Review: Dietary cation-anion difference to prevent hypocalcemia with emphasis on over-acidification in prepartum dairy cows.

Hypocalcemia remains a common metabolic disorder of dairy cattle; therefore, an efficient prevention is still challenging. Among the various prevention strategies for hypocalcemia is the use of anionic compounds to induce a mild metabolic acidosis during the prepartum period. Acid-base status can be readily assessed through urine pH. Accordingly, a target urine pH during the prepartum period between 6.0 and 6.8 has been recommended for Holstein cows; however, in several countries, including the US, certain nutritional strategies are still focused on benchmarking the urine pH to below 6.0. Unfortunately, over-acidification can have no advantages and/or detrimental effects on both the dam and her offspring. In this review, updated information regarding the use of anionic diets on prepartum dairy cows and the potential negative impact of such diets on both cow and calf performance are discussed. There is an urgent need for studies that will elucidate the pathophysiological mechanisms by which very acidotic diets may impact the well-being and productive efficiency of dairy cows, and the transgenerational effects of such diets on offspring performance and survival.

A single-center experience of parathyroidectomy in 1500 cases for secondary hyperparathyroidism: a retrospective study.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. With the deterioration of renal function, a certain proportion of CKD patients enter the uremic stage, and secondary hyperparathyroidism (SHPT) becomes a challenge. For refractory hyperparathyroidism, parathyroidectomy (PTX) plays a key role in reducing mortality and improving prognosis. Nevertheless, no consensus has been reached on the optimal surgical method. We aimed to provide evidence for the effectiveness of surgical treatment by summarizing the experience from our center. METHODS: Clinical data from 1500 patients undergoing parathyroidectomy were recorded, which included 1419 patients in a total parathyroidectomy without autotransplantation (tPTX) group, 54 patients in a total parathyroidectomy plus autotransplantation (tPTX + AT) group, and 27 patients in the other group. Perioperative basic data, intact parathyroid hormone (i-PTH) levels, serum calcium levels, serum phosphorus levels, pathological reports, coexisting thyroid diseases, short-term outcomes and complications were analyzed. Moreover, postoperative complications were compared between the tPTX and tPTX + AT groups. RESULTS: Parathyroid hormone, serum calcium and phosphorus levels decreased significantly post-surgery. Two patients died during the perioperative period. As the two most common complications, the incidences of severe hypocalcemia and hyperkalemia were 36.20% (543 cases) and 24.60% (369 cases), respectively. Pre-iPTH levels (OR = 1.001, 95% CI: 1.001-1.001, p < 0.01), serum alkaline phosphatase (ALP) levels (OR = 1.002, 95% CI: 1.001-1.002, p < 0.01) and the mass of excised parathyroid gland (OR = 3.06, 95% CI: 1.24-7.55, p = 0.02) were positively associated with postoperative severe hypocalcemia, while age and serum calcium were negatively associated with it. Pathological reports of resected parathyroid and thyroid glands indicated that 96.49% had parathyroid nodular hyperplasia, 13.45% had thyroid nodular hyperplasia, and 4.08% had thyroid papillary carcinoma. CONCLUSIONS: Parathyroidectomy is a safe and effective treatment for refractory secondary hyperparathyroidism. Severe hypocalcemia is the main complication, and coexistent thyroid diseases should never be neglected.

Claudin-2 and claudin-12 form independent, complementary pores required to maintain calcium homeostasis.

Calcium (Ca2+) homeostasis is maintained through coordination between intestinal absorption, renal reabsorption, and bone remodeling. Intestinal and renal (re)absorption occurs via transcellular and paracellular pathways. The latter contributes the bulk of (re)absorption under conditions of adequate intake. Epithelial paracellular permeability is conferred by tight-junction proteins called claudins. However, the molecular identity of the paracellular Ca2+ pore remains to be delineated. Claudins (Cldn)-2 and -12 confer Ca2+ permeability, but deletion of either claudin does not result in a negative Ca2+ balance or increased calciotropic hormone levels, suggesting the existence of additional transport pathways or parallel roles for the two claudins. To test this, we generated a Cldn2/12 double knockout mouse (DKO). These animals have reduced intestinal Ca2+ absorption. Colonic Ca2+ permeability is also reduced in DKO mice and significantly lower than single-null animals, while small intestine Ca2+ permeability is unaltered. The DKO mice display significantly greater urinary Ca2+ wasting than Cldn2 null animals. These perturbations lead to hypocalcemia and reduced bone mineral density, which was not observed in single-KO animals. Both claudins were localized to colonic epithelial crypts and renal proximal tubule cells, but they do not physically interact in vitro. Overexpression of either claudin increased Ca2+ permeability in cell models with endogenous expression of the other claudin. We find claudin-2 and claudin-12 form partially redundant, independent Ca2+ permeable pores in renal and colonic epithelia that enable paracellular Ca2+ (re)absorption in these segments, with either one sufficient to maintain Ca2+ balance.

Neutrophil ß-defensin gene expression of postpartum dairy cows is altered by prepartum dietary cation-anion difference.

The objective of this study was to evaluate expression of a cluster of genes encoding ß-defensin antimicrobial peptides in neutrophils of postpartum cows in relation to prepartum dietary cation-anion difference (DCAD), vitamin D, and postpartum disease. Pregnant dry Holstein cows (28 nulliparous and 51 parous) at 255 d gestation were blocked by parity and randomly assigned to 4 prepartum diets of positive (+130 mEq/kg) or negative (-130 mEq/kg) DCAD and either 3 mg vitamin D3 or 3 mg of 25-hydroxyvitamin D3 per 11 kg of dry matter/d. Treatment diets were fed from 255 d of gestation until calving. Peripheral blood neutrophils of 35 parous cows were collected at 0 and 3 d after calving and stimulated with 0 or 100 ng/mL of lipopolysaccharide (LPS). Furthermore, serum Ca and incidences of postpartum diseases were recorded for all cows. The mRNA transcripts of ß-defensin genes were quantified by real-time PCR, and data were analyzed with a general linear mixed model to test for fixed effects and interactions of day, level of DCAD, source of vitamin D, and incidence of disease. Effects of DCAD and vitamin D on neutrophil oxidative burst and phagocytosis were previously reported but were analyzed for effects of disease in the present study. Transcripts for DEFB1, DEFB3, DEFB4, DEFB5, DEFB7, DEFB10, and lingual antimicrobial peptide (LAP) in neutrophils were upregulated by LPS at 0 d but not at 3 d. Transcripts for DEFB4 and DEFB7 in LPS-stimulated neutrophils were greater in cows fed negative DCAD diets compared with positive DCAD. Source of vitamin D (vitamin D3 vs. 25-hydroxyvitamin D3) did not affect expression of ß-defensins in neutrophils. Cows with postpartum subclinical hypocalcemia (serum Ca <2.0 mM) had decreased DEFB3, DEFB4, DEFB6, DEFB7, DEFB10, and LAP expression in LPS-stimulated neutrophils compared with cows that did not experience subclinical hypocalcemia. Likewise, DEFB4, DEFB6, DEFB7, DEFB10, and LAP in LPS-stimulated neutrophils at 3 d postpartum were positively associated with serum Ca at 0 d postpartum. Transcripts for DEFB7, DEFB10 and LAP also were less abundant in neutrophils from cows with metritis compared with healthy cows. In conclusion, feeding a prepartum negative DCAD to improve postpartum serum Ca resulted in greater neutrophil ß-defensin expression, and greater neutrophil ß-defensin expression was positively associated with postpartum health.

Bone metabolism markers and hungry bone syndrome after parathyroidectomy in dialysis patients with secondary hyperparathyroidism.

OBJECTIVE: To explore the short-term variation in bone metabolic markers and the characteristics of hungry bone syndrome (HBS) after parathyroidectomy (PTX) with forearm autotransplantation in uremic patients with secondary hyperparathyroidism (SHPT) and to provide a basis for the pathogenesis, diagnosis and treatment of metabolic bone disease in SHPT. METHODS: A total of 115 patients with SHPT receiving PTX from July 2015 to December 2017, hospitalized at the First Affiliated Hospital of Nanjing Medical University, were enrolled in our study. We retrospectively analyzed the baseline clinical data, the levels of bone metabolism markers before and on the third day after PTX, and the risk factors predicting HBS. RESULTS: Preoperative baseline data showed that the levels of bone metabolic markers such as bone metabolism-regulating hormones: iPTH, calcitonin (CT); bone formation markers: phosphatase (ALP), osteocalcin (OC); bone resorption markers: type I collagen cross-linked N-telopeptides (NTX), type I collagen cross-linked C-telopeptides (CTX), tartrate-resistant acid phosphatase 5b (TRAP-5b) were all increased compared to normal levels. The levels of postoperative serum iPTH, CT, CTX and TRAP-5b decreased significantly compared to preoperative levels, while the levels of OC and ALP increased significantly. Of the 115 patients, 101 (87.8%) developed HBS after PTX. High preoperative serum ALP and low preoperative serum calcium level independently predicted the occurrence of HBS. Younger preoperative age, high preoperative serum ALP and iPTH level independently predicted the severity of HBS. CONCLUSIONS: In severe SHPT, both bone formation and resorption were active, which suggested the presence of high-turnover bone diseases characterized by up-regulation of osteoclasts-osteoblasts functionally coupling activation in the patients. PTX could promote osteoblast activity and reduce osteoclast activity. HBS was common after PTX. Preoperative higher serum ALP and lower calcium were independent predictors of the occurrence of HBS. Younger patients with higher preoperative ALP and PTH may need to closely monitor serum calcium levels and intensive calcium supplementation after PTX.

Thyrotoxic Periodic Paralysis with Hypokalemia in an Adult Male from Nepal: A Case Report.

Thyrotoxic periodic paralysis is rare complication of hyperthyroidism characterized by the sudden onset of hypokalemia and muscle paralysis. It is typically present in young Asian males. There are very few literatures regarding the occurrence of thyrotoxic hypokalemic periodic paralysis in Nepal. We reported a case of a 35-year-old male presented with the chief complaints of weakness of all four limbs of 1 day duration. He was diagnosed as a case of hyperthyroidism in the past, received treatment for 6 months and left medications on his own 6 months ago. Evaluation during admission revealed severe hypokalemia with serum potassium level 1.3mEq/l and high serum Triiodothyronine (>20.00µg/L) and low serum Thyroid Stimulating Hormone (<0.01µg/L). Potassium supplements resolved muscle weakness and the patient was restarted with anti-thyroid drugs. Hence, hypokalemic paralysis is a reversible cause of paralysis and high index of suspicion as well as timely interventions are required to prevent potential harm. Keywords: hyperthyroidism; hypokalemia; muscle paralysis; thyrotoxic periodic paralysis.

Reduced secretion of parathyroid hormone and hypocalcemia in systemic heterozygous ATP2B1-null hypertensive mice.

The ATP2B1 gene is associated with hypertension. We previously reported that systemic heterozygous ATP2B1-null (ATP2B1+/-) mice exhibited hypertension due to impaired endothelial nitric oxide synthase (eNOS) activity and decreased nitric oxide (NO) production. The ATP2B1 gene encodes plasma membrane calcium ATPase 1 (PMCA1), which has been thought to regulate only intracellular Ca2+ concentration. However, recently, it has been suggested that ATP2B1 works not only at cellular levels, but also throughout the entire body, including in the calcium metabolism, using small intestine-specific ATP2B1 knockout mice. To clarify the roles of ATP2B1 in the entire body and the effects of ATP2B1 on blood pressure, we examined the alterations of calcium related factors in ATP2B1+/- mice. ATP2B1+/- mice exhibited hypocalcemia. The expression of ATP2B1 in the kidney and small intestine decreased, and hypercalciuria was confirmed in ATP2B1+/- mice. The intact-PTH levels were lower, and bone mineral density was increased in these mice. These results suggest that hypocalcemia is mainly a result of inhibited bone resorption without compensation by PTH secretion in the case of ATP2B1 knockout. Moreover, NO production may be affected by reduced PTH secretion, which may cause the increase in vascular contractility in these mice. The ATP2B1 gene is important for not only intra-cellular calcium regulation but also for calcium homeostasis and blood pressure control.

Dietary Magnesium Alleviates Experimental Murine Colitis Through Upregulation of the Transient Receptor Potential Melastatin 6 Channel.

Background: Magnesium (Mg) is essential for human health and is absorbed mainly in the intestine. In view of the likely occurrence of an Mg deficit in inflammatory bowel disease (IBD) and the documented role of Mg in modulating inflammation, the present study addresses whether Mg availability can affect the onset and progression of intestinal inflammation. Methods: To study the correlation between Mg status and disease activity, we measured magnesemia by atomic absorption spectroscopy in a cohort of IBD patients. The effects of dietary Mg modulation were assessed in a murine model of dextran sodium sulfate (DSS)-induced colitis by monitoring magnesemia, weight, fecal occult blood, diarrhea, colon length, and histology. Expression of the transient receptor potential melastatin (TRPM) 6 channel was assessed by real-time reverse transcription polymerase chain reaction and immunohistochemistry in murine colon tissues. The effect of Mg on epithelial barrier formation/repair was evaluated in human colon cell lines. Results: Inflammatory bowel disease patients presented with a substantial Mg deficit, and serum Mg levels were inversely correlated with disease activity. In mice, an Mg-deficient diet caused hypomagnesemia and aggravated DSS-induced colitis. Colitis severely compromised intestinal Mg2+ absorption due to mucosal damage and reduction in TRPM6 expression, but Mg supplementation resulted in better restoration of mucosal integrity and channel expression. Conclusions: Our results highlight the importance of evaluating and correcting magnesemia in IBD patients. The murine model suggests that Mg supplementation may represent a safe and cost-effective strategy to reduce inflammation and restore normal mucosal function.

Comparison of 0.46% calcium diets with and without added anions with a 0.7% calcium anionic diet as a means to reduce periparturient hypocalcemia.

Most studies demonstrating that diets with low dietary cation-anion difference (DCAD) reduce hypocalcemia in cows add enough anions to the diet to reduce urine pH below 7.0. One objective of these experiments was to determine whether there is any benefit to periparturient plasma Ca concentration if diet anion addition results in a lesser degree of acidification of the cow and urine pH does not go below 7.0. Another method for reducing hypocalcemia involves feeding a prepartal diet that is Ca deficient. This places the cow in negative Ca balance before calving, stimulating parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D secretion before calving and thus promoting Ca homeostasis at calving. As practiced in the field, low-Ca diets are often about 0.5% Ca. Our second objective was to determine whether a 0.46% Ca diet would be sufficiently low in Ca to stimulate PTH secretion before calving. A meta-analysis of the literature suggests that a 0.5% Ca, low-DCAD diet will reduce hypocalcemia better than a 0.7% Ca diet. A third objective was to compare periparturient plasma Ca in cows fed 0.46 or 0.72% Ca diets with similar DCAD. In experiment 1, anions (primarily chloride) or anions plus Ca were added to a 1.4% K basal diet to create the following diets: 0.46% Ca and +167 mEq/kg of DCAD, 0.46% Ca and -13 mEq/kg of DCAD, and 0.72% Ca and -17 mEq/kg of DCAD. In experiment 2, the same amounts of anion were added to a 2.05% K basal diet to create the following diets: 0.46% Ca and +327 mEq/kg of DCAD, 0.46% Ca and +146 mEq/kg of DCAD, and 0.72% Ca and +140 mEq/kg of DCAD. In experiment 1, cows fed the diet with 0.46% Ca and +167 mEq/kg of DCAD had significantly lower plasma Ca concentration after calving than cows fed the 0.46 or 0.72% Ca diets with anions. Periparturient plasma Ca concentrations did not differ in cows fed the low-DCAD diets with 0.46 or 0.72% Ca. Urine pH was reduced from 8.27 in the diet with 0.46% Ca and +167 mEq/kg of DCAD to 7.07 and 7.41 in the 0.46 and 0.72% Ca anion diets, respectively. Precalving plasma PTH and 1,25-dihydroxyvitamin D concentrations were similar in cows fed the 0.46% Ca diets and the 0.72% Ca diets, suggesting that the 0.46% Ca diets were not low enough in Ca to place the cow in negative Ca balance before calving. In experiment 2, adding the anion supplements to a 2.05% K diet did not reduce urine pH below 8.0. Periparturient plasma Ca concentrations did not differ in cows in any group in experiment 2. Precalving diets that are 0.46% Ca fed ad libitum are too high in Ca to stimulate Ca homeostasis before calving. Adding anions to a diet can benefit periparturient cow plasma Ca concentration, but only if it alters acid-base status enough to reduce urine pH below 7.5.

Effect of prophylactic oral calcium supplementation on postpartum mineral status and markers of energy balance of multiparous Jersey cows.

The effects of prophylactic oral Ca supplementation on blood mineral status and markers of energy balance were evaluated on 205 multiparous Jersey cows at a commercial dairy. Postpartum, cows were systematically assigned to control (n = 105) or oral Ca supplementation (CaOS; 50 to 60 g of Ca as boluses; n = 100) at 0 and 1 d in milk (DIM). Blood samples for analysis of serum minerals (Ca, P, Mg, K, Na, Fe, Zn, and Cu) were collected before and 1 h after treatment at 0 and 1 DIM, and at 2 DIM. Urine pH was measured immediately before and 1 h after treatment administration (n = 96). A subset of 74 cows was evaluated for plasma glucose and fatty acid concentrations at 0, 1, and 2 DIM. Cows were classified according to their initial calcemic status (Ca status) as normocalcemic (NC; serum Ca >2.12 mmol/L) or subclinically hypocalcemic (SCH; serum Ca ≤2.12 mmol/L). Average serum Ca concentration was higher in CaOS than control cows (2.12 vs. 2.06 mmol/L); this treatment effect was higher for SCH [CaOS (2.03 mmol/L); control (1.89 mmol/L)] than NC cows [CaOS (2.22 mmol/L); control (2.22 mmol/L)]. The incidence of subclinical hypocalcemia was lower for CaOS than control cows (53 vs. 65%); however, at 2 DIM the prevalence of subclinical hypocalcemia tended to be higher for CaOS cows, mostly because it was higher for CaOS-NC than control-NC cows (70 vs. 25%). Urine pH was lower for CaOS than control cows (6.10 vs. 7.04). Lower serum Mg concentration was detected for CaOS-SCH (1.06 mmol/L) than for control-SCH (1.10 mmol/L) cows. Cows in the CaOS group had higher serum K (4.68 vs. 4.53 mmol/L), lower plasma glucose (2.97 vs. 3.10 mmol/L), and at 2 DIM higher plasma fatty acid concentrations (0.43 vs. 0.35 mmol/L) than control cows. Our results showed that postpartum serum Ca concentration increases with oral Ca supplementation, but calcemic status influenced treatment response. Future studies should evaluate the long-term implications on production and reproduction of oral Ca supplementation in Jersey cows.

Effects of prepartum dietary cation-anion difference and source of vitamin D in dairy cows: Health and reproductive responses.

The objectives of the experiment were to evaluate the effects of feeding diets with distinct dietary cation-anion difference (DCAD) levels and supplemented with 2 sources of vitamin D during the prepartum transition period on postpartum health and reproduction in dairy cows. The hypotheses were that feeding acidogenic diets prepartum would reduce the risk of hypocalcemia and other diseases, and the benefits of a negative DCAD treatment on health would be potentiated by supplementing calcidiol compared with cholecalciferol. Cows at 252 d of gestation were blocked by parity (28 nulliparous and 52 parous cows) and milk yield within parous cows, and randomly assigned to 1 of 4 treatments arranged as a 2 × 2 factorial, with 2 levels of DCAD, positive (+130 mEq/kg) or negative (-130 mEq/kg), and 2 sources of vitamin D, cholecalciferol or calcidiol, fed at 3 mg for each 11 kg of diet dry matter. The resulting treatment combinations were positive DCAD with cholecalciferol (PCH), positive DCAD with calcidiol (PCA), negative DCAD with cholecalciferol (NCH), and negative DCAD with calcidiol (NCA), which were fed from 252 d of gestation to calving. After calving, cows were fed the same lactation diet supplemented with cholecalciferol at 0.70 mg for every 20 kg of dry matter. Blood was sampled 7 d before parturition, and at 2 and 7 d postpartum to evaluate cell counts and measures of neutrophil function. Postpartum clinical and subclinical diseases and reproductive responses were evaluated. Feeding a diet with negative DCAD eliminated clinical hypocalcemia (23.1 vs. 0%) and drastically reduced the incidence and daily risk of subclinical hypocalcemia, and these effects were observed in the first 48 to 72 h after calving. The diet with negative DCAD tended to improve the intensity of oxidative burst activity of neutrophils in all cows prepartum and increased the intensity of phagocytosis in parous cows prepartum and the proportion of neutrophils with killing activity in parous cows postpartum (58.5 vs. 67.6%). Feeding calcidiol improved the proportion of neutrophils with oxidative burst activity (60.0 vs. 68.7%), reduced the incidences of retained placenta (30.8 vs. 2.5%) and metritis (46.2 vs. 23.1%), and reduced the proportion of cows with multiple diseases in early lactation. Combining the negative DCAD diet with calcidiol reduced morbidity by at least 60% compared with any of the other treatments. Cows with morbidity had lower blood ionized Ca and serum total Ca concentrations than healthy cows. Treatments did not affect the daily risk of hyperketonemia in the first 30 d of lactation. Despite the changes in cow health, manipulating the prepartum DCAD did not influence reproduction, but feeding calcidiol tended to increase the rate of pregnancy by 55%, which reduced the median days open by 19. In conclusion, feeding prepartum cows with a diet containing a negative DCAD combined with 3 mg of calcidiol benefited health in early lactation.

Transcription factor MafB may play an important role in secondary hyperparathyroidism.

The transcription factor MafB is essential for development of the parathyroid glands, the expression of which persists after morphogenesis and in adult parathyroid glands. However, the function of MafB in adult parathyroid tissue is unclear. To investigate this, we induced chronic kidney disease (CKD) in wild-type and MafB heterozygote (MafB+/-) mice by feeding them an adenine-supplemented diet, leading to secondary hyperparathyroidism. The elevated serum creatinine and blood urea nitrogen levels in heterozygous and wild-type mice fed the adenine-supplemented diet were similar. Interestingly, secondary hyperparathyroidism, characterized by serum parathyroid hormone elevation and enlargement of parathyroid glands, was suppressed in MafB+/- mice fed the adenine-supplemented diet compared to similarly fed wild-type littermates. Quantitative RT-PCR and immunohistochemical analyses showed that the increased expression of parathyroid hormone and cyclin D2 in mice with CKD was suppressed in the parathyroid glands of heterozygous CKD mice. A reporter assay indicated that MafB directly regulated parathyroid hormone and cyclin D2 expression. To exclude an effect of a developmental anomaly in MafB+/- mice, we analyzed MafB tamoxifen-induced global knockout mice. Hypocalcemia-stimulated parathyroid hormone secretion was significantly impaired in MafB knockout mice. RNA-sequencing analysis indicated PTH, Gata3 and Gcm2 depletion in the parathyroid glands of MafB knockout mice. Thus, MafB appears to play an important role in secondary hyperparathyroidism by regulation of parathyroid hormone and cyclin D2 expression. Hence, MafB may represent a new therapeutic target in secondary hyperparathyroidism.

Calcium homeostasis in diabetes mellitus.

Diabetes mellitus (DM) is becoming a lifestyle-related pandemic disease. Diabetic patients frequently develop electrolyte disorders, especially diabetic ketoacidosis or nonketotic hyperglycemic hyperosmolar syndrome. Such patients show characteristic potassium, magnesium, phosphate, and calcium depletion. In this review, we discuss a homeostatic mechanism that links calcium and DM. We also provide a synthesis of the evidence in favor or against this linking mechanism by presenting recent clinical indications, mainly from veterinary research. There are consistent results supporting the use of calcium and vitamin D supplementation to reduce the risk of DM. Clinical trials support a marginal reduction in circulating lipids, and some meta-analyses support an increase in insulin sensitivity, following vitamin D supplementation. This review provides an overview of the calcium and vitamin D disturbances occurring in DM and describes the underlying mechanisms. Such elucidation will help indicate potential pathophysiology-based precautionary and therapeutic approaches and contribute to lowering the incidence of DM.

Electrolytes: Calcium Disorders.

A normal serum calcium level is 8 to 10 mg/dL. The diagnosis of hypercalcemia (ie, levels 10.5 mg/dL or greater) should be confirmed with an albumin-adjusted or ionized calcium level. The two most common causes of hypercalcemia are hyperparathyroidism and malignancy. Drugs, notably lithium and thiazide diuretics, also can cause hypercalcemia. Patients with severe or symptomatic hypercalcemia should be treated initially with hydration to decrease calcium levels. The evaluation should include a parathyroid hormone (PTH) level. If the PTH level is low, cancer is a likely cause, particularly multiple myeloma, breast cancer, or lymphoma. If the PTH level is normal or elevated, hyperparathyroidism is the likely cause. Symptomatic patients with hyperparathyroidism and patients with certain clinical markers should be considered for surgery. For patients with mild disease, monitoring is an option. Hypocalcemia often is caused by vitamin D deficiency. Symptomatic patients and patients with calcium levels less than 7.6 mg/dL should be treated with intravenous calcium gluconate; concomitant magnesium deficiency should be addressed. There is no evidence that routine calcium and vitamin D supplementation reduces the risk of fractures, but studies have shown that vitamin D supplementation does decrease the number of falls in older adults at risk.

Peptide Receptor Radionuclide Therapy-Induced Gitelman-like Syndrome.

Peptide receptor radionuclide therapy (PRRT) is a molecular-targeted therapy in which a somatostatin analogue (a small peptide) is coupled with a radioligand so that the radiation dose is selectively administered to somatostatin receptor-expressing metastasized neuroendocrine tumors, particularly gastroenteropancreatic. Reported toxicities include myelotoxicity and nephrotoxicity, the latter manifesting as decreased kidney function, often developing months to years after treatment completion. We present a case of PRRT-induced kidney toxicity manifesting as a severe Gitelman-like tubulopathy with preserved kidney function. Because profound hypokalemia and hypocalcemia can lead to life-threatening arrhythmias, we highlight the necessity for careful monitoring of serum and urine electrolytes in patients receiving PRRT.

Risk factors and clinical course of hungry bone syndrome after total parathyroidectomy in dialysis patients with secondary hyperparathyroidism.

BACKGROUND: Hungry bone syndrome (HBS) is an important postoperative complication after parathyroidectomy for severe secondary hyperparathyroidism (SHPT). There is, however, little data in the literature on its detailed clinical course, and the associated risk factors remain controversial. METHODS: We did a single-center retrospective study on 62 consecutive dialysis patients who underwent total parathyroidectomy for SHPT to examine the risk factors, clinical course and outcome. Data on demographic characteristics, perioperative laboratory parameters including serum calcium, phosphate, alkaline phosphatase (ALP) and parathyroid hormone (PTH), drug treatment for SHPT and operative details of parathyroidectomy were collected. RESULTS: Seventeen (27.4%) patients developed severe postoperative hypocalcemia with HBS. The serum calcium dropped progressively while serum ALP rose after operation until 2 weeks later when serum calcium reached the trough and serum ALP peaked. Serum phosphate also fell but stabilized between 4 and 14 days. The total postoperative calcium and vitamin D supplementation was significantly larger, and hospital stay was significantly longer in the group with HBS as compared with those without HBS. Young age, high body weight, high preoperative ALP level, and low preoperative calcium level independently predicted the development of HBS while preoperative PTH and use of cinacalcet or paricalcitol did not. CONCLUSION: HBS was common after total parathyroidectomy in patients with SHPT, and it is important to closely monitor the postoperative serum calcium, phosphate and ALP levels in the following 2 weeks, especially for those at risk. The implications of our findings on perioperative management are discussed.

Vitamin D deficiency decreases adiposity in rats and causes altered expression of uncoupling proteins and steroid receptor coactivator3.

The vitamin D endocrine system is functional in the adipose tissue, as demonstrated in vitro, in cultured adipocytes, and in vivo in mutant mice that developed altered lipid metabolism and fat storage in the absence of either 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or the vitamin D receptor. The aim of the present study was to examine the role of vitamin D and calcium on body adiposity in a diet-induced vitamin D deficient rat model. Vitamin D-deficient rats gained less weight and had lower amounts of visceral fat. Consistent with reduced adipose tissue mass, the vitamin D-deficient rats had low circulating levels of leptin, which reflects body fat stores. Expression of vitamin D and calcium sensing receptors, and that of genes involved in adipogenesis such as peroxisome proliferator-activated receptor, fatty acid synthase and leptin were significantly reduced in white adipose tissue of deficient rats compared to vitamin D-sufficient rats. Furthermore, the expression of uncoupling proteins (Ucp1 and Ucp2) was elevated in the white adipose tissue of the deficient rat indicative of higher energy expenditure, thereby leading to a lean phenotype. Expression of the p160 steroid receptor coactivator3 (SRC3), a key regulator of adipogenesis in white adipose tissue was decreased in vitamin D-deficient state. Interestingly, most of the changes observed in vitamin D deficient rats were corrected by calcium supplementation alone. Our data demonstrates that dietary vitamin D and calcium regulate adipose tissue function and metabolism.

The human response to acute enteral and parenteral phosphate loads.

The human response to acute phosphate (PO4) loading is poorly characterized, and it is unknown whether an intestinal phosphate sensor mechanism exists. Here, we characterized the human mineral and endocrine response to parenteral and duodenal acute phosphate loads. Healthy human participants underwent 36 hours of intravenous (IV; 1.15 [low dose] and 2.30 [high dose] mmol of PO4/kg per 24 hours) or duodenal (1.53 mmol of PO4/kg per 24 hours) neutral sodium PO4 loading. Control experiments used equimolar NaCl loads. Maximum PO4 urinary excretory responses occurred between 12 and 24 hours and were similar for low-dose IV and duodenal infusion. Hyperphosphatemic responses were also temporally and quantitatively similar for low-dose IV and duodenal PO4 infusion. Fractional renal PO4 clearance increased approximately 6-fold (high-dose IV group) and 4-fold (low-dose IV and duodenal groups), and significant reductions in plasma PO4 concentrations relative to peak values occurred by 36 hours, despite persistent PO4 loading. After cessation of loading, frank hypophosphatemia occurred. The earliest phosphaturic response occurred after plasma PO4 and parathyroid hormone concentrations increased. Plasma fibroblast growth factor-23 concentration increased after the onset of phosphaturia, followed by a decrease in plasma 1,25(OH)2D levels; α-Klotho levels did not change. Contrary to results in rodents, we found no evidence for intestinal-specific phosphaturic control mechanisms in humans. Complete urinary phosphate recovery in the IV loading groups provides evidence against any important extrarenal response to acute PO4 loads.

Mineral and antioxidant management of transition dairy cows.

Transition management needs to be fully integrated to be effective. We discuss and demonstrate this concept in the context of a study that used these principles. The roles of calcium, magnesium, phosphorus and dietary anion cation difference in influencing the pathophysiology and incidence of hypocalcemia are highlighted. Recent understandings of the pivotal role of skeleton in metabolism are reviewed. Micronutrient mineral and vitamin needs are addressed in the context of exposure of periparturient cattle to oxidative stress and inflammatory disorders. This article provides a series of practical approaches to improving transition diets.

Correction of hypocalcemia allows optimal recruitment of FGF-23-dependent phosphaturic mechanisms in acute hyperphosphatemia post-phosphate enema.

Both parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are phosphaturic hormones. These hormones should increase in response to phosphate excess. However, they also regulate serum calcium; PTH increases serum calcium concentration and FGF23 suppresses renal production of calcitriol, favoring hypocalcemia. We report the case of an 83-year-old woman with hyperphosphatemia and hypocalcemia resulting from phosphate-containing enemas. PTH and calcitriol increased in response to hypocalcemia, and FGF23 increased in response to hyperphosphatemia. Unexpectedly, peak FGF23 did not coincide with peak serum phosphate. Rather, peak FG23 was observed only after severe hypocalcemia was partially corrected with exogenous calcium administration, even though serum phosphate had been already decreasing for 32 h. Correction of severe hypocalcemia was thus associated with peak FGF23 values and with a precipitous decrease in PTH. Peak FGF23 was followed by an accelerated decrease in serum phosphate and significant phosphaturia. This clinical report is consistent with experimental data in rats showing a blunted FGF23 response to high phosphate in the presence of severe hypocalcemia. Thus, complementary experimental and clinical data suggest that partial correction of severe hypocalcemia is required for optimal FGF23-mediated phosphaturia, which takes place despite correction of PTH levels. We believe this the first human report suggesting blunting of the FGF23 response to high phosphate by severe hypocalcemia.