Search Results (124)

Background/Objectives: Secondary hyperparathyroidism (SHPT) is a prevalent complication in end-stage renal disease, often necessitating surgical intervention when refractory to medical therapy. The optimal surgical strategy—subtotal parathyroidectomy (SPTX) versus total parathyroidectomy with/without autotransplantation (TPTX ± AT)—remains debated, especially considering postoperative complications like persistent HPT and hungry bone syndrome (HBS). This study aimed to compare early surgical outcomes and identify predictors for postoperative complications in patients undergoing SPTX and TPTX + AT. Methods: We conducted a retrospective, single-center observational study involving 93 dialysis patients who underwent PTX for drug-refractory SHPT. Patients were analyzed according to surgical procedure (SPTX vs. TPTX + AT), focusing on postoperative complications such as cervical bleeding, reintervention rates, and the incidence of HBS. Multivariate logistic regression was utilized to identify predictors of these outcomes. Results: TPTX + AT demonstrated superior control of HPT, with significantly lower rates of reintervention compared to SPTX (7.1% vs. 23.5%, p = 0.037). However, TPTX + AT was associated with a higher incidence of HBS (57.1% vs. 35.3%, p = 0.039). Independent predictors of reintervention included absence of concomitant thymectomy, preoperative hypercalcemia, fewer visualized glands preoperatively, and preoperative PTH > 2000 pg/mL. Elevated alkaline phosphatase levels (>300 U/L), severe bone pain, and the TPTX procedure itself were significant predictors of HBS. Conclusions: Surgical strategy for SHPT should be individualized, balancing the lower recurrence risk associated with TPTX + AT against its higher likelihood of postoperative hypocalcemia. Preoperative biochemical markers and clinical features could potentially influence operative decision-making and optimize patient outcomes. Full article

Background: Chronic kidney disease (CKD) is an established global health problem, with the increased prevalence of vascular inflammation, accelerated atherogenesis, and thrombotic risk all contributing to overall cardiovascular risk. The major CKD-specific risk factor is presumed to be the accumulation of uremic toxins in circulation and tissues, further accelerating the progression of CKD and its co-morbidities, including those of bone mineral disorders and cardiovascular diseases. Materials and Methods: In our narrative review, we focused on non-traditional cardiovascular risk factors, as they evolve with declined kidney function and are potentially further modulated by the choice of kidney replacement therapy. Results: Based on the data from the literature to date, the pre-eminent role of non-traditional risk factors emerges to mediate inflammation and increased cardiovascular mortality. In particular, patients receiving hemodialysis (HD) display dramatically increased CVD-mediated mortality. This intensified state of inflammation may be linked to the direct exposure of the bloodstream to a bio-incompatible environment in HD; for both complement-mediated and non-complement-mediated reactions, the possible contribution of neutrophil extracellular traps and complement activation-related pseudoallergy are reviewed in detail. Conclusions: Our narrative review emphasizes key elements of a bio-incompatible HD environment that may contribute to increased cardiovascular mortality in patients receiving HD. Summarizing these results may provide conceptual opportunities to develop new therapeutic targets. Full article

Fracture risk is a serious yet underrecognized complication among patients with chronic kidney disease (CKD), especially in those with stages G3-G5D. The overlap between CKD-Mineral and Bone Disorder (CKD-MBD) and osteoporosis leads to complex bone changes that increase the likelihood of fragility fractures. Studies show that 18% to 32% of CKD patients also have osteoporosis, and these individuals are more than 2.5 times as likely to suffer from fractures compared to those without CKD. In the advanced stages of the disease, fracture risk is up to four times higher than in the general population, with the femur, forearm, and humerus being the most commonly affected sites. Hip fractures are of particular concern as they are linked to longer hospital stays and higher rates of morbidity and mortality. Furthermore, dialysis patients who experience hip fractures have a mortality rate 2.4 times higher than those in the general population with similar fractures. This increased risk underscores the need for proactive bone health maintenance in CKD patients to prevent fractures and related complications. This review explores the underlying pathophysiological mechanisms, diagnostic challenges, and treatment options related to bone fragility in CKD. Diagnostic tools, such as bone mineral density (BMD) assessments, the trabecular bone score (TBS), and biochemical markers, remain underused, especially in advanced CKD stages. Recent treatment strategies emphasize a multidisciplinary, stage-specific approach, incorporating calcium and vitamin D supplements, anti-resorptive agents like denosumab, and anabolic therapies such as teriparatide and romosozumab. Effective management needs to be tailored to the patient’s bone turnover status and stage of CKD. Despite progress in understanding bone fragility in CKD, significant gaps remain in both diagnosis and treatment. Personalized care, guided by updated KDIGO recommendations and based on an interdisciplinary approach, is essential to reduce fracture risk and improve outcomes in this vulnerable population. Further research is needed to validate risk assessment tools and refine therapeutic protocols. Full article

It is now widely recognized that maintaining magnesium (Mg) homeostasis is critical for health, especially in the context of chronic kidney disease (CKD). Patients with CKD commonly develop hyperphosphatemia and secondary hyperparathyroidism, which are controlled by therapies targeting intestinal phosphate absorption and circulating calcium levels or by modulating parathyroid calcium sensing. Notably, Mg supplementation may provide dual benefits by promoting bone formation and maintaining normal mineralization with slightly elevated serum levels. Importantly, low Mg levels are associated with mortality risk in CKD, highlighting the importance of maintaining adequate serum Mg levels in these patients. Particularly, kidney transplant (KT) patients have lower circulating Mg levels, likely due to interactions with immunosuppressive treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown survival benefits in CKD and increased serum Mg levels, suggesting that Mg regulation may contribute to these outcomes. Overall, Mg plays a key role in CKD-associated mineral and bone disorders (CKD-MBD). Thus, understanding the mechanisms underlying the alteration of Mg homeostasis in CKD could improve clinical outcomes. This review summarizes the basic and clinical studies demonstrating (1) the key actions of Mg in CKD-MBD, including secondary hyperparathyroidism and bone abnormalities; (2) the distinctive profile of KT patients for Mg homeostasis; and (3) the interaction between commonly used drugs, such as SGLT2 inhibitors or immunosuppressive treatments, and Mg metabolism, providing a broad understanding of both the key role of Mg in the context of CKD and the treatments that should be considered to manage Mg levels in CKD patients. Full article

In patients with chronic kidney disease (CKD), cardiovascular events (CVA) are the main cause of morbidity and mortality. Vascular calcification, linked to bone mineral metabolism disorders such as elevated serum phosphate, parathyroid hormone (PTH), and FGF23, well-known uremic toxins, aggravate this risk. Calcimimetics are allosteric activators of the calcium-sensing receptor (CaSR), a G protein-coupled receptor that regulates PTH secretion and synthesis in response to changes in extracellular calcium in the parathyroid glands. Through direct and indirect mechanisms, they have demonstrated their efficacy in reducing the progression of vascular, valvular, and soft tissue calcification in experimental studies. Although clinical studies in dialysis patients did not achieve statistical significance in their primary objectives, positive results in subgroup analyses suggest that the lack of significance may be attributable to the short follow-up period. This finding highlights the need to consider early treatment strategies, especially in advanced stages of chronic kidney disease, to more effectively address the progression of vascular calcification through serum uremic toxins control. Full article

Chronic kidney disease (CKD) represents a major and widespread global health challenge. It affects over 800 million people worldwide, which is approximately 13% of the world’s population. Over the past 20 years, it has consistently ranked among the leading causes of death. As a result of its typically painless and asymptomatic presentation in the early stages of the disease, CKD is frequently diagnosed late, when the patient is already suffering from serious complications. In recent years, studies have identified novel biomarkers associated with the pathophysiology of CKD, including chronic inflammation, tubular injury, and CKD-related outcomes such as bone and mineral metabolism disorders, cardiovascular events, and all-cause mortality. Identifying and using these emerging biomarkers—like kidney injury molecule, N-acetyl–D-glucosaminidase, ficolins, the NLRP3 (nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3) inflammasome, soluble suppression of tumorigenicity-2, galectin-3, growth differentiation factor-15, soluble urokinase-type plasminogen activator receptor, sclerostin, the Dick-kopf proteins, and indexes such as the systemic inflammation response index—may lead to a significant advancement in early diagnosis, risk stratification, and personalized treatment strategies for CKD patients. Despite their potential, the routine clinical use of these novel biomarkers remains limited due to challenges such as high costs and the lack of standardized testing methods. There is still considerable room for advancement in both the diagnosis and management of CKD. Hopefully, increasingly more new biomarkers will become usable in clinical practice, ultimately improving care quality and outcomes for patients with CKD. Full article

Background/Objectives: Chronic kidney disease–mineral and bone disorder (CKD-MBD) and systemic inflammation contribute to mortality in hemodialysis (HD) patients. The primary aim of this study was to determine whether specific CKD-MBD markers and inflammatory biomarkers are associated with increased mortality risk in HD patients. Methods: We conducted a retrospective cohort study on 63 stage 5D CKD patients undergoing maintenance HD. Serum intact parathyroid hormone (iPTH), soluble Klotho, calcium, phosphorus, 25(OH)D (25-hydroxyvitamin D), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), C-reactive protein (CRP), and interleukin-6 (IL-6) were analyzed. A Cox regression analysis assessed mortality predictors, and linear regression analysis evaluated CKD-MBD–inflammation correlations. Results: Lower iPTH (<329.3 pg/mL) levels were the only significant mortality predictor (p = 0.042). Other CKD-MBD markers (calcium, phosphorus, 25(OH)D, VEGF, TGF-β) did not impact survival. Soluble Klotho correlated positively with IL-6 (r = 0.57, p < 0.001), suggesting a compensatory inflammatory response. Conclusions: Our findings demonstrate that low iPTH levels and advanced age are independent predictors of mortality in hemodialysis patients. The positive association between soluble Klotho and IL-6 suggests a potential compensatory inflammatory response. These results highlight the need for further research to clarify underlying mechanisms and to explore novel therapeutic strategies. Full article

Background: Chronic kidney disease–mineral and bone disorder (CKD-MBD) is a key contributor to complications, including ischemic heart disease (IHD), which significantly elevates mortality in patients with chronic kidney disease (CKD). This study aims to identify factors associated with IHD risk in pre-dialysis CKD and establish the minimum parathyroid hormone (PTH) threshold necessary to mitigate this risk. Methods: We retrospectively analyzed data from CKD stage 3–5ND patients aged over 18 years, followed from 2018 to 2022. IHD was identified using ICD-10 codes. An adjusted Cox regression model and joint modeling analysis were used to assess the association between risk factors and IHD. Results: A total of 1210 CKD patients were included in the analysis, with a median follow-up duration of 513.5 days (IQR 189–979). The incidence of IHD was 7.5%. PTH levels ≥166 ng/L (HR 1.87, 95% CI 1.05–3.35, p = 0.03) and age ≥65 years (HR 1.68, 95% CI 1.003–2.81, p = 0.04) were significantly associated with an increased risk of IHD. In joint modeling analysis, time-varying PTH, age ≥65 years, and diabetes mellitus (DM) were significantly associated with an increased risk of IHD, whereas ARB and statin use were associated with a reduced risk. Calcium and phosphate levels did not demonstrate significant associations with IHD risk. Conclusions: Baseline PTH levels ≥166 ng/L and time-varying PTH were independently and significantly associated with an increased risk of IHD. In contrast, calcium and phosphate levels showed no significant association with IHD risk. Full article

Background/Objectives: This study aimed to establish the regularities of changes in the content of matrix metalloproteinase 8 (MMP-8) and osteoprotegerin (OPG), the most well-known indicators of bone metabolism disorders, in the saliva of children with different severities of chronic kidney disease (CKD) who need orthodontic treatment. Methods: The study of MMP-8 and OPG content in saliva was carried out in 76 children in need of orthodontic treatment, who were divided into equal groups (G) of 19 people: G1—children with congenital malformations of the urinary tract, acquired renal pathology, and CKD stage 1 and 2, receiving medical therapy, as well as more having a deep distal bite formed by mandibular micrognathia; G2—children with a terminal stage of CKD, receiving renal replacement therapy in the volume of hemodialysis, with a characteristic distal bite of different etiology; G3—children one year after kidney transplantation, with a tendency to form an open distal bite, associated to a greater extent with maxillary macrognathia. G4—practically healthy children without renal pathology stratified by sex and age. Results: It was found that the content of MMP-8 and OPG in the saliva of children with different CKD stages who needed orthodontic treatment was significantly higher than the G4. The maximum values of MMP-8 were registered in G2. An increase in OPG content in saliva was observed in the G1 and G3. Conclusions: The identified changes in markers of mineral and bone disorders in the saliva of children with different stages of CKD show the possibility of their use as non-invasive predictive and prognostic markers for the diagnosis of preclinical stages of bone metabolic disorders. Full article

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. Full article

Background: Patients with end-stage chronic diseases, especially those undergoing hemodialysis (HD), often experience mineral bone disease (MBD), leading to hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone (PTH). Vitamin D deficiency and metabolism disorders are also common, resulting from impaired conversion of 25(OH)D3 to its active form, 1,25(OH)2D3, and reduced inactivation to 24,25(OH)2D3. This study aimed to assess the levels of 25(OH)D2, 25(OH)D3, 24,25(OH)2D3, 3-epi-25(OH)D3, and the vitamin D metabolism ratio (VMR) in patients with maintenance HD. Methods: A cross-sectional study was conducted on 66 HD patients (22–90 years, average 61.3 ± 16.4), with a control group of 206 adults without chronic kidney disease (CKD), both without cholecalciferol supplementation. Results: the HD patients had significantly lower 25(OH)D3 levels (15 ng/mL vs. 22 ng/mL) and higher deficiency rates (69% vs. 39%) compared to the controls. However, both groups showed similarly low levels of optimal vitamin D3. The HD patients had lower 24,25(OH)D3 levels (0.1 vs. 2.1 ng/mL) and a lower VMR (0.9% vs. 9%). 3-epi-25(OH)D3 levels and its ratio to 25(OH)D3 were significantly lower in the HD group. Alphacalcidol supplementation raised 1,25(OH)2D3 levels (30.4 vs. 16.2 pg/mL) without affecting other vitamin D metabolites. The HD patients had higher levels of 25(OH)D2 compared to the controls (0.61 vs. 0.31 ng/mL). Conclusions: Vitamin D3 reserves are lower, and both functional deficiency and impaired catabolism of vitamin D3 are present in HD patients compared to the general population. The VMR index is the most sensitive parameter for vitamin D3 deficiency assessment, highlighting the importance of measuring 24,25(OH)D3. Alphacalcidol supplementation increases 1,25(OH)2D3 levels without affecting other vitamin D metabolites. 25(OH)D2 is the only metabolite that was higher in HD patients than the controls. Full article

Background: Uremic tumoral calcinosis (UTC) is a rare yet severe complication of chronic kidney disease (CKD), predominantly occurring in patients undergoing renal replacement therapy (RRT). It is characterized by extensive soft tissue calcifications, frequently associated with chronic hyperphosphatemia and disruptions to calcium–phosphorus metabolism. Case report: This report describes a 34-year-old woman with end-stage renal disease (ESRD) secondary to lupus nephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD). She presented with a progressively enlarging calcified mass in the proximal phalanx of the third finger on her right hand, accompanied by functional impairment. Laboratory findings revealed persistent hyperphosphatemia (8.8 mg/dL), elevated parathyroid hormone levels (901 pg/mL), and low vitamin D levels (9 ng/mL), indicating significant disturbances to mineral metabolism. Imaging studies, including X-ray and whole-body 18F-Choline positron emission tomography/computed tomography (PET/CT), confirmed the presence of localized calcifications in the soft tissue of the proximal phalanx of the third finger on her right hand and parathyroid hyperplasia, respectively. Initial management included the optimization of phosphate binders and calcimimetic therapy, with the subsequent intensification of dialysis therapy. Transitioning to automated peritoneal dialysis (APD) with high-volume exchanges resulted in a notable improvement in biochemical parameters and the eventual remission of the calcified mass. Conclusion: This case underscores the importance of comprehensive management in dialysis patients, including dietary phosphate restriction, the appropriate use of non-calcium-based binders, and tailored dialysis regimens to prevent and treat CKD-related mineral and bone disorders. It also highlights the utility of imaging modalities such as PET/CT in diagnosing UTC and monitoring response to therapy. Further research is needed to elucidate the pathophysiology of UTC and optimize its management in dialysis patients. Full article

Background/Objectives: Children on dialysis have a 10-fold increase in cardiovascular disease (CVD)-related mortality when compared to the general population. The development of CVD in dialysis patients is attributed to Chronic Kidney Disease–Mineral Bone Disorder (CKD-MBD) and dyslipidemia. While the prevalence of dyslipidemia in adult dialysis patients has been described, there are limited data on prevalence, severity, and risk factors for pediatric dyslipidemia. Methods: Data from 1730 pediatric patients ≤ 21 years receiving maintenance hemodialysis or peritoneal dialysis with at least one lipid panel measurement were obtained from USRDS between 2001 and 2016. Disease etiology was classified as being glomerular (n = 1029) or non-glomerular (n = 701). Comparisons were made across etiologies using both linear and logistic regression models to determine the relationship between disease etiology and lipid levels. Results: The cohort had a mean age of 15.2 years and were 54.5% female. Adjusting for age, sex, race/ethnicity, modality, time with End Stage Kidney Disease (ESKD), and body mass index (BMI) and using non-glomerular etiology as the reference, glomerular disease [mean (95% CI)] was associated with +19% (+14.7%, +23.8%) higher total cholesterol level (183 mg/dL vs. 162 mg/dL), +21% (+14.8%, +26.6%) higher low density lipoprotein cholesterol level (108 mg/dL vs. 87 mg/dL), and +22.3% (+15.5%, +29.5%) higher triglyceride level (169 mg/dL vs. 147 mg/dL). Glomerular disease [OR (95% CI)] was associated with 3.0-fold [2.4, 3.9] higher odds of having an abnormal total cholesterol level, 3.8-fold [2.8, 5.0] higher odds of having an abnormal LDL-C level, and 1.9-fold [1.5, 2.4] higher odds of having an abnormal triglyceride level when compared to non-glomerular disease. Conclusions: Pediatric dialysis patients have a high prevalence of dyslipidemia, particularly from elevated triglyceride levels. Specifically, patients with glomerular disease have an even higher risk of dyslipidemia from elevated non-HDL cholesterol and triglyceride levels than patients with non-glomerular disease. The long-term impact of this unfavorable lipid profile requires further investigation. Full article

Chronic kidney disease (CKD) is an extremely widespread pathology characterized by numerous metabolic alterations, including impairments of calcium–phosphorus and of vitamin D metabolisms, which lead to a condition known as CKD–mineral and bone disorders (CKD-MBDs). In CKD children, this pathological condition induces anomalies in physiological growth processes, alterations in bone morphology, renal osteodystrophy and rickets. CKD-MBDs are not only associated with systemic complications but also show dental and maxillofacial manifestations in children. In fact, children affected by CKD-MBDs present defects in enamel development and dental anomalies when compared to healthy children. Therefore, the aims of this narrative review are to focus on the hard dental tissues and to investigate the possible correlation between the CKD-MBDs in children and the presence of developmental defects of enamel. In addition, the possible risk and protective factors of dental caries in CKD pediatric patients are analyzed. The review describes, with a multidisciplinary nephrological–dental approach, the pathogenic mechanisms that can cause anomalies in dental structure in CKD pediatric patients. Full article

Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage kidney disease (ESKD). To date, no trial has been adequately powered to evaluate the effects of different dialysis modalities on cardiovascular events or mortality. To properly assess the risks and benefits of each modality for individual patients, it is crucial to understand the unique cardiovascular risk factors in patients undergoing dialysis. This review explores the existing literature on cardiovascular risk assessment in this population. It examines the mechanisms contributing to increased risk, including volume overload, blood pressure abnormalities, mineral bone disorder, vascular calcification, uremia, anemia, and chronic inflammation. Additionally, we discuss data from trials assessing cardiovascular outcomes and compare various dialysis modalities, including in-center hemodialysis, frequent dialysis, nocturnal dialysis, and peritoneal dialysis. Full article