BACKGROUND

Vitamin D plays a major role in physiological processes that modulate mineral metabolism and immune function with probable link to several chronic and infectious conditions. Emerging data suggests a possible influence of vitamin D on glucose homeostasis. This study sought to provide preliminary information on vitamin D status among Ghanaian type 2 diabetics and assessed its association with glucose homeostasis.

METHODS

In a case control study, 118 clinically diagnosed Type 2 Diabetes Mellitus (T2DM) patients attending Diabetic Clinic at the Nkawie Government Hospital were enrolled between October and December 2015. Hundred healthy non-diabetics living in Nkawie district were selected as controls. Structured questionnaires were administered to obtain socio-demographic data. Venous blood samples were taken from both cases and controls to estimate their FBG, Lipid profile spectrophotometrically and IPTH, 25OHD by ELISA. Statistical analyses were performed using SPSS v20.0 Statistics.

RESULTS

The average age of the study participants was 58.81years for cases and 57.79year for controls. There was vitamin D deficiency of 92.4% among T2DM cases and 60.2% among the non diabetic controls. Vitamin D deficiency did not significantly associate with HOMA-β [T2DM: r2 = 0.0209, p = 0.1338 and Control: r2 = 0.0213, p = 0.2703] and HOMA-IR [T2DM: r2 = 0.0233, p = 0.1132 and Control: r2 = 0.0214, p = 0.2690] in both the controls and the cases.

CONCLUSIONS

Vitamin D deficiency is prevalent in both T2DM and non-diabetics. There is no association between vitamin D deficiency and insulin resistance or beta cell function in our study population. Vitamin D supplementation among type 2 diabetics is recommended.

A standard oral calcium loading test has been employed in a group of idiopathic hypercalciuria (IH) subjects and in a group of marginally hypercalcaemic subjects with primary hyperparathyroidism (PHPT) in whom the diagnosis was revealed by careful combined measurements of serum ionized calcium and immuno-reactive parathyroid hormone (iPTH). Initial values for serum ionized calcium and creatinine clearance were similar in IH and in a control group of normal subjects, whereas iPTH levels were normal or low. Following oral loading, serum ionized calcium rose to similar levels in both IH and control subjects, with no suggestion of relative hypercalcaemia due to a postulated intestinal hyperabsorption in the IH group. A renal tubular calcium 'leak' was however clearly evident in the IH group, in both the fasting and post-absorptive phase. In the marginally hypercalcaemic PHPT subjects on the other hand, a relative post-absorptive hypercalcaemia was clearly apparent, as well as a gross renal tubular calcium leakage. Thus careful preliminary separation of masked PHPT from IH subjects is an essential step before evaluation of response to oral calcium challenge in stone-forming subjects. When this is done, no evidence of a relative post-absorptive hypercalcaemia can be seen in the residual IH group, and hypercalciuria appears to be 'renal' rather than 'absorptive' in origin.

BACKGROUND

Chronic renal failure in women is frequently associated with endocrine disturbances leading to menstrual disorders. However, most studies on renal osteodystrophy have not taken into account the possible role of these hormonal disturbances on the pathogenesis of bone alterations seen in these patients. In the present study, we evaluated bone mineral metabolism in a group of young hemodialyzed women with persistent amenorrhea and compared them with similar women with regular menstruation.

METHODS

We studied 74 women who were further subdivided into 43 women with regular menstrual periods and 31 women with persistent amenorrhea, defined as the absence of menstrual bleeding for more than six months. In all patients, we performed a bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, intact parathyroid hormone (iPTH), sexual hormone determinations that included total estradiol, follicle-stimulating (FSH), and luteinizing hormone and markers of bone resorption such as the procollagen type 1 cross-linked carboxy-terminal telopeptide (ICTP).

RESULTS

Serum calcium, phosphorus, and iPTH were similar in both groups. Serum alkaline phosphatase was higher in amenorrheic women. Although the total serum estradiol concentration was normal in the amenorrheic women when compared with nonuremic women, the values were significantly lower than those in regularly menstruating women. Serum FSH and ICTP values were significantly higher in the amenorrheic women. Trabecular BMD in the lumbar spine was also significantly lower in the amenorrheic women compared with regularly menstruating dialysis patients. Lumbar spine BMD and total estradiol levels correlated significantly in the amenorrheic group.

CONCLUSIONS

These studies show that persistent amenorrheic young women on dialysis have lower trabecular BMD and evidence of increased bone resorption when compared with normal menstruating women on dialysis. The possible impact of these results in the natural history of the uremic osteodystrophy remains to be determined.

BACKGROUND

Options for controlling hemostasis during thyroidectomy include bipolar vessel sealing system and ultrasonic technology. The purpose of this study was to compare these energy-based devices on the performance of open thyroidectomy for benign disease with emphasis given to postoperative parathyroid function.

METHODS

Among the available energy-based devices, the LigaSure Precise (LP; Valleylab, Boulder, CO) and FOCUS Shears (FS; Ethicon Endo-Surgery, Cincinnati, OH) were evaluated. One hundred ninety-nine consecutive patients scheduled for open thyroidectomy were prospectively randomized into 2 similar-sized groups. Operative time, morbidity, incision length, postoperative pain, and hospital stay were analyzed. Postoperative hypoparathyroidism was monitored with serial determinations of intact parathyroid hormone (iPTH) and serum calcium.

RESULTS

Early postoperative measurement of iPTH plasma level, although within the reference range, was significantly lower in the FS group (p < .001). Oral calcium supplementation was significantly higher and prolonged in the FS group.

CONCLUSIONS

The present study demonstrates a significant difference of the rates for postoperative parathyroid malfunction when using different energy-based devices.

Although levels of serum immunoreactive parathyroid hormone (iPTH) increase with age in women, this could be caused by retention of non-biologically active PTH fragments by the aging kidney. In 102 normal women, aged 30 to 89 yr, serum iPTH increased with age by 58% (r = 0.33, p less than 0.001) with antiserum GP-1M (which has midmolecule specificity) and 43% (r = 0.32, p less than 0.001) with antiserum CH-12M (which may have whole molecule specificity); urinary cAMP/GFR excretion increased by 29% (r = 0.22, p less than 0.05). The results of these assays were validated by comparison with serum levels of biologically active PTH (BioPTH) in immunoextracts of serum followed by renal adenylate cyclase assay in a selected subgroup of 25 of the women. Serum BioPTH correlated with serum iPTH assessed by antiserum GP-1M (r = 0.48, p less than 0.05) and antiserum CH-12M (r = 0.48, p less than 0.05) but not with urinary cAMP. The data are consistent with an increase of parathyroid function with aging: clearly, we do not find decreased parathyroid function as would be expected if age-related bone loss was not mediated, in part, by PTH.

BACKGROUND

Exposure to inorganic arsenic (As) through drinking water during pregnancy is associated with lower birth size and child growth. The aim of the study was to assess the effects of As exposure on child growth parameters to evaluate causal associations.

RESULTS

Children born in a longitudinal mother-child cohort in rural Bangladesh were studied at 4.5 years (n=640) as well as at birth (n=134). Exposure to arsenic was assessed by concurrent and prenatal (maternal) urinary concentrations of arsenic metabolites (U-As). Associations with plasma concentrations of insulin-like growth factor 1 (IGF-1), calcium (Ca), vitamin D (Vit-D), bone-specific alkaline phosphatase (B-ALP), intact parathyroid hormone (iPTH), and phosphate (PO4) were evaluated by linear regression analysis, adjusted for socioeconomic factor, parity and child sex. Child U-As (per 10 µg/L) was significantly inversely associated with concurrent plasma IGF-1 (β=-0.27; 95% confidence interval: -0.50, -0.0042) at 4.5 years. The effect was more obvious in girls (β=-0.29; -0.59, 0.021) than in boys, and particularly in girls with adequate height (β=-0.491; -0.97, -0.02) or weight (β=-0.47; 0.97, 0.01). Maternal U-As was inversely associated with child IGF-1 at birth (r=-0.254, P=0.003), but not at 4.5 years. There was a tendency of positive association between U-As and plasma PO4 in stunted boys (β=0.27; 0.089, 0.46). When stratified by % monomethylarsonic acid (MMA, arsenic metabolite) (median split at 9.7%), a much stronger inverse association between U-As and IGF-1 in the girls (β=-0.41; -0.77, -0.03) was obtained above the median split.

CONCLUSIONS

The results suggest that As-related growth impairment in children is mediated, at least partly, through suppressed IGF-1 levels.

Various hormones have been implicated in the genesis of hypercalcemia in patients with malignancy. Ectopic secretion of PTH by tumor has been documented in only a few patients; rather, elevated levels of circulating iPTH have been presumed to reflect tumor production of hormone in most patients. Small fragments of PTH, as well as polypeptides larger than native PTH, have been described; their biological roles are unclear. The pattern of immunoreactivity, however, has been used to differentiate patients with ectopic hyperparathyroidism from patients with concomitant primary hyperparathyroidism. Vitamin D-like sterols produced by breast cancer seldom reach plasma levels necessary for physiological effects. Members of the prostaglandin family have been proposed to induce hypercalcemia through osteoclast activation or alteration of the immune system and also to affect the frequency of bone metastases. At present, no direct evidence is available to prove a direct role for these effects and prostaglandins are most useful as possible indicators of disease activity.

BACKGROUND

The former standard surgical treatment in patients with primary hyperparathyroidism (pHPT) has been bilateral cervical exploration. New localization techniques and the possibility of intraoperative measurement of intact parathormone (iPTH) permit a focused, minimally invasive parathyroidectomy (MIP). The introduction of MIP without complete neck exploration leads to the potential risk of missing thyroid pathology. The aim of the present study is to evaluate the value of MIP in respect to coexisting thyroid findings and their impact on preoperative workup for primary hyperparathyroidism.

METHODS

This is a prospective study including 30 consecutive patients with pHPT (median age 65 years; 17 females, 13 males). In all patients preoperative localization was performed by ultrasonography and 99m Tc-MIBI scintigraphy- Intraoperative iPTH monitoring was routinely done.

RESULTS

Ten patients (33%) had a concurrent thyroid finding requiring additional thyroid surgery, and two patients (7%) with negative localization results underwent bilateral neck exploration. Therefore, MIP was attempted in 18 (60%) patients. The conversion rate to a four gland exploration was 6% (1/18). The sensitivities of 99m Tc-MIBI scanning and ultrasonography were 83.3% and 76.6%, respectively. The respective accuracy rates were 83.3% and 76.6%. Of note, the combination of the two modalities did not improve the sensitivity and accuracy in our patient population. During a median follow-up of 40 months, none of the patients developed persistent or recurrent hypocalcaemia, resulting in a 100% cure rate.

CONCLUSIONS

Coexisting thyroid pathology is relatively frequent in patients with pHPT in our region. Among patients having pHPT without any thyroid pathology, the adenoma localization is correct with either ultrasonography or 99m Tc-MIBI scintigraphy in the majority of cases. MIP with iPTH monitoring are highly successful in this group of patients and this operative technique should be the method of choice.

Growing rats were fed a calcium-deficient diet for 12 days to induce bone loss and were subsequently placed on a calcium-replacement diet for 1 to 3 days to evoke bone repletion. Control animals were fed the calcium-replacement diet continuously. Twelve days of calcium deprivation resulted in a 21-fold increase in the number of endosteal osteoclasts in the tibial diaphysis as compared with controls. These osteoclasts, however, rapidly disappeared from the endosteum after restoration of dietary calcium. Only 14% of these endosteal osteoclasts remained after 1 day, and no osteoclasts were present after 3 days of calcium replenishment. During this time, plump osteoblasts replaced osteoclasts on the endosteal surface. The number of osteoclasts in the marrow space also changed strikingly. An 11-fold increase in the number of osteoclasts in the marrow space occurred during the calcium-deprivation phase. However, the greatest increase (39-fold) was observed during the first day of calcium replenishment. Thereafter, the number of osteoclasts in the marrow space declined and, after 3 days of calcium replenishment, returned to the control level. During calcium replenishment, acid phosphatase-positive fragments in the marrow space appeared concomitantly with osteoclast disintegration and fragmentation. The kinetic changes and acid phosphatase staining of these fragments suggest that the fragments are the products of disintegrating osteoclasts, a finding consistent with the hypothesis that the fate of some osteoclasts in vivo is cell death. At the end of calcium deprivation, serum iPTH levels and the production of 1,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 were significantly increased compared to controls. After 3 days of calcium replenishment, serum iPTH had decreased to control levels, but the production of 1,25-dihydroxyvitamin D3 was still elevated. Changes in serum iPTH and the production of 1,25-dihydroxyvitamin D3 cannot, therefore, be totally responsible for the observed decrease in osteoclast number during bone repletion. Bone repair after calcium deprivation may be a locally controlled phenomenon.

With the aim of evaluating bone phosphorus/hydroxyproline ratio (P/Hypro) as an index of osteomalacia, this bone index and the bone mineral content (BMC) have been investigated together with other indices of calcium metabolism in 27 gastrectomized patients. None of the patients had clinically manifest bone symptoms. The mean values of bone P/Hypro, BMC, plasma calcium and plasma magnesium were subnormal; the mean values of serum parathyroid hormone (iPTH) and plasma alkaline phosphatase were elevated. Mean serum 25-hydroxycholecalciferol (25-OH-D) did not differ from normal. A significant positive correlation was found between bone P/Hypro and serum 25-OH-D, but no significant correlation between bone P/Hypro and BMC. Serum 25-OH-D and bone P/Hypro were significantly lower and serum iPTH was significantly higher in a subgroup of 12 patients with no regular supplementary intake of vitamin D. In conclusion, the gastrectomized patients had blood biochemical evidence of a mild vitamin D insufficiency and the low bone P/Hypro values can be explained by mild osteomalacic changes in bone.

We measured serum osteocalcin concentrations in 82 pregnant and 21 nonpregnant women. Osteocalcin values declined in the second trimester, but returned to nonpregnant levels late in the third trimester. The mean serum osteocalcin concentration in 36 women during pregnancy (mean gestation, 26 weeks) of 2.8 ng/mL was significantly lower than that in nonpregnant women (6.4 ng/mL; P less than 0.001) or term pregnant women at delivery (6.1 ng/mL; n = 46). Serum immunoreactive PTH (iPTH) levels were significantly higher during pregnancy than in nonpregnant women [97 +/- 5 vs. 56 +/- 4 ng/L (mean +/- SE); P less than 0.001]. No significant correlations were found between maternal osteocalcin concentrations and serum phosphorus, alkaline phosphatase, or iPTH, but significant negative correlations were found between osteocalcin and total calcium or total protein. Osteocalcin concentrations in midtrimester amniotic fluid were very low (mean, 0.3 +/- 0.1 ng/mL; n = 11). In 29 lactating mothers, the mean serum osteocalcin level was 9.5 +/- 1.5 ng/mL, significantly higher than in any of the other groups (P less than 0.05), but their serum calcium and iPTH levels were normal. There was no correlation between serum osteocalcin and calcium or iPTH concentrations in lactating women. These changes are compatible with a sequence in which bone turnover is reduced during early pregnancy, rebounds in the third trimester, and increases in postpartum lactating women.

It has been proposed to cautiously supplement with vitamin D to any patient with asymptomatic primary hyperparathyroidism (PHTP) and a plasma 25-hydroxyvitamin D [25(OH)D] concentration <50 nmol/l. Evidence about the safeness of this intervention is limited to two studies. Our aim was to prospectively assess the biochemical effects of one-year 25(OH)D supplementation in this context. Twenty-seven patients were included in this study. Calcifediol was started at a dose of 480-960 IU/24 h (8-16 microg/24 h) and adjusted up to a maximum of 960 IU/24 h (16 microg/24 h). Basal calcium, phosphate, albumin, total alkaline phosphatase (ALP), creatinine, 24 h calcium urinary excretion, intact PTH (iPTH) and 25(OH)D were measured before and during vitamin D supplementation. The mean basal 25(OH)D was 28.7 +/- 8.0 nmol/l, and at 12 months was 71.5 +/- 32.5 nmol/l (P = 0.00 vs. baseline). After 3, 6 and 12 months iPTH levels were 141.7 +/- 108.4 ng/l (P = 0.00 vs. baseline), 131.1 +/- 95.7 ng/l (P = 0.03 vs. baseline) and 162.2 +/- 139.3 ng/l (P = ns vs. baseline). Mean calcium did not change. Mean urinary calcium excretion increased significantly (basal: 5.7 +/- 2.9 mmol/24 h, 12 months: 7.9 +/- 4.9 mmol/24 h, P = 0.02). Cautious calcifediol supplementation significantly increased mean 25(OH)D and temporarily reduced mean iPTH. It did not change mean serum calcium, but urinary calcium excretion increased significantly. We suggest that serum calcium and 24 h calciuria be measured at regular intervals in patients with PHTP, while on calcifediol supplementation.

BACKGROUND

Optimal treatment protocol to prevent symptomatic hypocalcemia following total thyroidectomy is still matter of debate. We prospectively evaluated the efficacy of a selective supplementation protocol based on both early postoperative intact parathyroid hormone (iPTH) and serum calcium levels.

METHODS

Two hundred thirty consecutive patients were divided in three different groups of treatment according to iPTH levels 4 h after total thyroidectomy (4 h-iPTH) and serum calcium levels in the first postoperative day (1PO-Ca): group A (4 h-iPTH>> 10 pg/ml, 1PO-Ca ≥ 8.5 mg/dl), no treatment; group B (4 h-iPTH>> 10 pg/ml, 1PO-Ca < 8.5 mg/dl), oral calcium (OC) 3 g per day; and group C (4 h-iPTH ≤ 10 pg/ml), OC 3 g + calcitriol (VD) 1 μg per day. Development of biochemical and/or symptomatic hypocalcemia was evaluated.

RESULTS

Fifty-nine patients (25.6%) had subnormal 4 h-iPTH levels (≤10 pg/ml) (group C). Among patients with normal 4 h-iPTH levels, 25 (10.9%) had subnormal 1PO-Ca (<8.5 mg/dl) (group B). The remaining 146 patients (63.5%) had normal 4 h-iPTH and 1PO-Ca levels (group A). One patient in group A, 2 in group B, and 18 in group C developed biochemical hypocalcemia. Only one patient in group C experienced major symptoms. Treatment was discontinued within 1 month in all the patients in group B. At a mean follow-up of 303 days, five patients in group C were still under supplementation treatment.

CONCLUSIONS

The proposed supplementation protocol seems efficacious in preventing symptomatic hypocalcemia. It could allow a safe and early discharge of most patients, thus avoiding the constraints and the costs of routine supplementation.

Serum immunoreactive parathyroid hormone (iPTH) levels were increased in a 15 year old girl with pseudohypoparathyroidism, hypocalcemia, hyperphosphatemia, and minimal phosphaturic and absent hypercalcemic responses to exogenous parathyroid extract (PTE). Following normalization of the serum calcium concentration with vitamin D, serum iPTH and phosphate concentrations returned to the normal range, and phosphaturia could be clearly stimulated and hypercalcemia induced by PTE. On the other hand, the urinary cyclic adenosine 3',5'-monophosphate (cyclic AMP) excretion could not be stimulated, suggesting that in this case, there appears to be no relationship between the urinary excretion of cyclic AMP and the phosphaturic effect of PTE. The minimal phosphaturic effect and the lack of hypercalcemic effects of PTE in untreated pseudohypoparathyroidism can be explained by the secondary hyperparathyroidism causing elevated iPTH levels rather than by a defect at the level of the receptor sites. A requirement of pharmacologic amounts of vitamin D per se, however, for the responsiveness of patients with pseudohypoparathyroidism to PTE cannot be ruled out.

Sarcoidosis is frequently attended by hypercalciuria and sometimes by hypercalcaemia. The type of hypercalciuria and its relationships with disease extension and activity have rarely been investigated. In order to clarify these issues we undertook an investigation by a calcium absorption test in 39 patients with untreated thoracic sarcoidosis, and tried to establish correlations with vitamin D3 metabolism and some features of the disease. We found three types of responses. Group I (n = 12) with a normal test had normal 1,25-(OH)2D3 and rare extrathoracic localisations. Group II (n = 14) with absorptive hypercalciuria had higher serum calcium; 1,25-(OH)2D3 (p less than 0.001) and the free 1,25-(OH)2D3 index (p less than 0.05) were raised. Sarcoidosis was more often inflammatory, developing and disseminated. Group III (n = 13) had resorptive hypercalciuria, and hypercalcaemia was frequent. 1,25-(OH)2D3 (p less than 0.01) and the free 1,25-(OH)2D3 index (p less than 0.05) were raised but to the same degree as in Group II. Sarcoidosis was more disseminated and developing than in Groups I and II. In the 39 patients, iPTH and nephrogenous cAMP were low. Post-calcium load urinary calcium/creatinine (Ca/Cr) and 1,25-(OH)2D3 were correlated (p less than 0.05). Extrathoracic extension was associated with higher fasting urinary Ca/Cr (p less than 0.001), and development with higher post-load urinary Ca/Cr (p less than 0.001). Thus, absorptive hypercalciuria is related to the development of sarcoidosis and can be explained by high free 1,25-(OH)2D3, while resorptive hypercalciuria seems to be linked with disease extension. In such a case, the mechanism of osteolysis is not solely accounted for by high 1,25(OH)2 vitamin D3 serum levels, and we postulate that some other factor is at work, related to the extent of the granulomatous process.

BACKGROUND

In this Phase 4 international study, efficacy and safety of paricalcitol-centred therapy were compared with that of cinacalcet-centred therapy for the treatment of chronic kidney disease (CKD)-associated secondary hyperparathyroidism (SHPT) in patients undergoing haemodialysis (ClinicalTrials.gov identifier NCT00977080).

METHODS

Patients ≥ 18 years of age with Stage 5 CKD and SHPT [intact parathyroid hormone (iPTH) level of 300-800 pg/mL, calcium level of 8.4-10.0 mg/dL and phosphate concentration of ≤ 6.5 mg/dL] who were undergoing haemodialysis were included. Patients were randomized by mode of paricalcitol administration [i.e. intravenous (IV) or oral strata] to receive paricalcitol- or cinacalcet-centred therapy for ≤ 28 weeks. Changes in metabolic markers [total alkaline phosphatase (AP), bone-specific AP and fibroblast growth factor-23 (FGF-23)] and the proportion of patients in each treatment group who achieved an iPTH level of 150-300 pg/mL during Weeks 8, 16 and 21-28 as a composite value were evaluated.

RESULTS

Compared with cinacalcet-centred therapy, levels of both bone turnover markers were significantly reduced from baseline with IV and oral paricalcitol-centred treatment (P < 0.05 for both dosing strata) at Weeks 8, 16 and 28. Levels of FGF-23 were increased with paricalcitol versus cinacalcet-centred treatment. A greater proportion of patients receiving paricalcitol-centred therapy achieved target iPTH levels (i.e. 150-300 pg/mL) throughout the study in the IV and oral dosing strata compared with patients receiving cinacalcet-centred treatment.

CONCLUSIONS

In patients with CKD and SHPT undergoing haemodialysis, paricalcitol-centred therapy reduced circulating bone turnover markers and iPTH levels and increased FGF-23 levels compared with cinacalcet-centred treatment.

BACKGROUND

ClinicalTrials.gov identifier NCT00977080.

OBJECTIVE

Fatigue is a common symptom in long-term dialysis patients. This study investigated possible clinical factors which may cause the development of fatigue in patients receiving peritoneal dialysis (PD). We also investigated the relationship between total solute clearance (TSC) and fatigue symptoms in PD patients.

METHODS

A cross-sectional study design was used to compare the clinical characteristics among groups of PD patients classified by different degrees of fatigue. The relationship among dialysis adequacy (including Kt/V(urea) and weekly creatinine clearance; C(cr)), clinical characteristics and fatigue symptoms were also assessed.

METHODS

The PD unit of a major university teaching hospital in Taipei, Taiwan.

METHODS

Consecutive patients who had received PD for a minimum duration of 4 months were recruited for participation in the study. Patients were excluded if they had a history of ischemic heart disease, severe heart failure (NYHA function III or IV), malignant neoplasm, active infection, major psychiatric problems, chronic obstructive pulmonary disease, or disturbed consciousness. Finally, a total of 64 patients, 31 of whom were receiving continuous ambulatory peritoneal dialysis and 33 who were receiving continuous cycling-assisted peritoneal dialysis, were enrolled in the study.

METHODS

Fatigue was evaluated using a specially designed questionnaire that includes fourteen items. Patients were divided into three groups according to their fatigue scores (FS): mild (FS, 0-3), moderate (FS, 4-8), and severe (FS, 9-14) fatigue. The demographic data, dialysis variables, and clinical parameters of patients were compared among these groups. The relationship between fatigue and TSC was also examined.

RESULTS

The FS were correlated with serum intact parathyroid hormone (iPTH) level and total cholesterol concentration (p < 0.05). A linear correlation was also noted between serum iPTH level and total cholesterol level. When the patients were divided into an adequate- and an inadequate-dialysis group according to values of TSC, Kt/V(urea) as well as weekly creatinine clearance, a significant correlation was found between weekly C(cr) and FS.

CONCLUSIONS

This study has demonstrated that dialysis adequacy plays a key role in the development chronic fatigue. In addition, weekly C(cr) was better correlated with fatigue than Kt/V(urea).

OBJECTIVE

Hypoparathyroidism and paralysis of the recurrent laryngeal nerve (RLN) still remain the most frequent specific complications of thyroid surgery. This study evaluates the effects of employment of a recently introduced device (LigaSure™ Small Jaw, LSJ), compared to the traditional clamp-and-tie (CT) technique, on the short- and long-term outcome of the patients who underwent thyroidectomy.

METHODS

This prospective, randomized study included 190 patients enrolled from October 2011 to July 2013. The numbers of patients in the LSJ group and the CT group were both 95. We studied the following: operative times, intraoperative and postoperative blood losses, intact parathormone (iPTH) and calcium serum levels, and the incidence of RLN paralysis.

RESULTS

The two cohorts were homogeneous for age, sex, surgical indication, BMI, ASA score, and estimated thyroid volume. Operation time has been 73.90 ± 23.35 min in group CT and 60.20 ± 22.36 min in group LSJ (p = 0.002). Intraoperative blood losses have been 47 ± 18 ml in group CT and 38 ± 14 in group LSJ (p = 0.002), while postoperative blood losses have been 45 ± 21 ml in group CT and 40 ± 20 in group LSJ (p = 0.105). The mean calcium blood level in group CT has been 8.12, 7.79, and 7.92 mg/dl in the first, second, and third postoperative days, respectively, as well as 8.26, 7.97, and 8.22 mg/dl for group LSJ (p>> 0.05). Basal and post-thyroidectomy iPTH levels have been 46.49 and 23.64 pg/ml in group CT (Δ = 49.15 %), as well as 51.06 and 27.73 (Δ = 45.69 %) in group LSJ (p>> 0.05). Permanent RLN paralysis was 1.05 % in LSJ group and 0 % in CT group.

CONCLUSIONS

The employment of LSJ reduces in a statistically significant way both operative times and intraoperative blood losses. No significant differences were found as far as postoperative RLN paralysis and hypoparathyroidism.

OBJECTIVE

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI™) 2003 and Kidney Disease: Improving Global Outcomes (KDIGO) 2009 have established guidelines for the treatement of secondary hyperparathyroidism. This study evaluated the impact of parathyroidectomy to achieve recommended values for parathyroid hormone, calcium, phosphorus and CaxPO(4) product in dialysis patients with severe secondary hyperparathyroidism that is resistant to medical treatment.

METHODS

This study included 43 consecutive patients who underwent parathyroidectomy for a severe form of secondary hyperparathyroidism (SHPT) that is unresponsive to medical treatment. The serum iPTH, calcium and phosphorus levels were measured prior to surgery, every morning after surgery for 5 days and on the first, sixth and eighth postoperative months.

RESULTS

Following parathyroidectomy, a significant decline in iPTH values was observed in all patients; however, after the 8-month study period, only one of these patients achieved a serum iPTH concentration within the K/DOQI recommended target range. Unlike iPTH, targeting for calcium, phosphorus and CaxPO(4) at the last follow-up were 55.8%, 60.5% and 93%, respectively. These values indicated a significant improvement in comparison to preoperative percentages. In regards to the KDIGO recommended guidelines, the iPTH levels did not significantly change at the end of our study compared to preoperative values; however, calcium levels significantly declined and phosphorus levels significantly improved compared to preoperative values.

CONCLUSIONS

Although the majority of patients fail to reach recommended iPTH values, parathyroidectomy remains a valuable tool to attain these NKF-K/DOQI recommendations for serum calcium, phosphorus and CaxPO(4) in dialysis patients with secondary hyperparathyroidism resistant to medical therapy. Parathyroidectomy was shown to be an inadequate intervention for achieving KDIGO recommendations.

Cinacalcet lowers parathyroid hormone levels. Whether it can prolong survival of people with chronic kidney disease (CKD) complicated by secondary hyperparathyroidism (SHPT) remains controversial, in part because a recent randomized trial excluded patients with iPTH <300 pg/ml. We examined cinacalcet's effects at different iPTH levels. This was a prospective case-cohort and cohort study involving 8229 patients with CKD stage 5D requiring maintenance hemodialysis who had SHPT. We studied relationships between cinacalcet initiation and important clinical outcomes. To avoid confounding by treatment selection, we used marginal structural models, adjusting for time-dependent confounders. Over a mean of 33 months, cinacalcet was more effective in patients with more severe SHPT. In patients with iPTH ≥ 500 pg/ml, the reduction in the risk of death from any cause was about 50% (Incidence Rate Ratio [IRR] = 0.49; 95% Confidence Interval [95% CI]: 0.29-0.82). For a composite of cardiovascular hospitalization and mortality, the association was not statistically significant, but the IRR was 0.67 (95% CI: 0.43-1.06). These findings indicate that decisions about using cinacalcet should take into account the severity of SHPT.

BACKGROUND

Elevated serum level of fibroblast growth factor-23 (FGF23) is associated with adverse outcomes in dialyzed patients.

OBJECTIVE

The CUPID study compared the efficacy of a cinacalcet-based regimen with conventional care (vitamin D and P binders) for achieving the stringent NKF-K/DOQI targets for peritoneal dialysis (PD) patients. Additionally, we analyzed change in FGF23 levels between two treatments to explore the cinacalcet effect in lowering FGF23.

METHODS

Multicenter, open-labeled, randomized controlled study.

METHODS

Seven university-affiliated hospitals in Korea.

METHODS

Overall, 66 peritoneal dialysis patients were enrolled.

METHODS

Sixty six patients were randomly assigned to treatment with either cinacalcet + oral vitamin D (cinacalcet group, n = 33) or oral vitamin D alone (control group, n = 33) to achieve K/DOQI targets. CUPID included a 4-week screening for vitamin D washout, a 12-week dose-titration, and a 4-week assessment phases. We calculated mean values of iPTH, Ca, P, Ca x P, during assessment phase and final FGF23 to assess the outcome.

METHODS

Achievement of >30% reduction of iPTH from baseline (primary) and FGF23 reduction (secondary).

RESULTS

72.7% (n = 24) of the cinacalcet group and 93.9% (n = 31) of the control group completed the study. Cinacalcet group received 30.2 ± 18.0 mg/day of cinacalcet and 0.13 ± 0.32 μg/d oral vitamin D (P < 0.001 vs. control with 0.27 ± 0.18 μg/d vitamin D). The proportion of patients who reached the primary endpoint was not statistically different (48.5% vs. 51.5%, cinacalcet vs. control, P = 1.000). After treatment, cinacalcet group experienced a significant reduction in FGF23 levels (median value from 3,960 to 2,325 RU/ml, P = 0.002), while an insignificant change was shown for control group (from 2,085 to 2,415 RU/ml). The percent change of FGF23 after treatment was also significantly different between the two groups (- 42.54% vs. 15.83%, P = 0.008). After adjustment, cinacalcet treatment was independently associated with the serum FGF23 reduction.

CONCLUSIONS

Cinacalcet treatment was independently associated with the reduction of FGF23 in our PD patients.

BACKGROUND

Controlled trials NCT01101113.

CONCLUSIONS

Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism.

BACKGROUND

Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism.

METHODS

Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined.

RESULTS

ucOC correlated positively with BAP (ρ = 0.489, p < 0.0001), TRACP-5b (ρ = 0.585, p < 0.0001) and intact parathyroid hormone (iPTH; ρ = 0.621, p < 0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients (p < 0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose (ρ = -0.303, p < 0.0001), hemoglobin A1C (ρ = -0.214, p < 0.01), and glycated albumin (ρ = -0.271, p < 0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH].

CONCLUSIONS

Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients.

OBJECTIVE

Few clinical trials conducted with cinacalcet have thoroughly addressed its effects of on bone metabolism. We assessed the effects of cinacalcet on bone markers in Japanese hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT).

METHODS

200 Japanese HD patients with intact PTH (iPTH) levels>> or = 300 pg/ml were enrolled. The dose of cinacalcet was titrated from 25 up to 100 mg/day to achieve iPTH levels < or = 250 pg/ml for 52 weeks.

RESULTS

At the end of the study visit, 57.8% of patients (115/199) had achieved iPTH levels < or = 250 pg/ml. Serum Ca, phosphorus (P) and Ca x P levels decreased rapidly and were maintained throughout the study. At week 52, all bone metabolic markers levels had decreased significantly from baseline. Although bone resorption markers gradually decreased throughout the study period, bone alkaline phosphatase significantly increased during the first 4 weeks and then gradually decreased.

CONCLUSIONS

The time courses of changes in bone markers after cinacalcet treatment resembled those observed after surgical parathyroidectomy (PTx), sometimes described as the hungry bone syndrome, indicating that cinacalcet treatment induces a rapid recovery in bone response to calcium. In addition, long-term efficacy and safety of cinacalcet were also observed in Japanese patients undertaking long-term hemodialysis (167.0 +/- 81.4 months).

BACKGROUND

Cardiovascular risk factors are a significant burden in end-stage renal disease patients under hemodialysis. Cardiovascular-related diseases are the leading cause of death among these patients and responsible for almost half of all deaths in dialysis patients. The influence of parathormone (PTH) on myocardial function as a toxin of uremia is attracting more attention and evaluation because of growing evidence that the effects of PTH on cardiac function may be the most serious consequence of secondary hyperparathyroidism in renal failure. In this study we aimed to consider the role of the excess PTH in the development of left ventricular hypertrophy (LVH) and its effects on LV ejection fraction in patients with end-stage renal disease under regular hemodialysis.

METHODS

This cross-sectional study was done on patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis treatment. Calcium, phosphorus, alkaline phosphatase and intact PTH (iPTH) were measured. Hypertensive patients were stratified into stages one to three. Echocardiography for left ventricular (LV) hypertrophy and ejection fraction (percent) were done and LV stratified into normal, mild, moderate and severe hypertrophy.

RESULTS

The total number of patients was 73 (F = 28, M = 45), consisting of 58 non-diabetic hemodialysis patients (F = 22, M = 36) and 15 diabetic hemodialysis patients (F = 6, M = 9). The age of patients was 46.5 +/- 16 years. The length of time patients had been on hemodialysis was 21.5 +/- 23.5 months. The LV ejection fraction (EF%) was 51 +/- 8 percent. Mean +/- SD of iPTH of total patients was 309 +/- 349 pg/ml. Mean +/- SD of iPTH of diabetic group and non-diabetic group was 234 +/- 265 pg/ml and 329 +/- 368 pg/ml respectively. The value of serum alkaline phosphatase of total patients was also 413 +/- 348 IU/L. Serum alkaline phosphatase (ALP) of diabetic group and non-diabetic group was 295 +/- 179 IU/L and 443 +/- 375 IU/L respectively. Serum albumin of total patients was 4 +/- 0.75 g/dl. Serum albumin of diabetic group and non-diabetic group was 3.6 +/- 0.7 g/dl and 4.2 +/- 0.7 g/dl respectively. Significant inverse correlation of serum ALP with percent of LV ejection fraction and marginal significant correlation of serum ALP with LVH were seen and marginal significant correlation of serum iPTH with LVH was also found. Significant inverse correlation between serum iPTH with percent of LV ejection fraction in non-diabetic HD patients was observed.

CONCLUSIONS

Adverse effects of secondary hyperparathyroidism on LV function and structure in this study shows the role of excess PTH in the development of left ventricular hypertrophy as well as low LV ejection fraction. In patients with end-stage renal disease under hemodialysis, more attention needs to be given to the control of secondary hyperparathyroidism to reduce the risk of cardiovascular morbidity and mortality in dialysis patients.