Idiopathic Hypercalcemia Research Articles

Successful treatment of a case of feline idiopathic hypercalcaemia with cinacalcet

Successful treatment of a case of feline idiopathic hypercalcaemia with cinacalcet

Exploring the relationship between calcitonin, ionized calcium, and bone turnover in cats with and without naturally occurring hypercalcemia.

This case-control study aimed to evaluate calcitonin response in naturally occurring hypercalcemia in cats and assess the relationships between calcitonin and ionized calcium (iCa) and examine relationships between calcitonin, iCa and bone turnover. Hypercalcemic cats (persistently increased iCa concentration [>1.40 mmol/l]) were identified retrospectively via a medical database search; additional hypercalcemic and normocalcemic cats were recruited prospectively. Data regarding routine biochemical and urine testing, diagnostic imaging and additional blood testing were obtained. Serum alkaline phosphatase (ALP) activity was used as a marker of bone turnover. Serum calcitonin concentration was analyzed using a previously validated immunoradiometric assay. Hypercalcemic cats with an increased calcitonin concentration (>0.9 ng/L) were termed responders. Group comparisons were performed using a Mann-Whitney test for continuous variables and a χ2 test for categorical variables. Spearman's correlation coefficient was used to examine the relationships between calcitonin, iCa and ALP. Twenty-six hypercalcemic and 25 normocalcemic cats were recruited. Only 5/26 (19.2%) of the hypercalcemic cats were identified as responders, and all were diagnosed with idiopathic hypercalcemia. There was no significant correlation between the concentrations of calcitonin and iCa (p = 0.929), calcitonin and ALP (p = 0.917) or iCa and ALP (p = 0.678) in hypercalcemic cats, however, a significant negative correlation was observed between calcitonin and ALP (p = 0.037) when normocalcemic and hypercalcemic cats with an elevated calcitonin concentration were analyzed together. The expected increase in calcitonin concentration was present in only a small subset of hypercalcemic cats; no correlation was found between iCa and calcitonin concentration. The inverse relationship between calcitonin and ALP in cats with increased calcitonin concentrations suggests that the ability of calcitonin to correct hypercalcemia may be related to the degree of bone turnover.

Ionized hypercalcemia can resolve with nutritional modification in cats with idiopathic hypercalcemia or chronic kidney disease.

Cats with ionized hypercalcemia that were fed diets with either more than 200 mg calcium per 100 kilocalories (kcal), a calcium:phosphorus (Ca:P) ratio greater than 1.4:1 or both, based on diet history, were included in this case series. Ionized hypercalcemia was documented at least twice in all cats before enrollment. Cats were referred for evaluation of ionized hypercalcemia (n = 5) or were incidentally found to have ionized hypercalcemia (n = 5). After medical workups, cats were diagnosed with either idiopathic hypercalcemia (IHC; n = 7) or chronic kidney disease (n = 3). Cats receiving medications to treat IHC (eg, alendronate, corticosteroids) were excluded. Nutritional recommendations were made to transition the cats to diets with less thn 200 mg calcium per 100 kcal and a Ca:P ratio less than 1.4:1. Ionized calcium (iCa) concentrations were rechecked in all cats, with a median recheck time of 9 weeks (range 3-20). Of the 10 cats, nine (90%) had a decrease in iCa. Of the 10 cats, six (60%) became normocalcemic after the diet change, three (30%) had a partial response and one (10%) did not respond. Of the four cats that did not achieve normocalcemia with a change in diet, two (50%) received chia seeds (1-2 g per day), and at the next recheck, both cats' iCa concentrations had normalized. Three cats had a long-term follow-up. Ionized normocalcemia was maintained for at least two consecutive follow-up visits over a median follow-up period of 33 weeks (range 12-34). Dietary calcium concentrations and the dietary Ca:P ratio appear to be important variables in considering nutritional approaches for hypercalcemic cats.

A retrospective case series on bisphosphonate related osteonecrosis of the jaw in 20 cats.

This retrospective study highlights the salient aspects of a series of feline patients affected with bisphosphonate related osteonecrosis of the jaw. Though more commonly published in human literature, this presentation is rare in cats. The authors hope that this study will assist in making this a more globally known entity with subsequent improved prognosis. Data was retrospectively obtained from the medical records between 2015 and 2021 of 20 cats with Medication Related Osteonecrosis of the Jaw. Data included patient information, clinical history, presenting complaint, systemic diseases, details referable to hypercalcemia and treatment thereof, bisphosphonate specifics (dose and duration), clinical presentation of the lesion, diagnostic testing including radiographic and histopathologic descriptions, treatment, and outcome. Pertinent results include that all 20 cats who developed Medication Related Osteonecrosis of the Jaw had been treated for idiopathic hypercalcemia with the bisphosphonate medication alendronate. Eighty-five percent of the cases had prior dental extractions at the site of MRONJ lesion. Ninety-five percent of the affected cats required a surgical procedure to control the disease. Thirty-five percent of cases required at least one revision surgery after the initial procedure was performed. Diagnosis of MRONJ was made by a correlation of diagnostic findings and patient history. No single diagnostic, or combination was pathognomonic for lesion diagnosis. As well, there were no statistically significant associations between patient variables assessed and the overall patient outcome. The case series reveals that cats with feline idiopathic hypercalcemia treated with alendronate may be at a risk for development of MRONJ, a serious oral condition with significant morbidity. Prior dental extraction sites in patients concurrently treated with bisphosphonate medications were often associated with MRONJ lesions. Therefore, any needed dental surgery should be performed prior to the use of bisphosphonates where possible. The authors have also included a relevant comparative literature review.

MP10-16 VITAMIN D SUPPLEMENTATION MAY CAUSE KIDNEY STONES - WHAT IS THE RISK? LESSONS FROM IDIOPATHIC INFANTILE HYPERCALCEMIA AND CYP24A1

You have accessJournal of UrologyCME1 Apr 2023MP10-16 VITAMIN D SUPPLEMENTATION MAY CAUSE KIDNEY STONES - WHAT IS THE RISK? LESSONS FROM IDIOPATHIC INFANTILE HYPERCALCEMIA AND CYP24A1 Alicja Tomaszewski, Cindy Lin, Joshua Chang, Katreya Lovrenert, John Weaver, Jessica Hannick, Lynn Woo, and Chen-Han Wilfred Wu Alicja TomaszewskiAlicja Tomaszewski More articles by this author , Cindy LinCindy Lin More articles by this author , Joshua ChangJoshua Chang More articles by this author , Katreya LovrenertKatreya Lovrenert More articles by this author , John WeaverJohn Weaver More articles by this author , Jessica HannickJessica Hannick More articles by this author , Lynn WooLynn Woo More articles by this author , and Chen-Han Wilfred WuChen-Han Wilfred Wu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003225.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Vitamin D is used to treat rickets, and has been proposed to reduce risk of osteoporosis, fractures, multiple sclerosis, and other conditions. However, it is contraindicated in people with infantile idiopathic hypercalcemia (IIH). IIH is a rare autosomal recessive disorder caused by impaired 24-hydroxylase enzyme activity encoded by the CYP24A1 gene; patients present with hypercalcemia from increased calcium absorption, increased osteoclast activity, and decreased calcium excretion, and vitamin D supplementation causes nephrolithiasis and nephrocalcinosis. The clinical prevalence of IIH is unknown. This study seeks to characterize the prevalence of IIH caused by frequencies of pathogenic variants in CYP24A1, which can improve screening and prevent complications from inappropriate vitamin D supplementation. METHODS: Known pathogenic variants of CYP24A1 causing IIH were generated from the Human Gene Mutation Database (HGMD). The 1000 Genomes (1KG) database was used to identify healthy individuals with CYP24A1 variants. HGMD and 1KG databases were intersected to find shared variants, and prevalence was calculated using the Hardy-Weinberg equation. RESULTS: After intersecting the HGMD database with the 1KG database, four disease-causing variants were identified in 9 individuals, all heterozygotes. This yields a carrier rate of 1 in 278 and an affected rate of 1 in 308,641. CONCLUSIONS: We estimate one in 308,641 is contraindicated with vitamin D supplement which will cause nephrolithiasis and nephrocalcinosis. Previous genetic analyses have characterized the prevalence of IIH using dbSNP which include both pathogenic and benign variants. We used HGMD to limit the variants that are disease-causing, and used 1KG to assess the frequencies in the general population. Further studies are needed to identify other contributing factors towards IIH, but this study provides an estimate of the clinical prevalence of IIH to identify patients for whom vitamin D supplementation is contraindicated. Source of Funding: © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e120 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alicja Tomaszewski More articles by this author Cindy Lin More articles by this author Joshua Chang More articles by this author Katreya Lovrenert More articles by this author John Weaver More articles by this author Jessica Hannick More articles by this author Lynn Woo More articles by this author Chen-Han Wilfred Wu More articles by this author Expand All Advertisement PDF downloadLoading ...

Ionized hypercalcemia in 238 cats from a referral hospital population (2009-2019).

Ionized calcium concentration ([iCa]) is more sensitive for detecting calcium disturbances than serum total calcium concentration but literature on ionized hypercalcemia in cats is limited. Urolithiasis is a possible adverse consequence of hypercalcemia. To describe clinical details of diagnoses associated with ionized hypercalcemia in cats and association with urolithiasis. Cats (238) seen between 2009 and 2019 at a referral hospital with [iCa] above the normal reference interval. Observational cross-sectional study. Signalment, serum biochemical and imaging findings were reviewed for cats with ionized hypercalcemia considered to be clinically relevant (>1.41 mmol/L). Data were summarized by cause of hypercalcemia (i.e., diagnosis). Diagnoses for the 238 cats with [iCa] >1.41 mmol/L included: acute kidney injury (AKI; 13%), malignancy-associated (10.1%), idiopathic hypercalcemia (IHC; 10.1%), chronic kidney disease/renal diet-associated (8.4%), iatrogenic (5.5%), primary hyperparathyroidism (2.1%), vitamin D toxicity (2.1%) and granulomatous disease (1.7%). In 112 cases (47.1%), no cause for ionized hypercalcemia could be determined (n=95), hypercalcemia was transient (n=12), or the cat was juvenile (<1 year; n=5). Urolithiasis was identified in 83.3% of AKI, 72.7% of iatrogenic, 61.1% of CKD/renal diet-associated and 50% of IHC cases that were imaged (<50% for other diagnoses). Diagnoses with a high proportion of concurrent total hypercalcemia included primary hyperparathyroidism (100%), vitamin D toxicity (100%), malignancy-associated (71.4%), granulomatous disease (66.7%) and IHC (65.2%). Ionized hypercalcemia was most commonly associated with kidney diseases, neoplasia or IHC. The proportion of urolithiasis cases varied by diagnosis.

Investigating hypercalcaemia in cats and dogs

Background: Hypercalcaemia is an important biochemical abnormality in dogs and cats and can lead to a wide variety of clinical signs, including polyuria, polydipsia and vomiting. It can be caused by several diseases of which the prognoses are variable. Both dogs and cats should undergo appropriate investigations, and cat owners in particular must be prepared for likely extensive investigation, excluding all known aetiologies, before a potential diagnosis of idiopathic hypercalcaemia. Understanding calcium physiology and pathophysiology can help both the general practitioner and referral practitioner streamline their investigation and achieve a rapid diagnosis. Hypercalcaemia has a well‐defined list of differential diagnoses and methodical investigation will allow the clinician to optimise patient outcome.Aim of the article: This article describes a stepwise approach to the investigation of patients with ionised hypercalcaemia, and highlights some of the key differences between dogs and cats.

Tratamento restaurador em paciente com Síndrome de Williams: relato de caso

ABSTRACT In Dentistry, any user with one or more limitations, of temporary or permanent mental nature, of physical, sensory, emotional or medical growth, is considered to be a Patient with Special Needs, preventing him from being subjected to a conventional dental situation. These patients form a group which may be considered at high risk for the development of oral diseases, according to the kind of pathogen. Among them, is the Williams-Beuren Syndrome, a rare congenital disease with cardiovascular involvement, mental retardation, dysmorphic face, idiopathic hypercalcemia, musculoskeletal problems, dental and growth anomalies. Familial and sporadic cases are thought to result from deletion of genetic material from adjacent genes located on the long arm of chromosome 7. This article reports a clinical case involving a four-year-old boy with Williams-Beuren Syndrome, referred to the clinic of the Specialization Course for Patients with Special Needs, at the São Leopoldo Mandic Dental Research Center, Campinas (SP). As the patient was resistant to dental care, in order to reduce anxiety and increase collaboration in clinical sessions, the Hixizine® medication was administered. For atraumatic restorative treatment and restorations, the following materials were used: Cleanjoy®, Futurabond DC®, Ionofil Plus® Grandioso®, Grandio® and Profluorid®. As result, it was possible to reach a level of excellence using the indicated materials and specific protocols. Based on this work and the lived experience, it can be observed that these patients can receive welcoming dental care in specialized clinics.

Short Bones, Renal Stones, and Diagnostic Moans: Hypercalcemia in a Girl Found to Have Coffin-Lowry Syndrome

Pathogenic variants in RPS6KA3 are associated with Coffin-Lowry syndrome (CLS), an X-linked semidominant disorder characterized by intellectual disability, stimulus-induced drop attacks, distinctive facial features, progressive kyphoscoliosis, and digit anomalies in hemizygous males. Heterozygous females may also have features of CLS; however, there can be considerable phenotypic variation, often attributed to ratios of X-inactivation in various tissue types. Although skeletal anomalies and short stature are hallmarks of CLS, hypercalcemia has not been reported. Here we describe a 30-month-old girl with gross motor delays, short stature, dysmorphic features, bilateral duplicated renal collecting systems, and no family history of hypercalcemia who required multiple admissions for idiopathic hypercalcemia necessitating bisphosphonate infusions at 12.5 and 15 months of age. A maternally inherited likely-pathogenic variant in RPS6KA3 was identified by trio exome sequencing, consistent with the diagnosis of CLS in the proband and her mother. Maternal history was notable only for decreased height compared to first-degree relatives, bilateral genu valgum, and a bicornuate uterus; she was later found to also have a partially duplicated left renal collecting system. Subsequent X-inactivation studies in blood aligned with the phenotypic variation between mother and daughter. Although hypercalcemia is not a reported feature in CLS, there is evidence of interrupted osteoblast differentiation, providing a potential mechanism for hypercalcemia in this genetic condition. The hypercalcemia in this case may represent a severe presentation of an unrecognized clinical feature in CLS that resolves with age. This case further highlights the intrafamilial phenotypic variation of CLS among females, suggesting X-inactivation as the underlying mechanism, and demonstrates the value of exome sequencing in patients for whom a genetic disorder is highly suspected but not identified despite thorough evaluation.

Corrigendum

Veterinary Record Case ReportsVolume 9, Issue 3 e120 CORRIGENDUMFree Access Corrigendum This article corrects the following: Suspected bisphosphate-related osteonecrosis of the jaw in a cat being treated with alendronate for idiopathic hypercalcaemia Emma Rogers-Smith, Nat Whitley, Clive Elwood, David Reese, Paula Wong, Volume 7Issue 3Veterinary Record Case Reports First Published online: August 22, 2019 First published: 09 June 2021 https://doi.org/10.1002/vrc2.120AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat In Rogers-Smith et al,1 there is a spelling error in the title of the published article. The title should read: Suspected bisphosphonate-related osteonecrosis of the jaw in a cat being treated with aldendronate for idiopathic hypercalcaemia REFERENCE 1Rogers-Smith E, Whitley N, Elwood C, Reese D and Wong P. Suspected bisphosphate-related osteonecrosis of the jaw in a cat being treated with alendronate for idiopathic hypercalcaemia. Vet Rec Case Rep. 2019; 7:e000798. https://doi.org/10.1136/vetreccr-2018-000798Wiley Online LibraryWeb of Science®Google Scholar Volume9, Issue3September 2021e120 ReferencesRelatedInformation

Analysis of vitamin D3 metabolites in survivors of infantile idiopathic hypercalcemia caused by CYP24A1 mutation or SLC34A1 mutation

Infantile hypercalcemia (IH), is a rare disorder caused by CYP24A1 or SLC34A1 variants which lead to disturbed catabolism of 25(OH)D3 and 125(OH)2D3 or increased generation of 125(OH)2D3. Aim of studyTo assess the status of 2425(OH)2D3 and other markers of vitamin D in IH survivors, in whom variants of CYP24A1 or SLC34A1 gene were found and to compare these unique biochemical features with those obtained from subjects who were diagnosed in the first year of life with hypercalcemia, elevated 25(OH)D3 and low PTH but in whom neither CYP24A1 nor SLC34A1 variant was found. Patients and methods16 IH survivors in whom CYP24A1 (n = 13) or SLC34A1 (n = 3) variants were found and 41 subjects in whom hypercalcemia was diagnosed in the first year of life but in whom CYP24A1 or SLC34A1 variants were not found were included in the study. 25(OH)D3, 3-epi-25(OH)D3, 25(OH)D2, 2425(OH)2D3 were assessed by liquid chromatography coupled with tandem mass spectrometry. 125(OH)2D3 concentrations were assessed by chemiluminescence. ResultsSubjects with CYP24A1 variants, despite normal 25(OH)D3 levels, had higher 25(OH)D3/2425(OH)2D3 ratio values (487; 265−1073 ng/mL) when compared to subjects with SLC34A1 variants (16; 16−23 ng/mL) and with subjects in whom CYP24A1 or SLC34A1 were not found (56; 9−56 ng/mL) (p = 0.00003). Separation of interfering metabolite further increased differences between subjects with and without CYP24A1 mutation. ConclusionsSurvivors of IH with CYP24A1 variant, despite being normocalcemic, still presented extremely high 25(OH)D3/2425(OH)2D3 ratio values. Separation of interfering compound further increased differences between subjects with CYP24A1 mutation and without this mutation.

Differential diagnosis of vitamin D-related hypercalcemia using serum vitamin D metabolite profiling.

Genetic causes of vitamin D-related hypercalcemia are known to involve mutation of 25-hydroxyvitamin D-24-hydroxylase CYP24A1 or the sodium phosphate co-transporter SLC34A1, which result in excessive 1,25-(OH)2 D hormonal action. However, at least 20% of idiopathic hypercalcemia (IH) cases remain unresolved. In this case-control study, we used precision vitamin D metabolite profiling based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) of an expanded range of vitamin D metabolites to screen German and French cohorts of hypercalcemia patients, to identify patients with altered vitamin D metabolism where involvement of CYP24A1 or SLC34A1 mutation had been ruled out and who possessed normal 25-OH-D3 :24,25-(OH)2 D3 ratios. Profiles were compared to those of hypercalcemia patients with hypervitaminosis D, Williams-Beuren syndrome (WBS), CYP24A1 mutation, and normal subjects with a range of 25-OH-D levels. We observed that certain IH and WBS patients exhibited a unique profile comprising eightfold to 10-fold higher serum 23,25,26-(OH)3 D3 and 25-OH-D3 -26,23-lactone than normals, as well as very low serum 1,25-(OH)2 D3 (2-5 pg/ml) and elevated 1,24,25-(OH)3 D3 , which we interpret implies hypersensitive expression of vitamin D-dependent genes, including CYP24A1, as a general underlying mechanism of hypercalcemia in these patients. Because serum 25-OH-D3 and 24,25-(OH)2 D3 remained normal, we excluded the possibility that the aberrant profile was caused by hypervitaminosis D, but instead points to an underlying genetic cause that parallels the effect of Williams syndrome transcription factor deficiency in WBS. Furthermore, we observed normalization of serum calcium and vitamin D metabolite profiles at follow-up of an IH patient where 25-OH-D was reduced to 9 ng/ml, suggesting that symptomatic IH may depend on vitamin D nutritional status. Other hypercalcemic patients with complex conditions exhibited distinct vitamin D metabolite profiles. Our work points to the importance of serum vitamin D metabolite profiling in the differential diagnosis of vitamin D-related hypercalcemia that can rationalize expensive genetic testing, and assist healthcare providers in selecting appropriate treatment. © 2021 American Society for Bone and Mineral Research (ASBMR).

Presymptomatic diagnosis of CYP24A1-related infantile idiopathic hypercalcemia: A case report

Vitamin D plays an important role in calcium homeostasis and bone mineralization. Inefficient inactivation of vitamin D leads to a condition called idiopathic infantile hypercalcemia (IIH). In the last decade mutations in CYP24A1, the gene responsible for vitamin D inactivation, were described as the main molecular cause of IIH.In this study, we present a family with two daughters diagnosed with IIH due to two different mutations in CYP24A1 gene. Based on next-generation sequencing (NGS), the elder daughter was diagnosed as carrying the mutations CYP24A1: c.1186C > T; (p.Arg396Trp) and c.428_430del; (p.Glu143del). Within this context, we were able to presymptomatically diagnose her newborn sister using Sanger sequencing technique.Screening for CYP24A1 mutations in families with IIH history helps preventing disease manifestations in newborn siblings. Thus, NGS combined with Sanger sequencing validation opens up the perspective of preventive medicine with great impact on IIH management, where stopping vitamin D administration is enough to prevent disease manifestation, in most cases.

Bisphosphonates in veterinary medicine: The new horizon for use.

Bisphosphonates (BPs) are characterized by their ability to bind strongly to bone mineral and inhibit bone resorption. However, BPs exert a wide range of pharmacological activities beyond the inhibition of bone resorption, including the inhibition of cancer cell metastases and angiogenesis and the inhibition of proliferation and apoptosis in vitro. Additionally, the inhibition of matrix metalloproteinase activity, altered cytokine and growth factor expression, as well as reductions in parameters of pain have also been reported. In humans, clinical BP use has transformed the treatment of post-menopausal osteoporosis, rare bone diseases such as osteogenesis imperfecta, as well as multiple myeloma and metastatic breast and prostate cancer, albeit not without infrequent but significant adverse events. Despite the well-characterized health benefits of BP use in humans, the evidence-base for the therapeutic efficacy of BPs in veterinary medicine is, by comparison, limited. Notwithstanding, BPs are used widely in small animal veterinary practice for the medical management of hyperparathyroidism, idiopathic hypercalcemia in cats, as well as for the palliative care of bone tumors which are common in dogs, and in particular, primary bone tumors such as osteosarcoma. Palliative BP treatment has also recently increased in veterinary oncology to alleviate tumor-associated bone pain. In equine veterinary practice, non-nitrogen-containing BPs are FDA-approved to control clinical signs associated with navicular syndrome in adult horses. However, there are growing concerns regarding the off-label use of BPs in juvenile horses. Here we discuss the current understanding of the strengths, weaknesses and current controversies surrounding BP use in veterinary medicine to highlight the future utility of these potentially beneficial drugs.

Idiopathic Hypercalcemia in Decompensated Cirrhosis: Reexploring an Entity in Oblivion

Hypercalcemia is a rare metabolic abnormality seen in patients with cirrhosis and is usually considered a paraneoplastic manifestation of hepatocellular carcinoma. Idiopathic hypercalcemia in cirrhosis is a diagnosis of exclusion, which is considered when all the causes of hypercalcemia have been ruled out. Here, we report a rare case of idiopathic hypercalcemia presenting as acute kidney injury in a case of decompensated cirrhosis, managed with adequate hydration and injection of ibandronate and intranasal calcitonin, leading to the normalization of serum calcium and resolution of acute kidney injury.

Etiological Profile of Nephrocalcinosis in Children from Southern India

To study the etiological profile and patterns of clinical presentation of nephrocalcinosis. In this observational study, patients 18 years or younger, referred to the pediatric nephrology clinic with nephrocalcinosis were evaluated for etiology. Symptoms/signs at presentation, estimated glomerular filtration rate (eGFR) at presentation and follow-up, and growth parameters were recorded. The etiology of nephrocalcinosis (n=54) included distal renal tubular acidosis (n=18; 33.3%), primary hyperoxaluria (n=9; 16.7%), Bartter syndrome (n=7; 13%), Dent disease (n=4; 7.4%), cystinosis, familial hypomagnesemia with hypercalciuria and idiopathic hypercalcemia of infancy (2 each). Idiopathic nephrocalcinosis was seen in 5 (9.3%) children. Clinical features included failure to thrive (53.7%), polyuria (44.4%), bony deformities (31.5%) and hypokalemic paralysis (11.1%). At a median (IQR) follow-up of 24 (8, 56) months, the mean (SD) eGFR had improved from 59 (25.5) to 77 (31.48) mL/min/1.73m2 (P<0.01). Consanguinity was present in 50% (27/54). Genetic analysis in 5 primary hyperoxaluria cases confirmed AGXT mutations in 4; and GRHPR mutation in 1 child. Distal RTA, primary hyperoxaluria and Bartter syndrome were the common etiologies of nephrocalcinosis in our patient population.

Severity of Ionized Hypercalcemia and Hypocalcemia Is Associated With Etiology in Dogs and Cats.

Background: Calcium disorders are common in small animals, but few studies have investigated the etiology of ionized hypercalcemia and hypocalcemia in large populations. This study aimed to determine the incidence of ionized calcium disorders in dogs and cats treated at a tertiary referral clinic and to describe the associated diseases.Methods: An electronic database of electrolyte analyses conducted at the Cornell University Hospital for Animals from 2007 to 2017 was searched. Dogs and cats with ionized hypercalcemia or hypocalcemia were identified based on institution reference intervals. Duplicate case entries were removed. Medical records were reviewed to identify the cause of the calcium abnormality. Chi-squared analysis with Bonferroni adjustment was performed to compare frequencies of disease processes between mild and moderate-severe disturbances.Results: The database included 15,277 dogs and 3,715 cats. Hypercalcemia was identified in 1,641 dogs and 119 cats. The incidence of canine and feline hypercalcemia was 10.7 and 3.2%, respectively. Hypocalcemia was identified in 1,467 dogs and 450 cats. The incidence of canine and feline hypocalcemia was 9.6% and 12.1%, respectively. The most common pathologic causes of hypercalcemia in dogs were malignancy-associated (12.9%), parathyroid-dependent (4.6%) and hypoadrenocorticism (1.7%). In cats, malignancy-associated hypercalcemia (22.7%), kidney injury (13.4%) and idiopathic hypercalcemia (12.6%) were most common. Dogs presenting with moderate-severe hypercalcemia vs. mild hypercalcemia were significantly more likely to have hyperparathyroidism, malignancy-associated hypercalcemia or hypervitaminosis D, whereas cats were significantly more likely to have malignancy-associated hypercalcemia or idiopathic hypercalcemia. The most common pathologic causes of hypocalcemia in dogs were critical illness (17.4%), kidney injury (10.4%) and toxicity (7.5%). In cats, kidney injury (21.6%), urethral obstruction (15.1%), and critical illness (14.7%) were most frequent. Dogs presenting with moderate-severe hypocalcemia were significantly more likely to have hypoparathyroidism, kidney injury, eclampsia or critical illness, whereas cats were significantly more likely to have kidney injury, soft tissue trauma or urethral obstruction.Conclusions: Mild calcium disturbances are most commonly associated with non-pathologic or transient conditions. Malignancy-associated hypercalcemia is the most common cause of ionized hypercalcemia in dogs and cats. Critical illness and kidney injury are frequent causes of ionized hypocalcemia in both species.

Suspected bisphosphate-related osteonecrosis of the jaw in a cat being treated with alendronate for idiopathic hypercalcaemia

An 8-year-old female neutered domestic shorthair diagnosed with idiopathic hypercalcaemia and undergoing weekly treatment with alendronate presented to Davies Veterinary Specialists for progressive facial swelling and discomfort 12 months after...

Serum Calcium and Phosphorus Levels in Hemodialysis Patients: A Large Population-Based Multicenter Study

Background: Mineral bone disorder is one of the major factors affecting mortality and morbidity in dialysis patients, which is called chronic kidney disease-mineral and bone disorder (CKD-MBD). Objectives: This study aimed to evaluate the laboratory parameters of mineral bone disorder in hemodialysis patients in Iran and their relationship with malnutrition and inflammation. Methods: This multicenter observational study was conducted in 2016 in 58 dialysis centers in Iran. Data of a total number of 7191 chronic hemodialysis patients aged older than 18 years with a dialysis duration of > 3 months were collected. Idiopathic hypercalcemia and history of parathyroidectomy were considered as the exclusion criteria. The serum levels of calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) were measured over a period of three months, and the findings were compared with the K/DOQI (National Kidney Foundation Dialysis Outcomes Quality Initiative) guidelines. Moreover, the serum level of C-reactive protein (CRP) and nutritional status based on geriatric nutritional risk index (GNRI) were assessed. Results: The percentage of the patients who had a serum iPTH level of 300 pg/mL was 29.3%. Hypercalcemia and hyperphosphatemia were observed in 20.6% and 34.2% of the patients, respectively. Moreover, 51.7%, 61.3%, 24.7%, and 84.7% of the patients, respectively, reached the K/DOQI target range of Ca, P, iPTH, and Ca × P product. The percentages of mild-to-severe malnutrition based on GNRI in patients whose iPTH level was within, below, and above the recommended range of K/DOQI guidelines were 30.7%, 34.1%, and 25.9%, respectively (P < 0.001). Furthermore, the serum level of CRP was significantly higher in low-serum PTH patients than in the other two groups. In total, only could 8.3% of the patients reach the four KDOQI target levels of CKD-MBD. Conclusions: The findings showed a significant percentage of patients had a low serum PTH level, which might be attributed to inflammatory and nutritional factors. Only had a small percentage of patients reached all the K/DOQI targets. Therefore, the effects of inflammatory and nutritional factors should also be considered, particularly in developing countries.

Renal phosphate handling and inherited disorders of phosphate reabsorption: an update.

Renal phosphate handling critically determines plasma phosphate and whole body phosphate levels. Filtered phosphate is mostly reabsorbed by Na+-dependent phosphate transporters located in the brush border membrane of the proximal tubule: NaPi-IIa (SLC34A1), NaPi-IIc (SLC34A3), and Pit-2 (SLC20A2). Here we review new evidence for the role and relevance of these transporters in inherited disorders of renal phosphate handling. The importance of NaPi-IIa and NaPi-IIc for renal phosphate reabsorption and mineral homeostasis has been highlighted by the identification of mutations in these transporters in a subset of patients with infantile idiopathic hypercalcemia and patients with hereditary hypophosphatemic rickets with hypercalciuria. Both diseases are characterized by disturbed calcium homeostasis secondary to elevated 1,25-(OH)2 vitamin D3 as a consequence of hypophosphatemia. In vitro analysis of mutated NaPi-IIa or NaPi-IIc transporters suggests defective trafficking underlying disease in most cases. Monoallelic pathogenic mutations in both SLC34A1 and SLC34A3 appear to be very frequent in the general population and have been associated with kidney stones. Consistent with these findings, results from genome-wide association studies indicate that variants in SLC34A1 are associated with a higher risk to develop kidney stones and chronic kidney disease, but underlying mechanisms have not been addressed to date.