Daily Urinary Calcium Excretion Research Articles

Обмен кальция и остеопороз у больных ишемической болезнью сердца в пожилом и старческом возрасте

im. To analyze the relationship between calcium and various clinical and laboratory parameters in old and very old patients with coronary artery disease (CAD) based on the determination of the blood concentration of ionized calcium and daily excretion of calcium in the urine. Materials and methods. This work was a cross-sectional study enrolled 102 patients (84 women and 18 men) with coronary artery disease with a mean age of 83.0±5.9 years. The blood level of ionized calcium (N 1.16–1.32 mmol/l), daily excretion of calcium in the urine (N 2.5– 7.5 mmol/l) and concentration of 25-hydroxycalciferol (25(OH)D) were determined in all patients. Along with this, the bone mineral density of the lumbar spine and proximal femur was analyzed using dual-energy x-ray absorptiometry. Results. The mean daily excretion of calcium in the urine was 1.39±1.1 mmol/l (0.17–7.44 mmol/l). 84.4% of patients had low calcium content in daily urine. The mean blood concentration of ionized calcium was 1.26±0.05 mmol/l (1.16–1.53 mmol/l). Hypercalcemia was observed in 8.3% of patients. Osteoporosis in the proximal femur was registered in 32.9% of patients, in the lumbar spine – in 18.1% of patients. In patients with normal vitamin D level the mean urinary calcium excretion was 1.77±1.2 mmol/l, with vitamin D deficiency – 1.1±0.7 mmol/l (p=0.07). In patients with low calcium excretion in the urine, the mean blood concentration of vitamin D was 18.7±7.7, with normal excretion – 28.5±10.8 ng/ml (p=0.007). Significant inverse relationships were registered between urinary calcium excretion and creatinine (r=-0.36; p<0.0001). In the group of patients with low urinary calcium excretion the mean creatinine level reached 102.3±23.9 µmol/l, with normal excretion – 84.9±11.2 µmol/l (p<0.0001). There was a significant direct correlation between daily urinary calcium excretion and glomerular filtration rate, estimated using the CKD-EPI formula (r=0.39; p<0.0001) and an inverse correlation between blood calcium and GFR (r=-0.26; p=0.01). Significant direct relationship was registered between the blood concentration of ionized calcium and the creatinine (r=0.2; p=0.05) and urea (r=0.32; p=0.04) concentration. Conclusion. The study results demonstrate a low level of calcium excretion in the urine in old and very old patients with coronary artery disease. The urine calcium excretion is primarily due to impaired renal function and low vitamin D concentration.

Primary Hyperparathyroidism in Homozygous Sickle Cell Patients: A Hemolysis-Mediated Hypocalciuric Hypercalcemia Phenotype?

Primary hyperparathyroidism (pHPT) has been reported to have a higher prevalence in sickle cell disease (SCD) patients, including a high rate of recurrence following surgery. However, most patients are asymptomatic at the time of diagnosis, with surprisingly infrequent hypercalciuria, raising the issue of renal calcium handling in SCD patients. We conducted a retrospective study including (1) 64 hypercalcemic pHPT non-SCD patients; (2) 177 SCD patients, divided into two groups of 12 hypercalcemic pHPT and 165 non-pHPT; (3) eight patients with a diagnosis of familial hypocalciuric hypercalcemia (FHH). Demographic and biological parameters at the time of diagnosis were collected and compared between the different groups. Determinants of fasting fractional excretion of calcium (FeCa2+) were also analyzed in non-pHPT SCD patients. Compared to non-SCD pHPT patients, our data show a similar ionized calcium and PTH concentration, with a lower plasmatic calcitriol concentration and a lower daily urinary calcium excretion in pHPT SCD patients (p < 0.0001 in both cases). Fasting FeCa2+ is also surprisingly low in pHPT SCD patients, and thus inadequate to be considered hypercalcemia, recalling the FHH phenotype. FeCa2+ is also low in the non-pHPT SCD control group, and negatively associated with PTH and hemolytic biomarkers such as LDH and low hemoglobin. Our data suggest that the pHPT biochemical phenotype in SCD patients resembles the FHH phenotype, and the fasting FeCa2+ association with chronic hemolysis biomarkers strengthens the view of a potential pharmacological link between hemolytic by-products and calcium reabsorption, potentially through a decreased calcium-sensing receptor (CaSR) activity.

Минералогический состав камней, факторы риска и метаболические нарушения у пациентов с кальций-оксалатным уролитиазом

To identify the most likely metabolic disturbances and risk factors for stone formation in a group of patients with calcium oxalate urolithiasis, and to establish the relationship between the mineralogical composition of calculi and impaired excretion of inhibitors and promoters of stone formation. Fifty patients with calcium oxalate urolithiasis were tested using a complex of physicochemical methods. Patients assessment included evaluation of quantitative mineralogical composition of calculi, daily urine pH profile and daily urinary excretion of urates, calcium, magnesium, oxalate, phosphate and citrate ions. The main mineralogical phase of the stones in over 80% of patients was calcium oxalate monohydrate; none of the patients had pure dihydrate stones. The most frequent metabolic disorders were hypocitraturia, hypercalciuria and hyperuricosuria. Predominant risk factors were excessive body weight and insufficient fluid intake. Only one patient had an idiopathic stone formation. It was established for the first time that patients with calcium oxalate stones, containing 10 or more mass percent of apatites had statistically significantly lower daily urinary calcium and oxalate excretion and simultaneously increased phosphate excretion. The study findings showed that patients with calculi based on calcium oxalate dihydrate should undergo testing for daily urinary excretion of calcium and citrate while pa-tients with calcium oxalate stones containing 10 or more mass percent of apatites should also be tested for daily phosphate excretion and urine pH-profile. Daily urinary citrate excretion was reduced in all study patients, and urate excretion was significantly increased, apparently due to an imbalanced diet and excessive intake of animal protein. Menopausal and postmenopausal women are at a particular risk due to low urinary citrate excretion and high urinary calcium excretion regardless of stone composition.

OSTEOPOROSIS IN CALCIUM PYROPHOSPHATE CRYSTAL DEPOSITION DISEASE

Objective: to study the incidence of osteoporosis (OP) in patients with calcium pyrophosphate crystal deposition disease (CPCDD). Subjects and methods. Eighty patients with CPCDD were examined. Bone mineral density (BMD) of the forearm, lumbar spine, and femoral neck was determined by dual-energy X-ray absorptiometry. Laboratory diagnosis involved determination of the blood levels of C-reactive protein, parathyroid hormone, calcium, magnesium, and phosphorus and the daily urinary excretion of calcium and phosphates. Results. The patients with OP were significantly older than those with normal BMD and osteopenia. Forearm bones were the most common isolated location of OP and osteopenia. Injuries in the history, traumatic fractures, and the intake of diuretics were somewhat more common in the patients diagnosed with OP. The incidence of hyperparathyroidism did not differ significantly in the groups.

High bone turnover persisting after vitamin D repletion: beware of calcium deficiency

Treatment of vitamin D deficiency with vitamin D is a common procedure when taking care of elderly patients, calcium supplementation being added only when calcium dietary intake is insufficient. Here, we report the case of a 58-year-old female who was referred to our unit because of suspicion of Paget's disease of the skull, based on elevated serum alkaline phosphatase and high skull methylene diphosphonate-technetium uptake. She had been prescribed cholecalciferol (100,000 IU/month) and calcium salts for the past 7 months after discovery of severe vitamin D deficiency by her primary care physician. No specific skull bone lesions were observed on both X-ray and computerized tomography. Serum calcium, phosphate and 25(OH) vitamin D levels were normal, while serum C-terminal cross-linked telopeptide, bone alkaline phosphatase and calcitriol were high and daily urinary calcium excretion was low. We found that she had not been compliant with the calcium prescription while vitamin D had been thoroughly taken. We suspected osteomalacia due to calcium deficiency. Both skull uptake and biological abnormalities normalised in few months after adding calcium supplementation to the vitamin D treatment, and spine bone mineral density increased by 9.5 % after 14 months of full treatment. The present case illustrates the necessity for adequate calcium intake during vitamin D repletion to normalise bone mineralisation and turnover and maintain the skeletal integrity.

Changes in Urine Parameters After Desert Exposure: Assessment of Stone Risk in United States Marines Transiently Exposed to a Desert Environment

Living in a desert environment has been associated with a higher incidence of kidney stone formation, likely because of concentrated urine output, higher production of vitamin D and genetic predisposition. We determined the changes in urinary parameters after a group of United States Marines temporarily transitioned from a temperate environment to a desert environment. A total of 50 Marines completed a questionnaire and performed 3, 24-hour urine collections before mobilization to the desert, after 30 days in the desert and 2 weeks after returning from the desert. Daily urine output decreased 68% to 0.52 L despite marked increased fluid intake (17 L per day). Total daily urinary excretion of calcium, uric acid, sodium, magnesium and potassium in the desert decreased by 70%, 41%, 53%, 22% and 36%, respectively. Urinary pH decreased from 6.1 to 5.6 while in the desert, and citrate and oxalate had minimal changes. After their return from the desert, apart from a decrease of 22% in oxalate, there were no statistically significant differences from baseline. While in the desert, relative supersaturation risks of uric acid and sodium urate were increased 153% and 56%, respectively. Brushite relative supersaturation decreased 24%. After their return there was no statistical difference from baseline. Our findings suggest that the kidneys preserved water and electrolytes while the Marines were subjected to the desert environment. Despite this conservation, relative saturations indicate increased risk of stones in healthy men exposed to a desert environment with rapid resolution upon return.

Protocol-based metabolic evaluation in high-risk patients with renal stones in North India

Context:Renal calculus disease has a lifetime recurrence rate of 80%. Protocol-based metabolic evaluation in high-risk subjects for recurrent renal stones reveals abnormalities in a large subset of subjects. However, such information is not available in Indian subjects.Aims:To evaluate the abnormalities by a protocol-based metabolic evaluation in patients at a high risk for recurrent renal stones.Settings and Design:Prospective, academic tertiary care center.Materials and Methods:Fifty North Indian patients (38 males and 12 females; mean age 38 ± 10.2 years) with recurrent or bilateral renal stones were evaluated. All subjects underwent a protocol-based evaluation involving estimation of serum total calcium, phosphorus, creatinine, albumin, iPTH, 25(OH)D3, 1,25(OH)2D3, and a calcium load test. Estimation of daily urinary excretion of volume, oxalate, calcium, uric acid, and citrate, and urinary acidification studies were performed.Statistical Analysis Used:Descriptive statistics and t-test.Results:An underlying disorder was detected in 48 (96%) patients. Almost half had two or more metabolic abnormalities. The metabolic abnormalities detected were: Hypercalciuria 26 (52%) patients, renal hypercalciuria 16 (32%), absorptive hypercalciuria 6 (12%), unclassified hypercalciuria 4 (8%), hyperoxaluria 27 (54%), hyperuricosuria 9 (18%), distal renal tubular acidosis 4 (8%; 2 complete and 2 partial), primary hyperparathyroidism 3 (6%), and hypocitraturia 14 (n=18, 77%). In two patients, the etiology could not be detected.Conclusions:Protocol-based metabolic evaluation reveals metabolic abnormalities in majority of patients with nephrolithiasis. The spectrums of metabolic abnormalities are different in Indian subjects as compared to the western population.

Slow progression of chronic renal failure in a woman of short stature and leg deformities: what is the link?

A 71-year-old woman presented at the outpatient clinic for the first time in 1973 with diffuse bone pain mainly in both wrists, shoulders and the spine. Clinical examination showed limb deformities (genu varum of the left leg, genu valgum of the right leg) and short stature (142 cm). At that time, she had already experienced multiple spontaneous fractures of the right and left femur. There was no family history of bone disorders (mother and father as well as seven brothers and sisters were healthy). Laboratory tests at that moment showed: sodium 141 mmol/L (normal range 133–145), potassium 3.9 mmol/L (3.5–5.1), chloride 104 mmol/L (95–108), bicarbonate 23 mmol/L (23–29), calcium 9.8 mg/dL (8.4– 10.2), phosphate 1.7 mg/dL (2.4–4.5), serum creatinine 0.72 mg/dL and alkaline phosphatase 120 U/L (53– 141). Hyperparathyroidism was excluded. Urine analysis showed a daily phosphate excretion of 597 mg (300– 1300), a daily calcium excretion of 39 mg (100–250) and a daily creatinine excretion of 852 mg (660–2200), corresponding to a fractional renal excretion of phosphate of 67%. At that time, the diagnosis of a congenital disorder with hypophosphataemia due to renal phosphate wasting, resulting in osteomalacia was considered. Treatment with oral phosphate and vitamin D replacement was initiated, resulting in a normalization of her serum calcium and phosphate. The following years, a few episodes of symptomatic hypoand hypercalcaemia (with nausea and vomiting) could not be prevented. Figure 1 shows the evolution over the years of the serum calcium and phosphate levels. Figure 2 shows the evolution of the daily urinary excretion of calcium and phosphate.

Bone mineral density and bone turnover markers of patients with Behçet's disease

Behçet's disease (BD) is a systemic inflammatory disease of unknown aetiology. The pathogenesis of rheumatological findings and the status of bone metabolism in this disease are unknown. Inflammatory diseases may predispose to a decrease in bone mineral density (BMD) and there are many studies concerning osteoporosis in chronic inflammatory diseases. The aim of this study was to investigate BMD and bone turnover markers in patients with BD. Thirty BD patients (17 male and 13 female patients, mean age 36.9+/-12.6 years) and a total of 30 age- and sex-matched healthy controls (17 male and 13 female controls, mean age 34.9+/-8.95 years) recruited from the general population were enrolled in the study. Bone mineral density was measured at the lumbar spine (L1-4) and the left hip (total hip) using dual energy X-ray absorptiometry. Serum samples were collected between 8 and 10 am after overnight fasting. Serum calcium (Ca), phosphate (P), parathormone (PTH), total alkaline phosphatase (ALP), osteocalcin (OC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were measured. Free deoxypyridinoline cross-links (DPD) in second-void urine and total daily urinary calcium excretion were analysed. No statistically significant difference in lumbar spine or femoral BMD and bone turnover markers were found between BD patients and control groups (P>0.05). Although it is difficult to draw definite conclusions because of the limited number of patients involved, our study indicates that bone mineral density and bone turnover markers in Behçet's disease were no different than in healthy subjects.

Renal handling of calcium and phosphorus in experimental renal hyperparathyroidism in dogs

Twenty-four hour urinary excretion, fractional excretion and the filtered load of calcium and phosphorus were monitored as hyperparathyroidism evolved in a model of progressive canine renal failure. Thirteen beagles of both sexes aged four and a half months were used. Nine of them were subjected to a renal damaging schedule (neomycine, 60 mg/kg/48 h, IM, 32 weeks) in order to induce chronic renal failure leading to secondary hyperparathyroidism (2HPT group). The remaining four were kept as the control group. The experiment was conducted over 32 weeks. Blood and 24 h urine were collected every four weeks. Calcium, phosphorus and creatinine were analyzed. Plasma parathormone and calcitonin were determined at weeks 0, 12, 24 and 32. The level of renal function in the 2HPT animals was reduced to 25% of that of the controls (endogenous creatinine clearance was 0.45 +/- 0.22 mL/min/kg as opposed to 1.81 +/- 0.54 mL/min/kg). Hyperparathyroidism was confirmed by a progressive increase in the levels of the parathyroid hormone. Calcitonin levels were not modified. A tendency to hypocalcaemia was observed, reaching statistically significant levels from the twenty-eighth week of the study, when hyperphosphataemia also became significant. Daily urinary excretion of calcium and phosphorus remained at values considered normal throughout the experiment with no alteration imputable to the impaired renal function. This is explained by the decrease in the filtered load of these elements (in both cases statistically significant from the 24th week on) being associated with an increase in their fractional excretion. Thus, calcium and phosphorus urinary excretion values could be maintained in a normal range up to the end of the experiment, showing that renal calcium handling in dogs with experimentally induced renal failure seems to differ from that observed in human patients.

Frequency of renal phosphate leak among patients with calcium nephrolithiasis

Nephrolithiasis is a frequent disorder affecting 10 to 15% of the population in Europe and the United States. More than 80% of renal stones are made of calcium oxalate and calcium phosphate. The main identified risks for calcium renal stone formation are hypercalciuria and urinary saturation. A urine phosphate (Pi) loss is often associated with hypercalciuria; furthermore, hyperphosphaturia increases urinary saturation. To determine whether urinary phosphate loss is associated with calcium urolithiasis, we measured renal Pi threshold (TmPi) in 207 stone formers with normal parathyroid hormone (PTH) serum concentration and in 105 control subjects. The TmPi followed a normal distribution in both groups. The mean TmPi was significantly lower in stone formers versus controls (0.72 +/- 0.13 vs. 0.87 +/- 0.18 mmol/L, P < 0.0001) because of a shift to the left of the TmPi distribution curve in the stone former population, with no evidence for bimodal distribution. Five percent of the controls had a TmPi <0.63 versus 19% of the stone formers. Daily urinary calcium excretion was significantly higher in stone formers than in controls. Calcium excretion was also significantly higher in stone formers with TmPi <0.63 mmol/L compared with those with TmPi > or =0.63. Serum PTH and ionized calcium concentrations were not different in stone formers and in control subjects, whatever the TmPi value. : A low TmPi is more frequently encountered in stone formers with a normal PTH concentration than in control subjects and is associated with a high urinary Ca excretion. The hypophosphatemia induced by a renal phosphate leak may predispose the subject to calcium stone formation by increasing the serum calcitriol level, calcium excretion, and urinary saturation.

Abnormal arachidonic acid content of red blood cell membranes and main lithogenic factors in stone formers

Increased arachidonic acid content in red blood cell membranes of stone formers (SF) has recently been reported and is hypothesized as representing the underlying causal factor for both hyperoxaluria and hypercalciuria. We performed the present study to see whether we could confirm this finding and to test whether any relationship exists between the fatty acid composition of red blood cell membranes and the main metabolic factors involved in stone formation. In 21 SF and 40 healthy controls subjects the fatty acid composition of red blood cell membranes was assessed. In addition, the following parameters were evaluated in SF: daily and fasting urinary calcium excretion, fractional intestinal calcium absorption, 1,25-dihydroxy-vitamin D, intact parathyroid hormone, hydroxyproline in fasting urine, daily urinary excretion of oxalate, citrate, urate, electrolytes, urea, sulphate, relative supersaturation for calcium oxalate monohydrate. The red blood cell membrane of SF had a lower content of arachidonic acid, linoleic acid, and docosahexaenoic acid than that of control subjects. Arachidonic acid content was not correlated with any of the parameters studied. However, when patients were grouped according to the degree of oxalate excretion, hyperoxaluric SF had a higher arachidonic acid content and arachidonic/linoleic acid ratio than SF with normal oxalate excretion. Our results do not confirm the finding of an increased arachidonic acid content of red blood cell membrane in SF. On the contrary, reduced arachidonic acid levels were found in our patients. However, hyperoxaluric SF had a relatively higher arachidonic acid content than SF with normal urinary oxalate excretion.

Association between Vitamin D Receptor Gene Polymorphism and Nephrolithiasis

Aims: To study the distribution of vitamin D receptor (VDR) gene alleles in hypercalciuric and nonhypercalciuric nephrolithiasis patients, hypothesizing that distinct biochemical parameters would be associated with different VDR genotypes. Methods: 12 hypercalciuric, 15 normocalciuric nephrolithiasis patients, and 150 healthy subjects were recruited. The individual genetic pattern for VDR was evaluated by DNA extraction followed by polymerase chain reaction amplification of the VDR gene and digestion with the restriction enzyme BsmI. Results: In the hypercalciuric group, Bb patients represented 50% (6/12); bb patients 33% (4/12), and BB cases were 16% (2/12). The VDR frequency distribution was not statistically different in hypercalciuric patients and controls (Bb 72%; bb 16%; BB 12%). In the nonhypercalciuric group, the prevalence of the bb genotype (7/15; 47%) was thrice the percentage of control subjects, while the percentage of BB patients was similar to that of the control group (2/15; 13%). Patients with the bb haplotype exhibited a higher daily urinary calcium excretion. Among hypercalciuric patients, after a calcium-restricted diet, bb patients showed a 39% reduction in daily urinary calcium excretion in comparison with a nonsignificant 13% reduction observed in BB subjects (p = 0.004). Conclusions: The effects of VDR gene polymorphism on calcium metabolism contribute to the understanding of the pathogenesis of urinary calculi.

An evidence‐based approach to hypercalciuria: is it really necessary for the study of the role of calcium in urolithiasis?

An abnormally raised 24-h urinary excretion of calcium has long been regarded as a common feature of calcium stone disease. However, hypercalciuria can be defined only by reference to a range of values measured in a representative population of individuals who have never suffered from stone disease. To date, there have been significant flaws in all published studies reporting normal ranges for daily urinary calcium excretion. There is no doubt that additional, carefully performed and documented investigations need to be undertaken to establish what is truly abnormal for a given population; the persistent use of arbitrarily defined limits may be hindering rather than helping to unravel the role of calcium in the pathogenesis of calcium stones.

Dietary protein intake and urinary excretion of calcium: a cross-sectional study in a healthy Japanese population

To evaluate whether habitual excess protein intake is a significant risk factor for calcium loss, we studied the relation between urinary excretion of calcium and protein intakes, in 349 male and 406 female Japanese aged 20-79 y. The subjects were apparently healthy, free-living, and consuming diets of their own choosing. We divided the subjects into two groups: those aged 20-49 y and those aged 50-79 y. In each group, we observed a significant positive correlation between daily urinary excretion of calcium and protein intake. Calcium excretion also correlated positively with daily urinary excretion of urea. Multivariate analyses revealed that in each age group the relation between calcium excretion and urea excretion remained significant even after sex, age, body weight, urinary sodium excretion, and calcium intake were adjusted for. The correlation of calcium excretion with animal protein intake was significantly positive in both sexes and in each age group whereas that with plant protein was not. We observed a significant positive correlation between daily calcium excretion and daily urinary excretion of sulfate. The correlation in 50-79-y old subjects remained significant even after sex, age, body weight, sodium excretion, and calcium intake were adjusted for. Our findings suggest that excess protein, especially that rich in sulfur-containing amino acids, in habitual diets may augment calcium excretion in the urine, at least in the elderly.

Decreased Lumbar Spine Bone Mass and Low Bone Turnover in Children and Adolescents with Insulin Dependent Diabetes Mellitus Followed Longitudinally

The effects of insulin dependent diabetes mellitus (IDDM) on bone metabolism are still not well defined. We evaluated total bone mineral content (TBMC) and bone mineral density (BMD) at the lumbar spine and femoral neck using dual X-ray absorptiometry in 26 IDDM children (15 M, 11 F) with a mean chronological age of 12.1+/-3.1 yr (range 7.1-14.2 yr). Duration of diabetes was 4.3+/-2.9 yr, with a mean glycosylated hemoglobin of 9.2+/-0.4%. BMD and TBMC standard deviation scores (Z-scores) were determined by comparing our results to controls matched for age, sex and pubertal status. BMD and bone formation and resorption markers were determined at the beginning of the study and after one year of follow up. Mean lumbar spine Z-score was -1.06+/-0.2, with negative values in 24 of 26 children (92.6%); 14/26 patients (53.8%) had a lumbar spine Z-score >1.0 SD below the mean. Mean lumbar spine Z-score remained unchanged after one year of follow up (-1.02+/-0.3). No significant differences were obtained in femoral neck BMD or TBMC between groups. No correlation was observed between lumbar spine BMD Z-scores and duration of IDDM or degree of diabetes control, as assessed by the mean glycosylated hemoglobin. Daily urinary calcium excretion was elevated in our patients initially and after one year of follow up; however, no correlation was obtained between lumbar spine BMD and 24 h urinary calcium excretion. Carboxy-terminal propeptide of type 1 collagen values and levels of urinary cross-linked N-telopeptides of type 1 collagen in the diabetic children were significantly lower than those of the matched controls. Osteoblastic activity as assessed by serum osteocalcin and by the carboxy-terminal propeptide of type I collagen and bone resorption as measured by cross-linked N-telopeptides of type 1 collagen did not correlate with the lumbar spine Z-scores. When IDDM patients were subdivided into males and females and into children with more than or less than 2 yr duration of diabetes since diagnosis, no differences between groups were found. These results suggest that insulin dependent diabetes in children is associated with low bone turnover resulting in a deficit in bone mass which may be manifested as osteopenia in the growing bone. This defect is already present in trabecular bone early on in the disease and seems not to be related to glycemic control.

Urinary N-acetyl-beta-D-glucosaminidase activity in rabbits with experimental hypercalciuria.

Routinely used renal function tests remain normal in uncomplicated hypercalciuria. The aim of this study was to assess the value of N-acetyl-beta-D-glucosaminidase (NAG), a sensitive marker of renal proximal tubular damage, in experimental hypercalciuria. Oral calcium providing 75 mg/kg per day elementary calcium and 20,000 IU/day vitamin D3 was administered for 15 days to 7 rabbits (Orytolagus cuniculus-New Zealand white) and 7 rabbits were given placebo as a control group. Serum calcium, phosphorus, and alkaline phosphatase, daily urinary calcium excretion and NAG/creatinine ratio were measured before and after drug administration. Kidneys were examined macroscopically and microscopically following the study period. Serum calcium, phosphorous and urinary calcium excretion increased, while alkaline phosphatase decreased significantly in response to drug treatment [10.8 +/- 1.5 vs. 12.2 +/- 1.3 mg/dl, 4.6 +/- 0.6 vs. 6.7 +/- 0.7 mg/ dl, 22.3 +/- 8.3 vs. 46.8 +/- 22.5 mg/kg per day, and 138.0 +/- 57.1 vs. 70.1 +/- 33.1 IU/l, respectively (P < 0.05)]. The NAG/creatinine ratio prior to the study (0.5 +/- 0.1 mU/ mg) was significantly different from that after the study (5.4 +/- 1.5 mU/mg, P < 0.01). In the control group, changes in serum and urinary parameters were not significant (P > 0.05). The relationship between the urinary NAG/ creatinine ratio and the daily urinary calcium excretion was statistically significant (r = 0.67, P < 0.05). In the study group, nephrocalcinosis was present in all rabbits except 1 (85.7%), whereas none of the control group rabbits had nephrocalcinosis. In conclusion, in rabbits urinary NAG excretion increases significantly in nephrocalcinosis induced by hypercalciuria.

Study on the cellular proliferation and endocrine activity of the parathyroid gland in hyperparathyroidism

Flow cytometric DNA analysis was performed in 21 cases of primary hyperparathyroidism (19 adenomas in 19 cases and 5 glands with primary hyperplasia) and 24 glands with secondary hyperplasia. Tissue intact-PTH concentration was measured in another 41 glands with secondary hyperplasia. Glands with adenoma had a higher proliferative index than normal glands or glands with secondary hyperplasia. In the adenoma group, there was a negative correlation between proliferative index and age, an indicator of the tumorous nature of adenomas. Daily urinary calcium excretion in case of adenoma and tissue intact-PHT concentration in glands with secondary hyperplasia also showed correlations with proliferative index, which demonstrates a close relationship between cellular proliferation and endocrine activity. Gland weight and proliferative index had no significant correlation in both groups. Therefore, another mechanism besides cellular proliferation and endocrine activity, such as number of non-functional parathyroid cells, should be considered.

Calcium homeostasis and hypercalciuria in hyperprostaglandin E syndrome

Children with hyperprostaglandin E syndrome, a neonatal variant of Bartter syndrome with enhanced renal and systemic formation of prostaglandin E2, have hypercalciuria, nephrocalcinosis, and osteopenia. Because prostaglandin E2 affects tubular calcium handling, stimulates the formation of calcitriol in vitro, and has osteolytic activity, we studied calcium homeostasis and the influence of prostaglandin E2 formation on hypercalciuria in nine patients with hyperprostaglandin E syndrome during long-term indomethacin treatment and after its withdrawal. Suppression of prostaglandin E2 formation by indomethacin resulted in improvement of biochemical and clinical features of hyperprostaglandin E syndrome. However, hypercalciuria, osteopenia, and nephrocalcinosis did not completely resolve. Despite a low calcium diet, daily urinary calcium excretion was enhanced during and after withdrawal of indomethacin treatment (median 6.3, range 5.3 to 14, and median 9.4, range 4.4 to 38 mg/kg per day, respectively). Daily urinary calcium excretion was greater after withdrawal than during indomethacin treatment. Urinary calcium excretion was not correlated with urinary prostaglandin E2 excretion. Plasma levels of intact parathyroid hormone (median 11, range 6.8 to 12 pmol/L) and calcitriol (median 157, range 108 to 236 pg/ml) were elevated during indomethacin treatment and decreased after withdrawal of indomethacin. These data suggest that hypercalciuria in hyperprostaglandin E syndrome is mainly due to a renal leak of calcium, which is caused by enhanced renal formation of prostaglandin E2 and a tubular defect not related to prostaglandin E2 formation. There is no evidence for prostaglandin-stimulated calcitriol formation. Decreasing plasma levels of parathyroid hormone in the presence of renal calcium losses after withdrawal of indomethacin treatment may be due to a bone resorption process caused by systemic prostaglandin formation; the process may contribute to hypercalciuria in the patient not receiving indomethacin.

Use of Random Urine Samples to Estimate Total Urinary Calcium and Phosphate Excretion

Calcium-to-creatinine and phosphate-to-creatinine ratios in random single-voided urine specimens were compared with 24-hour calcium and phosphate excretions, respectively, in 67 subjects who were selected prospectively to represent a wide range of renal and parathyroid function as well as urinary calcium and phosphate loss. Simple linear regression analysis revealed significant correlation between the spot urine calcium-to-creatinine ratio and 24-hour total calcium excretion and between the spot urine phosphate-to-creatinine ratio and 24-hour phosphate excretion. Calculating these simple ratios permits easy, rapid, correct, and inexpensive estimation of the daily urinary calcium and phosphate excretion.