The effect of local injections of paricalcitol into the parathyroid glands on parathyroid hormone levels, vascular calcification, and bone mineral density in patients with chronic kidney disease

Diagnosis, assessment, and treatment of bone turnover abnormalities in renal osteodystrophy

Influence of parathyroid mass on the regulation of PTH secretion

Fluorescence-Guided Minimally Invasive Parathyroidectomy: A Novel Surgical Therapy for Secondary Hyperparathyroidism

Objective Currently, parathyroid hormone (PTH) is mainly measured by the second generation intact PTH (iPTH) assay which detects both full-length (1-84)PTH and (7-84)PTH fragments. The third generation whole PTH (wPTH) assay however has turned out to be specific for (1-84) PTH. The aim of this study is to investigate the features of plasma iPTH, (1-84)PTH, (7-84)PTH levels in patients with stage 5 chronic kidney disease (CKD), and evaluate the effects of parathyroidectomy (PTX) on above markers in severe secondary hyperparathyroidism (SHPT) patients. Methods A cross-sectional study including 90 controls and 233 stage 5 CKD patients, and a prospective follow-up study in 31 severe SHPT patients were conducted. Plasma iPTH and (1-84)PTH levels were measured by the second and third generation assay, respectively. Circulating (7-84)PTH level was calculated by subtracting the (1-84)PTH value from the iPTH value. Results Plasma levels of iPTH, (1-84)PTH, (7-84)PTH were higher (P<0.01), and (1-84)PTH/iPTH was lower (P<0.01) in stage 5 CKD patients than in controls. For severe SHPT patients with PTX (n=74), plasma iPTH, (1-84)PTH and (7-84)PTH concentrations were significantly increased compared to non-PTX group (n=159) (P<0.01), and the increase of (7-84)PTH level was more striking than (1-84)PTH. Meanwhile, the value of (1-84)PTH/iPTH was decreased (P<0.01). Plasma iPTH level was strongly correlated with (1-84)PTH level (r=0.980, P<0.01) in stage 5 CKD patients. Also, both iPTH and (1-84)PTH levels were positively correlated with serum alkaline phosphatase, dialysis vintage and serum phosphorus (P<0.01). After PTX (median interval of follow-up: 7.1 months), plasma iPTH, (1-84)PTH, (7-84)PTH concentrations were decreased (by 92.9%, 89.7%, 95.8%, P<0.01, respectively) greatly and (1-84)PTH/iPTH was increased (P<0.01). Conclusions In stage 5 CKD patients, plasma iPTH, (1-84)PTH, (7-84)PTH levels are greatly increased while (1-84)PTH/iPTH is decreased, and PTX can significantly improve abnormality of above markers in severe SHPT patients. The second generation PTH assay overestimates the severity of SHPT, and the accurate measurement of (1-84)PTH by the third assays is more conducive to diagnosis and treatment of CKD and SHPT patients. Key words: Hyperparathyroidism, secondary; Renal insufficiency, chronic; Parathyroid hormone; Parathyroidectomy

CHAPTER 3

Bone Health in Chronic Kidney Disease–Mineral and Bone Disease

Complications of Progression of CKD

Overview of renal bone disease: Causes of treatment failure, clinical observations, the changing pattern of bone lesions, and future therapeutic approach: Management of comorbidities in kidney disease in the 21st century: Anemia and bone disease

The possibility of estimating the total weight of the parathyroid glands based on the plasma concentration of the parathyroid hormone (PTH) would be of great help when searching for the parathyroid glands during surgery on patients with secondary hyperparathyroidism. Thus, we studied the relationship between the levels of carboxyl-terminal PTH (C-PTH), midportion PTH (M-PTH) and intact PTH, and the weight of the parathyroid glands resected for secondary hyperparathyroidism. The subjects studied were 11 patients with secondary hyperparathyroidism caused by chronic renal failure. The pre- and post-operative differences in the plasma C-PTH levels and plasma M-PTH levels were significantly correlated with the weight of the resected parathyroid glands (p less than 0.001 for both), but there was no correlation between the differences in the levels of intact PTH and the weight of the resected parathyroid glands. From these relationships we estimated the weight of the residual parathyroid gland after parathyroidectomy using the levels of each PTH. All patients in whom the residual parathyroid gland was estimated to be heavy based on the levels of M-PTH showed recurrence of hyperparathyroidism after the parathyroidectomy. We therefore found that estimation of the weight of the parathyroid glands from the levels of M-PTH is both possible and useful.

Aim: to assess the dynamics of laboratory parameters (total calcium, inorganic phosphorus, albumin, and alkaline phosphatase levels) and parathyroid hormone (PTH) concentrations after administrating local injections of vitamin D receptor activators into the parathyroid glands of patients with secondary hyperparathyroidism in chronic kidney disease. The intial PTH concentration ranged from 300 to 600 pg/ml. This range was chosen to explore a more active strategy for managing the disease at its early stages and preventing the induction and progression of cardiovascular complications associated with secondary hyperparathyroidism.Methods: the study included 48 patients diagnosed with end-stage of chronic kidney disease, who were treated in the nephrology and dialysis department. The main group consisted of 34 patients who received two consecutive injections of a vitamin D receptor activator (Paricalcitol) into the most enlarged and technically accessible parathyroid gland under ultrasound guidance. The control group included 14 patients who continued with conservative treatment due to technical infeasibility of performing the injections. Effectiveness was assessed by comparing laboratory parameters before the intervention and six months after the injections in the main group, and among patients continuing standard medical therapy for secondary hyperparathyroidism.Results: the results showed a statistically significant reduction in parathyroid hormone levels after 3 and 6 months of treatment. In the control group, which continued to receive standard drug therapy, PTH and blood phosphate levels continued to rise. No undesirable effects or complications, such as hypocalcemia, bleeding, allergic reactions, and recurrent laryngeal nerve paralysis, were not observed throughout the observation period.Conclusion: this research confirms the efficacy of local injections of vitamin D receptor activators (Paricalcitol) in reducing PTH levels without significant complications or changes in calcium levels. This method could be employed to correct and prevent secondary hyperparathyroidism complications in early stages among patients with end-stage chronic kidney disease, offering a safer and more effective treatment option.

In vitamin D insufficiency, elevated parathyroid hormone (PTH) levels may contribute to adverse effect on bone. We assessed effects of PTH responses to vitamin D insufficiency on bone metabolism, density, and geometry. Using a cross-sectional design, we investigated 102 healthy postmenopausal women with low 25-hydroxy-vitamin D (< 50nmol/L) levels, who had either secondary hyperparathyroidism with elevated PTH levels (> 6.9pmol/L, N = 51) or normal PTH levels (N = 51). Bone mineral density (BMD) and bone geometry were assessed by Dual-Energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT) and high-resolution peripheral QCT (HRpQCT) scans. Bone metabolism was assessed by biochemistry including bone turnover markers. Levels of 25(OH)D were 38 (IQR 31-45) nmol/L with no differences between groups. PTH levels were 8.5 (IQR 7.5-9.5) in women with SHPT and 5.2 (4.4-6.6) pmol/L in women with normal PTH (p < 0.001). BMI and eGFR did not differ between groups. SHPT was associated with lower total- and trabecular bone area, lower cortical perimeter, and increased cortical area in tibia and radius. SHPT was associated with a lower weight-adjusted BMD at the lumbar spine (p < 0.05). High compared to normal PTH levels were associated with significantly lower plasma levels of 1,25(OH)2D, phosphate, but higher levels of osteocalcin and borderline higher levels of CTx. PTH correlated to osteocalcin and CTx. High PTH levels are associated with altered bone geometry, increased bone turnover, and reduced BMD at the spine. Whether an increased cortical thickness with a lower trabecular volume is an effect of PTH or not needs further elucidations.

Background. In this study, we endeavored to determine whether the incidence of cholelithiasis (CL) was increased in chronic renal failure (CRF) patients with secondary hyperparathyroidism on a peritoneal dialysis (PD) program. We also evaluated the factors that might have some influence on the development of CL. Methods. A total of 59 CRF patients undergoing PD were included in the study. We studied the following groups to determine whether parathyroid hormone (PTH) levels were increased in CRF-PD patients: twenty patients with secondary hyperparathyroidism (group 1) and 39 patients with normal PTH levels (group 2). PTH levels were maintained at three times the upper limit of normal. Biochemical parameters were obtained for each CRF-PD patient. All patients underwent abdominal ultrasonography to screen for the presence of cholelithiasis. For statistical analysis, χ2, t test, and logistic regression analysis were used; p < 0.05 was considered as significant. Results. We found an almost ten times higher incidence (25% vs. 2.6%) of CL in group 1 patients with statistical significance (p = 0.007). When the incidence of CL according to sex, creatinine, and PTH levels were considered, female gender, creatinine, and PTH levels were higher in group 1, which was also significant statistically. No significant relationship was detected between gallbladder stone formation and the other analyzed biochemical parameters. Conclusions. We found that the incidence of CL in CRF-PD patients with secondary hyperparathyroidism was higher than CRF-PD patients with normal PTH levels. It was also detected that female gender, high creatinine levels, and elevated PTH levels might influence the development of CL in CRF-PD patients.

Secondary Causes of Osteoporosis

Phosphorus directly controls parathyroid hormone (PTH) synthesis and secretion. Serum levels of the novel phosphate-regulating hormone, fibroblast growth factor 23 (FGF23), are positively correlated with hyperphosphatemia in patients with chronic kidney disease (CKD). Rats were fed a diet containing adenine for 4 weeks to establish CKD. Animals were then offered a diet containing sevelamer hydrochloride (sevelamer) or a normal diet for alternating 2 week periods over 8 weeks. Adenine-treated rats showed marked elevations of serum phosphorus, PTH and FGF23 levels associated with parathyroid hyperplasia and aortic calcification. Serum phosphorus, PTH and FGF23 levels decreased rapidly when sevelamer treatments commenced and recovered rapidly once they were discontinued. However, intermittent treatment with sevelamer successfully inhibited parathyroid hyperplasia and aortic calcification. In conclusion, phosphate-binder treatment can effectively inhibit the elevation of serum FGF23 levels, as well as PTH levels, under conditions of CKD. Setting up a period of reduced serum phosphorus levels, even if it is intermittent, is worthwhile for the inhibition of the development of parathyroid hyperplasia and aortic calcification.

less, no abnormal findings appeared during either the first-look operation or during subsequent imaging studies, including CT, 99m Tc