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Background: Carotid intima-media thickness (cIMT) is a measure of atherosclerotic vascular disease and a surrogate biomarker for cardiovascular risk in patients with chronic kidney disease (CKD). Mineral and bone disorders (MBD) are complications of CKD, contributing to vascular calcification and accelerated atherosclerosis. Increased fibroblast growth factor 23 (FGF23)—the earliest detectable serum abnormality associated with CKD-MBD—has been linked with cardiovascular disease in patients with CKD. This study aimed to identify factors and analyze the relationship associated with high cIMT, high FGF23, and poor MBD control in children with CKD. Methods: A cross-sectional study was conducted in Yogyakarta, Indonesia recruiting children with CKD. The correlations and factors between cIMT, FGF23, and MBD were explored. Results: We recruited 42 children aged 2–18 years old with CKD stages 2 to 5D. There were no significant correlations between cIMT and factors including advanced CKD, use of dialysis, body mass index, hypertension, anemia, MBD, FGF23 levels, and left ventricular mass index (LVMI). Patients with advanced CKD had poorly controlled anemia, hypertension, and higher LVMI. In multivariate analysis, CKD stages, hypertension stages, the presence of MBD, and LVMI were associated with FGF23 levels (p < 0.05). Conclusions: FGF23 levels increased with CKD progression, and MBD was more prevalent in advanced kidney disease. Elevated FGF23 is potentially associated with increased MBD prevalence in late-stage CKD. A larger study is needed to confirm the factors affecting cIMT in children with CKD. [ABSTRACT FROM AUTHOR]

Introduction: The body produces fibroblast growth factor-23 (FGF-23) to maintain normal phosphate levels when hyperphosphatemia occurs. Production of FGF-23 indirectly causes hypocalcemia. Phosphate and calcium disturbances also occur in chronic kidney disease (CKD), therefore this adaptation mechanism applies. This situation; however, only manifests in the early stages of CKD; if the estimated glomerular filtration rate (eGFR) is less than 30% of normal. This adaptation is no longer adequate and levels of calcium-phosphate (Ca×P) products and FGF-23 still rise. Objectives: In this study, the correlation between both the serum levels of FGF-23 and Ca×P products in CKD was analyzed. Patients and Methods: A cross-sectional study including 78 subjects with CKD stages 3 to 5 dialysis was conducted. Serum FGF-23 levels were determined using the enzyme-linked immunosorbent assay (ELISA) method and Ca×P product levels were calculated using the formula calcium (mg/dL) × phosphate (mg/dL). The Kolmogorov-Smirnov test and Spearman's test were conducted in the statistical study. If the P value is less than 0.05, the statistical findings are significant. Results: Serum FGF-23 levels and Ca×P product levels were shown to be significantly correlated. This analysis of the two correlations was independent of age and diabetes mellitus (DM). Based on stages of CKD, serum FGF-23 levels and Ca×P product levels were discovered to be significantly correlated only at stage 5 of non-dialysis. Conclusion: Increasing serum FGF-23 levels were correlated with increased Ca×P product levels, particularly in CKD stage 5 non-dialysis subjects. This correlation was independent of age and DM. [ABSTRACT FROM AUTHOR]

Background/Objectives: Chronic kidney disease and mineral bone disorders (CKD-MBD) are frequently associated with an increased risk of both vascular calcifications (VCs) and bone fractures (BFs). The complex pathogenesis of VCs and BFs involves various factors such as calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key players, such as the vitamin K-dependent proteins (VKDPs) matrix Gla protein (MGP) and bone Gla protein (BGP), have pivotal roles both for VCs and BFs. The VIKI study highlighted that hemodialysis patients treated with calcimimetics had higher levels of total BGP and MGP compared to those untreated, suggesting a potential protective effect of these drugs on BFs and VCs beyond the beneficial effect of reducing PTH levels. Methods: ETERNITY-ITA is a multi-center, comparative effectiveness, observational, longitudinal study that will enroll 160 hemodialysis patients (80 patients treated with Etelcalcetide and 80 age- and sex-matched patients treated with calcitriol or vitamin D analogs). Nephrologists will tailor the target dose of Etelcalcetide on an individual level to achieve the KDIGO PTH target. In the Etelcalcetide-treated group, the addition of calcitriol will be allowed when required by clinical practice (for correction of hypocalcemia). Conclusions: This study will evaluate the real-world effect of Etelcalcetide on VKDP levels, such as BGP and MGP, at 3, 9, and 18 months from baseline. The resulting preservation of vascular and bone health will be assessed for the first time by examining aortic and iliac artery calcifications and vertebral fractures, respectively. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) has emerged as one of the leading noncommunicable diseases affecting >10% of the population worldwide. Bone and mineral disorders are a common complication among patients with CKD resulting in a poor life quality, high fracture risk, increased morbidity and cardiovascular mortality. According to Kidney Disease: Improving Global Outcomes, renal osteodystrophy refers to changes in bone morphology found in bone biopsy, whereas CKD‐mineral and bone disorder (CKD‐MBD) defines a complex of disturbances including biochemical and hormonal alterations, disorders of bone and mineral metabolism and extraskeletal calcification. As a result, the management of CKD‐MBD should focus on the aforementioned parameters, including the treatment of hyperphosphatemia, hypocalcemia, abnormal PTH and vitamin D levels. Regarding the bone fragility fractures, osteoporosis and renal osteodystrophy, which constitute the bone component of CKD‐MBD, anti‐osteoporotic agents constitute the mainstay of treatment. However, a thorough elucidation of the CKD‐MBD pathogenesis is crucial for the ideal personalized treatment approach. In this paper, we review the pathology and management of CKD‐MBD based on the current literature with special attention to recent advances. [ABSTRACT FROM AUTHOR]

Background: Physical exercise (PE) can regulate inflammation, cardiovascular health, sarcopenia, anaemia, and bone health in the chronic kidney disease (CKD) population. Experimental and clinical studies both help us better understand the mechanisms that underlie the beneficial effects of the exercise, especially in renal anaemia and CKD-mineral bone disorders (CKD-MBDs). Here, we summarize this evidence, exploring the biological pathways involved, locally released substances, and crosstalk between tissues, but also the shortcomings of current knowledge. Summary: Anaemia: Both in healthy and CKD subjects, PE may mimic hypoxia, inhibiting PHDs; so hydroxylate HIF-α subunits may be translocated into the nucleus, resulting in dimerization of HIF-1α and HIF-1β, recruitment of p300 and CBP, and ultimately, binding to HREs at target genes to cause activation. However, in CKD subjects acute PE causes higher levels of lactate, leading to iron restriction by upregulating hepatic hepcidin expression, while chronic PE allows an increased lactate clearance and HIF-α and VEGFα levels, stimulating both erythropoiesis and angiogenesis. CKD-MBD: PE may improve bone health decreasing bone resorption and increasing bone formation throughout at least three main pathways: (a) increasing osteoprotegerin and decreasing RANKL system; (b) decreasing cytokine levels; and (c) stimulating production of myokines and adipokines. Key Messages: Future research needs to be defined to develop evidence-based exercise guidance to provide optimal benefit for CKD using exercise interventions as adjuvant therapy for CKD-related complications such as anaemia and CKD-MBD. [ABSTRACT FROM AUTHOR]

Background Bone mineral density (BMD) predicts fracture risk in patients with chronic kidney disease (CKD) and in the general population. However, few studies have investigated risk factors for bone loss in patients with CKD. The aim of this study was to investigate whether renal function is associated with the rate of BMD decline. Methods A prospective cohort study included 1006 patients with CKD stages 2–4 between 2011 and 2016. BMD was measured using dual-energy X-ray absorptiometry at baseline and 4 years. The eGFR was measured 2–6 times during the 4-year follow-up. We analyzed the decline in bone mineral density according to CKD stage and further compared the rate of BMD decline according to eGFR trajectories at each stage. Results Advanced CKD stage was associated with a faster rate of decline in total hip BMD [stage 2 −0.23, stage 3A −0.39, stage 3B −0.80, stage 4 −1.23% change/year in men (P < .001); stage 2 −0.86, stage 3A −1.19, stage 3B −1.20, stage 4 −1.58% change/year in women (P  < .03)]. Two distinct eGFR trajectories (Class 1 stable group; Class 2 rapid decline group) were observed. The rapid decline group showed a trend toward an increased rate of decline in total hip BMD. Subgroup analysis according to eGFR trajectories revealed a significant difference in BMD decline rate between stable and rapid decline groups. Conclusions Advanced CKD stage and accelerated decline in renal function were associated with rapid BMD decline in non-dialysis patients with CKD. [ABSTRACT FROM AUTHOR]

The "2024 ACVIM Forum Research Abstract Program" is a document that provides an index of research abstracts presented at the American College of Veterinary Internal Medicine (ACVIM) Forum. The abstracts cover a wide range of topics in veterinary medicine, including cardiology, equine health, gastroenterology, hematology, hepatology, immunology, infectious disease, nephrology/urology, neurology, kidney disease, feline chronic kidney disease, urinary tract health, and cancer treatment in dogs. It is important to note that the abstracts are not peer-reviewed and the opinions expressed in them are those of the authors and may not represent the views of the ACVIM. The document serves as a valuable resource for researchers and practitioners in the field, providing insights into ongoing research studies. However, further research is needed to confirm and expand upon the findings presented in these abstracts. [Extracted from the article]

This article explores the gap between knowledge and implementation in kidney care, emphasizing the need to translate evidence-based treatments into daily practice more quickly. It discusses the global issue of undiagnosed and untreated kidney disease, highlighting the importance of early diagnosis and optimal care to prevent complications. The text addresses barriers at various levels and calls for policies and improvements in healthcare systems to address these gaps. It emphasizes the importance of collaborative care models, involving various stakeholders, and the need for innovation and patient empowerment to achieve health equity. [Extracted from the article]

Chronic kidney disease mineral bone disorder (CKD-MBD) is a complex clinical syndrome responsible for the accelerated cardiovascular mortality seen in individuals afflicted with CKD. Current approaches to therapy have failed to improve clinical outcomes adequately, likely due to targeting surrogate biochemical parameters as articulated by the guideline developer, Kidney Disease: Improving Global Outcomes (KDIGO). We hypothesized that using a Systems Biology Approach combining machine learning with mathematical modeling, we could test a novel approach to therapy targeting the abnormal movement of mineral out of bone and into soft tissue that is characteristic of CKD-MBD. The mathematical model describes the movement of calcium and phosphate between body compartments in response to standard therapeutic agents. The machine-learning technique we applied is reinforcement learning (RL). We compared calcium, phosphate, parathyroid hormone (PTH), and mineral movement out of bone and into soft tissue under four scenarios: standard approach (KDIGO), achievement of KDIGO guidelines using RL (RLKDIGO), targeting abnormal mineral flux (RLFLUX), and combining achievement of KDIGO guidelines with minimization of abnormal mineral flux (RLKDIGOFLUX). We demonstrate through simulations that explicitly targeting abnormal mineral flux significantly decreases abnormal mineral movement compared with standard approach while achieving acceptable biochemical outcomes. These investigations highlight the limitations of current therapeutic targets, primarily secondary hyperparathyroidism, and emphasize the central role of deranged phosphate homeostasis in the genesis of the CKD-MBD syndrome. NEW & NOTEWORTHY: Artificial intelligence is a powerful tool for exploration of complex processes but application to clinical syndromes is challenging. Using a mathematical model describing the movement of calcium and phosphate between body compartments combined with machine learning, we show the feasibility of testing alternative goals of therapy for Chronic Kidney Disease Mineral Bone Disorder while maintaining acceptable biochemical outcomes. These simulations demonstrate the potential for using this platform to generate and test hypotheses in silico rapidly, inexpensively, and safely. [ABSTRACT FROM AUTHOR]

Vascular calcification is a crucial risk factor that affects the incidence and mortality of cardiovascular disease in chronic kidney disease patients. Modern medicine relies on calcium-phosphorus binding agents, calcium mimetics, active vitamin D, and hemodialysis to prevent and treat vascular calcification, however, their efficacy is unsatisfactory and adverse reactions often occur. Medical plant therapy can act as an integrative regulator in patients with chronic kidney disease-associated vascular calcification, which can significantly improve patients' symptoms, but its specific mechanism has not been fully elucidated yet. In this paper, we reviewed the domestic and international theoretical studies on the pathogenesis mechanism of chronic kidney disease-associated vascular calcification in recent years, summarized eight active ingredients of medicinal plants as well as four compound formulas for improving chronic kidney disease-associated vascular calcification, and explored the mechanism of action of herbal medicine, which will provide a new strategy for promoting the prevention and treatment of vascular calcification. [ABSTRACT FROM AUTHOR]

Purpose: Mineral bone disorder associated with chronic kidney disease (CKD-MBD) frequently persists after kidney transplantation (KTx), being due to pre-existing CKD-MBD, immunosuppressive therapies, and post-KTx hypophosphatemia. This study aimed to evaluate bone biomarkers and microarchitecture using high resolution peripheral quantitative computed tomography (HR-pQCT) at the time of KTx and 6 months thereafter and to compare these results with those of matched healthy controls (HC). Methods: This study presented the single-center subgroup of patients aged between 10 and 18 years included in the prospective "Bone Microarchitecture in the Transplant Patient" study (TRANSOS-NCT02729142). Patients undergoing a first KTx were matched (1:2) with HC from the "Vitamin D, Bones, Nutritional and Cardiovascular Status" cohort (VITADOS) on sex, pubertal stage, and age. Results: At a median (interquartile range, IQR) age of 15 [13; 16] years, 19 patients (6 girls, 7 pre-emptive KTx, 7 steroid-sparing immunosuppressive strategies) underwent a first KTx, with a median [IQR] parathyroid hormone level of 1.9 [1.4; 2.9] the upper limit of normal (ULN). Higher total and trabecular bone densities, along with superior trabecular microarchitecture, were observed at KTx compared to HC. Six months post-KTx, patients had significantly impaired trabecular parameters at the radius, while results were not significantly different at the weight-bearing tibia, neither cortical parameters at both sites. Six months post-KTx, 6 (32%) patients still present with metabolic acidosis, 10 (53%) persistent hyperparathyroidism (always < 2 ULN), and 5 (26%) elevated FGF23 levels; 11 (58%) received phosphate supplementation. Conclusions: Bone density and microarchitecture at the time of KTx were superior compared to HC, but radial trabecular bone microarchitecture impairment observed 6 months post-KTx may reflect subtle albeit present post-KTx CKD-MBD. What is Known? • Mineral bone disorder associated with chronic kidney disease (CKD-MBD) frequently persists after kidney transplantation (KTx) and is associated with morbidity. However, biochemical parameters and dual X-ray absorptiometry (DXA) are poor predictors of the underlying bone disease. What is new? • The present study on 19 adolescent KTx recipients with adequate CKD-MBD control at the time of KTx reveals no significant bone disease compared to matched healthy controls. Microarchitecture impairment observes 6 months post-KTx may reflect subtle, albeit present, post-KTx CKD-MBD. [ABSTRACT FROM AUTHOR]

For several years, alpha klotho has been considered as a candidate biomarker in chronic kidney disease (CKD), progression of CKD and CKD mineral bone disorders (CKD-MBD). The evidence on the relationship between klotho and kidney function is controversial in some areas. The aim of the study was to identify the influence of age, sex and breed on urinary alpha klotho, values in the early stages of CKD within the studied population and determine a reference interval in a group of healthy dogs. Significantly higher values were measured in older dogs over 6 years old (p = 0.026, p = 0.0007) and in the breed German Shepherd than Belgian Shepherd (p = 0.0401). On the basis of sex and in small breed dogs, no significant differences were noted. In dogs with CKD stage 2, alpha klotho values were significantly lower (p = 0.0135) than in healthy dogs. Within the studied population, a reference interval for urinary klotho to creatinine ratio (UrKl/Cr) was determined in the range of 3.94–23.55 pg/gCr. Since our findings show that alpha klotho is associated with older age, we assume that this may have influenced the results in the group of dogs with CKD stage 1 due to the presence of predominantly old dogs in this group. Future studies would be needed to consider age as a factor affecting urinary alpha klotho in dogs with CKD. [ABSTRACT FROM AUTHOR]

Background: Recently, chronic kidney disease (CKD)-mineral and bone disorder (MBD) has become one of common complications occurring in CKD patients. Therefore, development of a new treatment for CKD-MBD is very important in the clinic. In China, Fucoidan (FPS), a natural compound of Laminaria japonica has been frequently used to improve renal dysfunction in CKD. However, it remains elusive whether FPS can ameliorate CKD-MBD. FGF23-Klotho signaling axis is reported to be useful for regulating mineral and bone metabolic disorder in CKD-MBD. This study thereby aimed to clarify therapeutic effects of FPS in the CKD-MBD model rats and its underlying mechanisms in vivo and in vitro, compared to Calcitriol (CTR). Methods: All male rats were divided into four groups: Sham, CKD-MBD, FPS and CTR. The CKD-MBD rat models were induced by adenine administration and uninephrectomy, and received either FPS or CTR or vehicle after induction of renal injury for 21 days. The changes in parameters related to renal dysfunction and renal tubulointerstitial damage, calcium-phosphorus metabolic disorder and bone lesion were analyzed, respectively. Furthermore, at sacrifice, the kidneys and bone were isolated for histomorphometry, immunohistochemistry and Western blot. In vitro, the murine NRK-52E cells were used to investigate regulative actions of FPS or CTR on FGF23-Klotho signaling axis, ERK1/2-SGK1-NHERF-1-NaPi-2a pathway and Klotho deficiency. Results: Using the modified CKD-MBD rat model and the cultured NRK-52E cells, we indicated that FPS and CTR alleviated renal dysfunction and renal tubulointerstitial damage, improved calcium-phosphorus metabolic disorder and bone lesion, and regulated FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi-2a pathway in the kidney. In addition, using the shRNA-Klotho plasmid-transfected cells, we also detected, FPS accurately activated ERK1/2-SGK1-NHERF-1-NaPi-2a pathway through Klotho loss reversal. Conclusion: In this study, we emphatically demonstrated that FPS, a natural anti-renal dysfunction drug, similar to CTR, improves renal injury-related calcium-phosphorus metabolic disorder and bone abnormality in the CKD-MBD model rats. More importantly, we firstly found that beneficial effects in vivo and in vitro of FPS on phosphorus reabsorption are closely associated with regulation of FGF23-Klotho signaling axis and ERK1/2-SGK1-NHERF-1-NaPi-2a pathway in the kidney. This study provided pharmacological evidences that FPS directly contributes to the treatment of CKD-MBD. [ABSTRACT FROM AUTHOR]

Background The longitudinal changes in hip-bone microstructures and estimated bone strength in dialysis patients, and the impact of chronic kidney disease–mineral and bone disorder (CKD-MBD) biomarkers on these changes, remain insufficiently explored. Methods This retrospective study examined changes in cortical and trabecular bone compartments and estimated bone-strength indices, obtained by using 3D-SHAPER software, in the hip regions of 276 dialysis patients over up to 2.5 years. We used multivariate mixed models to investigate the associations between time-dependent CKD-MBD biomarkers and bone health metrics. Results There was a significant decrease in areal bone mineral density (aBMD), integral volumetric BMD (vBMD), trabecular vBMD, cortical thickness and cortical surface BMD (sBMD). Similar deteriorations were found in estimated bone-strength indices [cross-sectional area (CSA), cross-sectional moment of inertia (CSMI), section modulus (SM) and buckling ratio]. Neither serum calcium nor phosphate levels were significantly associated with changes in three-dimensional parameters or estimated bone-strength indices. In contrast, serum alkaline phosphatase levels showed a significant inverse correlation with aBMD and CSA. The intact-parathyroid hormone (i-PTH) was significantly inversely correlated with aBMD, integral vBMD, trabecular vBMD, cortical thickness, cortical vBMD, CSA, CSMI and SM. When applying the KDIGO criteria as a sensitivity analysis, the higher PTH group had significant negative associations with aBMD, integral vBMD, cortical vBMD, cortical thickness and cortical sBMD. Notably, the lower PTH group showed a positive significant correlation with integral vBMD and trabecular vBMD. Conclusions Elevated PTH, not low PTH, was associated with deterioration of hip-bone microstructures. Better management of PTH levels may play a crucial role in the hip-bone microstructure in dialysis patients. [ABSTRACT FROM AUTHOR]

In people with chronic kidney disease (CKD), the physiology of vitamin D is altered and leads to abnormalities in bone and mineral metabolism which contribute to CKD mineral and bone disorder (CKD-MBD). Observational studies show an association between vitamin D deficiency and increased risk of mortality, cardiovascular disease and fracture in CKD. Although vitamin D therapy is widely prescribed in people with CKD, clinical trials to date have failed to demonstrate a clear benefit of either nutritional vitamin D supplementation or active vitamin D therapy in improving clinical outcomes in CKD. This review provides an updated critical analysis of recent trial evidence on vitamin D therapy in people with CKD. [ABSTRACT FROM AUTHOR]

Managing mineral bone disease (MBD) could reduce cardiovascular risk and improve the survival of dialysis patients. Our study focuses on the impact of calcium bath exposure in dialysis patients by comparing peritoneal dialysis patients (PD, intervention group) and hemodialysis patients (HD, control group). We assessed various factors, including calcium, phosphorus, magnesium, PTH, vitamin D 25-OH, C-terminal telopeptide (CTX), and FGF-23 levels, as well as the calcium bath six hours before the blood sample and the length of daily calcium exposure. We enrolled 40 PD and 31 HD patients with a mean age of 68.7 ± 13.6 years. Our cohort had median PTH and FGF-23 levels of 194 ng/L (Interquartile range [IQR] 130-316) and 1296 pg/mL (IQR 396-2698), respectively. We identified the length of exposure to a 1.25 mmol/L calcium bath, phosphate levels, and CTX as independent predictors of PTH (OR 0.279, p = 0.011; OR 0.277, p = 0.012; OR 0.11, p = 0.01, respectively). In contrast, independent predictors of FGF-23 were phosphate levels (OR 0.48, p < 0.001) and serum calcium levels (OR 0.25, p = 0.015), which were affected by the calcium bath. These findings suggest that managing dialysate calcium baths impacts phosphaturic hormones and could be a critical factor in optimizing CKD-MBD treatment in PD patients, sparking a new avenue of research and potential interventions. [ABSTRACT FROM AUTHOR]

Background: Promoting physical activity among young individuals with cardiovascular disease (CVD) risk factors such as hypertension, diabetes, or chronic kidney disease can lower systolic blood pressure (BP). We sought to determine whether a 6-month intervention using a physical activity tracker was feasible and effective, compared with usual care. Methods: Participants were recruited at a single academic medical center. Those aged 8–30 years were randomized in a 2:1 ratio to either the intervention (use of a Fitbit physical activity tracker coupled with feedback regarding the participant's step count) or usual care. The primary feasibility outcomes were screening-to-enrollment ratio and 6-month retention rates; the primary clinical outcome was a change in systolic BP from 0–6 months. Results: Sixty-three participants were enrolled (57% male; mean age: 18 ± 4 years). The screening-to-enrollment ratio was 1.8:1. Six-month retention was 62% in the intervention group and 86% in the control group (p = 0.08). Mean change in systolic BP in the intervention group was not significantly different from the control group at 6 months (− 2.3 mmHg; 95% CI − 6.5, 1.8 vs. 3.0 mmHg; 95% CI − 2.5, 8.4, respectively, p = 0.12). Conclusions: Among children and young adults at elevated CVD risk, the use of a physical activity tracker coupled with tailored feedback regarding their step count progress was feasible but not sustained over time. Physical activity tracker use did not have a statistically significant effect on BP after 6 months. Augmented strategies to mitigate risk in young patients at high risk for early-onset CVD should be explored. This trial is registered at ClinicalTrials.gov (NCT03325426). [ABSTRACT FROM AUTHOR]

The choice of dialysate buffer in hemodialysis is crucial, with acetate being widely used despite complications. Citrate has emerged as an alternative because of its favorable effects, yet concerns persist about its impact on calcium and magnesium levels. This study investigates the influence of citrate dialysates (CDs) with and without additional magnesium supplementation on CKD-MBD biomarkers and assesses their ability to chelate divalent metals compared to acetate dialysates (ADs). A prospective crossover study was conducted in a single center, involving patients on thrice-weekly online hemodiafiltration (HDF). The following four dialysates were compared: two acetate-based and two citrate-based. Calcium, magnesium, iPTH, iron, selenium, cadmium, copper, zinc, BUN, albumin, creatinine, bicarbonate, and pH were monitored before and after each dialysis session. Seventy-two HDF sessions were performed on eighteen patients. The CDs showed stability in iPTH levels and reduced post-dialysis total calcium, with no significant increase in adverse events. Magnesium supplementation with CDs prevented hypomagnesemia. However, no significant differences among dialysates were observed in the chelation of other divalent metals. CDs, particularly with higher magnesium concentrations, offer promising benefits, including prevention of hypomagnesemia and stabilization of CKD-MBD parameters, suggesting citrate as a viable alternative to acetate. Further studies are warranted to elucidate long-term outcomes and optimize dialysate formulations. Until then, given our results, we recommend that when a CD is used, it should be used with a 0.75 mmol/L Mg concentration rather than a 0.5 mmol/L one. [ABSTRACT FROM AUTHOR]

The article discusses the global burden of kidney disease and the gaps in kidney care, particularly in low- and middle-income countries. It highlights the high death rates and economic burden associated with chronic kidney disease (CKD) and the disparities in prevention, early detection, diagnosis, and treatment. The text emphasizes the importance of integrating kidney care into national non-communicable disease strategies and strengthening health systems. It also discusses the challenges in managing CKD, including the need for regulation and monitoring of drug manufacturing, the importance of real-world data, and strategies to improve CKD management. The article addresses the cost and availability of medication for individuals with kidney disease, highlighting the paradoxical situation in high-income countries and the catastrophic health expenditure in low- and middle-income countries. It calls for pharmaceutical companies to ensure diverse participation in research studies and fair pricing of effective drugs. The article also emphasizes the need to focus on children with kidney diseases and suggests strategies to improve kidney disease care, including the use of polypills and digital technologies. It concludes with a call to action to address barriers and disparities in access to diagnosis and treatment and to ensure equitable kidney care worldwide. [Extracted from the article]

Introduction: Chronic kidney disease-mineral and bone disease (CKD-MBD) is a complication of chronic kidney disease (CKD) involving derangements in serum calcium and phosphate. This study aims to evaluate hypo- and hypercalcaemia and their associated outcomes among pre-dialysis CKD patients.Methods: A retrospective cohort study was performed and included all adult CKD stage 4-stage 5 patients who were on treatment for CKD-MBD between 2016 and 2017. Each patient was followed up for 3 years. Hypo- and hypercalcaemia were defined as serum corrected calcium (Ca2+) <2.10 and >2.46 mmol/L, respectively. Outcomes evaluated included all-cause mortality and cardiovascular events. Multivariate Cox regression analysis was done to evaluate the association of hypocalcaemia and/or hypercalcaemia with the clinical outcomes. Severity of hypocalcaemia episode was classified as 'mild' (Ca2+: between 1.90 and 2.10 mmol/L) and 'severe' (Ca2+: <1.90 mmol/L). Severity of hypercalcaemia was classified as 'mild' (Ca2+: between 2.47 and 3.00 mmol/L), moderate (Ca2+: between 3.01 and 3.50 mmol/L) and severe (Ca2+: >3.50 mmol/L).Results: Of the 400 patients, 169 (42.2%) and 94 (23.5%) patients experienced hypocalcaemia and hypercalcaemia, respectively. Severe hypocalcaemia was more prevalent in CKD stage 5 compared to CKD stage 4 (96 [40.5%] vs. 36 [25.9%], P = 0.004). Results from multivariate analyses after adjustment showed that hypocalcaemia and/or hypercalcaemia were not associated with all-cause mortality (P > 0.05) or the occurrence of cardiovascular events (P > 0.05).Conclusion: Hypocalcaemia and hypercalcaemia episodes were prevalent among pre-dialysis CKD patients. Studies with longer follow-up durations are required to assess the effects of calcium derangements on clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Renal osteodystrophy is a serious complication of advanced chronic kidney disease (CKD). It predisposes the patient to fragility fracture and an increased risk of mortality. Case Report: We present the case of a 50-year-old male patient with stage 4 CKD and consequent renal osteodystrophy, who presented with a history of a recent provoked seizure, a severe electrolyte imbalance, and excruciating pain in the hip region. He had no history of a fall or trauma. A radiographic evaluation confirmed the rare finding of a bilateral femoral neck fracture. Upon stabilizing the patient, he was surgically managed with a bilateral hemiarthroplasty. A postoperative radiograph revealed a well-fixed prosthesis with no post-surgical complications. The patient had a full recovery. At the last follow-up visit, the patient was fully functional and had resumed normal activities. Conclusions: This is a rare report with unusual mechanism of injury, involving a case of bilateral femoral neck fragility fractures, secondary to renal osteodystrophy in a stage 4 CKD patient. It draws the attention of medical care providers to the high risk of femoral fragility fractures that are secondary to renal osteodystrophy. Hemiarthroplasty is a safe and highly efficacious surgical option for managing such cases. This case also reiterates the dire need for greater public awareness and knowledge of CKD. Early diagnosis and treatment can substantially mitigate the associated morbidity and mortality. [ABSTRACT FROM AUTHOR]

The kidneys play an important role in the regulation of phosphate and calcium balance and serum concentrations, coordinated by fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D (1,25D). In patients with chronic kidney disease (CKD), this regulation is impaired, leading to CKD-mineral and bone disorder (CKD-MBD), characterized by decreased 1,25D, elevated FGF23, secondary hyperparathyroidism, hyperphosphatemia, bone abnormalities, and vascular and soft-tissue calcification. While bone abnormalities associated with CKD-MBD, known as renal osteodystrophy, have been recognized as the most typical interaction between the kidney and bone, a number of other kidney–bone interactions have been identified, for which our knowledge of the pathogenesis of CKD-MBD has played an important role. This article summarizes recent findings on CKD-MBD and explores the crosstalk between the kidney and bone from the perspective of CKD-MBD. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of paricalcitol on bone metabolism and transforming growth factor-β（ TGF-β）/bone morphogenetic protein-7（ BMP-7）/Smad signaling pathway in rats with renal osteodystrophy（ ROD）. Methods: Total 90 rat were randomly divided into 6 groups: control group， model group， paricalcitol low-dose（ 0.2 μg/kg） group， paricalcitol medium-dose group （0.4 μg/kg） group， paricalcitol high-dose（ 0.8 μg/kg） group， calcitriol（ 10 μg/kg） group， with 15 rats in each group. Rats in control group were fed with ordinary feed， and rats in other groups were fed with feed containing adenine to induce the establishment of ROD model. After grouping and drug treatment， the blood urea nitrogen （BUN） and blood creatinine （Scr） levels， blood calcium and blood phosphorus levels， femoral bone mineral density （BMD）， maximum load， elasticity modulus and yield load， serum inflammatory fac-tors IL-6 and IL-17 levels of each group were measured； and the expression of TGF-β/BMP-7/Smad pathway protein in bone tissue was detected with Western blot. Another 45 rats were randomly divided into 3 groups: paricalcitol （0.8 μg/kg） group， TGF-β inhibition （LY2157299， 150 mg/kg） group， paricalcitol （0.8 μg/kg）+TGF-β inhibition （LY2157299，150 mg/kg） group， with 15 rats in each group. ROD model was established with the same method. After drug treatment， the renal function indexes and femoral biomechanical indexes were measured. Results: Compared with control group， the blood calcium level， BMD， elastic modulus， maximum load， yield load， bone tissue TGF-β/BMP-7/Smad pathway proteins TGF-β and BMP-7 expressions， p-Smad3/Smad3 were significantly re-duced in the model group （P<0.05）， the BUN and Scr levels， blood phosphorus level， and serum IL-6 and IL-17 levels were signifi-cantly increased （P<0.05）. Compared with the model group， the blood calcium level， BMD， elastic modulus， maximum load， yield load， bone tissue TGF-β/BMP-7/Smad pathway protein TGF-β and BMP-7 expression， p-Smad3/Smad3 were significantly increased in the paricalcitol low， medium and high dose groups and calcitriol group （P<0.05）， the BUN and Scr levels， blood phosphorus level， and serum IL-6 and IL-17 levels were significantly reduced， and paricalcitol groups showed a dose-dependent relationship （P<0.05）， there was no significant difference in the indexes of rats in high-dose paricalcitol group and calcitriol group （P>0.05）. Compared with paricalcitol+TGF-β inhibition group， the renal function indexes BUN， SCR and blood phosphorus level in paricalcitol group were de-creased（ P<0.05）， while the blood calcium level， BMD， elastic modulus， maximum load and yield load were increased（ P<0.05）. In TGF-β inhibition group， the renal function indexes BUN， SCR and blood phosphorus levels were increased（ P<0.05）， while the blood calcium level， BMD， elastic modulus， maximum load and yield load were decreased （P<0.05）. Conclusion: Paricalcitol can activate the TGF-β/BMP-7/Smad signaling pathway， inhibit inflammation， improve renal function and abnormal bone metabolism in ROD rats， reduce blood phosphorus level， increase blood calcium level and bone density， repair bone biomechanics， and improve the symptoms of osteodystrophy. [ABSTRACT FROM AUTHOR]

Excessive dietary phosphorus is a concern among patients with kidney failure undergoing dialysis treatment because it may contribute to hyperparathyroidism and hyperphosphatemia. A long‐standing but untested component of the low‐phosphorus diet is the promotion of refined grains over whole grains. This paper reviews the scientific premise for restricting whole grains in the dialysis population and estimates phosphorus exposure from grain products based on three grain intake patterns modeled from reported intakes in the general US population, adjusting for the presence of phosphorus additives and phosphorus bioavailability: (1) standard grain intake, (2) 100% refined grain intake, and (3) mixed (50/50 whole and refined grain) intake. Although estimated phosphorus exposure from grains was higher with the mixed grain pattern (231 mg/day) compared to the 100% refined grain pattern (127 mg/day), the amount of additional phosphorus from grains was relatively low. Given the lack of strong evidence for restricting whole grains in people with CKD, as well as the potential health benefits of whole grains, clinical trials are warranted to address the efficacy and health impact of this practice. [ABSTRACT FROM AUTHOR]

Background Fibroblast growth factor 23 (FGF-23) and other markers of chronic kidney disease–mineral and bone disorder (CKD-MBD) provide valuable insights into disease processes, treatment options and patient prognosis. However, limited research has explored potential associations with ethnicity or season, particularly in multi-ethnic populations residing in high-latitude regions. Methods We evaluated CKD-BMD markers in a diverse cohort of CKD patients, who were participants of The CANADIAN AIM to PREVENT (the CAN AIM to PREVENT) study. FGF-23, calcium, phosphate, 25-hydroxyvitamin D (25-OHD) and intact parathyroid hormone (iPTH) in 1234 participants with pre-dialysis CKD (mean estimated glomerular filtration rate: 41.8 ± 14.3 mL/min) were analyzed. Mixed-effects general linear regression models adjusted for demographic and biological factors were used to compare repeated measurements across patient groups categorized by ethnicity (East Asian, White, South Asian, Black, Southeast Asian) and seasons. Results Compared with other groups, White participants exhibited 8.0%–18.5% higher FGF-23 levels, Black participants had 0.17–0.32 mg/dL higher calcium levels, White participants had 10.0%–20.1% higher 25-OHD levels, South Asian participants had 7.3%–20.1% lower 25-OHD levels and Black participants had 22.1–73.8% higher iPTH levels, while East Asian participants had 10.7%–73.8% lower iPTH levels. Seasonal variations were also observed. FGF-23 levels were 11.9%–15.5% higher in summer compared with other seasons, while calcium levels were 0.03–0.06 mg/dL lower in summer. 25-OHD levels were 5.6%–10.6% higher in summer and autumn compared with other seasons. Conclusions This study shows that FGF-23 and CKD-MBD markers in a Canadian pre-dialysis CKD cohort vary independently by ethnicity and season. Further research is needed to understand the reasons and clinical significance of these findings. [ABSTRACT FROM AUTHOR]

Context The impairment of bone microarchitecture is a key determinant of skeletal fragility in patients with chronic kidney disease (CKD). The trabecular bone score (TBS) has been developed as a reliable noninvasive index of bone quality. However, its utility in this setting is still debated. Objective The aim of this systematic review and meta-analysis was to summarize the available evidence about TBS as a marker of skeletal fragility across the spectrum of CKD. Methods PubMed/Medline, EMBASE, and Cochrane Library databases were systematically searched until July 2023 for studies reporting data about TBS in patients with CKD. Effect sizes were pooled through a random-effect model. Results Compared to controls, lower TBS values were observed in CKD patients not on dialysis (−0.057, 95%CI:[−0.090, −0.024], P <.01), in dialysis patients (−0.106, 95%CI:[−0.141, −0.070], P <.01), and in kidney transplant recipients (KTRs) (−0.058, 95%CI:[−0.103, −0.012], P =.01). With respect to fracture risk, TBS was able to predict incident fractures in nondialysis patients at unadjusted analyses (hazard ratio [HR] per SD decrease: 1.45, 95%CI:[1.05, 2.00], P =.02), though only a nonsignificant trend was maintained when fully adjusting the model for FRAX® (HR = 1.26, 95%CI:[0.88, 1.80], P =.21). Dialysis patients with prevalent fractures had lower TBS values compared to unfractured ones (−0.070, 95% CI:[−0.111, −0.028], P <.01). Some studies supported a correlation between TBS and fracture risk in KTRs, but results could not be pooled due to the lack of sufficient data. Conclusion CKD patients are characterized by an impairment of bone microarchitecture, as demonstrated by lower TBS values, across the whole spectrum of kidney disease. TBS can also be helpful in the discrimination of fracture risk, with lower values being correlated with a higher risk of prevalent and incident fractures. [ABSTRACT FROM AUTHOR]

Calcitriol and calcimimetics are used to treat hyperparathyroidism secondary to chronic kidney disease (CKD). Calcitriol administration and the subsequent increase in serum calcium concentration decrease parathyroid hormone (PTH) levels, which should reduce bone remodeling. We have previously reported that, when maintaining a given concentration of PTH, the addition of calcimimetics is associated with an increased bone cell activity. Whether calcitriol administration affects bone cell activity while PTH is maintained constant should be evaluated in an animal model of renal osteodystrophy. The aim of the present study was to compare in CKD PTH‐clamped rats the bone effects of calcitriol and calcimimetic administration. The results show that the administration of calcitriol and calcimimetic at doses that induced a similar reduction in PTH secretion produced dissimilar effects on osteoblast activity in 5/6 nephrectomized (Nx) rats with secondary hyperparathyroidism and in Nx rats with clamped PTH. Remarkably, in both rat models, the administration of calcitriol decreased osteoblastic activity, whereas calcimimetic increased bone cell activity. In vitro, calcitriol supplementation inhibited nuclear translocation of β‐catenin and reduced proliferation, osteogenesis, and mineralization in mesenchymal stem cells differentiated into osteoblasts. In conclusion, besides the action of calcitriol and calcimimetics at parathyroid level, these treatments have specific effects on bone cells that are independent of the PTH level. [ABSTRACT FROM AUTHOR]

Chronic kidney disease–mineral and bone disorder (CKD-MBD) frequently occurs in hemodialysis patients and is a common cause of osteoporosis. Regular dual-energy X-ray absorptiometry (DXA) scans are used to monitor these patients, but frequent, cost-effective, and low-dose alternatives are needed. This study proposes an automatic CKD-MBD assessment model using histogram equalization and a squeeze-and-excitation block-based residual U-Net (SER-U-Net) with hand diagnostic radiography for preliminary classification. The process involves enhancing image contrast with histogram equalization, extracting features with the SE-ResNet model, and segmenting metacarpal bones using U-Net. Ultimately, a correlation analysis is carried out between the calculated dual metacarpal cortical percentage (dMCP) and DXA T-scores. The model's performance was validated by analyzing clinical data from 30 individuals, achieving a 93.33% accuracy in classifying bone density compared to DXA results. This automated method provides a rapid, effective tool for CKD-MBD assessment in clinical settings. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to investigate the impact of the use of varying input parameters on resulting bone plasma clearance (Ki) and other kinetic modelling parameters in a group of patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). Methods: Raw PET/CT data and blood data were systematically analyzed using five different VOIs for the input functions in the left ventricle and in the thoracic aorta. Standardized VOIs were placed in four thoracic vertebrae and the results pooled and averaged. The basic image-derived input functions (IDIFs) were corrected for partial volume effect and spill-over and modified by substitution of the terminal image exponential with the corresponding plasma-exponentials derived from blood samples. Ki was then calculated using both a non-linear regression (NLR) analysis and a graphical Patlak analysis and compared. Results: Our original results were reproducible with an inter-observer difference of approximately 6%. The correction factors varied with the VOI volumes from 0.73 ± 0.17 for the largest LV-VOI (48.7 ± 25.3 cm³) to 0.99 ± 0.10 for the AOVOI (3.4 ± 1.2 cm³). The mean NLR-Ki results varied between 0.0378 ± 0.0112 and 0.0432 ± 0.0095 ml/min ml-1 with a fixed vB and 0.0408 ± 0.0111 and 0.045 ± 0.0102 ml/min ml-1 with a free-fitted vB. The corresponding Patl-Kiresults varied between 0.0302 ± 0.0071 and 0.0325 ± 0.0070 ml/min ml-1, having lesser differences and variances. The input functions with least variance and mean differences compared with NLR results were derived from the left ventricle with a VOI volume of 19.2 ± 11.3 cm³ corrected for PVE and Bg with a mean Ki-difference: 0.0097 ± 0.0370 ml/min ml-1 and 95% confidence limits (-0.023 to 0.004). Conclusions: Our results indicated that a VOI with a volume of approximately 20 cm³ with a correction factor of 0.83 ± 0.13 results in Patlak results with the least variance and difference compared with the NLR results. The use of free-fitted vB in the NLR analysis showed the most robust results in all input series. The Patlak results were in comparison generally lower than the NLR results (-17.3% to -23.4%) but very robust across the various input series and with results comparable to previously published data and are therefore recommended for future analysis. [ABSTRACT FROM AUTHOR]

Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes. [ABSTRACT FROM AUTHOR]

The global derangement of mineral metabolism that accompanies chronic kidney disease (CKD-MBD) is a major driver of the accelerated mortality for individuals with kidney disease. Advances in the delivery of dialysis, in the composition of phosphate binders, and in the therapies directed towards secondary hyperparathyroidism have failed to improve the cardiovascular event profile in this population. Many obstacles have prevented progress in this field including the incomplete understanding of pathophysiology, the lack of clinical targets for early stages of chronic kidney disease, and the remarkably wide diversity in clinical manifestations. We describe in this review a novel approach to CKD-MBD combining mathematical modelling of biologic processes with machine learning artificial intelligence techniques as a tool for the generation of new hypotheses and for the development of innovative therapeutic approaches to this syndrome. Clinicians need alternative targets of therapy, tools for risk profile assessment, and new therapies to address complications early in the course of disease and to personalize therapy to each individual. The complexity of CKD-MBD suggests that incorporating artificial intelligence techniques into the diagnostic, therapeutic, and research armamentarium could accelerate the achievement of these goals. [ABSTRACT FROM AUTHOR]

Fanconi's syndrome (FS) is characterized by type-2 renal tubular acidosis, short stature, and renal rickets, along with glycosuria, aminoaciduria, hypophosphaturia, and urinary bicarbonate wasting. The genetic form of FS has been linked to HNF4A variants. Although additional clinical features such as hearing impairment have recently been associated with HNF4A-linked FS, its ocular manifestation has not been described. Presenting a case of a 5-year-old male child with bilateral progressive corneal opacification and the presence of bilateral greyish-white deposits in the interpalpebral region since infancy. A next-generation sequencing (NGS)-based genetic testing was performed for the child followed by parental genetic testing for the identified variant. Furthermore, relevant works of literature were reviewed related to this condition. Detailed corneal findings showed a bilateral band-shaped keratopathy (BSK) in the patient. Physical and systemic findings showed signs consistent with FS. Sequencing analysis revealed a novel heterozygous c.635C>T, (p.Pro212Leu) variant in the HNF4A gene in the proband and mother, while the father had a normal genotype. Our case highlights the occurrence of BSK in an exceptionally rare manifestation of hereditary FS linked to HNF4A gene variant. The variant exists both in proband and asymptomatic mother. Therefore, the variable penetrance which is known to exist in HNF4A is acknowledged in this context. This report suggests the first documented instance establishing a plausible connection between BSK and HNF4A-associated FS, characterized by the variable penetrance attributed to the HNF4A gene. [ABSTRACT FROM AUTHOR]

Osteoporosis (OP) is a common bone metabolic disease. With the increase of aging in China, OP is a public health problem that is widely concerned in China today. Fructus ligustri lucidi (FLL), as a kidney-tonifying traditional Chinese medicine, is widely used in clinical practice and has unique advantages in the prevention and treatment of OP. Research has shown that FLL extract has a bone protective effect and reduces bone loss. However, its mechanism of action is not completely clear. Hence, this article employs databases like CNKI and PubMed to conduct a comprehensive search for pertinent domestic and international literature published within the last 15 years, utilizing keywords such as OP, FLL, osteogenesis, among others. Drawing upon existing research, this article primarily examines the preventive and therapeutic mechanism of FLL in relation to OP, including calcium balance, oxidative stress, bone metabolism, and parahormone effect. The aim is to furnish a foundation for future investigation on the role of FLL in preventing and treating OP, while also offering insights into the potential of traditional Chinese medicine in addressing this condition. [ABSTRACT FROM AUTHOR]

Background. Today, diabetes mellitus is an actual problem, characterized by a progressive increase in the number of patients with a high frequency of complications that require early diagnosis and timely treatment. Diabetic nephropathy is among the most common microvascular lesions. Patients may have clinical manifestations of diabetic kidney disease that go beyond the classic symptoms and have extrarenal consequences in the form of bone mineral disorders. The purpose of the work is to carry out a comprehensive assessment of early markers of kidney damage and changes in bone disorder indicators in patients with type 2 diabetes and to identify correlations between the studied parameters. Materials and methods. Eighty patients with type 2 diabetes participated in the study. They were divided according to the glomerular filtration rate: GFR < 60 ml/min/m² (1st group, n = 26), GFR ≥ 60 ml/min/m² (2nd group, n = 54). Results. Analysis of early markers of kidney damage revealed some significant differences between the groups. Indicators of daily urine albumin-creatinine ratio, serum cystatin C, parathyroid hormone, uric acid, and vitamin D-binding protein were significantly higher in patients with GFR < 60 ml/min/m². The average level of vitamin D (25OH) in both groups corresponded to a deficient state, and the 1st group was marked by a statistically significantly lower level compared to the 2nd group: 12.32 ± 4.84 and 16.72 ± 5.82 ng/ml, respectively (p = 0.001). In the 1st group, vitamin D deficiency was observed in 92.3 % of cases, and in the 2nd group, in 74.1 % (p = 0.56). According to the correlation analysis, some reliable relationships were found: in the 1st group, there was a negative correlation between GFR and parathyroid hormone (r = –0.816, p < 0.001). An inverse correlation was revealed between GFR and cystatin C in the 1st (r = –0.862, p < 0.001) and 2nd groups (r = –0.322, p = 0.18). Among all examined participants, there was a linear negative correlation between GFR and uric acid (r = –0.452, p < 0.001). Vitamin D (25OH) didn’t have a significant relationship with GFR, however, we found a negative correlation with the daily urine albumin-creatinine ratio (r = –0.253, р = 0.024) and cystatin C (r = –0.303, p = 0.006), which confirms the role of cholecalciferol in mineral bone disorders in patients with chronic kidney disease. In our study, an inverse correlation was found between GFR and vitamin D-binding protein in the 1st (r = –0.436, p = 0.26) and 2nd group (r = –0.283, p = 0.038), which probably indicates a possible compensatory response of transport protein to initial mineral bone disorders in patients with diabetic kidney disease. Conclusions. Early detection of bone mineral disorders in diabetic kidney disease is important to increase the efficiency of managing patients with type 2 diabetes and timely treatment, prevention of cardiovascular complications and bone metabolism disorders. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 35 year old woman with generalized maxillary and mandibular bone expansion, a condition related to renal osteodystrophy. It describes the patient's symptoms, including asymptomatic mandibular swelling and abnormal radiographic findings, alongside her medical history of systemic lupus erythematosus and chronic kidney disease with regular hemodialysis.

Abstract This study investigated whether Ki–Patlak derived from a shortened scan time for dynamic 18F-NaF PET/CT in chronic kidney disease (CKD) patients undergoing hemodialysis can provide predictive accuracy comparable to that obtained from a longer scan. Twenty-seven patients on chronic hemodialysis, involving a total of 42 scans between December 2021 and August 2023 were recruited. Dynamic 18F-NaF PET/CT scans, lasting 60–90 min, were immediately acquired post-injection, covering the mid-twelfth thoracic vertebra to the pelvis region. Ki–Patlak analysis was performed on bone time–activity curves at 15, 30, 45, 60, and 90 min in the lumbar spine (L1–L4) and both anterior iliac crests. Spearman’s rank correlation (rs) and interclass correlation coefficient were used to assess the correlation and agreement of Ki–Patlak between shortened and standard scan times. Bone-specific alkaline phosphatase (BsAP) and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were tested for their correlation with individual Ki–Patlak. Strong correlations and good agreement were observed between Ki–Patlak values from shortened 30-min scans and longer 60–90-min scans in both lumbar spine (rs = 0.858, p

Sagliker syndrome (SS) develops in chronic kidney disease patients because of insufficiently treated secondary hyperparathyroidism (SHPT) at an early stage. Studies indicating the potential association of the pathophysiology of the syndrome with genetic mutations are available. Phenotypic characteristics such as Brown tumors, lytic non-neoplastic bone lesions resulting from abnormal bone metabolism, deformities in the mandible and maxilla, irregularly spaced teeth, hypertrophic prominence of the lips, short neck, and slender upper and lower extremities are prominent in these patients. Brown tumors are often found in the metaphyses of the long bones, pelvis, maxilla, and costae, with significant involvement observed in our patient’s bilateral costae. The facial deformities in our patient were consistent and similar to the phenotype findings in other cases reported in the literature. In patients with chronic kidney disease (CKD), anemia is frequently observed because of increased SHPT, with a direct toxic effect on erythropoietin synthesis and erythropoietin progenitors in bone marrow. While anemia is common, bone marrow fibrosis and pancytopenia are much rarer. Although hyperparathyroidism is considered to be the responsible factor in the pathophysiology of SS, the literature does not report an association between SS and bone marrow fibrosis, making our case the first presentation of such an association. The high prevalence and early onset of coronary artery diseases (CAD) in patients with CKD are associated with a combination of systemic inflammation, oxidative stress, hypertension, vascular calcification, and disruptions in bone metabolism. In the patient’s medical history, there was no presence of hypertension, diabetes, smoking, or a family history of these conditions. SHPT in end-stage renal disease has been shown to accelerate vascular calcification and subclinical atherosclerosis. The presence of early-onset CAD in our patient, despite the absence of traditional risk factors, raises the question of whether hyperparathyroidism, a prominent factor in this syndrome, played a significant role in its etiology.

This study investigated whether Ki–Patlak derived from a shortened scan time for dynamic 18F-NaF PET/CT in chronic kidney disease (CKD) patients undergoing hemodialysis can provide predictive accuracy comparable to that obtained from a longer scan. Twenty-seven patients on chronic hemodialysis, involving a total of 42 scans between December 2021 and August 2023 were recruited. Dynamic 18F-NaF PET/CT scans, lasting 60–90 min, were immediately acquired post-injection, covering the mid-twelfth thoracic vertebra to the pelvis region. Ki–Patlak analysis was performed on bone time–activity curves at 15, 30, 45, 60, and 90 min in the lumbar spine (L1–L4) and both anterior iliac crests. Spearman's rank correlation (rs) and interclass correlation coefficient were used to assess the correlation and agreement of Ki–Patlak between shortened and standard scan times. Bone-specific alkaline phosphatase (BsAP) and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were tested for their correlation with individual Ki–Patlak. Strong correlations and good agreement were observed between Ki–Patlak values from shortened 30-min scans and longer 60–90-min scans in both lumbar spine (rs = 0.858, p < 0.001) and anterior iliac crest regions (rs = 0.850, p < 0.001). The correlation between BsAP and Ki–Patlak in the anterior iliac crests was weak and statistically insignificant. This finding suggests that a proposed shortened dynamic 18F-NaF PET/CT scan is effective in assessing bone metabolic flux in CKD patients undergoing hemodialysis, offering a non-invasive alternative approach for bone turnover prediction. [ABSTRACT FROM AUTHOR]

Background: Environmental fluoride exposure at elevated levels is potentially linked to kidney injury, and may contribute to chronic kidney disease of uncertain etiology (CKDu) as a risk factor. However, this link remains unclear, and examining the risk of kidney damage from early life fluoride exposure may provide important insights. Hence, this study aimed to investigate associations of fluoride exposure with pediatric kidney health in CKDu impacted and unimpacted communities in Sri Lanka. Methods: Considering the geographical variations in environmental fluoride, climate, and prevalence of CKDu, four study groups were established within selected education zones in CKDu-endemic dry zone regions (D-En), and CKDu-nonendemic regions within the dry (D-NE), wet (W-NE), and intermediate (I-NE) climatic zones. The study population included 922 school students (11–18 years of age). Participants in each group were divided into four subgroups based on quartiles of respective urinary fluoride (UF) distribution for comparison of urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and albumin-creatinine ratio (ACR). Results: UF levels in participants particularly in CKDu endemic dry zone regions were significantly high compared to the other regions. Significantly high median urinary NGAL (in D-NE) and ACR (in D-EN, and W-NE) levels were observed in subgroups of higher UF quartiles. Albuminuria was not particularly identified in subjects with high UF excretion. Urinary KIM-1 showed no significant variation across the UF quartile subgroups. Linear regression identified weak associations of UF with kidney injury biomarkers. Conclusions: Fluoride exposure is particularly high in CKDu-endemic dry zone communities. As implied by kidney injury biomarkers, a strong link between fluoride exposure and pediatric kidney health was not evident at the observed exposure levels in the study regions. [ABSTRACT FROM AUTHOR]

Background: Microscopic nephrocalcinosis is a common pathological feature of chronic kidney disease (CKD) in cats. Detection of macroscopic nephrocalcinosis using ultrasonography and its implications remain unexplored. Objectives: Identify risk factors associated with ultrasound‐diagnosed nephrocalcinosis and evaluate the influence of nephrocalcinosis on CKD progression. Animals: Thirty‐six euthyroid client‐owned cats with CKD. Methods: Prospective cohort study. Cats with CKD with and without ionized hypercalcemia were enrolled for renal ultrasonography. Cats were categorized according to the presence or absence of ultrasound‐diagnosed nephrocalcinosis. Binary logistic regression was performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression was assessed using linear mixed models. Results: Ultrasound‐diagnosed nephrocalcinosis was evident in 61% of CKD cats overall, with increased prevalence (81%) in those with hypercalcemia. At enrollment, higher blood ionized calcium concentration (odds ratio [OR], 1.27 per 0.1 mg/dL; P =.01), plasma phosphate concentration (OR, 1.16 per 0.1 mg/dL; P =.05), plasma creatinine concentration (OR, 1.29 per 0.1 mg/dL; P =.02) and alanine aminotransferase activity (OR, 2.08 per 10 U/L; P =.04) were independent nephrocalcinosis risk factors. The rate of change in log‐transformed fibroblast growth factor‐23 differed significantly between groups (P =.04). Cats with CKD and nephrocalcinosis had increasing plasma creatinine concentrations (.03 ±.01 mg/dL/month; P =.04) and phosphate concentrations (.06 ±.02 mg/dL/month; P <.001) and decreasing body weight (.02 ±.01 kg/month; P <.001) over time. Conclusions and Clinical Importance: Nephrocalcinosis is prevalent in cats with CKD, especially in those with hypercalcemia. This pathological feature appears to be associated with CKD progression in cats. [ABSTRACT FROM AUTHOR]

This document contains several abstracts related to kidney diseases and research. The first abstract discusses the presence of renal progenitor cells (RPCs) as a potential biomarker for renal injury in various diseases. The second abstract focuses on a new treatment option for Autosomal Dominant Polycystic Kidney Disease (ADPKD) using small molecule activation of long form PDE4 enzymes. The third abstract explores the investigation of genetic and environmental modifiers of ADPKD through a specific PKD2 variant. The fourth abstract examines the effects of low-salt and high-salt diets on kidney immune cells and endothelial cells. The final abstract discusses the relationship between KIR-HLA-I genetic mismatch and the development of antibody-mediated rejection and microvascular inflammation after renal transplantation. [Extracted from the article]

Patients with chronic kidney disease (CKD) experience a several-fold increased risk of fracture. Despite the high incidence and the associated excess morbidity and premature mortality, bone fragility in CKD, or CKD-associated osteoporosis, remains a blind spot in nephrology with an immense treatment gap. Defining the bone phenotype is a prerequisite for the appropriate therapy of CKD-associated osteoporosis at the patient level. In the present review, we suggest 10 practical 'tips and tricks' for the assessment of bone health in patients with CKD. We describe the clinical, biochemical, and radiological evaluation of bone health, alongside the benefits and limitations of the available diagnostics. A bone biopsy, the gold standard for diagnosing renal bone disease, is invasive and not widely available; although useful in complex cases, we do not consider it an essential component of bone assessment in patients with CKD-associated osteoporosis. Furthermore, we advocate for the deployment of multidisciplinary expert teams at local, national, and potentially international level. Finally, we address the knowledge gaps in the diagnosis, particularly early detection, appropriate "real-time" monitoring of bone health in this highly vulnerable population, and emerging diagnostic tools, currently primarily used in research, that may be on the horizon of clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To discuss the improvement effect of Shenshuai Yingyang Capsule in the renal osteodystrophy model rats and its effect on the bone morphogenetic protein (BMP)-7/Smads signaling pathway, and to clarify the relationship between renal function and bone metabolism in the renal osteodystrophy model rats. Methods: Fifty SPF SD rats were selected, and 10 of which were randomly chosen as control group, and the remaining 40 rats were used to establish the renal osteodystrophy model. Thirty successful modeling rats were divided into model group, positive control group, and Shenshuai Yingyang Capsule group, and there were 10 rats in various groups. The rats in control and model groups were given saline, the rats in positive control group were given 0. 01 mg·kg-1 calcitriol, and the rats in Shenshuai Yingyang Capsule group were given 1. 2 g·kg-1 Shenshuai Yingyang Capsule, all the rats were treated for 12 weeks. HE staining was used to observe the pathomorphology of femur tissue of the rats in various groups; automatic biochemical analyzer and chemiluminescence were used to detect the kidney function and calcium-phosphorus metabolism indicators in serum of the rats in various groups; realtime fluorescence quantitative PCR (RT-qPCR) method was used to detect the expression levels of BMP-7 and Smad1/5/8 mRNA in femur tissue of the rats in various groups; Western blotting method was used to detect the expression levels of BMP-7, phosphorylated BMP-7 (p-BMP-7), Smad1/5/8, and phosphorylated-Smad1/5/8 (p-Smad1/5/8) proteins in femur tissue of the rats in various groups. Results: The HE staining results showed that there was normal trabecular arrangement in control group with unchanged osteoblasts and osteoid area. In model group, the trabecular width and average osteoid area were increased, while the number of osteoblasts was decreased. In positive control and Shenshuai Yingyang Capsule groups, the trabecular width and average osteoid area were decreased, and the number of osteoblasts was increased. Compared with control group, the levels of blood urea nitrogen (BUN) and serum creatinine (Scr) of the rats in model group were increased (P<0. 05); compared with model group, the levels of BUN and Scr of the rats in positive control and Shenshuai Yingyang Capsule groups were decreased (P<0. 05); compared with positive control group, the levels of BUN and Scr of the rats in Shenshuai Yingyang Capsule group were decreased (P<0. 05). Compared with control group, the level of calcium ion (Ca2+) in serum of the rats in model group was decreased (P<0. 05), and the levels of phosphorus ion (P3-), parathyroid hormone (PTH), and alkaline phosphatase (ALP) were increased (P< 0. 05); compared with model group, the levels of Ca2+ in serum of the rats in positive control and Shenshuai Yingyang Capsule groups were increased (P<0. 05), and the levels of P3-, PTH, and ALP were decreased (P<0. 05); compared with positive control group, the level of Ca2+ in serum of the rats in Shenshuai Yingyang Capsule group was increased, and the levels of P3-, PTH, and ALP were decreased (P<0. 05). The RT-qPCR results showed that compared with control group, the expression levels of BMP-7 and Smad1/5/8 mRNA in femur tissue of the rats in model group were decreased (P<0. 05); compared with model group, the expression levels of BMP-7 and Smad1/5/8 mRNA of the rats in positive control drug group and Shenshuai Yingyang Capsule group were increased (P<0. 05); compared with positive control group, the expression levels of BMP-7 and Smad1/5/8 mRNA in femur tissue of the rats in Shenshuai Yingyang Capsule group were increased (P<0. 05). The Western blotting results showed that compared with control group, the expression levels of BMP-7, p-BMP-7, Smad1/5/8, and p-Smad1/5/8 proteins in femur tissue of the rats in model group were decreased (P<0. 05); compared with model group, the expression levels of BMP-7, p-BMP-7, Smad1/5/8, and p-Smad1/5/8 proteins in femur tissue of the rats in positive control group and Shenshuai Yingyang Capsule group were increased (P<0. 05); compared with positive control group, the expression levels of BMP-7, p-BMP-7, Smad1/5/8, and p-Smad1/5/8 proteins in femur tissue of the rats in Shenshuai Yingyang Capsule group were increased (P<0. 05). Conclusion: Shenshuai Yingyang Capsule can improve the kidney function and calcium-phosphorus metabolism disorders in the renal osteodystrophy model rats, promote the proliferation of the bone marrow stromal cells, and enhances the bone metabolism; its mechanism may be related to the activation of BMP-7/Smads signaling pathway. [ABSTRACT FROM AUTHOR]

A 63-yr-old woman with end-stage CKD secondary to glomerulonephritis, on hemodialysis therapy, presented with scoliosis, back pain, and progressive loss of physical function for which corrective surgery was planned. Optimization of bone health was requested by the surgeon as a DXA scan had revealed osteoporosis at spine, hip, and forearm. Due to previous subtotal parathyroidectomy and normal parathyroid hormone and bone-specific alkaline phosphatase levels, a low bone turnover state was suspected. An iliac bone biopsy was performed and revealed low bone turnover, a mineralization defect, and severe osteoporosis. The patient was treated with calcium and intensified vitamin D supplementation, followed by a 2-yr course of teriparatide. Monitoring of bone turnover markers indicated a bone anabolic response to therapy, and a repeat DXA showed increases in BMD at spine and hip. A repeat biopsy at end of treatment showed normal bone turnover and mineralization. This case demonstrates the complicated bone health of patients with advanced CKD. As there are no randomized trials for fracture pretention in patients with CKD, care must be individualized and is often based on expert opinion. The use of bone biopsy is safe and informative in guiding therapy. [ABSTRACT FROM AUTHOR]

Hyperphosphataemia represents a significant challenge in the management of chronic kidney disease, exerting a pronounced influence on the pathogenesis of cardiovascular complications and mineral bone disorders. Traditional approaches to address hyperphosphataemia involve implementing dietary phosphate restrictions, administering phosphate binders, and, in cases of end-stage renal disease, resorting to dialysis. Unfortunately, these interventions frequently prove inadequate in maintaining phosphate levels within recommended ranges. Additionally, commonly employed pharmacological agents are not immune to eliciting adverse events, thereby limiting their prescription and therapeutic adherence. There is a growing focus on exploring novel therapeutic strategies in this context. The current discussion centres on tenapanor, a pharmacological agent predominantly acting as a selective inhibitor of sodium/hydrogen exchanger isoform 3 (NHE3). Its mechanism of action involves modulating tight junctions, resulting in reduced sodium absorption and intestinal paracellular permeability to phosphate. Furthermore, tenapanor downregulates sodium-dependent phosphate 2b transport protein (NaPi2b) expression, thereby impeding active transcellular phosphate transport. Clinical trials have elucidated the efficacy and safety profile of tenapanor. This evidence hints at a potential paradigm shift in the management of hyperphosphataemia. However, the burgeoning optimism surrounding tenapanor warrants tempered enthusiasm, as further research remains indispensable. The imperative lies in meticulously delineating its efficacy and safety contours within the crucible of clinical practice. In this review, we synthesize the intricate interplay between hyperphosphataemia and Chronic Kidney Disease-Mineral Bone Disorder, and we discuss the existing pharmacological interventions for hyperphosphataemia and explore emerging treatment paradigms that offer novel perspectives in managing elevated phosphate levels in CKD patients. [ABSTRACT FROM AUTHOR]

Complications at bone and cardiovascular levels characterize mineral-bone disorder associated with chronic kidney disease (CKD-MBD). It occurs in nephropathic patients with poor adherence to treatment. We present a clinical case that suffered two complications associated with this entity: osteitis fibrosa cystica and stroke due to calcium embolism, which we describe. With proper management, its incidence is drastically reduced, which is why close surveillance and active followup of patients is essential. [ABSTRACT FROM AUTHOR]

Background Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of chronic kidney disease–mineral and bone disorders (CKD-MBD) and bone fragility fractures in the COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) project. Methods COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 haemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and parathyroid hormone (PTH) (exposure), was assessed using standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. Results During a median follow-up of 24 months, 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months, respectively. Baseline serum phosphate >6.1 mg/dL (reference value 4.3–6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models {hazard ratio (HR) 1.53 [95% confidence interval (CI) 1.10–2.13] and HR 1.44 (95% CI 1.02–2.05)}. The significant association persisted after competitive risk analysis [subHR 1.42 (95% CI 1.02–1.98)] but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH >800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. Conclusions Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in haemodialysis patients. [ABSTRACT FROM AUTHOR]

Purpose of review: Mineral and bone disorder (MBD) is a prevalent complication in chronic kidney disease (CKD), significantly impacting overall health with multifaceted implications including fractures, cardiovascular events, and mortality. Despite its pervasive nature, effective treatments for CKD-MBD are lacking, emphasizing the urgency to advance understanding and therapeutic interventions. Bone metabolism intricacies, influenced by factors like 1,25 dihydroxy vitamin D, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23), along with intrinsic osseous mechanisms, play pivotal roles in CKD. Skeletal abnormalities precede hormonal changes, persisting even with normalized systemic mineral parameters, necessitating a comprehensive approach to address both aspects. Recent findings: In this review, we explore novel pathways involved in the regulation of systemic mineral bone disease factors, specifically examining anemia, inflammation, and metabolic pathways. Special emphasis is placed on internal bone mechanisms, such as hepatocyte nuclear factor 4α, transforming growth factor-β1, and sclerostin, which play crucial roles in the progression of renal osteodystrophy. Summary: Despite advancements, effective treatments addressing CKD-MBD morbidity and mortality are lacking, necessitating ongoing research for novel therapeutic targets. [ABSTRACT FROM AUTHOR]