Pre-Transplant Calcimimetic Use and Dose Information Improves the Accuracy of Prediction of Tertiary Hyperparathyroidism after Kidney Transplantation: A Retrospective Cohort Study.

Tertiary hyperparathyroidism (THPT) is characterized by elevated parathyroid hormone and serum calcium levels after kidney transplantation (KTx). To ascertain whether pre-transplant calcimimetic use and dose information would improve THPT prediction accuracy, this retrospective cohort study evaluated patients who underwent KTx between 2010 and 2022. The primary outcome was the development of clinically relevant THPT. Logistic regression analysis was used to evaluate pre-transplant calcimimetic use as a determinant of THPT development. Participants were categorized into four groups according to calcimimetic dose, developing two THPT prediction models (with or without calcimimetic information). Continuous net reclassification improvement (CNRI) and integrated discrimination improvement (IDI) were calculated to assess ability to reclassify the degree of THPT risk by adding pre-transplant calcimimetic information. Of the 554 patients, 87 (15.7%) developed THPT, whereas 139 (25.1%) received pre-transplant calcimimetic treatment. Multivariate logistic regression analysis revealed that pre-transplant calcimimetic use was significantly associated with THPT development. Pre-transplant calcimimetic information significantly improved the predicted probability accuracy of THPT (CNRI and IDI were 0.91 [p < 0.001], and 0.09 [p < 0.001], respectively). The THPT prediction model including pre-transplant calcimimetic information as a predictive factor can contribute to the prevention and early treatment of THPT in the era of calcimimetics.

The association between proton pump inhibitors and hyperparathyroidism: a potential mechanism for increased fracture-results of a large observational cohort study.

Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture; however, the mechanism is unclear. PPI users taking calcium supplements were more likely to have hyperparathyroidism compared to non-users (OR 1.56, CI 1.08-2.23, p = 0.018). This highlights the importance of monitoring PPI use, especially in older adults. PURPOSE: Proton pump inhibitors (PPIs) are associated with increased risk of osteoporotic fracture. Hyperparathyroidism may be implicated, but few studies have considered this relationship. This study evaluated the relationship between PPI use and hyperparathyroidism in older adults. METHODS: Participants were from the TUDA study, a large cross-sectional cohort of older Irish adults. Participants with an estimated glomerular filtration rate (eGFR) < 30 ml/min and serum calcium > 2.5 mmol/l were excluded to avoid hyperparathyroidism due to chronic renal disease and primary hyperparathyroidism. Hyperparathyroidism was defined as a parathyroid hormone (PTH) > 65 pg/ml. Multivariate regression models were used to analyse the relationship between PPI use and hyperparathyroidism. RESULTS: A total of 4139 participants met the inclusion criteria, of whom 37.8% (n = 1563) were taking PPI medication. PPI use was identified in 41.4% of calcium supplement users and 35.4% of non-calcium supplement users. Overall, compared to non-users of PPIs, those taking PPIs were older (74.8 vs 72.9 years, p < 0.001) and had a higher prevalence of hyperparathyroidism (17.8 vs 11.0%, p < 0.001). In those taking calcium supplements (but not in non-users), PPI use was significantly associated with hyperparathyroidism (OR 1.56, CI 1.08-2.23, p = 0.018) after adjusting for age, sex, body mass index, serum vitamin D, eGFR, timed-up-and-go, dairy intake, medications, and comorbidities. DISCUSSION: The results are consistent with the hypothesis of PPIs reducing calcium absorption, leading to a rise in PTH which could mediate increased fracture risk. No relationship of PPI use with hyperparathyroidism was observed in non-users of calcium supplements, possibly owing to lower dietary calcium intake. These results highlight the importance of monitoring PPI use, especially in older adults at risk of fracture.

Treatment of hypokalemia with amiloride unmasked hypercalcemia and hyperparathyroidism: A case report.

Colonic pseudo-obstruction, also called Ogilvie's syndrome, occurs due to impaired intestinal propulsion, and may be caused by electrolyte imbalances such as hypokalemia and some endocrine disorders such as hyperparathyroidism. Secretory diarrhea due to intestinal pseudo-obstruction can cause hypokalemia. Diuretics such as amiloride can be used to treat hypokalemia, however in this case, treatment with amiloride induced hypercalcemia and unmasked hyperparathyroidism. A 73-year-old female with a history of hypertension and parathyroid adenoma presented with recurrent colonic pseudo-obstruction and chronic hypokalemia. Her hypokalemia was treated with amiloride, causing hypercalcemia of 14.4 mg/dL, elevated PTH, and altered mental status. Amiloride was subsequently discontinued with improvement in her symptoms, and her hyperparathyroidism was treated with cinacalcet. To our knowledge, this is the first report of amiloride unmasking hyperparathyroidism and inducing hypercalcemia.

Effect of Endogenous Parathyroid Hormone on Bone Geometry and Skeletal Microarchitecture.

Parathyroid hormone (PTH) has anabolic or catabolic effects on bones; however, the skeletal effect of endogenous PTH on cortical and trabecular bones is not yet clear. Therefore, we aimed to examine the effects of an excess and a deficiency of endogenous PTH on the lumbar spine trabecular bone score (TBS) and bone geometry using dual-energy X-ray absorptiometry. We retrospectively included 70 patients with primary hyperparathyroidism (PHPT), 26 patients with idiopathic or postoperative hypoparathyroidism (HypoPT), and 96 normal controls matched by age, sex, and body mass index. The bone mineral density (BMD) at the lumbar spine, femur neck, and total hip was higher in the HypoPT, followed by the controls and PHPT group (all P < 0.001). The TBS was significantly decreased in the PHPT group compared to the controls (P = 0.021); however, statistical significance disappeared after adjusting for the lumbar BMD (P = 0.653). There were no significant differences in the TBS between the HypoPT group and controls as well as the PHPT and HypoPT group. As for bone geometry parameters, the cross-sectional area, cross-sectional moment of inertia, and section modulus were higher in the HypoPT, followed by the controls and PHPT group (all P < 0.001); statistical significance remained after adjusting for the total hip BMD. We also observed a significantly increased cortical neck width in the HypoPT group compared to the PHPT group (P = 0.009). The buckling ratio was higher in the PHPT than the HypoPT group and controls (P = 0.018 and P = 0.013, respectively). The present study demonstrated that an excess of endogenous PTH had catabolic effects on both cortical and trabecular bones. Under conditions of endogenous PTH deficiency, the effect on cortical bone was pronounced, but that on trabecular bone was modest.

Use of calcimimetics in children with normal kidney function.

The calcium-sensing receptor (CaSR) plays an important role in the homeostasis of serum ionized calcium by regulating parathyroid hormone (PTH) secretion and tubular calcium handling. Calcimimetics, which act by allosteric modulation of the CaSR, mimic hypercalcemia resulting in suppression of PTH release and increase in calciuria. Mostly used in children to treat secondary hyperparathyroidism associated with advanced renal failure, we have shown that calcimimetics can also be successfully used in children with bone and mineral disorders in which elevated PTH plays a detrimental role in skeletal pathophysiology in the face of normal kidney function. The current review briefly discusses the role of the CaSR and calcimimetics in calcium homeostasis, and then addresses the potential applications of calcimimetics in children with normal kidney function with disorders in which suppression of PTH is beneficial.

Lessons learned from the management of Hungry Bone Syndrome following the removal of an Atypical Parathyroid Adenoma.

Hungry Bone Syndrome (HBS) refers to rapid, profound, and prolonged hypocalcemia associated with hypophosphatemia and hypomagnesemia occurring in patients with increased bone turnover after successful management of the underlying disorder. We describe a male patient with primary hyperparathyroidism (PHPT), in whom HBS was diagnosed 6 months after parathyroidectomy. Histopathologic examination revealed an atypical parathyroid adenoma (APA), while immunohistochemistry showed cell proliferation index Ki-67 10% and overexpression of cyclin D1 (>90%). Preoperative treatment with vitamin D3 had normalized 25OHD and alkaline phosphatase levels, reflected in an improvement in bone turnover prior to surgery. Postoperative treatment for HBS with alfacalcidol, calcium, vitamin D3 and magnesium was administered for a long period. This treatment prevented severe postoperative hypocalcemia and he was discharged two days later. Preoperative cinacalcet treatment did not reduce hypercalcemia implying that the tumor had lack of calciumsensing receptors (CaSR). In conclusion, preoperative restoration of low 25OHD levels is essential for prevention of HBS. Postoperative treatment with active metabolites of vitamin D must be initiated as early as possible, in order to prevent or minimize the development of HBS, and to reduce the duration of hospitalization.

Mineralocorticoid Receptor Blockers and Aldosterone to Renin Ratio: A Randomized Controlled Trial and Observational Data.

Current guidelines recommend to withdraw mineralocorticoid receptor (MR) blocker treatment for at least 4 weeks when measuring the aldosterone to renin ratio (ARR) as a screening test for primary aldosteronism (PA). We aimed to evaluate the effect of MR blocker treatment on ARR and its components, plasma aldosterone concentration (PAC), and direct renin concentration (DRC). First, we performed a post-hoc analysis of the effect of eplerenone on parathyroid hormone levels in primary hyperparathyroidism (EPATH) study, a randomized controlled trial (RCT) in 110 patients with primary hyperparathyroidism (pHPT). Patients were 1:1 randomly assigned to receive either 25 mg eplerenone once daily (up-titration after 4 weeks to 50 mg/day) or placebo for 8 weeks. Second, we measured the ARR in 4 PA patients from the Graz Endocrine Causes of Hypertension Study (GECOH) before and after MR blocker treatment. Ninety-seven participants completed the EPATH trial, and the mean treatment effect (95% confidence interval) for log(e)ARR was 0.08 (-0.32 to 0.48) ng/dl/µU/ml (p=0.694). The treatment effect was 0.71 (0.47 to 0.96; p<0.001) ng/dl for log(e)PAC and 0.64 (0.19 to 1.10; p=0.006) µU/ml for log(e)DRC, respectively. In the 4 PA patients, the ARR decreased from 11.24±3.58 at baseline to 2.70±1.03 (p=0.013) ng/dl/µU/ml after MR blocker treatment. In this study with limited sample size, MR blocker treatment did not significantly alter the ARR in pHPT patients but significantly reduced the ARR in PA patients. Diagnostic utility of ARR and its components for PA diagnostics under MR blocker treatment warrants further study.

Discovery of evocalcet, a next-generation calcium-sensing receptor agonist for the treatment of hyperparathyroidism.

The calcium-sensing receptor (CaSR) plays an important role in sensing extracellular calcium ions and regulating parathyroid hormone secretion by parathyroid gland cells, and the receptor is a suitable target for the treatment of hyperparathyroidism. Cinacalcet hydrochloride is a representative CaSR agonist which widely used for the hyperparathyroidism. However, it has several issues to clinical use, such as nausea/vomiting and strong inhibition of CYP2D6. We tried to improve these issues of cinacalcet for a new pharmaceutical agent as a preferable CaSR agonist. Optimization from cinacalcet resulted in the identification of pyrrolidine compounds and successfully led to the discovery of evocalcet as an oral allosteric CaSR agonist. Evocalcet, which exhibited highly favorable profiles such as CaSR agonistic activity and good DMPK profiles, will provide a novel therapeutic option for secondary hyperparathyroidism.

Early introduction of oral paricalcitol in renal transplant recipients. An open-label randomized study.

In stable renal transplant recipients with hyperparathyroidism, previous studies have indicated that vitamin D agonist treatment might have anti-proteinuric effects. Animal studies indicate possible anti-fibrotic and anti-inflammatory effects. Early introduction of paricalcitol in de novo renal transplant recipients might reduce proteinuria and prevent progressive allograft fibrosis. We performed a single-center, prospective, randomized, open-label trial investigating effects of paricalcitol 2 µg/day added to standard care. Participants were included 8 weeks after engraftment and followed for 44 weeks. Primary end point was change in spot urine albumin/creatinine ratio. Exploratory microarray analyses of kidney biopsies at study end investigated potential effects on gene expression. Secondary end points included change in glomerular filtration rate (GFR), pulse wave velocity (PWV), and endothelial function measured by peripheral arterial tonometry as reactive hyperemia index (RHI). Seventy-seven de novo transplanted kidney allograft recipients were included, 37 receiving paricalcitol. Paricalcitol treatment lowered PTH levels (P = 0.01) but did not significantly reduce albuminuria (P = 0.76), change vascular parameters (PWV; P = 0.98, RHI; P = 0.33), or influence GFR (P = 0.57). Allograft gene expression was not influenced. To summarize, in newly transplanted renal allograft recipients, paricalcitol reduced PTH and was well tolerated without negatively affecting kidney function. Paricalcitol did not significantly reduce/prevent albuminuria, improve parameters of vascular health, or influence allograft gene expression.

Calcimimetic and Calcilytic Drugs: Feats, Flops, and Futures.

The actions of extracellular Ca(2+) in regulating parathyroid gland and kidney functions are mediated by the extracellular calcium receptor (CaR), a G protein-coupled receptor. The CaR is one of the essential molecules maintaining systemic Ca(2+) homeostasis and is a molecular target for drugs useful in treating bone and mineral disorders. Ligands that activate the CaR are termed calcimimetics and are classified as either agonists (type I) or positive allosteric modulators (type II); calcimimetics inhibit the secretion of parathyroid hormone (PTH). Cinacalcet is a type II calcimimetic that is used to treat secondary hyperparathyroidism in patients receiving dialysis and to treat hypercalcemia in some forms of primary hyperparathyroidism. The use of cinacalcet among patients with secondary hyperparathyroidism who are managed with dialysis effectively lowers circulating PTH levels, reduces serum phosphorus and FGF23 concentrations, improves bone histopathology, and may diminish skeletal fracture rates and the need for parathyroidectomy. A second generation type II calcimimetic (AMG 416) is currently under regulatory review. Calcilytics are CaR antagonists that stimulate the secretion of PTH. Several calcilytic compounds have been evaluated as orally active anabolic therapies for postmenopausal osteoporosis but clinical development of all of them has been abandoned because they lacked clinical efficacy. Calcilytics might be repurposed for new indications like autosomal dominant hypocalcemia or other disorders beyond those involving systemic Ca(2+) homeostasis.

Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease.

BACKGROUND/AIMS: Vitamin D insufficiency and secondary hyperparathyroidism (SHPT) are associated with increased morbidity and mortality in chronic kidney disease (CKD) and are poorly addressed by current treatments. The present clinical studies evaluated extended-release (ER) calcifediol, a novel vitamin D prohormone repletion therapy designed to gradually correct low serum total 25-hydroxyvitamin D, improve SHPT control and minimize the induction of CYP24A1 and FGF23. METHODS: Two identical multicenter, randomized, double-blind, placebo-controlled studies enrolled subjects from 89 US sites. A total of 429 subjects, balanced between studies, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency were randomized 2:1 to receive oral ER calcifediol (30 or 60 µg) or placebo once daily at bedtime for 26 weeks. Most subjects (354 or 83%) completed dosing, and 298 (69%) entered a subsequent open-label extension study wherein ER calcifediol was administered without interruption for another 26 weeks. RESULTS: ER calcifediol normalized serum total 25-hydroxyvitamin D concentrations (>30 ng/ml) in >95% of per-protocol subjects and reduced plasma intact parathyroid hormone (iPTH) by at least 10% in 72%. The proportion of subjects receiving ER calcifediol who achieved iPTH reductions of ≥30% increased progressively with treatment duration, reaching 22, 40 and 50% at 12, 26 and 52 weeks, respectively. iPTH lowering with ER calcifediol was independent of CKD stage and significantly greater than with placebo. ER calcifediol had inconsequential impact on serum calcium, phosphorus, FGF23 and adverse events. CONCLUSION: Oral ER calcifediol is safe and effective in treating SHPT and vitamin D insufficiency in CKD.

The other side of vitamin D therapy: a case series of acute kidney injury due to malpractice-related vitamin D intoxication
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BACKGROUND: Vitamin D deficiency is highly prevalent in Indian Kashmir. Many people get injectable vitamin D (600,000 IU/injection). At times, the dose prescribed is far above the permissible limit. We report 62 patients with malpractice-related vitamin D intoxication, presenting with hypercalcemia and acute kidney injury (AKI). METHODS: The diagnosis was made on basis of (1) history of multiple intramuscular vitamin D injections (2) toxic serum levels of 25-OH vitamin D and (3) exclusion of common causes of hypercalcemia (malignancy and hyperparathyroidism). Their presentation was either de novo AKI in 51 (group 1) or acute on top of chronic kidney disease in 11 (group 2). RESULTS: The mean age was 60 ± 14 vs. 62 ± 13 years, approximate number of vitamin D injections received ranged from 4 to 28 (2.4 - 16.8 million units) vs. 3 to 24 (1.8 - 14.4 million units), mean creatinine at presentation was 3.2 ± 0.9 vs. 4.5 ± 1.1 mg/dL, which decreased to 1.2 ± 0.2 vs. 3.3 ± 1.0 mg/dL, mean serum calcium on admission was 13.7 ± 1.4 vs. 13.6 ± 2.0 mg/dL which decreased to 10.7 ± 1.2 vs. 11.0 ± 1.0 mg/dL on follow-up of 7.2 ± 0.6 months, mean vitamin D level was 313.3 ± 54.8 (range 235 - 375) vs. 303.7 ± 48.4 (range 210 - 375) nmol/L and mean PTH was 18.1 ± 9.6 (range 6.2 - 32) vs. 52.3 ± 12.6 (range 28 - 88) pg/mL in group 1 vs. group 2, respectively. The clinical presentation was weakness, constipation, abdominal pain, nausea, vomiting, anorexia, altered sensorium, and oliguria. The treatment received was intravenous fluids (normal saline) in all in group 1 and in 8/11 in group 2, short course of steroids (prednisolone) in 44, and bisphosphonate in 6. CONCLUSION: This is the largest case series of AKI secondary to vitamin D toxicity ever reported.
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Vitamin D receptor agonist VS-105 improves cardiac function in the presence of enalapril in 5/6 nephrectomized rats.

Vitamin D receptor (VDR) agonists (VDRAs) are commonly used to manage hyperparathyroidism secondary to chronic kidney disease (CKD). Patients with CKD experience extremely high risks of cardiovascular morbidity and mortality. Clinical observations show that VDRA therapy may be associated with cardio-renal protective and survival benefits in patients with CKD. The 5/6 nephrectomized (NX) Sprague-Dawley rat with established uremia exhibits elevated serum parathyroid hormone (PTH), hypertension, and abnormal cardiac function. Treatment of 5/6 NX rats with VS-105, a novel VDRA (0.05 and 0.5 µg/kg po by gavage), once daily for 8 wk in the presence or absence of enalapril (30 mg/kg po via drinking water) effectively suppressed serum PTH without raising serum calcium. VS-105 alone reduced systolic blood pressure (from 174 ± 6 to 145 ± 9 mmHg, P < 0.05) as effectively as enalapril (from 174 ± 6 to 144 ± 7 mmHg, P < 0.05). VS-105 improved cardiac functional parameters such as E/A ratio, ejection fraction, and fractional shortening with or without enalapril. Enalapril or VS-105 alone significantly reduced left ventricular hypertrophy (LVH); VS-105 plus enalapril did not further reduce LVH. VS-105 significantly reduced both cardiac and renal fibrosis. The lack of hypercalcemic toxicity of VS-105 is due to its lack of effects on stimulating intestinal calcium transport and inducing the expression of intestinal calcium transporter genes such as Calb3 and TRPV6. These studies demonstrate that VS-105 is a novel VDRA that may provide cardiovascular benefits via VDR activation. Clinical studies are required to confirm the cardiovascular benefits of VS-105 in CKD.

Influence on quality of life from an early cinacalcet prescription for secondary hyperparathyroidism in dialysis.

OBJECTIVE: The goal of this study is to compare patient-reported quality of life (PRQOL) evolution between two groups of end-stage renal disease patients with secondary hyperparathyroidism (SHPT). The first with a cinacalcet prescription within 3 months after a diagnosis of SHPT (early group) and a second group of patients with a later or no cinacalcet prescription (nonearly group). PATIENTS AND METHODS: From 2009 to 2012, we conducted a multicenter pharmaco-epidemiologic study in Lorraine region (France) including all consecutive patients on maintenance dialysis for at least 3 months with a diagnosis of SHPT (PTH > 500 pg/ml or first cinacalcet prescription). PRQOL was estimated using the Kidney Disease Quality Of Life-Short Form questionnaire, at baseline and at 6 and 12 months follow-up. Change in PRQOL was compared between the groups and adjusted with a propensity score. RESULTS: We included 124 patients: 44 in the early group and 80 in the nonearly group. The mental component summary score was lower in the early group, at baseline (43.6 ± 6.6 vs 46.6 ± 7.6; p = 0.030), and at the follow-up assessment (42.6 ± 6.9 vs 45.7 ± 7.9; p = 0.033). We found no difference between the groups in change in PRQOL, for all dimensions, even after adjustment with the propensity score. Mean serum alkaline phosphatase levels were normal in both groups at baseline (80.9 ± 32.5 vs 95.1 ± 39.6; p = 0.41). CONCLUSION: Cinacalcet prescription immediately following diagnosis of SHPT does not seem to be associated with better PRQOL evolution at 1 year. Mean serum alkaline phosphatase levels suggest that physicians should consider waiting for another PTH assay result before starting cinacalcet in case of a PTH rise.

Propensity score matching and persistence correction to reduce bias in comparative effectiveness: the effect of cinacalcet use on all-cause mortality.

PURPOSE: The generalisability of randomised controlled trials (RCTs) may be limited by restrictive entry criteria or by their experimental nature. Observational research can provide complementary findings but is prone to bias. Employing propensity score matching, to reduce such bias, we compared the real-life effect of cinacalcet use on all-cause mortality (ACM) with findings from the Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE) RCT in chronic haemodialysis patients. METHODS: Incident adult haemodialysis patients receiving cinacalcet, recruited in a prospective observational cohort from 2007-2009 (AROii; n = 10,488), were matched to non-exposed patients regardless of future exposure status. The effect of treatment crossover was investigated with inverse probability of censoring weighted and lag-censored analyses. EVOLVE ACM data were analysed largely as described for the primary composite endpoint. RESULTS: AROii patients receiving cinacalcet (n = 532) were matched to 1790 non-exposed patients. The treatment effect of cinacalcet on ACM in the main AROii analysis (hazard ratio 1.03 [95% confidence interval (CI) 0.78-1.35]) was closer to the null than for the Intention to Treat (ITT) analysis of EVOLVE (0.94 [95%CI 0.85-1.04]). Adjusting for non-persistence by 0- and 6-month lag-censoring and by inverse probability of censoring weight, the hazard ratios in AROii (0.76 [95%CI 0.51-1.15], 0.84 [95%CI 0.60-1.18] and 0.79 [95%CI 0.56-1.11], respectively) were comparable with those of EVOLVE (0.82 [95%CI 0.67-1.01], 0.83 [95%CI 0.73-0.96] and 0.87 [95%CI 0.71-1.06], respectively). CONCLUSIONS: Correcting for treatment crossover, we observed results in the 'real-life' setting of the AROii observational cohort that closely mirrored the results of the EVOLVE RCT. Persistence-corrected analyses revealed a trend towards reduced ACM in haemodialysis patients receiving cinacalcet therapy.

Effect of cinacalcet cessation on hyperparathyroidism in kidney transcaplant patients after long-term dialysis therapy.

BACKGROUND: Cinacalcet is a promising therapy widely used in dialysis patients with hyperparathyroidism resistant to conventional therapy. However, reports regarding the influence of cinacalcet cessation after long-term use on kidney transplantation patients are few. METHODS: This retrospective observational study included 40 dialysis patients who underwent kidney transplantation. Creatinine, corrected calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone levels were assessed before and after kidney transplantation according to pretransplant treatment of chronic kidney disease-mineral and bone disorder. RESULTS: Ultrasonography revealed enlargement of the parathyroid in all patients treated with cinacalcet. Although the data at the time of kidney transplantation were comparable, the serum levels of calcium, alkaline phosphatase, and intact parathyroid hormone after kidney transplantation were higher in patients treated with cinacalcet than in those treated without. However, serum phosphate levels in the cinacalcet group were slightly higher at the time of kidney transplantation and significantly lower 3 months later. CONCLUSIONS: Mineral abnormalities persisted in kidney transplant patients with enlarged parathyroid glands after discontinuation of cinacalcet treatment. Parathyroidectomy should be considered in kidney transplant candidates with the risk of developing refractory hyperparathyroidism after transplantation.

Pre-operative fibrous osteodystrophy and severe, refractory, post-operative hypocalcemia following parathyroidectomy in a dog.

A 13-year-old dog exhibited dramatic, radiographic osteopenia consistent with fibrous osteodystrophy secondary to primary hyperparathyroidism. Following parathyroidectomy, the dog developed severe, prolonged hypocalcemia, but was successfully treated and discharged 32 d after surgery. A variety of factors may have contributed to this dog's hypocalcemia including hypoparathyroidism and hungry bone syndrome.

Ostéodystrophie fibreuse préopératoire et hypocalcémie grave, réfractaire postopératoire après une parathyroïdectomie chez un chien. Un chien âgé de 13 ans a manifesté une ostéopénie radiographique dramatique conforme à une ostéodystrophie fibreuse secondaire à un hyperparathyroïdisme primaire. Après une parathyroïdectomie, le chien a développé une hypocalcémie grave et prolongée, mais il a été traité avec succès et a reçu son congé 32 jours après la chirurgie. Divers facteurs peuvent avoir contribué à l'hypocalcémie de ce chien, y compris l'hypoparathyroïdisme et l'hypocalcémie par avidité osseuse.(Traduit par Isabelle Vallières).

The effect of cholecalciferol for lowering albuminuria in chronic kidney disease: a prospective controlled study.

BACKGROUND: Growing evidence indicates that vitamin D receptor activation may have antiproteinuric effects. We aimed to evaluate whether vitamin D supplementation with daily cholecalciferol could reduce albuminuria in proteinuric chronic kidney disease (CKD) patients. METHODS: This 6-month prospective, controlled, intervention study enrolled 101 non-dialysis CKD patients with albuminuria. Patients with low 25(OH) vitamin D [25(OH)D] and high parathyroid hormone (PTH) levels (n = 50; 49%) received oral cholecalciferol (666 IU/day), whereas those without hyperparathyroidism (n = 51; 51%), independent of their vitamin D status, did not receive any cholecalciferol, and were considered as the control group. RESULTS: Cholecalciferol administration led to a rise in mean 25(OH)D levels by 53.0 ± 41.6% (P < 0.001). Urinary albumin-to-creatinine ratio (uACR) decreased from (geometric mean with 95% confidence interval) 284 (189-425) to 167 mg/g (105-266) at 6 months (P < 0.001) in the cholecalciferol group, and there was no change in the control group. Reduction in a uACR was observed in the absence of significant changes in other factors, which could affect proteinuria, like weight, blood pressure (BP) levels or antihypertensive treatment. Six-month changes in 25(OH)D levels were significantly and inversely associated with that in the uACR (Pearson's R = -0.519; P = 0.036), after adjustment by age, sex, body mass index, BP, glomerular filtration rate and antiproteinuric treatment. The mean PTH decreased by -13.8 ± 20.3% (P = 0.039) only in treated patients, with a mild rise in phosphate and calcium-phosphate product [7.0 ± 14.7% (P = 0.002) and 7.2 ± 15.2% (P = 0.003), respectively]. CONCLUSIONS: In addition to improving hyperparathyroidism, vitamin D supplementation with daily cholecalciferol had a beneficial effect in decreasing albuminuria with potential effects on delaying the progression of CKD.

The EVOLVE study is negative, so what does this 'bitter pill' of disappointment mean now for renal patients?

The extremely high morbidity and mortality experienced by subjects with chronic kidney disease (CKD) has often been described and reviewed, but this familiarity should not breed indifference to the huge burden of premature cardiovascular disease ­ something which becomes more obvious, but increasingly challenging to treat, as GFR declines, or proteinuria increases. The health outcomes for a middle-aged person entering renal replacement therapy are as bad as those seen with a major solid organ malignancy; while there has been modest progress in improving outcomes over the last two decades, the diagnosis of significant or progressive CKD should and thus still does continue to cast a shadow over patients, carers and healthcare professionals alike.