Prior to TDAPA, Medicare beneficiaries with ESKD faced varying out-of-pocket costs for calcimimetics at the point of pharmacy depending on presence and magnitude of low-income subsidies (LISs). TDAPA differentially alleviated barriers to filling these costly medications.

To assess whether calcimimetic prescriptions increased post-TDAPA among patients subject to high out-of-pocket costs prior to the policy change (patients with Part D coverage without LIS and those lacking Part D coverage).

In this longitudinal cohort study, a difference-in-differences analysis was performed at the patient-quarter level. The sample included adult Medicare fee-for-service beneficiaries undergoing maintenance dialysis between July 1, 2016, and December 31, 2020, at US outpatient dialysis facilities. The US Renal Data System, a national registry of patients with ESKD, was used to collect patient, facility, and claims data. The data analysis occurred between May 2023 and October 2024.

LIS extent for patients with Part D coverage (fully subsidized, partially subsidized, not subsidized); presence of Medicare Part D coverage; and whether the patient-quarter was before/after TDAPA implementation.

The main outcome was having 1 or more filled calcimimetic prescriptions per quarter of the study period. A linear regression model was estimated, adjusting for demographics, dialysis modality and access, comorbidities, and facility characteristics, with 2-way fixed effects at the patient and quarter level.

A total of 509 765 adult Medicare fee-for-service beneficiaries were included in the analysis. The cohort had a mean (SD) age of 64 (14) years, was 57% male, 4% Asian, 38% Black, 15% Hispanic, 41% non-Hispanic White, and 3% other race and ethnicity. In adjusted difference-in-differences models, TDAPA's estimated effect was an absolute increase of 9.8 percentage points (pp) (95% CI, 9.3-10.2 pp) in calcimimetic prescriptions for patients with Part D but no subsidy and a 2.2 pp (95% CI, 1.8-2.6 pp) increase for patients with partial LIS compared to patients with full LIS.

The results of this longitudinal cohort study showed that after transitioning calcimimetic coverage from Part D to Part B via TDAPA, calcimimetic prescriptions increased in a graded manner, with the largest increases experienced by patients previously subject to the highest out-of-pocket prescription drug costs. Medicare's TDAPA policy has the potential to expand access to medications for patients.

People with chronic kidney disease (CKD) are at increased risk of fractures in comparison to the non-CKD population, and fractures are associated with high mortality and worsening quality of life. However, the approach for evaluation of bone disease and fracture risk in CKD is different from the approach in the general population.

The authors conducted a literature review of PubMed to include studies on pathophysiology of CKD mineral bone disorder, fracture risk assessment, and therapeutic options in the setting of CKD.

The higher risk observed in the CKD population is related to the complex interplay of changes in bone turnover (T), mineralization (M), and volume (V), along with other risk factors accumulated as glomerular filtration rate declines. The diagnosis of the type of renal osteodystrophy is not based only on assessment of bone density and traditional risk factors for osteoporosis. There are limitations of currently available fracture risk tools in the CKD population. Treatment choice should take into consideration the 3 components of the TMV classification along with the stage of kidney disease and comorbidities, but the assessment of these components has not been well established.

Current data are limited on efficacy and safety of treatments for fracture prevention in CKD. As new medications for the treatment of osteoporosis become available, there is an urgency to establish more clear guidelines for the diagnosis, fracture risk stratification, and treatment of bone disease in CKD.

Kidney transplantation is the optimal form of renal replacement therapy, but the long-term survival rate of kidney graft has not improved significantly. Currently, no well-validated model exists for predicting long-term kidney graft survival over an extended observation period.

Recipients undergoing allograft kidney transplantation at the Organ Transplantation Center of the First Affiliated Hospital of Kunming Medical University from 1 August 2003 to 31 July 2023 were selected as study subjects. A nomogram model was constructed based on least absolute selection and shrinkage operator (LASSO) regression, random survival forest, and Cox regression analysis. Model performance was assessed by the C-index, area under the curve of the time-dependent receiver operating characteristic curve, and calibration curve. Decision curve analysis (DCA) was utilized to estimate the net clinical benefit.

The machine learning-based nomogram included cardiovascular disease in recipients, delayed graft function in recipients, serum phosphorus in recipients, age of donors, serum creatinine in donors, and donation after cardiac death for kidney donation. It demonstrated excellent discrimination with a consistency index of 0.827. The calibration curves demonstrated that the model calibrated well. The DCA indicated a good clinical applicability of the model.

This study constructed a nomogram for predicting the 20-year survival rate of kidney graft after allograft kidney transplantation using six factors, which may help clinicians assess kidney transplant recipients individually and intervene.

Patients on dialysis often develop hyperphosphatemia, contributing to an increased risk of cardiovascular events and mortality. Currently, several types of phosphate binders (PBs) exist for the treatment of hyperphosphatemia, but they are sometimes associated with drug-specific side effects and high pill burden, making it difficult to control serum phosphorus appropriately. Tenapanor, which has a novel mechanism to reduce serum phosphorus via selective sodium/proton exchange transporter 3 inhibition, was approved for hyperphosphatemia in Japan in 2023. Four phase 3 studies of tenapanor have been performed in Japan and have demonstrated its efficacy and safety as a single-agent drug, add-on effects to PBs for patients with refractory hyperphosphatemia that cannot be improved with PBs alone, and reduction of the pill burden associated with PBs. This review provides an overview of the characteristics and previous clinical studies of tenapanor and describes the clinical benefits of tenapanor over current therapy in patients on dialysis.

Vitamin D deficiency is common in patients with chronic kidney disease (CKD) and associates with poor outcomes. Current clinical practice guidelines recommend supplementation with nutritional vitamin D as for the general population. However, recent large-scale clinical trials in the general population failed to demonstrate a benefit of vitamin D supplementation on skeletal or non-skeletal outcomes, fueling a debate on the rationale for screening for and correcting vitamin D deficiency, both in non-CKD and CKD populations. In a collaboration between the European Renal Osteodystrophy initiative of the European Renal Association (ERA) and the European Society for Paediatric Nephrology (ESPN), an expert panel performed an extensive literature review and formulated clinical practice points on vitamin D supplementation in children and adults with CKD and after kidney transplantation. These were reviewed by a Delphi panel of members from relevant working groups of the ERA and ESPN. Key clinical practice points include recommendations to monitor for, and correct, vitamin D deficiency in children and adults with CKD and after kidney transplantation, targeting 25-hydroxyvitamin D levels >75 nmol/l (>30 ng/ml). Although vitamin D supplementation appears well-tolerated and safe, it is recommended to avoid mega-doses (≥100 000 IU) and very high levels of 25 hydroxyvitamin D (>150-200 nmol/l, or 60-80 ng/ml) to reduce the risk of toxicity. Future clinical trials should investigate the benefit of vitamin D supplementation on patient-relevant outcomes in the setting of vitamin D deficiency across different stages of CKD.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic complication of chronic kidney disease (CKD), resulting in high morbidity and mortality. However, effective treatment strategies are lacking. The pathogenesis of CKD-MBD is unclear but involves feedback mechanisms between calcium, phosphorus, parathyroid hormone, vitamin D and other factors, in addition to FGF23, Klotho, Wnt inhibitors, and activin A. Construction of a perfect animal model of CKD-MBD with clinical characteristics is important for in-depth study of disease development, pathological changes, targeted drug screening, and management of patients. Currently, the modeling methods of CKD-MBD include surgery, feeding and radiation. Additionally, the method of CKD-MBD modeling by surgical combined feeding is worth promoting because of short time, simplicity, and low mortality. Therefore, this review based on the pathogenesis and clinical features of CKD-MBD, combined with the current status of animal models, outlines the advantages and disadvantages of modeling methods, and provides a reference for further CKD-MBD research.

Diabetes is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide. While both haemodialysis (HD) and peritoneal dialysis (PD) are commonly used treatment options for ESKD, the choice of dialysis modality in diabetic ESKD patients remains a critical decision influenced by various patient-related, healthcare system, and socio-economic factors. This article examines the factors influencing the selection of dialysis modalities for diabetic patients, with a focus on the challenges and opportunities in low-resource settings. Key considerations include the impact of comorbidities such as peripheral arterial disease and CKD-related mineral bone disorder (MBD), as well as patient preferences, caregiver burden, and the availability of healthcare infrastructure. The article highlights the need for personalized approaches to dialysis selection, considering both clinical outcomes and quality of life. It also emphasizes the potential benefits of home dialysis, including home HD and PD, in improving patient autonomy and long-term survival. The article advocates for better government policies, increased awareness, and improved support systems to enhance the accessibility and efficacy of dialysis treatments, particularly in underserved populations. Further research comparing the outcomes of different dialysis modalities across diverse settings is essential to guide global treatment strategies for diabetic ESKD patients.

This study compared the efficacy of microwave ablation (MWA) and parathyroidectomy (PTX) in the treatment of secondary hyperparathyroidism (SHPT) and evaluated the improvement of bone metabolic markers (BMMs) and bone mineral density (BMD).

Eligible patients with SHPT treated between January 2019 and August 2022 were enrolled in the study and were divided into two groups: MWA and PTX. Outcome measures included the treatment success rate, percentage of patients whose intact parathyroid hormone (iPTH) concentration was within the target range, serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), osteocalcin (OC), C-terminal cross-linked telopeptide of type I collagen (β-CXT), and BMD. Data on the procedure time, intraoperative blood loss volume, length and cost of hospitalization, incidence of postoperative complications, and recurrence rates were analyzed.

A total of 107 patients with SHPT-48 in the MWA group and 59 in the PTX group- were included in the study. There were no significant differences in baseline data between the two groups (p>0.05). At the final follow-up, both therapies decreased iPTH, Ca, P, ALP, OC, and β-CXT levels and increased BMD (p<0.05). Nonetheless, the decrease in iPTH, ALP, OC, and β-CXT was more pronounced 6 and 12 months after PTX (p<0.05). The percentage of patients whose iPTH level was within the target range was significantly higher in the MWA group (p<0.05). The incidence of severe hypocalcemia was significantly lower in the MWA group (p<0.05).

MWA can improve BMMs and BMD, and is a minimally invasive approach with great potential for treating patients with SHPT who cannot tolerate PTX.

This study evaluates TBS for estimating bone microarchitecture in ESRD patients using HR-pQCT as the reference technique.

TBS correlates significantly with vBMD and bone microarchitecture, unlike aBMD.

TBS may complement bone health assessment in ESRD patients by offering additional information alongside aBMD.

Given the high fracture risk, non-invasive techniques for assessing bone fragility in chronic kidney disease (CKD) remain important. Trabecular bone score (TBS) may provide additional information that could help guide treatment and follow-up decisions. The aim of this study is to investigate whether TBS reflects bone microarchitecture in end-stage renal disease (ESRD) patients, using high-resolution peripheral quantitative computed tomography (HR-pQCT) as the reference technique. Additionally, we aim to identify parameters associated with a low TBS.

Seventy-five ESRD patients were included at the time of kidney transplantation (KTx). Areal bone mineral density (aBMD) was analyzed using dual-energy X-ray absorptiometry (DXA). TBS was assessed from the L1-L4 area during DXA. Volumetric BMD (vBMD) and bone microarchitecture at tibia and radius sites were analyzed using HR-pQCT.

In ESRD patients, those with TBS < 1.370 were older and had a higher body mass index (BMI). In contrast to T-score-based classification (≤ -2.5 or > -2.5), low TBS was linked to significantly lower trabecular and cortical vBMD, reduced trabecular bone volume fraction (BV/TV) and trabecular number (Tb.N), and increased trabecular separation (Tb.Sp). In multivariate analysis, older age, higher BMI, and lower Tb.N remained independently associated with low TBS, while no HR-pQCT parameters were linked to low aBMD (T-score ≤ -2.5).

TBS correlates with both trabecular and cortical parameters measured by HR-pQCT, potentially offering a complementary perspective on bone microstructure compared to aBMD. At the time of KTx, a low TBS appears to better discriminate patients with significantly lower vBMD than aBMD alone.

Chronic kidney disease (CKD) is a leading condition in terms of prevalence and overall health impact. With the increased life expectancy of the CKD population and the improvement in medical care, controlling musculoskeletal complications remains a tough challenge. Patients with CKD are prone to falls, fractures and sarcopenia, enhancing the risk of death. A multitude of mechanisms contribute to fractures, and treatment is suboptimal; therefore, prevention must stand out as a key step. This review aims to provide an overview of the most relevant data regarding the impact of nutrition on bone disorders and sarcopenia in CKD. The newest relevant studies emphasize that plant protein intake is associated with a lower production of uremic toxins, lower serum phosphorus levels, and stronger bones. We conclude that patients with CKD should adopt specific diets tailored to the presence of osteoporosis, renal osteodystrophy, and muscle wasting. Low-protein diets or plant-dominant diets containing an adequate amount of protein could be better choices for predialysis patients with CKD in order to protect their bones and muscles, whereas in the dialysis population, a higher protein intake could be essential to prevent osteoporosis and sarcopenia. In all patients with CKD, focusing on antioxidant food intake could provide a strong antiaging benefit through ensuring good musculoskeletal health.

Uremic secondary hyperparathyroidism (SHP) refers to the biochemical abnormalities that characterize CKD-MBD. However, historically parathyroid hormone (PTH) is identified as the key culprit hormone and the essential biomarker of secondary hyperparathyroidism. SHP represents the adaptive response to several mineral abnormalities that initiate and maintain increased PTH secretion through classical mineral derangements and more recently elucidated hormonal dysregulations. Among classic factors involved in the pathogenesis of SHP, phosphate, calcium, and calcitriol have a prominent role. The discovery of new pathogenetic factors involved in the development of SHP (and the eventual CKD-MBD) including fibroblast growth factor-23 (FGF23) and klotho provides new hypothesis and perspectives to our understanding of this complex metabolic disturbance. Recently more than serum phosphate a critical role in regulating FGF23 synthesis and the progression of CKD is ascribed to phosphate pool, reflected by production of glycerol-3-phosphate and the formation of excessive CPP-2. Finally, also skeletal resistance to PTH action, due to dysregulation of the Wnt-β-catenin system and intestinal dysbiosis, affecting the PTH actions on bone are causal factor of SHP. Identifying all the actors at play is mandatory to allow the most precise therapeutic prescription in the individual patient. This paper aims to review, in particular, the pathophysiology of SHP, which is essential to envisage the eventual therapeutic options for the associated MBD.

Managing diabetes in patients on peritoneal dialysis (PD) is challenging due to the combined effects of dietary glucose, glucose from dialysate, and other medical complications. Advances in technology that enable continuous biological data collection are transforming traditional management approaches. This review explores how multiomics technologies and artificial intelligence (AI) are enhancing glucose management in this patient population. Continuous glucose monitoring (CGM) offers significant advantages over traditional markers, such as hemoglobin A1c (HbA1c). Unlike HbA1c, which reflects an mean glucose level, CGM provides real-time, dynamic glucose data that allow clinicians to make timely adjustments, leading to better glycemic control and outcomes. Multiomics approaches are valuable for understanding genetic factors that influence susceptibility to diabetic complications, particularly those related to advanced glycation end products (AGEs). Identifying genetic polymorphisms that modify a patient's response to AGEs allows for personalized treatments, potentially reducing the severity of diabetes-related pathologies. Metabolomic analyses of PD effluent are also promising, as they help identify early biomarkers of metabolic dysregulation. Early detection can lead to timely interventions and more tailored treatment strategies, improving long-term patient care. AI integration is revolutionizing diabetes management for PD patients by processing vast datasets from CGM, genetic, metabolic, and microbiome profiles. AI can identify patterns and predict outcomes that may be difficult for humans to detect, enabling highly personalized recommendations for diet, medication, and dialysis management. Furthermore, AI can assist clinicians by automating data interpretation, improving treatment plans, and enhancing patient education. Despite the promise of these technologies, there are limitations. CGM, multiomics, and AI require significant investment in infrastructure, training, and validation studies. Additionally, integrating these approaches into clinical practice presents logistical and financial challenges. Nevertheless, personalized, data-driven strategies offer great potential for improving outcomes in diabetes management for PD patients.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a multifaceted condition commonly seen in people with reduced kidney function. It involves a range of interconnected issues in mineral metabolism, bone health and cardiovascular calcification, which are linked to a lower quality of life and shorter life expectancy. Although various epidemiological studies show that the laboratory changes defining CKD-MBD become more common as the glomerular filtration rate declines, the pathophysiology of CKD-MBD is still largely unexplained. We herein review the current understanding of CKD-MBD, provide a conceptual framework to understand this syndrome, and review the genetic and environmental factors that may influence the clinical manifestation of CKD-MBD. However, a deeper understanding of the pathophysiology of CKD-MBD is needed to understand the phenotype variability and the relative contribution to organ damage of factors involved in CKD-MBD to develop more effective interventions to improve outcomes in patients with CKD.

To investigate the association between imaging findings and histopathological characteristics of parathyroid glands in patients with secondary hyperparathyroidism (SHPT).

Seventy-four glands from 21 patients with SHPT who underwent parathyroidectomy were evaluated for their pathological characteristics. The detection rates of parathyroid glands using ultrasound (US) and 99Tc-MIBI-SPECT/CT (MIBI) were compared. Glands were classified as either US-positive or US-negative, and MIBI-positive or MIBI-negative. Morphological and pathological differences between the positive and negative groups were systematically analysed.

The detection rates for parathyroid glands were 71% with US, 65% with MIBI, and 82% when combining both methods. US and MIBI showed similar localization accuracy in SHPT (P = .38). MIBI-positive glands had significantly larger oxyphil nodules compared with MIBI-negative glands (area: 10.92 mm² vs 3.09 mm², P < .01; area proportion: 61% vs 30%, P = .002), while no significant differences were found in chief nodules. The US-positive group had fewer and smaller chief nodules (number: 2 vs 9, P = .005; area: 1.53 mm² vs 11.08 mm², P = .033) and a higher percentage of oxyphil nodules (74% vs 33%, P = .003) compared with the US-negative group. Thirteen glands undetected by both US and MIBI had smaller oxyphil nodule areas (3.59 vs 13.24 mm²) and lower oxyphil nodule area percentages (25% vs 68%). These pathological features, including adipose infiltration, intra-gland haemorrhage, cyst formation, and calcification, showed no correlation with the gland's imaging results.

US and MIBI had similar value in preoperative localization of SHPT. Parathyroid glands with more and larger oxyphil nodules were more likely to be detected by both MIBI and US.

Kidney transplant recipients (KTRs) have an elevated fracture risk. While dual-energy X-ray absorptiometry (DXA) is commonly used to assess areal bone mineral density (aBMD), it does not capture all aspects of bone quality. We investigated the long-term effects on bone DXA-derived indices of bone quality in KTRs treated with denosumab and untreated with denosumab. This is a retrospective study, including KTRs treated with denosumab and untreated age and sex-matched KTR controls. DXA-derived parameters, including trabecular bone score (TBS) and 3D-DXA parameters, were measured at the lumbar spine and femur at baseline and after four years. Hierarchical linear models were used to assess the between-group effect of treatment over time, also adjusting for site-specific aBMDs. We enrolled 23 KTRs treated with denosumab and 23 KTR denosumab-untreated KTRs. Significant between-group differences over time in favor of the denosumab group were observed for TBS (0.843, 95%CI 0.439; 1.248,p < 0.001), trabecular volumetric BMD at the total hip (Tb.vBMD TH) (13.492, 95%CI 1.707; 25.278, p = 0.003), cortical volumetric BMD at the femoral neck (Ct.vBMD FN) (28.766, 95%CI 8.373; 49.158, p = 0.008), cortical surface BMD at the total hip (c.sBMD TH) (10.507, 95%CI 4.140; 16.873,p = 0.002), cortical surface at the femoral neck (c.sBMD FN) (8.795, 95%CI 2.818; 14.771, p = 0.006), and cortical thickness at the total hip (Ct.th.TH) (0.075, 95%CI 0.020; 0.130, p = 0.010). After adjusting for BMD, the differences on TBS and Ct.vBMD FN and c.sBMD FN remained significant. Denosumab treatment in KTRs was associated with better outcomes in terms of bone quality and geometry parameters, independent of changes in aBMD.

The kidneys produce daily about 180 liters of urine but only about 2 liters are excreted. The proximal tubule plays an important role in reabsorbing the majority of filtered urine and many metabolites such as sugars, amino acids, salts or phosphate that are contained in this large volume. Reabsorption of these important metabolites is mediated by a diverse group of highly specialized transport proteins. Another group of transport proteins in the proximal tubule is responsible for the active secretion of metabolic waste products or toxins and drugs into urine. All these transporters have in common that they are directly linked to kidney metabolism and indirectly to whole-body metabolism and functions. In recent years, it has become evident that modulation of these transporters may influence the onset, progression and consequences of kidney disease. This review summarizes recent developments in this field and discusses some examples of drugs already in clinical use or in development. The examples include inhibitors of sugar transporters (SGLT2 inhibitors) that are successfully used in patients with kidney disease, diabetes or heart failure. Likewise, indirect inhibitors (acetazolamide) of an transporter absorbing sodium in exchange for protons (NHE3) are used mostly in patients with heart failure or for prevention of high altitude disease, while direct inhibitors show promise in preclinical studies to reduce damage in episodes of acute kidney disease or high blood pressure. Modulators of transporters mediating the excretion of urate have been used in patients with gout and are also discussed to prevent kidney disease. Novel drugs in development target transporters for phosphate, amino acids, or toxin and drug excretion and may be helpful for specific conditions associated with kidney disease. The advantages and challenges associated with these (novel) drugs targeting proximal tubule transport are discussed.

The proximal tubule is responsible for reabsorbing about 60% of filtered solutes and water and is critical for the secretion of metabolic waste products, drugs and toxins. A large number of highly specialized ion channels and transport proteins belonging to the SLC and ABC transporter families are involved. Their activity is directly or indirectly linked to ATP consumption and requires large quantities of energy and oxygen supply. Moreover, the activity of these transporters is often coupled to the movement of Na+ ions thus influencing also salt and water balance, as well as transport and regulatory processes in downstream segments. Because of their relevance for systemic ion balance, for renal metabolism or for affecting regulatory processes, proximal tubule transporters are attractive targets for existing drug and for novel strategies to reduce kidney disease progression or to alleviate the consequences of decreased kidney function. In this review, the relevance of some major proximal tubule transport systems as drug targets in individuals with chronic kidney disease (CKD) is discussed. Inhibitors of the sodium-glucose cotransporter 2, SGLT2, are now part of standard therapy in patients with CKD and/or heart failure. Also, indirect inhibition of Na+/H+-exchangers by carbonic anhydrase inhibitors and uricosuric drugs have been used for decades. Inhibition of phosphate and amino acid transporters have recently been proposed as novel principles to remove excess phosphate or to protect the proximal tubule metabolically, respectively. In addition, organic cation and anion transporters involved in drug and toxin excretion may serve as targets of new drugs. The advantages and challenges associated with (novel) drugs targeting proximal tubule transport are discussed.

End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients.

We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both CBPB and NCBPB (mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality.

Out of 69 368 incident dialysis patients, 22 326, 5020, 2853 and 39 169 were included in the CBPB, NCBPB, mixed and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared with non-users. Specifically, only the CBPB group showed a reduced risk of vertebral [adjusted hazard ratio (aHR) 0.83 (0.76-0.92)], hip [aHR 0.81 (0.74-0.89)] and distal radius [aHR 0.88 (0.78-0.99)] fractures compared with non-users. This relationship presented in a time-dependent manner with fracture risk reduction in patients taking CBPB for 3-6 months [aHR 0.9 (0.83-0.99)] and ≥6 months [aHR 0.83 (0.78-0.89)], compared with those using CBPB for <3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared with non-users.

Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared with non-users.

Over the last decades, in addition to the improvement of pathophysiological knowledge regarding the role and mechanisms of action of vitamin D, there has been a progressive advancement in analytical technologies for its measurement, as well as in methodological standardization. A significant number of scientific works, meta-analyses, and guidelines have been published on the importance of vitamin D and the need for supplementation in deficient individuals. However, it appears necessary to clarify the fundamental elements related to the measurement of vitamin D (both at the strictly analytical and post-analytical levels) and the scientific evidence related to the efficacy/safety of supplementation. In particular, there is a need to discuss current recommended levels for deficiency, insufficiency and possible toxicity in the light of evidence from standardization projects. Additionally, given the important interrelations between vitamin D, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF23), the analytical issues and clinical utility of these biomarkers will be discussed.

Renal osteodystrophy (ROD) is a skeletal pathology associated with chronic kidney disease-mineral and bone disorder (CKD-MBD) that is characterized by aberrant bone mineralization and remodeling. ROD increases the risk of fracture and mortality in CKD patients. The underlying mechanisms of ROD remain elusive, partially due to the absence of an appropriate animal model. To address this gap, we established a stable mouse model of ROD using an optimized adenine-enriched diet and conducted exploratory analyses through ribonucleic acid sequencing (RNA-seq).

Eight-week-old male C57BL/6J mice were randomly allocated into three groups: control group ( n = 5), adenine and high-phosphate (HP) diet group ( n = 20), and the optimized adenine-containing diet group ( n = 20) for 12 weeks. We assessed the skeletal characteristics of model mice through blood biochemistry, microcomputed tomography (micro-CT), and bone histomorphometry. RNA-seq was utilized to profile gene expression changes of ROD. We elucidated the functions of differentially expressed genes (DEGs) using gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA). DEGs were validated via quantitative real-time polymerase chain reaction (qRT-PCR).

By the fifth week, adenine followed by an HP diet induced rapid weight loss and high mortality rates in the mouse group, precluding further model development. Mice with optimized adenine diet-induced ROD displayed significant abnormalities in serum creatinine and blood urea nitrogen levels, accompanied by pronounced hyperparathyroidism and hyperphosphatemia. The femur bone mineral density (BMD) of the model mice was lower than that of control mice, with substantial bone loss and cortical porosity. ROD mice exhibited substantial bone turnover with an increase in osteoblast and osteoclast markers. Transcriptomic profiling revealed 1907 genes with upregulated expression and 723 genes with downregulated expression in the femurs of ROD mice relative to those of control mice. Pathway analyses indicated significant enrichment of upregulated genes in the sphingolipid metabolism pathway. The significant upregulation of alkaline ceramidase 1 ( Acer1 ), alkaline ceramidase 2 ( Acer2 ), prosaposin-like 1 ( Psapl1 ), adenosine A1 receptor ( Adora1 ), and sphingosine-1-phosphate receptor 5 ( S1pr5 ) were successfully validated in mouse femurs by qRT-PCR.

Optimized adenine diet mouse model may be a valuable proxy for studying ROD. RNA-seq analysis revealed that the sphingolipid metabolism pathway is likely a key player in ROD pathogenesis, thereby providing new avenues for therapeutic intervention.

Hyperphosphatemia in advanced CKD often accompanies high PTH and FGF23 levels, impaired bone mineralization, ectopic calcifications, and increased cardiovascular risks. Novel treatments are now available to lower serum phosphorus effectively. However, safety, tolerability, and patient adherence must be evaluated to determine the best therapeutic option for hyperphosphatemia.

This review examines available treatment strategies for hyperphosphatemia in CKD patients and new emerging treatments, emphasizing the latest inhibitors of active phosphate absorption.

Despite the numerous compounds available, managing hyperphosphatemia in CKD remains challenging. While many phosphate binders exist, they often have limitations and side effects. Aluminum carries significant toxicity risks. Calcium-based binders are effective but can cause hypercalcemia and vascular calcification. Lanthanum is absorbed in the gut, but its long-term tissue deposition appears clinically irrelevant. Sevelamer reduces vascular calcification but has inconclusive data and gastrointestinal side effects. Iron-based binders are effective but may cause gastrointestinal discomfort and lack long-term outcome data. New inhibitors of intestinal phosphate absorption show promise with low pill burden but need more clinical validation. Although these newer compounds might eventually improve phosphate management in CKD patients, enhancing adherence and reducing pill burden, future studies are required to elucidate the best treatment for hyperphosphatemia.

Kidney diseases are related to the aging process. Ovarian senescence and the loss of estrogen's renoprotective effects are directly associated with a decline in renal function and indirectly with an accumulation of cardiometabolic risk factors. The latter can predispose to the development of chronic kidney disease (CKD). Conversely, CKD diagnosed during reproductive life adversely affects ovarian function.

To set out an individualized approach to menopause management in women with CKD.

Literature review and consensus of expert opinion.

Menopause hormone therapy can be given to women with CKD. The regimen should be selected on the basis of patient preference and the individual's cardiovascular risk. The dose of hormonal and non-hormonal preparations should be adjusted in accordance with the patient's creatinine clearance. The management of a postmenopausal woman with CKD should focus on lifestyle advice as well as regular monitoring of the main cardiovascular risk factors and evaluation of bone mineral density. Tailored multidisciplinary advice should be given to women with comorbidities such as diabetes, dyslipidemia, and hypertension. Management of osteoporosis should be based on the severity of the CKD.

Phosphate binders are commonly used in patients receiving kidney replacement therapy (KRT), aiming to reduce and maintain serum phosphorus. Chronic kidney disease-mineral and bone disorder has been linked to reduced lifespan and worsened quality of life. This study aims to examine the efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate in patients receiving KRT.

The data sources examined were MEDLINE (PubMed), Scopus, and the Cochrane Central Register of Controlled Clinical Trials with a search deadline of October 2023. We examined randomized controlled trials that compared sucroferric oxyhydroxide versus sevelamer carbonate in the adult population receiving KRT. We performed a meta-analysis combining the data from trials, using R-studio.

Inclusion criteria were met by five randomized trials. There was no statistically significant difference in the reduction of serum phosphorus between the two groups (MD: -0.07 mmol/L, 95% CI-random effects: -0.15 to 0.02). In the same line, a non-statistically significant difference was observed in serum i-PTH reduction between the two drugs (MD = -1.53 mg/dL, 95% CI = (-4.45, 1.4), p = 0.26, random effects model). No statistically significant difference was observed in all adverse events between the two groups (odds ratio: 1.11, 95% CI: 0.65-1.88, random effects model). Further analysis of gastrointestinal adverse events revealed that sevelamer carbonate increases gastrointestinal adverse events by up to 60% (odds ratio: 1.60, 95% CI: 1.31-1.97, common (fixed) effect model).

This meta-analysis of randomized trials showed that both drugs, sucroferric oxyhydroxide and sevelamer equally and effectively controlled serum phosphorus levels, whereas sucroferric oxyhydroxide revealed a better profile in terms of gastrointestinal adverse events. Sucroferric oxyhydroxide is a valuable option for patients receiving KRT when sevelamer carbonate is more difficult to tolerate.

Low serum parathyroid hormone (PTH) is an accepted marker for adynamic bone disease which is characterized by increased morbidity and mortality in maintenance hemodialysis (MHD) patients. In light of the known cross-sectional associations between PTH and malnutrition-inflammation syndrome, we aimed to examine the longitudinal associations between PTH with changes in nutritional and inflammatory parameters and clinical outcomes in MHD patients with low PTH.

This historical prospective and longitudinal study analyzed a clinical database at a single hemodialysis center, containing the medical records of 459 MHD patients (mean age of 71.4 ± 12.9 years old, 171 women), treated between the years 2007-2020. Bone turnover, nutritional and inflammatory marker levels were recorded at 0, 6, 12, 18, 24, 30, and 36 months followed by a median of 24 additional months of clinical observations. According to previous use of vitamin D analogs and/or calcium-sensing receptor agonists, the study participants were divided into treatment-related and disease-related groups. A linear mixed effects model was adjusted for baseline demographics and clinical parameters.

Of 459 MHD patients, 81 (17.6%) had PTH lower than 150pg/mL. Among them, 30 patients had treatment-related and 51 had disease-related low PTH. At baseline, MHD patients with treatment-related low PTH had a higher rate of diabetes compared to the disease-related group. In a linear mixed effects model, increased PTH over time was associated with decreased levels of alkaline phosphatase and C-reactive protein and with increased hemoglobin and albumin, but not the geriatric nutritional risk index at 3-year follow-up. The survival rate did not differ between the groups, with the risk of hospitalizations due to fractures being higher (HR: 4.04 with 95% CI: 1.51-10.8) in the disease-related group. Statistical significance of this association was abolished after adding C-reactive protein or alkaline phosphatase to the multivariate models.

Low serum PTH in MHD patients behaves differently depending on its cause, with a higher risk of fractures in the disease-related group. This association is dependent on inflammation. Our results should be verified in larger epidemiological studies.

Bone Health ECHO (Extension of Community Healthcare Outcomes) is a growing family of online educational programs. Its mission is to enhance delivery of best practice skeletal healthcare worldwide. Each program typically consists of a didactic lecture and discussion of clinical cases with diagnostic and treatment dilemmas. Here we present a Bone Health ECHO case of a 39-year-old man who has received hemodialysis for 12 years. This case is characterized by the development of chronic kidney disease - mineral and bone disorder (CKD-MBD) which was managed using conservative treatment to maintain phosphate and calcium levels within the reference range in spite of severe secondary hyperparathyroidism, after the patient declined parathyroidectomy. Although this patient had multiple vertebral fractures with height loss, his bone mineral density was higher than expected for his age and gradually increased over the period of observation. Whole-exome sequencing showed a heterozygous, likely pathogenic variant in LEMD3 gene (13 exon HG38, chr12:65246271dup, с.2682dup in a heterozygous state), which may explain the high bone mass phenotype. As a result of the ECHO presentation, we decided that successful treatment of CKD-MBD would be the most effective approach to managing his bone fragility. His high bone mass phenotype was most likely associated with LEMD3 gene variant. This patient does not require any specific anti-osteoporotic treatment at this time; however, he is likely to benefit from parathyroid surgery.

Objective: Osteoporosis is prevalent in patients with chronic kidney disease (CKD), with risk increasing as CKD progresses, subsequently elevating fracture risk. While previous studies have shown a link between low skeletal muscle mass and osteoporosis in the general population, there is limited research exploring this relationship in patients with advanced CKD (stages 3-5D). This study aimed to evaluate whether skeletal muscle area (SMA), as measured by abdominal CT, is correlated with bone mineral density (BMD) in advanced CKD patients beginning hemodialysis. Methods: This single-center, retrospective cohort study included patients who started maintenance hemodialysis at Daejeon St. Mary's Hospital from January 2018 to September 2021. Patients who underwent abdominal CT and BMD assessments within three months of dialysis initiation were enrolled, resulting in a sample of 87 individuals. Baseline characteristics were analyzed, with patients stratified by sex and SMA quartiles. Pearson's correlation and multivariate regression analyses were conducted to the relationship between SMA and BMD T-scores. Results: The study cohort had an average age of 65.4 years, with 52.9% of participants being male. Male patients exhibited significantly higher SMA and BMD T-scores in both the lumbar spine and femur compared to female patients. SMA showed the strongest positive correlation with BMD at both sites (lumbar spine, r = 0.424; femur, r = 0.514; p < 0.001). Multivariate analysis identified SMA as an independent positive predictor of BMD, while alkaline phosphatase (ALP) was independently associated with lower femur BMD. In the SMA-based subgroup analysis, patients with lower SMA had significantly lower BMD T-scores and a higher risk of osteoporosis. Logistic regression indicated that patients in the lowest SMA quartile had substantially increased odds of osteoporosis compared to those in the highest quartile, with an adjusted odds ratio of 30.59 (p = 0.008). Conclusions: Lower skeletal muscle mass is significantly associated with lower bone density and a higher risk of osteoporosis in advanced CKD patients initiating hemodialysis. SMA, as measured by abdominal CT, may serve as a useful marker for identifying patients at elevated osteoporosis risk in this population.

The diagnosis of sarcopenia in patients on peritoneal dialysis (PD) in clinics is limited owing to its relatively complicated process and the need for expensive assessment equipment. This study aimed to develop and validate sex-specific nomogram models based on body mass index (BMI), handgrip strength, and other routine follow-up examination indicators to predict sarcopenia in patients on PD.

From March 2023 to February 2024, 699 eligible patients were recruited from the PD centers of two tertiary hospitals in southeastern China. Routine follow-up examination indicators such as age, BMI, biochemical indicators, dialysis adequacy, handgrip strength, and five-repetition sit-to-stand test, were used as potential predictive variables. Multivariate logistic regression analyses were used to separately determine the predictive factors for men and women. Nomogram models were constructed based on the results of the multivariate analyses, which were internally validated using a bootstrap re-sampling method (n = 2000). Predictive performance was validated using a receiver operating characteristic (ROC) curve.

The prevalence of sarcopenia in Chinese patients on PD was 13.92%. The nomogram models based on multivariate analyses revealed both handgrip strength and BMI as independent predictors of sarcopenia in men and women on PD. The bootstrap-corrected area under the ROC curves of the models was 0.924 (95% CI: 0.888-0.959) and 0.936 (95% CI, 0.906-0.966) for men and women, respectively. The calibration curves of both models demonstrated high consistency between the observed and anticipated values.

The two nomogram models based on BMI and handgrip strength demonstrated good predictive ability for sarcopenia in male and female patients on PD. Subsequently, these may be used as convenient and inexpensive methods for the early detection and timely management of sarcopenia in patients on PD.

Observational studies suggest a U-shaped association between serum potassium (K⁺) levels and mortality in patients with chronic heart failure (CHF). However, the mode of death in patients with HF and K⁺ disorders remains speculative. To investigate the association between potassium disorders and the mode of death in patients with CHF. A retrospective cohort of 10,378 CHF outpatients was analyzed over an average of 3.28 ± 2.5 years. Kaplan-Meier method, Cox proportional hazards regression models, Poisson regression models adjusting for confounders, and e-value determination (e' > 1.6) were used to observe associations between potassium disorders and outcomes. Chagas etiology (p < 0.01) and triple HF therapy (p < 0.01) were associated with hyperkalemia. Atrial fibrillation was associated with hypokalemia (p < 0.01). Chronic kidney disease (CKD) (p < 0.01) and diabetes (p = 0.03) were associated with both. Hypertension was inversely related to hyperkalemia (p < 0.01); age was inversely related to hypokalemia. Associations with mortality were significant for Chagas (p < 0.01, e-value 2.16), stroke (p < 0.01, e-value 1.85), hypokalemia (p = 0.02, e-value 1.94), severe hyperkalemia (p = 0.08, e-value 1.93), and CKD (p < 0.01, e-value > 1.63). Decompensated HF or cardiogenic shock was the cause of death in 54% of patients with normokalemia, 67.8% with hypokalemia, 44.9% with mild hyperkalemia, 57.8% with moderate hyperkalemia, and 69% with severe hyperkalemia. Most patients with hypokalemia and severe hyperkalemia died from decompensated HF (p = 0.007). Data suggest hypokalemia and severe hyperkalemia, along with Chagas and CKD, are associated with death. Unexpectedly, progressive HF was the most frequent mode of death rather than arrhythmias. Further studies are needed to confirm these findings and explore the underlying mechanisms.

The management of chronic kidney disease (CKD) is a global health challenge. Elevated levels of inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), are associated with higher mortality rates in patients with CKD. Moreover, increased fibroblast growth factor 23 (FGF23) levels are a strong predictor of adverse clinical outcomes in CKD. The production of Klotho, which plays a protective role is decreased in patients with CKD. However, the relationship between FGF23-Klotho and levels of inflammatory factors in patients with CKD is unclear. This study aimed to explore the effects of changes in the FGF23-Klotho axis on inflammatory factors in patients with CKD, with a view to providing ideas for novel treatments of CKD. Clinical data were collected from 85 patients with CKD and 17 healthy subjects admitted to the Department of Nephrology of Henan Provincial People's Hospital between June-August 2023. The differences in biochemical indicators at various stages of CKD and healthy people were analyzed. Using enzyme-linked immunosorbent assay and immunohistochemistry, changes in the FGF23-Klotho axis, and their relationship with interleukin 6 (IL-6) and TNF-α were assessed. FGF23 levels gradually increased from CKD stages 1 to 5, with significant differences observed between stages 3 to 5. Klotho levels significantly decreased in CKD stages 3-5. The levels of C-reactive protein (CRP), IL-6, and TNF-α gradually increased. Overall, FGF23 expression was negatively correlated with Klotho levels and positively correlated with CRP, IL-6, and TNF-α levels. In renal tubular epithelial cells, knockdown of Klotho and overexpression of FGF23 increased the expression of inflammatory factors; however, their levels were significantly lower than that of the Klotho knockdown group. Collectively, these findings demonstrate that in CKD, the FGF23-Klotho axis promotes the expression of inflammatory cytokines in renal tubular epithelial cells.