Metastatic Calcification in Allograft Kidney Due to Persistent Secondary Hyperparathyroidism: A Rare Cause of Graft Dysfunction.

Successful kidney transplant corrects mineral and bone disorderto a large extent; however, disorders can persistin up to 80% ofrecipients.We describe a case of persistent hyperparathyroidism with graft dysfunction and metastatic calcification in graft biopsy. A 48-yearold renal transplant recipient developed graft dysfunction 3 weeks after kidney transplant. During pretransplant workup, the recipient was found to have severe secondary hyperparathyroidism (intact parathyroid hormone level of 2000 pg/mL), which was managed and well controlled before transplant. Graft dysfunction was evaluated using algorithmic approach. Prerenal causes, tacrolimus toxicity, and infections were ruled out. Graft biopsy revealed several foci of tubular and parenchyma calcific deposits (microcalcinosis) with tubular injury. The patient was restarted on medical management of hyperparathyroidism, and he showed improvement over 6 weeks, along with creatinine level returning to nadir value. Vascular and graft calcification is an independent predictor of long-term graftfunction and overall mortality. This report describes the challenges that we faced in diagnosis and management of persistent hyperparathyroidism, as no randomized controlled trials and guidelines are available.

The clinical efficacy of combined ESA and Roxadustat treatment for renal anemia in hemodialysis patients with secondary hyperparathyroidism: A case series.

RATIONALE: Pharmacological mechanism of Roxadustat in the treatment of renal anemia. PATIENT CONCERNS: To investigate the efficacy and safety of combined Roxadustat and erythropoiesis stimulator (ESA) treatment of renal anemia in hemodialysis patients with secondary hyperparathyroidism. DIAGNOSES: A retrospective analysis was conducted on hemodialysis patients with renal anemia and secondary hyperparathyroidism treated with ESAs alone, who were admitted to our hospital from March 2022 to December 2022. INTERVENTIONS: The patients were treated with Roxadustat combined with ESAs for 3 months, during which oral iron supplementation was given, and the changes in Hb levels and laboratory-related indicators before and after the combined treatment were analyzed. OUTCOMES: The results showed that a total of 13 patients received combination therapy, with a significant increase in Hb compared to ESAs alone (t = -3.955, P = .002). The Hb qualification rate was 38.46%, and the ∆Hb response rate was 76.92%. The parathyroid hormone significantly decreased with a statistically significant difference (Z = -2.062b, P = .039). Hemoglobin (RBC), total iron binding capacity, and serum ferritin (male) were significantly increased compared to ESAs alone. Total cholesterol and low-density lipoprotein were significantly lower than ESAs alone. The differences in the changes in the above indicators were statistically significant (P < .05). There was no statistically significant difference in changes in other laboratory-related indicators (P > .05). No adverse reactions were observed during the combined treatment of 13 patients. LESSONS SUBSECTIONS: The combination of Roxadustat and ESAs can effectively improve renal anemia in hemodialysis patients with secondary hyperparathyroidism, as well as improve indicators of hyperparathyroidism and blood lipid levels with high levels of safety. This combined treatment thus provides a new and safe treatment method for these patients.

Persistent uncertainties in optimal treatment approaches of secondary hyperparathyroidism and hyperphosphatemia in patients with chronic kidney disease.

PURPOSE OF REVIEW: This review is a critical analysis of treatment results obtained in clinical trials conducted in patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT), hyperphosphatemia, or both. RECENT FINDINGS: Patients with CKD have a high mortality rate. The disorder of mineral and bone metabolism (CKD-MBD), which is commonly present in these patients, is associated with adverse outcomes, including cardiovascular events and mortality. Clinical trials aimed at improving these outcomes by modifying CKD-MBD associated factors have most often resulted in disappointing results. The complexity of CKD-MBD, where many players are closely interconnected, might explain these negative findings. We first present an historical perspective of current knowledge in the field of CKD-MBD and then examine potential flaws of past and ongoing clinical trials targeting SHPT and hyperphosphatemia respectively in patients with CKD.

Secondary hyperparathyroidism in chronic kidney disease: A narrative review focus on therapeutic strategy.

Chronic kidney disease (CKD) affects over 10% of the global population. One crucial complication of CKD is secondary hyperparathyroidism (SHPT), marked by elevated parathyroid hormone levels due to hyperphosphataemia, hypocalcaemia, and low active vitamin D from impaired renal function. SHPT increases risks of bone deformities, vascular calcification, cardiovascular events and mortality. This review examines SHPT treatment strategies in patients with CKD. First-line treatments include phosphate binders, vitamin D receptor activators and calcimimetics. When these fail, invasive options like parathyroidectomy (PTX) and thermal ablation are considered. PTX effectively reduces symptoms and improves radiological outcomes, outperforming medical treatment alone in reducing cardiovascular risk and mortality. Thermal ablation techniques, such as microwave, radiofrequency, laser or high-intensity focused ultrasound, offer less invasive alternatives with promising results. Future research should explore the molecular mechanisms of parathyroid gland hyperplasia and evaluate various treatments' impacts.

Construction and validation of a risk prediction model for early hungry bone syndrome in maintenance hemodialysis patients post-parathyroidectomy. / ç»´æŒæ€§è¡€æ¶²é€æžæ‚£è€ ç”²çŠ¶æ—è ºåˆ‡é™¤æœ¯åŽæ—©æœŸéª¨é¥¥é¥¿ç»¼åˆå¾é£Žé™©é¢„æµ‹æ¨¡åž‹çš„æž„å»ºä¸ŽéªŒè¯.

OBJECTIVES: Parathyroidectomy (PTX) is an effective treatment for refractory secondary hyperparathyroidism (SHPT), but it can lead to hungry bone syndrome (HBS), significantly threatening the health of maintenance haemodialysis (MHD) patients. While previous studies have analyzed the risk factors for HBS post-PTX, the predictive performance and clinical applicability of these risk models need further validation. This study aims to construct and validate a risk prediction model for HBS in MHD patients with SHPT post-PTX. METHODS: A retrospective analysis was conducted on 368 MHD patients with SHPT who underwent PTX at Changsha Jieao Nephrology Hospital from January 2020 to December 2021. Patients were divided into a HBS group and a non-HBS group based on the occurrence of HBS. General data, surgical information, and biochemical indicators were compared between the 2 groups. Multivariate logistic regression was used to identify factors influencing HBS, and a risk prediction model was established. The model's performance was evaluated using receiver operator characteristic (ROC) curves, decision curves, and calibration curves. External validation was performed on 170 MHD patients with SHPT who underwent PTX at the Third Xiangya Hospital of Central South University from January to December 2022. RESULTS: The incidence of HBS post-PTX in MHD patients with SHPT was 60.60%. Logistic regression analysis identified preoperative bone involvement (OR=3.908, 95% CI 2.179 to 7.171), preoperative serum calcium (OR=7.174, 95% CI 2.291 to 24.015), preoperative intact parathyroid hormone (iPTH) (OR=1.001, 95% CI 1.001 to 1.001), preoperative alkaline phosphatase (ALP) (OR=1.001, 95% CI 1.000 to 1.001), and serum calcium on the first postoperative day (OR=0.006, 95% CI 0.001 to 0.038) as independent risk factors for HBS (all P<0.01). The constructed risk prediction model demonstrated good predictive performance in both internal and external validation cohorts. The internal validation cohort showed an accuracy of 0.821, sensitivity of 0.890, specificity of 0.776, Youden index of 0.666, and area under the curve (AUC) of 0.882 (95% CI 0.845 to 0.919). The external validation cohort showed an accuracy of 0.800, sensitivity of 0.806, specificity of 0.799, Youden index of 0.605, and AUC of 0.863 (95% CI 0.795 to 0.932). CONCLUSIONS: Preoperative bone involvement, serum calcium, iPTH, ALP, and serum calcium on the first postoperative day are influencing factors for HBS in MHD patients with SHPT post-PTX. The constructed risk prediction model based on these factors is reliable.

Metabolomic profile of secondary hyperparathyroidism in patients with chronic kidney disease stages 3-5 not receiving dialysis.

Introduction: Secondary hyperparathyroidism (SHPT) is a common and serious complication of chronic kidney disease (CKD). Elucidating the metabolic characteristics of SHPT may provide a new theoretical basis for its prevention and treatment. This study aimed to perform a metabolomic analysis of SHPT in patients with CKD stages 3-5 not receiving dialysis. Methods: A total of 76 patients with CKD, 85 patients with CKD-SHPT, and 67 healthy controls were enrolled in this study. CKD was diagnosed according to the criteria specified in the Kidney Disease Improving Global Outcomes 2012 guidelines. SHPT was diagnosed by experienced clinicians according to the Renal Disease Outcomes Quality Initiative Clinical Practice Guidelines. Serum renal function markers and the lipid profile were analyzed. Untargeted ultra performance liquid chromatography-tandem mass spectrometry was used to analyze the serum metabolites of patients with CKD and SHPT. Multivariate analysis of the data was performed using principal component analysis and partial least square discriminant analysis. Serum differential metabolites were identified and further characterized using databases. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes database. Correlations between differential metabolites and clinical parameters were determined using the Spearman correlation. Results: The serum metabolomic profiles of patients with CKD with and without SHPT differed significantly. Differential metabolites were mainly enriched in the top four Kyoto Encyclopedia of Genes and Genomes pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; sphingolipid metabolism; glycerophospholipid metabolism; and phenylalanine metabolism. In total, 31 differential metabolites were identified; of these, L-tryptophan and (R)-(+)-1-phenylethylamine were decreased, while other amino acids and their derivatives, uremia toxins, carnitine, and lipids, were increased significantly in patients with SHPT compared to those without. The 14 lipid metabolites were positively correlated with levels of Urea, serum creatinine, cystatin C, and triglycerides and negatively correlated with the estimated glomerular filtration rate and levels of total and high- and low-density lipoprotein cholesterol. Discussion: Disturbed amino acid and lipid metabolism were more apparent in patients with SHPT than in those without. This metabolomic profile of SHPT may provide a therapeutic foundation for its future clinical management.

Estimating the global prevalence of secondary hyperparathyroidism in patients with chronic kidney disease.

Background: Chronic kidney disease (CKD)-related secondary hyperparathyroidism (SHPT) is associated with higher morbidity and death. The goal of this study was to mine the SHPT data already available to do a meta-analysis on the global prevalence of SHPT caused by CKD. Methods: Embase, Medline, Web of Science, Cochrane Central Databases, and Google Scholar were searched to identify studies on the prevalence of SHPT due to CKD from inception to November 2023. Pooled prevalence was calculated using the DerSimonian-Laird random effects model with a logit transformation. Results: Twenty-one eligible studies involving 110977 patients were included. Our results revealed that the estimated global prevalence of SHPT due to CKD was 49.5% (95% CI 30.20-68.18), regardless of the diagnostic criteria. For subgroup analysis, Southern Asia (84.36%, 95% CI 79.35-88.34) had a significantly higher SHPT prevalence than other geographic regions. SHPT due to CKD was most prevalent in China (85.14%, 95% CI 81.74-88.00). Conclusions: SHPT due to CKD is highly prevalent. This necessitates awareness and therapeutic approaches from primary care physicians, medical professionals, and health strategy authorities. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024514007.

Evaluating Health Literacy Resources for Secondary Hyperparathyroidism in End-Stage Kidney Disease.

INTRODUCTION: Parathyroidectomy is recommended for severe secondary hyperparathyroidism (SHPT) due to end-stage kidney disease (ESKD), but surgery is underutilized. High quality and accessible online health information, recommended to be at a 6th-grade reading level, is vital to improve patient health literacy. This study evaluated available online resources for SHPT from ESKD based on information quality and readability. METHODS: Three search engines were queried using the terms "parathyroidectomy for secondary hyperparathyroidism," "parathyroidectomy kidney/renal failure," "parathyroidectomy dialysis patients," "should I have surgery for hyperparathyroidism due to kidney failure?," and "do I need surgery for hyperparathyroidism due to kidney failure if I do not have symptoms?" Websites were categorized by source and origin. Two independent reviewers determined information quality using JAMA (0-4) and DISCERN (1-5) frameworks, and scores were averaged. Cohen's kappa evaluated inter-rater reliability. Readability was determined using the Flesch Kincaid Reading Ease, Flesch Kincaid Grade Level, and Simple Measure of Gobbledygook tools. Median readability scores were calculated, and corresponding grade level determined. Websites with reading difficulties >6th grade level were calculated. RESULTS: Thirty one (86.1%) websites originated from the U.S., with most from hospital-associated (63.9%) and foundation/advocacy sources (30.6%). The mean JAMA and DISCERN scores for all websites were 1.3 ± 1.4 and 2.6 ± 0.7, respectively. Readability scores ranged from grade level 5-college level, and most websites scored above the recommended 6th grade level. CONCLUSIONS: Patient-oriented websites tailoring SHPT from ESKD are at a reading level higher than recommended, and the quality of information is low. Efforts must be made to improve the accessibility and quality of information for all patients.

Serum parathormone, vitamin D and cardiovascular risk factors and markers: A pilot study.

BACKGROUND AND AIMS: Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. The aim of this study was to evaluate the associations of serum vitamin D and parathormone (PTH) concentrations with blood pressure values and hypertension-mediated target organ damage (HMOD), including left ventricular (LV) hypertrophy and carotid plaque (CP). METHODS AND RESULTS: We enrolled consecutive patients admitted to the Hypertension Center of Federico II University Hospital in Naples, Italy. All patients underwent carotid doppler ultrasound and echocardiography, measurement of vitamin D and PTH levels and main clinical and laboratory parameters. A total of 126 patients (mean age 54 years, 68% males) were enrolled. Pearson's correlation analysis indicated that PTH levels directly correlated with age, diabetes, dyslipidemia, hypertension, fasting glucose, and LV mass, and inversely with glomerular filtration rate, LDL cholesterol, and vitamin D. Vitamin D levels correlated inversely with PTH, diabetes and CP. Multivariate regression models indicated that an increased LV mass was associated with the presence of obesity (ß = 0.342; P = 0.001). Maximal intima-media thickness was significantly associated with older age (ß = 0.303; P = 0.033). Combined presence of low vitamin D/high PTH levels were associated with more than 4-fold increased risk of having CP in both univariate (OR = 4.77, p = 0.0001) and multivariate regression analysis (OR = 4.52, p = 0.014). CONCLUSION: In a population at high cardiovascular risk, vitamin D and PTH levels were not directly associated with blood pressure values and HMOD. Secondary hyperparathyroidism due to vitamin D deficiency is associated with carotid atherosclerosis independently of other common cardiovascular risk factors.

Surgical Management of Secondary and Tertiary Hyperparathyroidism.

Secondary hyperparathyroidism (SHPT) often arises from kidney disease and is characterized by elevated parathyroid hormone (PTH) levels. The reported optimal PTH level to balance the compensatory physiologic response in SHPT with the pathologic morbidity and mortality has changed over time with our evolving understanding. Parathyroidectomy for kidney-related hyperparathyroidism requires consideration of the patient's dialysis status, potential for kidney transplantation, and medical history. Extent of parathyroidectomy and intraoperative decision-making requires consideration to maximize cure with the risk of permanent hypoparathyroidism. Parathyroidectomy for kidney-related hyperparathyroidism can provide a reduction in morbidity, mortality, and improved kidney allograft function and survival.

Comparative effects of calcitriol and calcimimetic on bone health in renal insufficiency.

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 ß-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.

[Thoracoscopic resection of recurrent atypically located parathyroid adenoma of anterior mediastinum in a patient with hyperparathyroidism undergoing renal replacement therapy]. / Torakoskopicheskoe udalenie retsidivnoi atipichno raspolozhennoi adenomy okoloshchitovidnoi zhelezy perednego sredosteniya u patsientki s giperparatireozom, nakhodyashcheisya na zamestitel'noi pochechnoi terapii.

We present successful surgical treatment of a patient with chronic kidney disease (CKD) and hyperparathyroidism undergoing renal replacement therapy. At baseline, parathyroidectomy via cervical access was performed for parathyroid adenomas. After 6 years, clinical and laboratory relapse of disease required thoracoscopic resection of atypically located anterior mediastinal adenoma. This case demonstrates that this disease is one of the most difficult in modern medicine requiring a special approach in diagnosis and treatment. Patients with CKD and hyperparathyroidism need for follow-up, control of total and ionized serum calcium, inorganic phosphorus and parathormone, osteodensitometry, ultrasound and scintigraphy of thyroid and parathyroid glands, and, if necessary, CT or MRI of the neck and chest organs.

Secondary hyperparathyroidism in chronic kidney disease: pathophysiology, current treatments and investigational drugs.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease (CKD). It begins as an adaptive increase in parathyroid hormone levels to prevent calcium and phosphate derangements. Over time, this condition becomes maladaptive and is associated with increased morbidity and mortality. Current therapies encompass phosphate-lowering strategies, vitamin D analogues, calcimimetics and parathyroidectomy. These approaches harbor inherent limitations, stimulating interest in the development of new drugs for SHPT to overcome these limitations and improve survival and quality of life among CKD patients. AREAS COVERED: This review delves into the main pathophysiological mechanisms involved in SHPT, alongside the treatment options that are currently available and under active investigation. Data presented herein stem from a comprehensive search conducted across PubMed, Web of Science, ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP) spanning from 2000 onwards. EXPERT OPINION: The advancements in investigational drugs for SHPT hold significant promise for enhancing treatment efficacy while minimizing side effects associated with conventional therapies. Although several challenges still hinder their adoption in clinical practice, ongoing research will likely continue to expand the available therapeutic options, refine treatment strategies, and tailor them to individual patient profiles.

Pharmaceutical Management of Secondary Hyperparathyroidism and the Role of Surgery: A 5-Year Retrospective Study.

Background and Objectives: Secondary hyperparathyroidism (SHPT) poses a common condition among patients with chronic kidney disease (CKD) due to the chronic stimulation of the parathyroid glands as a result of persistently low calcium levels. As a first option for medical treatment, vitamin D receptor analogs (VDRAs) and calcimimetic agents are generally used. Apart from cinacalcet, which is orally taken, in recent years, another calcimimetic agent, etelcalcetide, is being administered intravenously during dialysis. Materials and Methods: In a 5-year retrospective study between 2018 and 2023, 52 patients undergoing dialysis were studied. The aim of this study is to highlight the possible effects and/or benefits that intravenously administered calcimimetic agents have on CKD patients. A total of 34 patients (65.4%) received cinacalcet and etelcalcetide while parathormone (PTH) and calcium serum levels were monitored on a monthly basis. Results: A total of 29 out of 33 patients (87.9%) that received treatment with etelcalcetide showed a significant decrease in PTH levels, which rose up to 57% compared to the initial values. None of the included patients needed to undergo parathyroidectomy (PTx) due to either extremely high and persistent PTH levels or severe side effects of the medications. It is generally strongly advised that parathyroidectomies should be performed by an expert surgical team. In recent years, a significant decrease in parathyroidectomies has been recorded globally, a fact that is mainly linked to the constantly wider use of new calcimimetic agents. This decrease in parathyroidectomies has resulted in an important decrease in complications occurring in cervical surgeries (e.g., perioperative hemorrhage and nerve damage). Conslusions: Despite the fact that these surgical complications cannot be easily compared to the pharmaceutical side effects, the recorded decrease in parathyroidectomies is considered to be notable, especially in cases of relapse where a difficult reoperation would be considered based on previously published guidelines.

Prognosis and factors related to severe secondary hyperparathyroidism in long-term peritoneal dialysis patients.

Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.

A comparison of surgical treatments for tertiary hyperparathyroidism. A systematic review.

INTRODUCTION: Tertiary hyperparathyroidism develops in patients who have secondary hyperparathyroidism that persists despite successful kidney transplantation or in patients who are on chronic dialysis.