Parathyroidectomy Versus Cinacalcet for the Treatment of Secondary Hyperparathyroidism in Hemodialysis Patients

Background Secondary hyperparathyroidism in patients with end stage renal disease on dialysis is associated with bone pain and fractures in addition to cardiovascular morbidity. Cinacalcet is the most commonly used drug to treat such patients, but it has never been compared to surgery. The goal of this study is to compare the long-term outcomes and survival between cinacalcet and parathyroidectomy in the treatment of secondary hyperparathyroidism in hemodialysis patients. Methods Adult patients on hemodialysis who were treated with cinacalcet or parathyroidectomy in the United States Renal Data System were included. Patients treated with surgery (n = 2023) were compared using 1:1 propensity score matching ratio to a cohort of patients treated with cinacalcet. A Cox regression analysis was conducted to compare the overall mortality. Results The propensity score matching successfully created two groups with similar demographics. Patients in the surgery group had a higher mean peak PTH level prior to therapy (2066.8 vs 1425.4, P < 0.001). No difference was observed in the development of new-onset coronary artery disease (7.7% vs 7.9%, P = 0.8) or cerebrovascular disease (7% vs 6.7%, P = 0.8). Surgical patients had a higher rate of pathologic fractures (27.8% vs 24.9%, P = 0.04). Survival analysis showed that patients undergoing surgery had a better 5-year survival (65.6% vs 57.8%) and were less likely to die within the study period (HR 0.77, 95% CI 0.7–0.85, P < 0.0001). Conclusions Patients on dialysis undergoing parathyroidectomy for the treatment of secondary hyperparathyroidism have a better overall survival than those treated with cinacalcet.

Recommend-Response and Complications Comparing Radiofrequency Ablation Versus Parathyroidectomy for Secondary Hyperparathyroidism in Dialysis Patients

Introduction : To compare the efficacy and safety of ultrasound(US)-guided radiofrequency ablation (RFA) and parathyroidectomy (PTX) in the treatment of secondary hyperparathyroidism (SHPT). Methods In this retrospective study, we divided patients into PTX (n=53) and RFA (n=47) groups. The primary outcomes were the proportion of patients achieved the target range of iPTH concentrations(124-558pg/mL) and the long-term prognosis. The secondary outcomes were the differences in the changes of iPTH, calcium, and phosphorus over time and the incidence of adverse events. Results There was rarely difference in baseline characteristics between the two groups. Primary outcomes: The iPTH concentrations of 25.8% of patients in the PTX group and 51.3% of the RFA group were within the recommended range at the endpoint (P=0.031). Survival analysis revealed that the difference in all-cause mortality and cumulative response rate between the two groups was not statistically significant (P=0.902, P=0.141, respectively). Secondary outcomes: The iPTH concentrations in PTX group and RFA group dropped sharply after treatment and were 82.30±163.21pg/mL and 279.96±306.57pg/mL (P<0.001). There was no difference in the trend of iPTH, calcium, and phosphorus levels between the two groups over time(P>0.05). In addition, the incidence of infection and the hospital stay in the RFA group were significantly less. And preoperative bone-specific alkaline phosphatase concentration was a risk factor for postoperative hypocalcemia. Conclusion US-guided RFA was minimally invasive and no less than PTX in terms of cumulative response rate and complications in the treatment of severe SHPT in maintenance dialysis patients and may be used as an alternative technique to PTX, which need further studies to confirm.

KIDNEY STONE DISEASE AND OSTEOPOROSIS - TOPIC ISSUES OF COMORBIDITY

the prevalence of kidney stone disease (KSD) and osteoporosis (OP) increases every year. In the prevention of osteoporosis, it is important to consume a sufficient amount of calcium-rich foods in the daily diet, as well as the use of calcium. One of the important reasons for the insufficient use of calcium-containing products and medicines is the anxiety not only of patients, but, very importantly, of doctors as much as possible. This has serious justification, as nephrolithiasis occurs in approximately 5% of the population, and the risk of developing kidney stones during life is 8-10%. It is believed that secondary hyperparathyroidism, which is caused by hypocalcemia due to insufficient consumption of calcium-containing products and impaired renal function, leads to increased bone resorption, formation of kidney stone disease. It is important to consider that against the background of hypertensive, atherosclerotic kidney disease, tubulo-interstitial lesions of the kidneys with decreasing glomerular filtration rate decreases the synthesis of 1α-hydroxylase - an enzyme by which 25-hydroxycholecalciferol (25 (OH) active D3, calcium) form of vitamin D3–1.25 dihydroxycholecalciferol (1.25 (OH) 2D3, calcitriol - D-hormone) and secondary hyperparathyroidism develops. In this case, the purpose of correction along with the treatment of urolithiasis (spa treatment, given the attendance of the presence of KSD, to carry out the distance lithotripsy), intake of active metabolites of vitamin D (should be started with low doses, independent of the initial PTH concentration, and then titrated based on the PTH response) conducting X-ray densitometry.

Leptin and adiponectin in patients with chronic kidney disease and secondary hyperparathyroidism

Background. The results of studies evaluating the levels of adiponectin, leptin and their ratios in chronic kidney disease (CKD) are conflicting. It is assumed that hyperleptinemia and changes in adiponectin clearance are consequences of a decrease in the glomerular filtration rate, they exacerbate renal impairment and may affect the prognosis of survival due to cardiovascular events. It is known that secondary hyperaparathyroidism is the most frequent complication of CKD, which not only affects calcium-phosphorus metabolism and bone tissue, but also contributes to the development of pathological processes involving other hormonal and metabolic markers. Of greatest interest is the assessment of adipocytokine levels in the development of secondary hyperparathyroidism against the background of CKD as an independent factor of increasing cardiovascular risks. The purpose of the study was to assess adipocytokine levels (adiponectin, leptin) and their ratios in patients with different stages of chronic kidney disease and their relationship with manifestations of secondary hyperparathyroidism. Materials and methods. This cross-sectional study enrolled 160 people with CKD and 40 healthy individuals as a comparison group. Results. Leptin level reduction and an increase in the proportion of patients with hypoleptinemia with a decrease in the glomerular filtration rate were found, which may be an important factor determining nutritional status. Correlations were revealed between leptin level, body mass index (ρ = 0.411) and patients’ age (ρ = 0.189), as well as between leptin/adiponectin and adiponectin/leptin ratios (ρ = 0.395 and ρ = –0.395) and body mass index in patients with CKD persisting in subgroups by stage of renal failure. A relationship was found with sex for leptin and a decrease in its levels below normal values in both men and women. Conclusions. The proportion of patients with hyperadiponectinemia was significantly higher among those with end-stage CKD compared to patients with stages 1–2. There was no statistically significant relationship between adipocytokine and parathyroid hormone levels and the presence of secondary hyperparathyroidism in patients examined.

Impact of Dexmedetomidine On Secondary Hyperparathyroidism Recurrence In Uremic Patients Who Received Parathyroidectomy With Auto-Transplantation: A Retrospective Propensity-Matched Study

Background: Recurrence of secondary hyperparathyroidism (SHPT) remains a big challenge in uremic patients who underwent total parathyroidectomy with auto-transplantation (tPTX-AT). However, the relationship between perioperative intervention and recurrence of SHPT remains unclear. Dexmedetomidine has been used safely and effectively in uremic patients’ anesthesia. The aim of the study was to explore the effect of dexmedetomidine on the recurrence of SHPT and speculate the possible mechanism of action.Methods: Records of patients who underwent tPTX-AT between 2017 and 2018 were retrospectively analyzed. The study consisted of patients who received dexmedetomidine intra-operatively and the controls were patients who did not receive dexmedetomidine. The primary endpoint was the difference in the recurrence of SHPT one year after surgery between the two groups. The secondary endpoint was health-related quality of life scores. Analysis included propensity score matching and multivariable logistic regression. Results: Of 354 patients, 133 patients received dexmedetomidine intraoperatively, and the total recurrence rate of SHPT was 10.2%. After propensity score matching, patients who received dexmedetomidine had a 3.80-fold decreased risk of SHPT recurrence (odds ratio, 0.263; 95% confidence interval, 0.081 to 0.854; P=0.026) and exhibited a better quality of life in terms of physical functioning and general health, and less emotional role limitations compared with those in control group.Conclusion: In uremic patients who received tPTX-AT, there was an association between dexmedetomidine use and decreased risk of SHPT recurrence. Further studies are needed to accurately assess the effects and mechanism of action of dexmedetomidine on the prognosis of this population.

Chronic kidney disease alters Pin1 phosphorylation and parathyroid hormone mRNA binding proteins leading to secondary hyperparathyroidism

Parathyroid hormone (PTH) regulates calcium metabolism and bone strength. Chronic kidney disease (CKD) leads to secondary hyperparathyroidism (SHP) which increases morbidity and mortality. High PTH expression in SHP is due to increased PTH mRNA stability mediated by changes in PTH mRNA interaction with stabilizing AUF1 and destabilizing KSRP. Pin1 isomerizes target proteins, including mRNA binding proteins. In SHP, Pin1 isomerase activity is decreased and phosphorylated KSRP fails to bind PTH mRNA, resulting in high PTH mRNA stability and levels. The molecular mechanisms underlying Pin1 regulation and their effect to increase PTH expression are unknown. We show by mass-spectrometry (MS) the CKD induced changes in rat parathyroid proteome and phosphoproteome profiles. Parathyroid Pin1 Ser16 and Ser71 phosphorylation, that disrupts Pin1 activity, is enhanced in acute and chronic kidney failure rats. Accordingly, pharmacologic Pin1 inhibition increases PTH expression in parathyroid organ cultures and transfected cells, through the PTH mRNA protein binding cis element and KSRP phosphorylation. Therefore, CKD leads to parathyroid loss of Pin1 activity by inducing Pin1 phosphorylation. This predisposes parathyroids to increase PTH production through modified PTH mRNA-KSRP interaction that is dependent on KSRP phosphorylation. CKD induced Pin1 and KSRP phosphorylation and the Pin1-KSRP-PTH mRNA axis thus drive secondary hyperparathyroidism.

Perioperative metabolism in patients with secondary hyperparathyroidism and methods of its correction

It is important to study changes in metabolism in patients with secondary hyperparathyroidism (SHPT) during parathyroid surgical interventions (PTSI), as well as to search for ways to correct them. Aim. To study metabolism in patients with SHPT with PTSI and assess the possibilities of its correction. Materials and methods. The study was prospective, not randomized. We studied 135 patients with SHPT with end-stage chronic renal failure who underwent PTSI (72 men and 63 women, aged from 19 to 73 years). Preoperative risk ASA III–IV. General anesthesia using the inhalation anesthetic sevoflurane and the narcotic analgesic fentanyl in low-flow mechanical ventilation. Operational monitoring was complemented by the use of indirect calorimetry. In group I (n = 70), the metabolic rate (MR) and basal metabolism rate (BMR) were determined against the background of standard intensive therapy. In group II (n = 65) – target metabolic rate (TMR) and the metabolic disorders (MD) were additionally determined, and intensive therapy was supplemented with glucocorticoids. Results. The baseline MR in both groups were low, close to BMR. The MR of patients in group I remained low during the entire PTSI (P < 0.05). In group II, from the stage of removal of the parathyroid glands, a steady increase in the MR, with a significant excess of the baseline MR and BMR (P < 0.05), was noted. TMR decreased while exceeding the MR. Group II patients woke up and were transferred to the ward faster compared to group I, and nausea and vomiting were 2.5 times less frequent (9.2 % in group II, 22.9 % in group I). 12 hours after PTSI, feeling of pain, according to the VAS scale, was lower than in group I (P < 0.05). During the day after PTSI, the indicators of the acid-base state of the venous blood of both groups did not change significantly, and the level of ionized calcium decreased (P < 0.05), which required additional intravenous administration of 10 % calcium gluconate. Conclusions. Perioperative energy monitoring makes it safer to carry out PTSI in patients with SHPT. Additional definition of the TMR and the MD allows for more efficient construction of intensive therapy.