Excessive Urinary Calcium Excretion Research Articles

Isolated idiopathic hypoparathyroidism that developed in adulthood: a case report

Hypoparathyroidism is a rare endocrine disease. In most cases in adult patients, the cause of hypoparathyroidism is damage or removal of parathyroid glands during surgical interventions on the neck; other causes are rarely observed.Case report. A 52-year-old man with episodes of seizures, intense muscle pain, progressing for 7 years and resistance to treatment with myorelaxant, anxiolytics and nonsteroidal anti-inflammatory drugs was examined and hypocalcemia associated with low parathyroid hormone and excessive urinary calcium excretion was found. Ultrasound examination didn't reveal any changes in parathyroid glands. The patient was diagnosed with idiopathic hypoparathyroidism. Treatment with calcium supplements and active metabolites of vitamin D led to an improvement in clinical symptoms and laboratory parameters.Discussion. Hypoparathyroidism as part of several genetic syndromes was excluded due to the late- onset of the disease and the absence of concomitant diseases. Ultrasound of the parathyroid glands made it possible to rule out metastasis and storage diseases. It is recommended to perform genetic testing of the chromosomes 22 and 10 to exclude rare variants of syndromic hypoparathyroidism with the late-onset in the form of isolated hypocalcemia.

Evidence of disordered calcium metabolism in adolescent girls with type 1 diabetes: An observational study using a dual-stable calcium isotope technique

Type 1 diabetes (T1D) is associated with skeletal abnormalities including low bone density and increased fracture risk. The pathophysiology underlying T1D related skeletal fragility remains unknown. The objective of this study was to use a dual-stable calcium isotope method to investigate the effects of T1D on calcium absorption and estimated calcium retention in adolescent females. Twenty adolescent females with T1D were admitted for a 24-h calcium absorption study using oral (44Ca) and intravenous (42Ca) stable isotopes for determination of percent gastrointestinal calcium absorption and estimated calcium retention. Five out of twenty participants were found to have negative estimated calcium retention. Participants with negative calcium retention had greater urinary calcium excretion [202mg/d (IQR: 178–213)] compared to those with positive calcium retention [101.5mg/d (IQR: 82–122)], p=0.01, but similar calcium intake and percent calcium absorption. With the exception of one outlier, 24-h urine calcium was significantly associated with hemoglobin A1c (Pearson's r=0.55, p=0.02). 50% of participants consumed less than the RDA for calcium; fractional calcium absorption was inversely correlated with calcium intake in participants not meeting the RDA (Spearman's rho −0.65, p=0.04). In conclusion, one-quarter of adolescent girls with T1D were found to have negative estimated calcium retention at a time when bone mineral accrual should be ongoing. This appeared to be the result of excess urinary calcium excretion as opposed to diminished gastrointestinal calcium absorption. Insufficient calcium availability for bone deposition during adolescence could impair bone mineral accrual and contribute to skeletal fragility.Trial registered: ClinicalTrials.gov Reg No. NCT03156179

Cystoscopic diagnosis of polypoid cystitis in two pet rabbits.

CASE DESCRIPTION AS-year-old male Dwarf rabbit and 4-year-old female Mini-Rex rabbit were evaluated because of anorexia and urine scalding of the perineum. CLINICAL FINDINGS Abdominal radiography revealed a diffuse increase in the opacity of the urinary bladder attributable to urinary sludge. In 1 rabbit, abdominal ultrasonography revealed several mass-like lesions protruding from the mucosal surface into the lumen of the urinary bladder. Rabbits were anesthetized, and cystoscopy was performed with a rigid 2.7-mm, 30° endoscope. Histologic analysis of tissue samples obtained through the cystoscope operating channel revealed findings consistent with polypoid cystitis. TREATMENT AND OUTCOME To remove the urinary sludge from each rabbit, the urinary bladder was filled with sterile saline (0.9% NaCl) solution and emptied with a gentle massage several times until the ejected fluid was transparent. Rabbits were treated with NSAIDs, antimicrobials (chosen following microbial culture of urine and antimicrobial susceptibility testing), bathing of the perineum, and a low-calcium diet. The male rabbit died of unrelated causes 18 months later; postmortem examination findings confirmed the polypoid cystitis. The female rabbit remained disease free through to last follow-up (12 months after initial evaluation). CLINICAL RELEVANCE This was the first report of polypoid cystitis in pet rabbits. Although ultrasonographic findings supported this diagnosis, a definitive diagnosis was achieved through cystoscopy and lesion biopsy. Treatments administered were intended to reduce the potential sources of irritation. Research is needed to investigate the effectiveness of the applied interventions and the association between excessive urinary calcium excretion and polyploid cystitis in rabbits.

Diphtheria Toxin- and GFP-Based Mouse Models of Acquired Hypoparathyroidism and Treatment With a Long-Acting Parathyroid Hormone Analog.

Hypoparathyroidism (HP) arises most commonly from parathyroid (PT) gland damage associated with neck surgery, and is typically treated with oral calcium and active vitamin D. Such treatment effectively increases levels of serum calcium (sCa), but also brings risk of hypercalciuria and renal damage. There is thus considerable interest in using PTH or PTH analogs to treat HP. To facilitate study of this disease and the assessment of new treatment options, we developed two mouse models of acquired HP, and used them to assess efficacy of PTH(1-34) as well as a long-acting PTH analog (LA-PTH) in regulating blood calcium levels. In one model, we used PTHcre-iDTR mice in which the diphtheria toxin (DT) receptor (DTR) is selectively expressed in PT glands, such that systemic DT administration selectively ablates parathyroid cells. For the second model, we generated GFP-PT mice in which green fluorescent protein (GFP) is selectively expressed in PT cells, such that parathyroidectomy (PTX) is facilitated by green fluorescence of the PT glands. In the PTHcre-iDTR mice, DT injection (2 × 5 μg/kg, i.p.) resulted in moderate yet consistent reductions in serum PTH and sCa levels. The more severe hypoparathyroid phenotype was observed in GFP-PT mice following GFP-guided PTX surgery. In each model, a single subcutaneous injection of LA-PTH increased sCa levels more effectively and for a longer duration (>24 hours) than did a 10-fold higher dose of PTH(1-34), without causing excessive urinary calcium excretion. These new mouse models thus faithfully replicate two degrees of acquired HP, moderate and severe, and may be useful for assessing potential new modes of therapy. © 2015 American Society for Bone and Mineral Research.

An association between urinary cadmium and urinary stone disease in persons living in cadmium-contaminated villages in northwestern Thailand: A population study

Excessive urinary calcium excretion is the major risk of urinary stone formation. Very few population studies have been performed to determine the relationship between environmental cadmium exposure and urinary stone disease. This population-based study examined an association between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and prevalence of urinary stones in persons aged 15 years and older, who lived in the 12 cadmium-contaminated villages in the Mae Sot District, Tak Province, northwestern Thailand. A total of 6748 persons were interviewed and screened for urinary cadmium and urinary stone disease in 2009. To test a correlation between urinary excretion of cadmium and calcium, we measured urinary calcium content in 1492 persons, who lived in 3 villages randomly selected from the 12 contaminated villages. The rate of urinary stones significantly increased from 4.3% among persons in the lowest quartile of urinary cadmium to 11.3% in the highest quartile. An increase in stone prevalence with increasing urinary cadmium levels was similarly observed in both genders. Multiple logistic regression analysis revealed a positive association between urinary cadmium levels and stone prevalence, after adjusting for other co-variables. The urinary calcium excretion significantly increased with increasing urinary cadmium levels in both genders, after adjusting for other co-variables. Elevated calciuria induced by cadmium might increase the risk of urinary stone formation in this environmentally exposed population.

Bisphosphonates in the management of idiopathic hypercalciuria associated with osteoporosis: a new trick from an old drug

Idiopathic hypercalciuria (IHC) is defined as a 24-hour urinary calcium excretion that exceeds 4 mg/kg/day, regardless of gender and in absence of systemic diseases or pharmacological treatments that may cause normocalcemic hypercalciuria (eg sarcoidosis, normocalcemic primary hyperparathyroidism, vitamin D intoxication, hyperthyroidism). Patients with IHC and nephrolithiasis often present increased bone turnover, decreased bone mineral density (BMD) and increased susceptibility to fragility fractures. Although the pathogenesis of IHC seems complex and multifactorial, recent evidences suggest that cells involved in bone resorption may play a critical role in the chain of events leading to the excessive urinary calcium excretion. Therefore, it has been proposed that bisphosphonates, potent inhibitors of bone resorption, may have beneficial effects in hypercalciuric patients with low BMD. This manuscript reports recent findings regarding the role of bone tissue in the pathogenesis of IHC, and supports the use of bisphosphonates in such conditions. It also reviews the literature on the effects of bisphosphonates in subjects with osteoporosis-associated IHC.

Pathophysiology of hypercalciuria in children

Urinary excretion of calcium is the result of a complex interplay between three organs—namely, the gastrointestinal tract, bone, and kidney—which is finely orchestrated by multiple hormones. Hypercalciuria is believed to be a polygenic trait and is influenced significantly by diet. This paper briefly reviews calcium handling by the renal tubule in normal and in hereditary disorders as it relates to the pathophysiology of hypercalciuria. The effects of dietary sodium, potassium, protein, calcium, and phosphate on calcium excretion, and the association of hypercalciuria with bone homeostasis is discussed, leading to recommendations on means to address excessive urinary calcium excretion.

4q33-qter deletion and absorptive hypercalciuria: Report of two unrelated girls

We report on two unrelated girls with multiple malformations, each of whom had a der(4)t(4;?)(q33;?) chromosome--an unbalanced translocation chromosome with deletion of the 4q33-qter segment and addition of a segment of an unknown chromosome. One of the two girls had asymptomatic kidney stones. Both had excess urinary calcium excretion (0.53 and 0.84 mg/mg creatinine, respectively), exaggerated excretion on oral calcium load, and reduced but excessive excretion on restricted calcium intake. The urinary calcium excretion of their parents was normal. Both girls were thus diagnosed to have sporadic absorptive hypercalciuria. It was deduced that the 4q33-qter segment contains the putative gene for absorptive hypercalciuria.

Hypogonadism does not mediate urinary calcium loss in pituitary-grafted rats

Rats rendered chronically hyperprolactinemic by implantation of extra anterior pituitary glands (AP) under the kidney capsule have excess urinary calcium excretion. Although serum testosterone levels are normal in male AP-grafted rats, more subtle androgen deficiency might contribute to the increased calcium loss. Female AP-grafted rats lose the normal estrous cycle, which might also alter calcium homeostasis. The urinary calcium and calcium/sodium excretion ratio in gonadectomized AP-grafted rats of both sexes were compared with that of otherwise intact AP-grafted rats and muscle-grafted control rats. AP-grafted rats had increased urinary calcium excretion and calcium/sodium excretion ratio, regardiess of gonadal status. Treatment of castrated male AP-grafted animals with testosterone or dihydrotestosterone did not have a significant effect on urinary calcium loss, nor did estrogen replacement of ovariectomized female AP-grafted rats. These studies indicate that the hypercalciuria of the AP-grafted rat is not mediated via an anti-gonadal effect of the prolactin-secreting pituitary graft.

Increased serum concentrations of 1,25(OH) 2 vitamin D in children with fasting hypercalciuria

Inappropriately elevated concentrations of 1,25(OH)2 vitamin D in serum appear to be responsible for excessive gastrointestinal absorption of dietary calcium in patients with absorptive hypercalciuria. We have examined serum 1,25(OH)2 vitamin D concentrations in another group of children with hypercalciuria in whom urinary calcium excretion was excessive after an overnight fast. Eleven children with idiopathic fasting hypercalciuria (IH) (urinary calcium excretion greater than 4 mg/kg/24 hr and fasting urinary calcium/urinary creatinine ratio greater than 0.21) and seven healthy children were observed while they were eating a diet containing 1 gm calcium per day. Fasting serum 1,25(OH)2 vitamin D concentrations were elevated in children with IH compared with control values (35.3 +/- 3.2 vs 21 +/- 2 pg/ml, P = 0.003), whereas fasting serum parathyroid hormone, 25-OH vitamin D, phosphorus, and ionized calcium concentrations were similar in the two groups. These data suggest that disordered 1,25(OH)2 vitamin D metabolism occurs in children with fasting IH. Absorptive and fasting IH may represent a spectrum of a single disorder characterized by excessive urinary calcium excretion and inappropriately elevated serum concentrations of 1,25(OH)2 vitamin D.