Normocalcemic hyperparathyroidism: Intervention to differentiate primary from secondary hyperparathyroidism.

BACKGROUND: Normocalcemic hyperparathyroidism can occur, but surgery should not be considered until common etiologies for secondary hyperparathyroidism are comprehensively excluded. Calcium deficiency is an underrecognized cause of normocalcemic parathyroid hormone elevation, and we aim to determine if the implementation of a preoperative calcium challenge can be used to reduce unnecessary parathyroidectomy. METHODS: Consecutive patients referred for parathyroidectomy (1/21-6/22) with normocalcemia (serum calcium <10 mg/dL) and concurrently elevated parathyroid hormone levels were routinely treated with supplemental calcium and vitamin D3, and follow-up laboratory studies were assessed. RESULTS: A total of 29/314 (9%) patients had normocalcemic parathyroid hormone elevation with mean calcium, parathyroid hormone, and vitamin D 25OH levels of 9.5 ± 0.3 mg/dL, 109.9 ± 34.9 pg/mL, and 42.7 ± 23.8 ng/mL respectively. Confounding factors included estimated glomerular filtration rate <60 in 2, loop diuretic use in 4, and prior gastric bypass or gastric sleeve surgery in 4. Follow-up biochemical evaluation was available in 27 (92%); results were unchanged in 7 patients (26%); normalization of parathyroid hormone levels with persistently normal calcium levels occurred in 15 (55%), thus confirming secondary hyperparathyroidism and hypercalcemia with elevated parathyroid hormone levels (classic primary hyperparathyroidism) was diagnosed in 5 (19%). Parathyroid exploration has been completed for 3 of 5 patients with classic primary hyperparathyroidism to date. CONCLUSION: A preoperative calcium challenge was prospectively initiated in normocalcemic patients with parathyroid hormone elevation, and there was high compliance (92%). Short-interval calcium supplementation revealed ∼50% to have resolved secondary hyperparathyroidism due to insufficient calcium intake, which avoided unnecessary surgery. In contrast, classic patients were unveiled in 20%, allowing for prompt and correct surgical intervention.

The Effectiveness of Alternate-day Cinacalcet Therapy for Secondary Hyperparathyroidism in Noncompliant Hemodialysis Patients.

Chronic kidney disease (CKD) is defined as an abnormality of the kidney's structure or function that is present for more than 3 months. Secondary hyperparathyroidism is a consequence of CKD, which eventuates with a decrease in the glomerular filtration rate. This study aimed to evaluate the effectiveness of alternate-day cinacalcet in noncompliant dialysis patients compared with a daily dose. The effects on the levels of intact parathyroid hormone (iPTH), calcium, and phosphorus were measured, and the compliance of patients with our protocol was observed. We followed the patients' (n = 134) iPTH levels every 3 months and their serum calcium and phosphorous monthly for 6 months and compared the results with 6 months of data from patients receiving daily doses of cinacalcet. The patients' mean age was 49.54 ± 16.17 years, the mean duration of dialysis was 6.44 ± 5.10 years, and 37.3% had diabetic nephropathy. The mean dose of alternate-day cinacalcet was 61.92 ± 26.59 mg. The level of iPTH before and after the change was 924.63 ± 474.132 pg/mL and 787.87 ± 496.49 pg/mL, respectively (P = 0.001), and the mean serum calcium level before and after was 8.56 ± 1.91 mg/dL and 8.85 ± 1.25 mg/dL, respectively (P = 0.035). The level of serum phosphorous before and after the change was 4.81 ± 1.32 mg/dL and 5.08 ± 2.3 mg/dL, respectively (P = 0.204). Cinacalcet produced significant reductions in iPTH with intermittent (three times per week) doses and thus was more cost-effective and had better compliance.

Nutritional Secondary Hyperparathyroidism and Fibrous Osteodystrophy in a Captive African Penguin (Spheniscus demersus) Similar to Osteomalacia in Poultry.

A 9-yr-old female black-footed African penguin (Spheniscus demersus) was presented for necropsy after a history of reproductive abnormalities, paresis of limbs, weakness, and sudden death. Postmortem examination revealed soft keel, collapsed rib cage with beading of the ribs, and bilateral parathyroid enlargement. Classic histologic lesions of fibrous osteodystrophy with osteomalacia were observed in the ribs, vertebrae, and to a lesser extent in the femur and tibiotarsus associated with hyperplasia of parathyroid glands. This represents the first report of nutritional secondary hyperparathyroidism in birds of the order Spheniciformes, most likely caused by low levels of calcium supplementation during egg laying. The reproductive abnormalities observed in this penguin and others from the same group (asynchronous egg-laying cycles, abnormal breeding behavior) were most likely exacerbated by the lack of an adequate photoperiod mimicking the natural daylight pattern.

Reporte de caso­Hiperparatiroidismo secundario nutricional y osteodistrofia fibrosa en un pingüino africano (Spheniscus demersus) en cautiverio similar a la osteomalacia observada en de aves de corral. Una hembra de pingüino africano de patas negras (Spheniscus demersus) de nueve años fue sometida a necropsia después de un historial de anomalías reproductivas, paresia de extremidades, debilidad y muerte súbita. El examen post mortem reveló que la quilla del esternón estaba blanda, la caja torácica colapsada, se observaron "perlas raquíticas" en las costillas y agrandamiento bilateral de las paratiroides. Se observaron lesiones histológicas clásicas de osteodistrofia fibrosa con osteomalacia en las costillas, vértebras y en menor medida, en el fémur y tibiotarsus asociadas con hiperplasia de glándulas paratiroides. Esto representa el primer informe de hiperparatiroidismo secundario nutricional en un ave del orden Spheniciformes, muy probablemente causado por un bajo nivel de suplementos de calcio durante la producción de huevos. Las anomalías reproductivas observadas en este pingüino y otros del mismo grupo (ciclos de puesta de huevos asincrónicos, comportamiento de reproducción anormal) probablemente se vieron exacerbadas por la falta de un fotoperíodo adecuado que imitara el patrón de luz natural.

Cinacalcet for Severe Secondary Hyperparathyroidism in Children with End-stage Kidney Disease.

Advanced chronic kidney disease with mineral and bone disorder have a significant obstacles to control serum bone profile [serum intact parathyroid hormone (iPTH), calcium and phosphorus] which subsequently have major effect on optimal bone strength, final adult height, and cardiovascular health. A retrospective, observational study, including a total of 36 children with end-stage kidney disease (ESKD). Fourteen children who were prescribed cinacalcet had been compared with the remaining 22 children who were managed with standard care. We report the efficacy and safety of cinacalcet for treatment of refractory secondary hyperparathyroidism (SHPT) in children with ESKD. After 6 months of cinacalcet treatment, the mean level of iPTH serum level decreased by 56% from 202 pmol/L [95% confidence interval (CI): 150-253] to 88 pmol/L (95% CI: 41-136), compared to the change observed in the control group (P <0.001). None of our patients reported serious adverse effects or developed hypocalcemia. Cinacalcet could be an effective and safe alternative to treat severe SHPT in children with ESKD. Further long-term and large-scale studies are necessary to confirm its safety and efficacy.

Biochemical spectrum of parathyroid disorders diagnosed at a tertiary care setting.

OBJECTIVE: To determine the clinical and biochemical pattern of parathyroid disorders in a tertiary care setting.. METHODS: The cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from September 2017 to February 2018, and comprised patients with suspected parathyroid disorders. A panel of biochemical tests were used for diagnosis of parathyroid disorders, which included parathyroid hormone levels, total calcium, ionized calcium, inorganic phosphorus, alkaline phosphatase, magnesium, total vitamin D and urinary calcium-to-creatinine ratio. SPSS 24 was used for data analysis. RESULTS: Of the 384 subjects, 248(65%) were male and 136(35%) were female. Overall mean age was 48±19years. Of the total, 302(786%) had parathyroid issues, with 244(81%) having secondary hyperparathyroidism. Mean serum total calcium, phosphorus, ionized calcium, magnesium and total vitamin D were 8.98±1.52 mg/dl, 4.0±1.30 mg/dl, 4.65±0.52 mg/dl, 2.11±0.27 mg/dl and 20.5±8.52 ngml respectively. Of the patients diagnosed with secondary hyperparathyroidism, 72.2% patients had chronic kidney disease and 20.2% had isolated vitamin D deficiency. CONCLUSIONS: Parathyroid disorders had significant impact on bone health. Moreover, secondary hyperparathyroidism was seen to be emerging as a major endocrine problem, especially in chronic kidney disease patients and vitamin D-deficient individuals.

Pregnant Patient on Hemodialysis Who Showed Remarkable Improvement of Severe Hyperparathyroidism by Strict Serum Phosphorus Control.

We encountered a pregnant hemodialysis patient with severe hyperparathyroidism (HPT). Although her disease was considered to be refractory to medical treatment, the serum intact parathyroid hormone (PTH) level remarkably improved without manifestation of hypercalcemia through only strict serum phosphorus control, mainly via intensification of dialysis. The very strong correlation between the serum phosphorus level and serum intact PTH level suggested the possibility of secondary HPT. She ultimately gave birth to a healthy baby. The clinical course of the patient's HPT and the growth of the child have been good for more than six years.

The effectiveness of cinacalcet: a randomized, open label study in chronic hemodialysis patients with severe secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is associated with high incidences of cardiovascular disease, bone fracture, and mortality. This study was conducted to demonstrate the effectiveness of cinacalcet treatment on chronic kidney disease-mineral bone disorder (CKD-MBD) markers in chronic hemodialysis patients with severe SHPT. METHODS: In phase 1, 30 adult HD patients were randomized to cinacalcet or control groups for 12 weeks to explore the achievement of >30% reduction of iPTH. In phase 2, 45 patients were participated to further explore the effect of cinacalcet on CKD-MBD parameters for 24-week follow up and 12 additional weeks after cinacalcet discontinuation. RESULTS: In phase 1, the baseline serum iPTH levels were not different [1374 (955, 1639) pg/mL in the control group vs. 1191 (1005, 1884) pg/mL in the cinacalcet group], the percentage of patients achieving iPTH target were significantly higher in the treatment group [80% vs. 13%, p = .001]. In phase 2, the significant reductions of iPTH, FGF-23, tartrate-resistant acid phosphatase 5b, and slightly decreased size of parathyroid gland and stabilized vascular calcification were observed at 24-week follow up and markedly rebounded after discontinuation of cinacalcet. CONCLUSIONS: The effectiveness of cinacalcet were still obviously demonstrated even in chronic HD patients with severe SHPT. In addition, the improvements of bone markers and FGF-23, and stabilization of vascular calcification were observed. Therefore, cinacalcet can provide salutary effects on CKD-MBD in severe SHPT and might be an initially effective PTH-lowering therapy prior to surgical parathyroidectomy as well as an alternative treatment in the patients unsuitable for surgery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02056730. Date of registration: February 4, 2014.

Pharmacodynamics of evocalcet for secondary hyperparathyroidism in Japanese hemodialysis patients.

BACKGROUND: This study investigated the pharmacokinetics, pharmacodynamics, and safety of multiple doses of evocalcet in Japanese secondary hyperparathyroidism (SHPT) patients receiving hemodialysis. METHODS: In this multicenter, open-label study, conducted between August 2013 and March 2014, 27 patients received multiple doses of 1 and 4 mg evocalcet for 14 days, followed by an extension period of multiple doses of 8 and 12 mg evocalcet for 7 days using an intra-patient dose escalation protocol. Pharmacodynamic parameters consisted of measurement of intact parathyroid hormone (PTH), serum-corrected calcium, serum phosphorus and intact fibroblast growth factor 23 concentrations. Safety was assessed by analysis of adverse events. RESULTS: Plasma evocalcet levels reached steady state 3 days after the first day of administration. Pharmacodynamic analyses showed that evocalcet effectively reduced intact PTH and serum-corrected calcium levels. Adverse events (AEs) occurred in 29.6 and 62.5% of patients receiving multiple doses of 1 or 4 mg, respectively. The AE 'blood calcium decreased' occurred in eight patients (33.0%) after multiple doses of 4 mg. All events were mild, except for one patient with a moderate AE (abnormal liver function) and one patient with a severe adverse drug reaction (blood calcium decreased). CONCLUSION: Multiple doses of evocalcet reduced intact PTH levels with a concomitant decrease in serum calcium levels. Evocalcet was well tolerated in SHPT patients receiving hemodialysis.

Secondary Hyperparathyroidism: Pathogenesis and Latest Treatment.

The classic pathogenesis of secondary hyperparathyroidism (SHPT) began with the trade-off hypothesis based on parathyroid hormone hypersecretion brought about by renal failure resulting from a physiological response to correct metabolic disorder of calcium, phosphorus, and vitamin D. In dialysis patients with failed renal function, physiological mineral balance control by parathyroid hormone through the kidney fails and hyperparathyroidism progresses. In this process, many significant genetic findings have been established. Abnormalities of Ca-sensing receptor and vitamin D receptor are associated with the pathogenesis of SHPT, and fibroblast growth factor 23 has also been shown to be involved in the pathogenesis. Vitamin D receptor activators (VDRAs) are widely used for treatment of SHPT. However, VDRAs have calcemic and phosphatemic effects that limit their use to a subset of patients, and calcimimetics have been developed as alternative drugs for SHPT. Hyperphosphatemia also affects progression of SHPT, and control of hyperphosphatemia is, therefore, thought to be fundamental for control of SHPT. Currently, a combination of a VDRA and a calcimimetic is recognized as the optimal strategy for SHPT, and for other outcomes such as reduced cardiovascular disease and improved survival. The latest findings on the pathogenesis and treatment of SHPT are summarized in this review.

Hipometilación del gen de la PTH por elevado fósforo de la dieta: un posible agravante epigenético de la severidad del hiperparatiroidismo secundario en la enfermedad renal crónica / Hypomethylation of the PTH gene due to high dietary phosphorus: a possible aggravating of severe secondary hyperparathyroidism in chronic renal failure

Introducción: En pacientes con enfermedad renal crónica (ERC), la hiperfosfatemia agrava tanto la hiperplasia paratiroidea como la síntesis y secreción de PTH. La mayor hiperplasia se asocia a descensos en la expresión génica de los receptores de calcio (CaSR), vitamina D (VDR) y también de α-Klotho, induciendo resistencia de la glándula paratiroides para responder tanto al tratamiento como a los aumentos de FGF23. Este estudio examinó la posible contribución epigenética del fósforo elevado en agravar el hiperparatiroidismo secundario (HPTS). Material y métodos: Se comparó el grado de metilación mediante pirosecuenciación de bisulfito en secuencias ricas en CpG de los promotores en los genes del CaSR, VDR, PTH y α-Klotho en ADN de glándulas paratiroides de ratas urémicas alimentadas con dieta con contenido normal y elevado en fósforo. Resultados: La dieta rica en fósforo incrementó la expresión de PTH y causó una marcada reducción del grado de metilación en el promotor del gen de PTH. En cambio, las regiones promotoras de los genes de CaSR, VDR y α-Klotho no mostraron diferencias significativas en el porcentaje de metilación entre ambos grupos de ratas, no siendo, por tanto, éste el mecanismo determinante de la disminución de la expresión de estos genes observada en el HPTS. Conclusiones: Las alteraciones epigenéticas inducidas por la dieta rica en fósforo en el HPTS, en particular la hipometilación del gen de la PTH, podrían contribuir a los aumentos que se producen en la síntesis y secreción de esta hormona. La identificación de los mecanismos implicados permitiría diseñar mejores tratamientos para el HPTS en fases tempranas de la ERC (AU)

Introduction: Hyperphosphataemia aggravates both parathyroid hyperplasia and PTH secretion in patients with chronic kidney disease (CKD). Hyperplasia is associated with decreases in calcium receptor expression (CaSR), vitamin D (VDR) and α-Klotho, inducing resistance of the parathyroid gland to respond both to treatment and to increases in FGF23. This study examined the possible epigenetic contributions of raised phosphorus to aggravate secondary hyperparathyroidism (SHPT) in patients with (CRD). Material and methods: The degree of methylation was compared by pyrosequencing of bisulfite in CpGrich sequences of the promoters in the CaSR, VDR, PTH and α-Klotho genes in parathyroid gland DNA from uremic rats fed a normal and high phosphorus diet. Results: The diet rich in phosphorus increased PTH expression and caused a marked reduction in the degree of methylation in the promoter of the PTH gene. In contrast, the promoter regions of the CaSR, VDR and α-Klotho genes did not show significant differences in the percentage of methylation between the two groups of rats. Thus, it was not the determining mechanism for the decrease of the expression of these genes observed in the SHPT. Conclusions: The epigenetic alterations induced by the phosphorus rich diet in SHPT, particularly the PTH gene hypomethylation, could contribute to the increases that occur in the synthesis and secretion of this hormone. The identification of the mechanisms involved would allow better treatments for SHPT to be designed in the early stages of CKD (AU)

Weight Loss and Nutritional Outcomes 10 Years after Biliopancreatic Diversion with Duodenal Switch.

BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD/DS) is the most effective bariatric surgical procedure, but major concerns exist about the nutritional consequences. OBJECTIVES: The study reported weight loss and nutritional outcomes of 80 patients with a follow-up of at least 10 years. SETTING: The follow-up was conducted at a university hospital as well as in a private practice institution in France. METHODS: Eighty patients operated on between February 2002 and May 2006 were reviewed. Weight outcomes were analyzed as well as complete biological status. Revisions were reported as well as the number of patients taking vitamin supplementation. RESULTS: A follow-up of 141 ± 16 months was available for 87.7% of the patients at least 10 years from surgery. Preoperative BMI decreased from 48.9 ± 7.3 to 31.2 ± 6.2 kg/m2 with an EWL of 73.4 ± 26.7% and a TWL of 35.9% ± 17.7%. Despite weight regain ≥10% of the weight loss in 61% of the cases, 78% of the patients maintained a BMI <35. Fourteen percent of the patients had a revision. Normal vitamin D levels were found in 35.4%. The overall PTH level was 91.9 ± 79.5 ng/mL, and 62% of the patients had hyperparathyroidism. Other deficiencies were less frequent but fat-soluble deficiencies as well as a PTH >100 ng/mL were significantly associated with the absence of vitamin supplementation. CONCLUSION: BPD/DS maintains a significant weight loss, but remains associated with side effects leading to revision and multiple vitamin deficiencies. The most severe deficiencies are related to the lack of supplementation compliance.

Rates of secondary hyperparathyroidism after bypass operation for super-morbid obesity: An overlooked phenomenon.

BACKGROUND: With over 110,000 bariatric operations performed in the United States annually, it is important to understand the biochemical abnormalities causing endocrine dysfunction associated with these procedures. Here we compare 2 malabsorptive procedures, duodenal switch and Roux-en-Y gastric bypass, to determine the role malabsorption plays in secondary hyperparathyroidism in this population. METHODS: Data from all super-obese patients undergoing duodenal switch or Roux-en-Y gastric bypass between August 2002 and October 2005 were prospectively collected. Postoperatively, all patients received 1,200 mg of calcium citrate and 1,000 IU vitamin D3 per American Society for Metabolic and Bariatric Surgery guidelines. Beginning in 2007, duodenal switch patients were instructed to add daily vitamin D3 10,000 IU. Statistical analyses included Student t test, multivariate, and univariate logistic regression. RESULTS: Of 283 patients with a body mass index ≥50, 170 (60.1%) underwent duodenal switch, while 113 (39.9%) underwent Roux-en-Y gastric bypass. Of 132 (46.6%) patients with secondary hyperparathyroidism, 101 (59.4%) had undergone duodenal switch and 31 (27.4%) had undergone Roux-en-Y gastric bypass. Symptoms were more common in the duodenal switch group (33 patients [19.4%]) than Roux-en-Y gastric bypass (11 patients [9.7%]). Multivariate logistic regression demonstrated that the extent of bypass and duration of follow-up were the only 2 independent predictive risk factors for developing secondary hyperparathyroidism. Although vitamin D levels improved with increased vitamin D3 supplementation in 2007, rates of secondary hyperparathyroidism increased. CONCLUSION: Despite routine postoperative calcium and vitamin D3 supplementation, secondary hyperparathyroidism is common after Roux-en-Y gastric bypass and duodenal switch. The degree of iatrogenic malabsorption correlates with the incidence of secondary hyperparathyroidism. These rates suggest current supplementation guidelines are not sufficient in preventing secondary hyperparathyroidism. Further work is needed to better define the sequelae of long-term hyperparathyroidism.

Conversion of oral alfacalcidol to oral calcitriol in the treatment of secondary hyperparathyroidism in chronic hemodialysis patients.

PURPOSE: The optimal vitamin D3 therapy for the treatment of secondary hyperparathyroidism (SHPT) in chronic hemodialysis patients is still controversial. Recent studies suggest that uremia in end-stage renal disease is associated with enzymatic hepatic dysfunction altering 25-hydroxylation of vitamin D3. The goal of our study was to compare the efficacy of calcitriol, the fully hydroxylated active form of vitamin D3, to alfacalcidol which needs 25-hydroxylation to be effective, for the treatment of SHPT in chronic hemodialysis patients. METHODS: We retrospectively reviewed 45 chronic hemodialysis patients who were switched from oral alfacalcidol to oral calcitriol for the treatment of SHPT. Parathyroid hormone (PTH), serum calcium and serum phosphorus levels were compared pre- and post-conversion using paired Student's t tests. RESULTS: The mean dose of active vitamin D3 decreased from 3.50 mcg/week at baseline to 2.86 mcg (P < 0001) after the switch from alfacalcidol to calcitriol. PTH significantly decreased from 94.4 to 82.6 pmol/L (-11.8 pmol/L, P = 0.02). The mean corrected calcium increased from 2.17 to 2.25 mmol/L (+0.08 mmol/L, P < 0.001) without any clinically significant hypercalcemia, and phosphorus levels were stable. Results were similar in a subgroup of patients (n = 17) for whom the medication was administrated during the hemodialysis session, ensuring a complete compliance. CONCLUSIONS: According to our study, calcitriol in equal dosage is more effective than alfacalcidol in lowering serum PTH level in chronic hemodialysis patients. This suggests that calcitriol may be the optimal active vitamin D3 for the treatment of SHPT in chronic hemodialysis patients.

Efficacy of microwave ablation for severe secondary hyperparathyroidism in subjects undergoing hemodialysis.

Severe secondary hyperparathyroidism (SHPT) is a serious problem in patients undergoing hemodialysis. The efficacy and safety of microwave ablation (MWA), a minimally invasive treatment, for severe SHPT are as yet unclear. To clarify the role of MWA, we administered it to patients with severe SHPT and assessed its efficacy and safety. This was a prospective, single-center, single-arm, clinical trial. We enrolled patients with severe SHPT attending our hemodialysis center who met the inclusion and exclusion criteria. We then assessed primary outcome measures (serum concentrations of intact parathyroid hormone) and secondary outcome measures (serum concentrations of calcium and phosphorus). Twenty-six patients were enrolled in this study, 10 of whom (38.46%) were responsive to MWA and 16 (61.54%) of whom were not. The main complication was hypocalcemia (10 cases, 38.46%), which had occurred in all cases by one week after administration of MWA. Responding patients with hypocalcemia all achieved normal serum calcium concentrations within seven months and non-responding patients within three months. There were no changes in serum phosphorus concentrations after MWA in either responders or non-responders. Microwave ablation is relatively ineffective in patients with severe SHPT undergoing maintaining hemodialysis and should not be the initial therapy in such cases.

Prevalence and correlates of 25-hydroxyvitamin D deficiency in the Chronic Kidney Disease in Children (CKiD) cohort.

BACKGROUND: Vitamin D plays an important role in the mineral and bone disorder seen in chronic kidney disease (CKD). Deficiency of 25-hydroxyvitamin D (25OHD) is highly prevalent in the adult CKD population. METHODS: The prevalence and determinants of 25OHD deficiency (defined as a level <20 ng/ml) were examined longitudinally in 506 children in the CKiD cohort. Predictors of secondary hyperparathyroidism and the determinants of 1,25-dihydroxyvitamin D (1,25(OH)2D) levels were also evaluated. RESULTS: Deficiency of 25OHD was observed in 28 % of the cohort at enrollment. Significant predictors of 25OHD deficiency were older age, non-white race, higher body mass index, assessment during winter, less often than daily milk intake, non-use of nutritional vitamin D supplement and proteinuria. Lower values of glomerular filtration rate (GFR), serum 25OHD, calcium and higher levels of FGF23 were significant determinants of secondary hyperparathyroidism. Lower GFR, low serum 25OHD, nephrotic-range proteinuria, and high FGF23 levels were significant determinants of serum 1,25(OH)2 D levels. CONCLUSIONS: Deficiency of 25OHD is prevalent in children with CKD and is associated with potentially modifiable risk factors such as milk intake, nutritional vitamin D supplement use, and proteinuria. 25OHD deficiency is a risk factor for secondary hyperparathyroidism and decreased serum 1,25(OH)2D in children with CKD.

Current recommended 25-hydroxyvitamin D targets for chronic kidney disease management may be too low.

OBJECTIVE: It is uncertain whether increasing 25-hydroxyvitamin D (25-D) levels in chronic kidney disease (CKD) patients above those recommended by current guidelines result in progressive amelioration of secondary hyperparathyroidism. Our objective was to identify a potential therapeutic 25-D target which optimally lowers plasma parathyroid hormone (PTH) without producing excessive hypercalcemia or hyperphosphatemia in CKD. METHODS: We performed a cross-sectional analysis of 14,289 unselected stage 1-5 CKD patients from US primary care and nephrology practices utilizing a laboratory-based CKD clinical decision support service between September 2008 and May 2012. Estimated glomerular filtration rate (eGFR), plasma PTH, and serum 25-D, calcium, and phosphorus results were analyzed. RESULTS: In CKD stages 3-5, progressively higher 25-D pentiles contained progressively lower mean PTH levels. Regression analysis of log PTH on 25-D was significant in all CKD stages with no evidence of a decreasing effect of 25-D to lower PTH until 25-D levels of 42-48 ng/ml. Progressively higher 25-D concentrations were not associated with increased rates of hypercalcemia or hyperphosphatemia. CONCLUSIONS: We found evidence for an optimal level of 25-D above which suppression of PTH progressively diminishes. This level is more than twice that currently recommended for the general population. We found no association between these higher 25-D levels and hyperphosphatemia or hypercalcemia. Additional prospective trials seem appropriate to test the idea that 25-D levels around 40-50 ng/ml could be a safe and effective treatment target for secondary hyperparathyroidism in CKD.

Predicting postoperative total calcium requirements after parathyroidectomy in secondary hyperparathyroidism.

BACKGROUND/AIMS: To prevent hypocalcemia after parathyroidectomy (PTX), parenteral calcium is required in addition to oral calcitriol and calcium. After switching to oral calcium, patients can be discharged from the hospital. The aim of this study was to analyze the clinical characteristics and outcomes of PTX performed at a single Korean center and to investigate the associated laboratory factors used to analyze the total amount of postoperative calcium required. METHODS: We enrolled 91 hemodialysis patients undergoing PTX from November 2003 to December 2011. We collected clinical and laboratory data preoperatively, 12 and 48 hours postoperatively, at discharge, and 3 and 6 months postoperatively. RESULTS: In total, 59 patients underwent PTX with autotransplantation (AT), 6 underwent total PTX without AT, 11 underwent subtotal PTX, and 15 underwent limited PTX. Total PTX without AT showed the lowest recurrence rate. At all postoperative time points, the mean levels of serum calcium, phosphorus, and intact parathyroid hormone (iPTH) decreased significantly, compared with preoperative levels; however, alkaline phosphatase (ALP) increased significantly from 48 hours postoperatively to discharge (p < 0.001). On multiple linear regression analysis, the total amount of injected calcium during hospitalization showed a significant correlation with preoperative ALP (p < 0.001), preoperative iPTH (p = 0.037), and Δphosphorus at 48 hours (p < 0.001). We developed an equation for estimating the total calcium requirement after PTX. CONCLUSIONS: Preoperative ALP, preoperative iPTH, and Δphosphorus at 48 hours may be significant factors in estimating the postoperative calcium requirement. The formula for postoperative calcium requirement after PTX may help to predict the duration of postoperative hospitalization.

Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism.

BACKGROUND AND OBJECTIVES: Cinacalcet and vitamin D are often combined to treat secondary hyperparathyroidism (SHPT) in patients on dialysis. Independent effects on fibroblast growth factor-23 (FGF-23) concentrations in patients on hemodialysis administered cinacalcet or vitamin D analogs as monotherapies during treatment of SHPT are evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter, randomized, open-label study to compare the efficacy of cinacalcet versus traditional vitamin D therapy for management of secondary hyperparathyroidism among subjects undergoing hemodialysis (PARADIGM) was a prospective, phase 4, multicenter, randomized, open-label study conducted globally. Participants (n=312) were randomized 1:1 to cinacalcet (n=155) or vitamin D analog (n=157) for 52 weeks. Levels of FGF-23 were measured at baseline and weeks 20 and 52. The absolute and percentage changes from baseline in plasma FGF-23, parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and calcium-phosphorus product (Ca×P) were assessed. Correlations and logistic regression were used to explore relationships between changes in FGF-23 and changes in PTH, Ca, P, and Ca×P from baseline to week 52 by treatment arm. RESULTS: Median (quartiles 1, 3) decrease in FGF-23 concentrations was observed in the cinacalcet arm (-40%; -63%, 16%) compared with median increase in the vitamin D analog arm (47%; 0%, 132%) at week 52 (P<0.001). Changes in FGF-23 in both arms were unrelated to changes in PTH (cinacalcet: r=0.17, P=0.11; vitamin D analog: r=-0.04, P=0.70). Changes in FGF-23 in the vitamin D analog but not the cinacalcet arm were correlated with changes in Ca (cinacalcet: r=0.11, P=0.30; vitamin D analog: r=0.32, P<0.01) and P (cinacalcet: r=0.19, P=0.07; vitamin D analog: r=0.49, P<0.001). Changes in FGF-23 were correlated with changes in Ca×P in both arms (cinacalcet: r=0.26, P=0.01; vitamin D analog: r=0.57, P<0.001). Independent of treatment arm, participants with reductions in P or Ca×P were significantly more likely to show reductions in FGF-23. CONCLUSIONS: During treatment of SHPT, cinacalcet use was associated with a decrease in FGF-23 concentrations, whereas vitamin D analogs were associated with an increase. The divergent effects of these treatments on FGF-23 seem to be independent of modification of PTH. It is possible that effects of cinacalcet and vitamin D analogs on FGF-23 may be mediated indirectly by other effects on bone and mineral metabolism.