Decrease In Serum Calcium Research Articles

Milk allergy and vitamin D deficiency rickets: a common disorder associated with an uncommon disease

Cow's milk allergy is one of the most common allergies in infancy. It has an excellent prognosis since most cases resolve by 4 years of age. The complications associated with milk allergy include delayed growth and atopic conditions, such as asthma, allergic rhinitis, atopic dermatitis, and other food allergies. To report a case of vitamin D deficiency rickets in a 2-year-old boy with cow's milk allergy. We describe a patient with clinical and biochemical evidence of rickets, including decreased serum calcium, phosphate, and 25-hydroxy vitamin D levels and an elevated alkaline phosphatase level. A dietary history revealed the prolonged absence of dietary vitamin D because the child did not tolerate cow's milk. Skin prick testing and measurement of specific IgE to cow's milk were performed to determine whether there was an allergy to cow's milk. Results of skin prick testing and measurement of specific IgE to cow's milk confirmed an IgE-mediated sensitivity to cow's milk. Introduction of appropriate supplementation into the child's diet resulted in complete resolution of his symptoms. This case emphasizes that the management of cow's milk allergy involves strict avoidance of the allergenic food while also ensuring that essential dietary requirements are met. A dietary history is crucial at all pediatric visits, and inquiry about supplementation of vitamins and minerals is important, especially in children with food allergies.

Cinacalcet hydrochloride: calcimimetic for the treatment of hyperparathyroidism

Mineral metabolism disorders, including those related to secondary hyperparathyroidism, affect a large number of patients with chronic kidney disease and are associated with increased relative risk of morbidity and mortality in hemodialysis patients. The traditional therapy of secondary hyperparathyroidism based on vitamin D compounds and calcium-based phosphate binders is often limited by the increase of serum calcium and phosphorus levels limiting the dose that can be given safely, and thus, preventing the attainment of treatment targets. Cinacalcet hydrochloride (Sensipar®, Mimpara®, Parareg®) is the first in a new class of therapeutic agents, the calcimimetics, that increase the sensitivity of calcium-sensing receptors to the extracellular calcium ions, thus lowering parathyroid hormone production and release, decreasing serum calcium and phosphorous concentrations simultaneously. Different randomized, double-blind, placebo-controlled trials evaluated the safety and ability of cinacalcet hydrochloride treatment to improve achievement of target levels of parathyroid hormone, calcium, phosphorus and calcium phosphorus product in dialysis patients. Cinacalcet hydrochloride has also demonstrated to be effective in reducing parathyroid hormone and serum calcium concentrations in patients with primary hyperparathyroidism. On the basis of available data, calcimimetics represent an important innovation and will change the management of mineral metabolism disorders in patients with chronic kidney disease and primary hyperparathyroidism.

Intravenous zoledronic acid effectively decreases serum calcium in primary hyperparathyroidism

To evaluate the efficacy and safety of zoledronic acid in preventing bone loss in patients with hormone-sensitive prostate cancer and bone metastases who were receiving androgen deprivation therapy.Patients received zoledronic acid 4 mg as a 15-minute infusion every 3 weeks for 1 year. Bone mineral density of the lumbar spine (L2 to L4) and total hip was measured by dual-energy x-ray absorptiometry at baseline and 12 months. Biochemical markers of bone turnover (N-telopeptide and bone alkaline phosphatase) and serum creatinine levels were evaluated at baseline and during the study. Skeletal-related events were assessed at each study visit.Of the 221 enrolled patients, 202 and 221 patients were included in the efficacy and safety analyses, respectively. The mean increase in bone mineral density of the lumbar spine and total hip was 7.7% (P <0.001) and 3.6% (P <0.001), respectively. Decreases in N-telopeptide and bone alkaline phosphatase levels were significant and sustained. The median time to the first skeletal-related event was not reached; 11.9% of patients had a skeletal-related event. Arthralgia (20.4%), nausea (14%), fatigue (14%), and back pain (12.2%) were the most common adverse events. Adverse events due to renal function deterioration were infrequent. The mean maximal change in serum creatinine level from baseline was 0.3 mg/dL.Zoledronic acid administration for 1 year to patients with hormone-sensitive prostate cancer and bone metastases who were receiving androgen deprivation therapy was safe and prevented bone loss, as demonstrated by significant increases in bone mineral density and sustained suppression of biochemical markers of bone turnover.

Alteraciones electrolíticas inducidas por la preparación para los estudios de imagen del colon

An adequate bowel cleansing is needed prior to radiologic and endoscopic procedures. However, it may have a number of adverse effects, including abnormalities of calcium-phosphorus homeostasis. This was an observational prospective study in a hospital practice setting. We included consecutive inpatients (n = 47) subjected to a barium enema or colon endoscopy. Prior cleansing was done as indicated by the attending physician by using a low-salt oral poliethylenglicol (PEG) solution, oral sodium phosphate or a phosphate-containing enema. PEG solution frequently caused mild increases in serum sodium, and decreases in serum potassium. Oral phosphate caused a significant increase in serum phosphorus and parathormone concentrations, whereas it decreased serum calcium. Mild hyperphosphatemia was found in 57% of cases, and hypocalcemia in 36%. Phosphate enema also increased serum phosphate, causing mild hyperphosphatemia (33% cases). Although in the whole subgroup of enema-treated patients there were no significant changes in serum calcium, mild hypocalcemia was found in 27% cases. Bowel cleansing procedures, particularly those using oral phosphate salts, frequently induce hyperphosphatemia and other abnormalities in serum electrolytes. Although usually transitory and without overt clinical consequences, clinicians should be aware of this potential risk, especially in elderly patients and those with impaired renal function.

Current Pharmacological Options for the Management of Primary Hyperparathyroidism

Drugs for treating primary hyperparathyroidism can be divided into two main groups: (i) antiresorptive drugs that inhibit the increased bone turnover, which can be divided into estrogen-like compounds (estrogen, oral contraceptives and selective estrogen receptor modulators [SERMs]), bisphosphonates and calcitonin; and (ii) drugs that interfere with parathyroid hormone (PTH) secretion (currently only cinacalcet is available). No drugs that interfere with PTH action are currently available. Available studies suggest that all classes of drugs are able to lower serum calcium levels. However, calcitonin does so only temporarily. Estrogen-containing compounds (hormone replacement therapy) may be less attractive because of the potential risk of breast cancer, cardiovascular disease and deep vein thromboembolism. Oral contraceptives have not been shown to be able to prevent fractures in the general population, and no data are available on their effect in women with primary hyperparathyroidism. The only SERM marketed for hyperparathyroidism is raloxifene and this has not been associated with an increased risk of breast cancer and cardiovascular diseases, and has been shown to be able to prevent vertebral fractures in postmenopausal women with osteoporosis. Two small trials suggest that raloxifene may increase bone mineral density (BMD) and decrease serum calcium levels in patients with primary hyperparathyroidism. Bisphosphonates have been shown to decrease serum calcium and increase BMD in patients with primary hyperparathyroidism, but PTH levels may increase. Cinacalcet effectively induces a sustained decrease in serum calcium and PTH for up to 1 year. However, BMD does not seem to increase. No data on hard endpoints such as fractures, kidney stones, cardiovascular disease etc. are available for any of the drugs available for the treatment of primary hyperparathyroidism.

Acute Renal Failure and Hypercalcemia

Hypercalcemia can result from excessive bone resorption, renal calcium retention, excessive intestinal calcium absorption, or a combination of these conditions. Hypercalcemia may also provoke acute renal failure (ARF) or hypertension, or aggravate the tubular necrosis that is frequently found in cases of ARF. The association of ARF and hypercalcemia was studied retrospectively in eight patients based in the data in their charts. Data are expressed as median and percentile (25th; 75th). Our results show that ARF associated with hypercalcemia was related with comorbidity in all cases (cancer, multiple myeloma, hyperparathyroidism, sarcoidosis, vitamin D intoxication, and leprosy). Maximum median serum creatinine levels were 3.3 mg/dL (2.7, 3.8 mg/dL) before treatment and 1.1 mg/dL (0.9, 1.3 mg/dL) after treatment. Maximum total median serum calcium was 15.9 mg/dL (13.5, 19.8 mg/dL) before treatment and 9.1 mg/dL (8.4, 9.7 mg/dL) after treatment. Maximum median ionized serum calcium was 2.1 mmol/L (1.8, 2.2 mmol/L) before treatment and 1.1 mmol/L (1.0, 1.2 mmol/L) after treatment. Different kinds of treatment induced a rapid fall in serum calcium concentration. All patients were treated with hydration and diuretics, and three patients also received calcitonin. Serum creatinine concentration always fell simultaneously with the decrease in serum calcium in all cases. All patients progressed with nonoliguric renal failure. In conclusion, in ARF, patients are frequently hypocalcemic. Usually, the presence of hypercalcemia associated with ARF is indicative of the presence of comorbidity, as observed in all eight patients studied here. There was an improvement of renal function in all cases as serum calcium levels decreased.

Oral administration of β-cryptoxanthin prevents bone loss in ovariectomized rats

The effect of beta-cryptoxanthin, a kind of carotenoid, on ovariectomy-induced bone loss was investigated. beta-cryptoxanthin was isolated from Satsuma mandarin (Citrus unshu. MARC). beta-cryptoxanthin (5 or 10 microg/100 g body weight) was orally administered once daily for 3 months to ovariectomized (OVX) rats. OVX induced a significant increase in body weight and a significant decrease in serum calcium and inorganic phosphorus concentrations as compared with those of sham-operated (control) rats. These alterations induced by OVX were significantly prevented by the administration of beta-cryptoxanthin (5 or 10 microg/100 g). The analysis using a peripheral quantitative computed tomography (pQCT) showed that OVX induced a significant decrease in mineral content and mineral density in the femoral-diaphyseal and -metaphyseal tissues and polar strength strain index in the metaphyseal tissues. These decreases were significantly prevented by the administration of beta-cryptoxanthin (5 or 10 microg/100 g). Moreover, OVX induced a significant decrease in calcium content and alkaline phosphatase activity in the femoral-diaphyseal and -metaphyseal tissues and deoxyribonucleic acid (DNA) content in the metaphyseal tissues. These decreases were significantly prevented by the administration of beta-cryptoxanthin (5 or 10 microg/100 g). This study demonstrates that beta-cryptoxanthin has a preventive effect on OVX-induced bone loss in vivo.

Autoinfarction of the parathyroid gland diagnosed by power Doppler ultrasonography in a patient with secondary hyperparathyroidism

Spontaneous remission due to parathyroid infarction of secondary hyperparathyroidism (SHPT) [1,2] is very rare compared to that of primary hyperparathyroidism [3,4]. It is possible that the diagnosis of parathyroid infarction is missed in patients with SHPT because parathyroid infarction often occurs in only one of the enlarged glands. Lately, neck ultrasound examination has become a more beneficial and specific method for the diagnosis of enlarged parathyroid glands, in contrast to classic diagnostic techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and scintigraphy [1,2]. The diagnosis of parathyroid infarction reported in previous studies, however, was often based on CT, MRI and scintigraphy findings and only a few studies have reported such diagnosis by emergency power Doppler ultrasonography of the neck. Here, we present a haemodialysis patient with autoinfarction of the left parathyroid gland diagnosed by emergency power Doppler ultrasonography of the neck. The spontaneous infarction of the parathyroid gland was associated with a small to moderate decrease in serum calcium and parathyroid harmone (PTH) values, but PTH remained markedly elevated. Case report

Relative hypoparathyroidism induced by interferon treatment in a hemodialysis patient

Several authors have documented beneficial effects of interferon (IFN) in chronic hepatitis C virus (HCV) infection among the dialysis population. Reports about mineral metabolism disturbances during IFN treatment are scarce, especially in dialysis patients. We report the case of a 49-year-old woman on hemodialysis with chronic HCV infection who developed significant decrease in serum calcium (Ca) and phosphorus (P) levels accompanied by relative hypoparathyroidism while being under treatment with alpha-IFN. These changes were closely related to IFN treatment, because they disappeared after INF was discontinued, reaching Ca and P levels which were similar to those of the pre-IFN period. Because IFN may induce immune disorders, several autoimmune markers were analyzed. All of them were negative or within the normal range. To further explore these mineral metabolism disturbances, a number ofparathyroid hormone (PTH) secretion-inhibiting factors, such as aluminum, magnesium, 25-hydroxyvitamin D, and calcitriol were excluded as a cause for these changes. We suggest that mineral metabolism should be carefully observed during interferon treatment in dialysis patients.

Phosphate binder therapy for attainment of K/DOQI™ bone metabolism guidelines

Phosphate binder therapy for attainment of K/DOQI™ bone metabolism guidelines

Long-term results in renal transplant patients with allograft dysfunction after switching from calcineurin inhibitors to sirolimus

Switching from calcineurin inhibitors (CNIs) to sirolimus might improve renal function in chronic renal transplant patients. In a prospective study, we assessed long-term efficacy and safety parameters in 43 renal transplant recipients who were switched from a CNI (cyclosporin A, 65%; and tacrolimus, 35%) to sirolimus for either chronic allograft dysfunction (n = 38) or recurrent cutaneous cancers (n = 5). A kidney biopsy was done in 79% of patients prior to conversion, and showed either chronic allograft nephropathy (n = 26) or CNI nephrotoxicity (n = 7). Conversion was either abrupt or progressive, with CNI withdrawal over 3 weeks. All patients also received steroids with or without mycophenolate mofetil or azathioprin. Patient data were recorded at baseline (D0), at 1 (D30) and 6 months (D180), and at 1, 1.5 and 2 years post-conversion. After a mean post-conversion follow-up of 27+/-1.5 months, 58% of the patients were still on sirolimus. The survival of intent to treat patients and grafts was 95.3 and 93%, respectively. Overall, there was significant improvement in renal function, creatinine clearance increasing from 49.4+/-14.9 to 53+/-16.3 ml/min at D30 (P = 0.01), and to 54.7+/-20 ml/min at D180 (P = 0.01). Thereafter, creatinine clearance was not different from baseline, i.e. 54.7+/-21.7, 52.8+/-20 and 51.7+/-20.3 ml/min at years 1, 1.5 and 2, respectively. We divided the patients into two groups: responders (n = 29), those with an increase in creatinine clearance at 6 months post-conversion compared with D0, and non-responders (n = 14), those with a decrease in creatinine clearance at 6 months post-conversion compared with D0. In univariate analysis, factors predictive of response included proteinuria at D0 and the magnitudes of the differences between D30 and D0 for serum creatinine and lactate dehydrogenase. The conversion was associated with (i) significant decreases in serum calcium, phosphorus and uric acid, and in haemoglobin levels; (ii) significant increases in serum alkaline phosphatase, total cholesterol, parathyroid hormone, and the number of patients on statin and recombinant erythropoietin therapies; and (iii) the appearance of de novo proteinuria of >1 g/day in 28% of patients (P < 0.0009), which was >2 g/day in 12% of the entire cohort. Kidney biopsies in 17 patients 2 years after conversion showed the same Banff scores as observed at baseline. We identified three independent predictive factors for a renal response to the switch: absence of proteinuria, presence of antihypertensive therapy at D0 and serum lactate dehydrogenase level at D30. Conversion from CNIs to sirolimus in renal transplant patients with chronic allograft nephropathy was associated with improved renal function; however, 33% of the patients developed overt proteinuria.

Renal effects of high dose celecoxib (C) during 2 phase II trials for hormone resistant prostate cancer (HRPC)

4751 Background It is unknown if high doses of Cox -2 inhibitors in cancer regimens have adverse renal effects. Concerns include acute renal failure (ARF), hyperkalemia (hyper K), proteinuria and hypertension. Methods 33 patients (pts) with HRPC and median (med) age of 74 years (56–95) were treated in 2 phase II trials (Kasimis and Zhong: Proc ASCO 2005 subm). All received high dose C 400 mg bid po for a med period of 4 months (M) (2–6); 25 received Docetaxel, and 8 received Epirubicin and Extramustine Phosphate. Chemistries, UA, and blood pressure (BP) were measured at baseline and every M. All ARF and hyper K episodes were evaluated by a nephrologist. Results Table shows that estimated glomerular filtration rate (e-GFR), creatinine (creat), K and BP did not change during C treatments at 1 and at the final M compared to baseline. Minor, clinically unimportant decreases in serum calcium and bicarbonate, and increases in chloride were noted. 7 mild and reversible episodes of ARF (>50% rise in creat) occurred in 6 pts during 142 Ms of treatment (1 episode/20 Ms) due to volume depletion in 3, obstruction in 2, sepsis in 1, and contrast in 1. C was not a major precipitating factor and 6 of 7 pts continued C after ARF without recurrences (1 pt withdrew after renal function improved). 3 pts had solitary episodes of mild hyper K (5.5–6.0 mmol/L); 1 pt with DM nephropathy receiving ACE had 3 episodes of hyper K, reaching 6.6 mmol/L. After ACE was stopped in 2 pts, hyper K never recurred. No pts developed increasing proteinuria. Conclusion High dose C was well tolerated. The incidence of ARF and hyper K was low, and causes were attributed to other factors. No differences in renal function (creat, e-GFR), K, and BP were noted during 142 Ms of C treatment compared to baseline, and no pts developed persistent proteinuria. No significant financial relationships to disclose.

Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis

Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis. Hyperphosphatemia in patients with ESRD leads to secondary hyperparathyroidism, renal osteodystrophy, and is independently associated with mortality risk. The exact mechanism by which hyperphosphatemia increases mortality risk is unknown, but it may relate to enhanced cardiovascular calcification. National Kidney Foundation K/DOQI bone metabolism and disease guidelines recommend maintenance of serum phosphorus (P) below 5.5 mg/dL, and Ca x P product less than 55 mg(2)/dL(2). Although calcium-based phosphate binders (CBPB) are cost effective, long-term safety concerns relate to their postulated role in progression of cardiovascular calcification. Sevelamer hydrochloride has been recommended as an alternative noncalcium phosphate binder. Results from the Calcium Acetate Renagel Evaluation (CARE study) indicate that calcium acetate is more effective than sevelamer in controlling serum phosphorous and Ca x P product in hemodialysis patients. In the Treat-to-Goal study, dialysis patients treated with sevelamer had slower progression of coronary and aortic calcification than patients treated with CBPB. The mechanism underlying the beneficial effect of sevelamer is unknown, but may relate to decreased calcium loading or to dramatic reductions in LDL cholesterol in sevelamer-treated patients. At present, evidence incriminating CBPB in the progression of cardiovascular calcification in ESRD remains largely circumstantial. As calcium acetate is more efficacious and cost effective than sevelamer, it remains an accepted first-line phosphate binder. In this review, we will examine these issues and provide rational guidelines for the use of calcium-based phosphate binders in patients on maintenance hemodialysis.

New strategy to attenuate pulse wave velocity in haemodialysis patients

Pulse wave velocity (PWV) is commonly elevated in haemodialysis (HD) patients having cardiovascular diseases. Disturbances in calcium-phosphate metabolism are among the established cardiovascular risk factors in HD patients. The present study was performed to assess the effect of sevelamer on PWV in HD patients. Fifteen patients, who had been treated with calcium carbonate as a phosphate binder, were entered into the study. Changes in PWV during the 6 months before sevelamer administration were compared with PWV changes during 6 months of receiving sevelamer. Serum biochemistry parameters were also assessed. Compared with the preceding control period, the sevelamer period resulted in decreased serum calcium (9.9+/-0.1 to 9.6+/-0.1 mg/dl, n = 15; P<0.01) in association with reductions in oral calcium load (4.3+/-0.4 to 2.3+/-0.6 g/day; P<0.001). Serum phosphorus and whole parathyroid hormone remained unchanged. Sevelamer reduced serum total cholesterol (167+/-7 to 148+/-6 mg/dl; P<0.001) and LDL-cholesterol (85+/-8 to 65+/-7 mg/dl; P<0.001), without modifying HDL-cholesterol or triglycerides. Finally, sevelamer reversed the increase in PWV observed during the control period (from 46+/-16 to -20+/-9 cm/s/month; P<0.01). In chronic HD patients, sevelamer decreased serum total- and LDL-cholesterol as well as calcium. Moreover, our findings suggest that treatment with sevelamer attenuates the progressive increase in PWV observed during calcium carbonate treatment.

Cellular and molecular mechanisms of secondary hyperparathyroidism

The objective of this review is to share important basic research insights into the mechanisms of secondary hyperparathyroidism. An understanding of these mechanisms is essential to more effectively treating the disease. Central underlying abnormalities are increased parathyroid hormone (PTH) gene expression and secretion, and parathyroid cell proliferation. Significant progress has been made in understanding these abnormalities at the cellular and molecular level, particularly their regulation. Studies point to a prominent role of calcium, phosphate and vitamin D as regulators of PTH and parathyroid cell proliferation. 1,25[OH]2 vitamin D3 decreases PTH synthesis and secretion. Small decreases in serum calcium and prolonged increases in serum phosphate as may occur in patients with chronic failure, increase PTH secretion, PTH gene expression, and parathyroid cell proliferation. Regulation at the level ofPTH gene expression is particularly significant given the limited amount of preformed mature PTH. It is now known that calcium and phosphate regulate PTH gene expression through changes in protective parathyroid cytosolic proteins that bind to an instability element in the PTH mRNA 3'-untranslated region and influence transcript stability. These findings may help guide the development of novel therapies for secondary hyperparathyroidism.

Osteopenia: a bone disorder associated with diabetes mellitus

Although osteopenia has been associated with human diabetes mellitus, the pathogenesis of diabetic osteopenia is unclear. In the present study, we evaluated the effect of diabetes on histomorphometry, bone mineral density (BMD)-measured by dual-energy X-ray absorptiometry (DXA)-and biomarkers of bone metabolism in rats up to 120 days after the onset of experimental diabetes. Female Wistar rats with a regular estrous cycle were randomly divided into two groups: control rats (n = 15) and diabetic rats without insulin treatment (n = 25). Diabetes was induced by injection of alloxan and was confirmed by the determination of blood glucose concentration (>250 mg/dl). The results revealed an approximate threefold increase of femoral trabecular distance in diabetic rats compared to controls. Conversely, trabecular thickness and bone trabecular volume were reduced twofold and 77%, respectively. BMD in both the metadiaphyseal region and total area of the femur was found to be clearly reduced in diabetic animals, with no significant differences between the groups. Serum alkaline phosphatase (ALP) and tartarate-resistant acid phosphatase (TRAP) activities showed significant six- and twofold increases, respectively, in diabetic rats. There were significant decreases in serum calcium and albumin concentrations in diabetic rats, but no difference was observed in serum magnesium, phosphorus, or creatinine concentrations between the groups. Overall, our findings support the conclusion that the diabetic state is associated with alterations in bone turnover, resulting in the development of osteopenia, which is related to the time of evolution of the disorder.

Uses and Effectiveness of Pamidronate Disodium for Treatment of Dogs and Cats with Hypercalcemia

Uncorrected hypercalcemia can cause clinical signs such as polyuria, polydipsia, vomiting, diarrhea, lethargy, and depression and contributes to the development of primary renal failure and soft tissue mineralization. Treatment of hypercalcemia includes diagnosis and treatment of the underlying disease process and some combination of extracellular fluid volume expansion by administration of fluids intravenously and administration of glucocorticosteroids, salmon calcitonin, and furosemide. Bisphosphonates such as pamidronate disodium also may be safe and effective in the treatment of hypercalcemia. The purpose of our study was to characterize the efficacy and safety of pamidronate in the treatment of hypercalcemia attributable to several different disease processes in the dog and cat. Seven dogs and 2 cats were administered pamidronate at a dose of 1.05‐2.0 mg/kg IV for a variety of disease processes, including neoplasia (n = 4), calcipotriene toxicity (n = 3), nocardiosis (n = 1), and idiopathic hypercalcemia with chronic renal failure (n = 1). In all the animals, IV pamidronate administration rapidly decreased serum calcium concentrations without evident toxicosis. Two animals received pamidronate several times without obvious toxicosis. On the basis of the findings in our retrospective study, pamidronate may be a safe and effective drug with which to lower both serum total and ionized calcium concentrations in patients with hypercalcemia arising from a wide variety of underlying disease processes.

Uses and Effectiveness of Pamidronate Disodium for Treatment of Dogs and Cats with Hypercalcemia

Uncorrected hypercalcemia can cause clinical signs such as polyuria, polydipsia, vomiting, diarrhea, lethargy, and depression and contributes to the development of primary renal failure and soft tissue mineralization. Treatment of hypercalcemia includes diagnosis and treatment of the underlying disease process and some combination of excracellular fluid volume expansion by administration of fluids intravenously and administration of glococorticosteroids, salmon calcitonin, and furosemide. Bisphosphonates such as pamidronate disodium also may be safe and effective in the treatment of hypercalcemia. The purpose of our study was to characterize the efficacy and safety of pamidronate in the treatment of hypercalcemia attritutable to several different disease processes in the dog and cat. Seven dogs and 2 cats were administered pamidronate at a dose of 1.05-2.0 mg/kg IV for a variety of disease processes, including neoplasia (n = 4), calcipotriene toxicity (n = 3), nocardiosis (n = 1), and idiopathic hypercalcemia with chronic renal failure (n = 1). In all the animals, IV pamidronate administration rapidly decreased serum calcium concentrations without evident toxicosis. Two animals received pamidronate several times without obvious toxicosis. On the basis of the findings in our retrospective study, pamidronate may be a safe and effective drug with which to lower both serum total and ionized calcium concentrations in patients with hypercalcemia arising from a wide variety of underlying disease processes.

Role of non‐selective adenosine receptor blockade and phosphodiesterase inhibition in cisplatin‐induced nephrogonadal toxicity in rats

1. It is well documented that cisplatin (CDDP) treatment increases the expression of adenosine A(1) receptors in both kidney and testes. However, the effect of adenosine at these receptors is controversial. Adenosine A(1) receptors have been documented to be involved in either cytoprotection or aggravation of nephrotoxicity. The aim of the present study was to examine the effect of the non-selective adenosine receptor inhibitor theophylline and the phosphodiesterase inhibitor pentoxifylline on CDDP-induced renal and testicular toxicity. 2. Male Wister rats were divided into six groups. Two control groups received plain drinking water and a third control group received theophylline 0.8 mg/mL in the drinking water for 2 weeks. One group of animals drinking plain water was injected intraperitoneally (i.p.) with pentoxifylline 50 mg/kg per day for 2 weeks. The remaining groups were treated in the same manner and received single dose of CDDP 7 mg/kg, i.p., 1 week after starting theophylline and pentoxifylline treatment and all animals were killed 1 week after CDDP treatment. 3. Rats treated with CDDP developed nephrotoxicity, as demonstrated by increased kidney and testes weight as a percentage of total bodyweight, blood urea nitrogen and serum creatinine levels and decreased serum calcium and albumin levels. In addition, CDDP treatment resulted in an increase in the production of malondialdehyde (MDA) and decreases in total nitrate/nitrite levels, as well as depletion of reduced glutathione (GSH) content and glutathione peroxidase (GPX) activity in both the kidney and testes. Administration of theophylline in the drinking water to CDDP-treated rats resulted in exacerbation of the indices of nephrotoxicity, depletion of GSH content and GPX activity levels, with increased MDA production and platinum accumulation in both the kidney and testes. However, pentoxifylline administration reduced CDDP-induced biochemical changes and reduced platinum accumulation in both organs. Histopathological examination of the kidney revealed that CDDP treatment produced multifocal tubular atrophy, atypical reparative changes of the tubular epithelium and marked tubular necrosis. Animals treated with the theophylline/CDDP combination showed extensive widespread damage with intratubular calcification. However, pentoxifylline treatment ameliorated the overt changes induced by CDDP treatment. 4. Theophylline exacerbates the deleterious effects of CDDP on rat kidney and testes. However, pentoxifylline alleviates CDDP-induced renal and testicular toxicity.

Pathogenesis of parathyroid dysfunction in end-stage kidney disease

Small decreases in serum calcium (Ca(2+)) and more-prolonged increases in serum phosphate (Pi) stimulate the parathyroid (PT) to secrete parathyroid hormone (PTH). 1,25-Dihydroxyvitamin D(3) [1,25(OH)(2) D(3)] decreases PTH synthesis and secretion. The prolonged decrease in serum Ca(2+) and 1,25(OH)(2) D(3), or increase in serum Pi, observed in patients with chronic renal failure leads to a secondary increase in serum PTH. This secondary hyperparathyroidism involves increases in PTH gene expression, synthesis, and secretion and, if chronic, to proliferation of the PT cells. A low serum Ca(2+) leads to an increase in PTH secretion, PTH mRNA stability, and PT cell proliferation. Pi also regulates the PT in a similar manner. The effect of Ca(2+) on the PT is mediated by a membrane Ca(2+) receptor. 1,25(OH)(2) D(3) decreases PTH gene transcription. Ca(2+) and Pi regulate the PTH gene post transcriptionally by regulating the binding of PT cytosolic proteins, trans factors, to a defined cis sequence in the PTH mRNA 3'-untranslated region, thereby determining the stability of the transcript. The PT trans factors and cis elements have been defined.