Higher Urinary Calcium Excretion Research Articles

Correlation Between CT-Based Bone Mineral Density and Kidney Stone Size and Their Association with 24-Hour Urinalysis Biometrics in Patients with Urinary Stones

Background: The association between chronic nephrolithiasis and several systemic conditions has been established in previous studies. Patients with recurrent urinary stones generally experience more urinary calcium loss, resulting in a lower bone mineral density (BMD). Dual-energy X-ray absorptiometry (DEXA) is the standard imaging method for diagnosing a low BMD. However, imaging imposes significant cost and radiation burden on patients. Objectives: We aimed to assess the relationship between 24-hour urinalysis biometrics and bone mineral content, retrieved from non-contrast computed tomography (CT) imaging, which is routinely preformed for urinary stone patients as a primary evaluation. Patients and Methods: The sample population for this retrospective study included urinary stone patients, undergoing percutaneous nephrolithotomy (PCNL) during 2015-2019, with available 24-hour urinalysis and CT imaging records. Stone size was defined as the maximum stone diameter on the CT image. BMD for each subject was also calculated at the vertebral L1 level, with CT attenuation measured in Hounsfield units (HU). According to the literature, a cutoff value of 160 HU was selected to distinguish normal BMD from low BMD. Results: The present results showed a significant association between the stone size and BMD (P < 0.05). Moreover, patients with a low BMD had a higher urinary calcium excretion in the 24-hour urinalysis (P < 0.05). Evaluation of urine chemical composition and stone size demonstrated a significant association between hypercalciuria and urinary stone volume (P < 0.05). Conclusion: A low BMD detected by CT imaging in patients with urinary stones is associated with abnormal 24-hour urinalysis biometrics and larger stones; therefore, it should be properly assessed.

MON-193 RENAL TRANSPLANTATION IN A PATIENT WITH FAMILIAL SYNDROME OF HYPOCALCEMIA WITH HYPERCALCIURIA

The calcium sensing receptor regulates the secretion of parathyroid hormone in response to changes in the extracellular calcium concentration and mutations that result in gain of function of this receptor are associated with with familial hypocalcemia with hypercalciuria. The high urinary calcium excretion leads to nephrocalcinosis and renal insufficiency. We present a case of a patient with end stage kidney disease due to nephrocalcinosis from familial hypocalcemia with hypercalciuria, who subsequently underwent renal transplantation with complete resolution of hypercalciuria. This is the first reported case of renal transplantation in a patient with familial hypocalcemic hypercalciuria. Case report: 58 year old female developed end stage kidney disease due to nephrocalcinosis. Nephrocalcinosis was secondary to familial hypoparathyroidism and she had known mutations in calcium sensing receptors and hence chronic hypocalcemia (1.8-1.9mmol/l) and hypercalciuria( 3.2mmol/l) . She subsequently underwent non directed living donor transplantation. Within 1 week after renal transplantation the urinary calcium concentration was measured and this was completely within normal limits with urine calcium concentration of 1 mmol/l and calcium/creatinine ratio of 0.29 ( normal range 0.06- 0.45mole ratio). Subsequent urine calcium concentrations are less than 0.20mmol/l and her graft function remains excellent. Discussion: This is the first case report of successful renal transplantation in a case of familial hypoparathyroidism with known gain of function or activating mutation of calcium sensing receptor which results in hypocalcemia and hypercalciuria. The calcium sensing receptor gene is expressed in the parathyroid glands and kidneys . This receptor regulates the the secretion of parathyroid hormone and reabsorption of calcium by the renal tubules in response to alterations of serum calcium levels. Gain of function mutation of the calcium sensing receptor gene will suppress the parathyroid hormone and increase the excretion of urinary calcium at inappropriately low serum calcium levels. The high urinary calcium concentration drives polyuria and dehydration and hence subsequently leads to nephrocalcinosis and renal insufficiency. With renal transplantation, we are essential replacing the affected abnormal calcium sensing receptors with normal calcium sensing receptor and hence normalising urinary calcium, thereby eliminating the risk of nephrocalcinosis in the graft. Conclusions: Renal transplantation is a safe and effective way of treating end stage kidney disease in patients with nephrocalcinosis due to familial hypocalcemia and hypercalciuria.

MON-532 Urinary Calcium Indices in Primary Hyperparathyroidism (PHPT) and Familial Hypocalciuric Hypercalcaemia (FHH): Is There a Need for Better Discrimination?

Introduction: Primary hyperparathyroidism (PHPT) has a prevalence of around 1% and requires surgery for definite treatment. On the other hand, familial hypocalciuric hypercalcaemia (FHH) is much rarer and does not need specific treatment. There may be considerable overlap in biochemical features in these conditions. Urine calcium indices are used to help with the differential diagnosis, but their reliability in making this distinction is not clear. The aim of this retrospective cohort study was to review urinary calcium values in patients with proven PHPT and those with genetically proven FHH. Methods: Over six years (2011-2016), 265 patients with PHPT underwent surgery. Of these, 14 patients with intermittent or persistent hypercalcaemia within 6 months after surgery were excluded leaving 251 patients (female to male ratio 5:1) for final analysis. In the FHH arm, only genetically proven cases (n = 10) were included. Results: In the PHPT arm, pre-operative data was available for 24 hr urine calcium excretion (UCE) and fractional excretion of calcium (FeCa) in 93 patients; 24 hr UCE only in 95 patients; and FeCa only in 43 patients. 24 hr UCE was low (i.e. <2.5 mmol/L/24 hr) in 8 of 188 patients (sensitivity for PHPT - 95.7%). FeCa was low (<0.01) in 16 of 136 patients (sensitivity for PHPT - 88.2%). Most of the false negative (for PHPT) readings (all of 24 hr UCE and 87.5% of FeCa) could be explained by low vitamin D levels (<50 nmol/L), chronic kidney disease 3b or worse and drugs such as indapamide. In the subgroup of 93 patients who had both 24hr UCE and FeCa, low FeCa was seen in 10 patients, low 24 hr UCE in 5 patients and only one patient had low levels of both tests. In the FHH arm, both 24 hr UCE and FeCa results were available for 6 patients; 24 hr UCE only for 2 patients and FeCa only for 2 patients. Five of eight patients with 24 hr UCE had at least one normal or high level of urinary calcium and three of eight patients with FeCa had levels consistent with a diagnosis of PHPT. Conclusions: Vitamin D deficiency and chronic kidney disease should be considered as causes of low urine calcium excretion in patients with features of primary hyperparathyroidism. A significant proportion of gene positive FHH patients may have normal or high urinary calcium excretion at some stage. Research into better discrimination between these conditions would be clinically useful.

In vivo effects of renal Npt2a inhibition

Hyperphosphatemia is common in patients with chronic kidney disease and associated with increased mortality. Oral phosphate binders and dietary phosphate restriction are the current management protocols for patients with hyperphosphatemia; however, their effectiveness is insufficient. In the kidney, the sodium‐phosphate cotransporter Npt2a is responsible for bulk uptake of phosphate in the proximal tubule. Recently, an orally bioavailable selective Npt2a inhibitor (Npt2a‐I, PF‐06869206) has been described to reduce phosphate uptake in HEK cells transfected with mouse or rat Npt2a. So far, its physiological in vivo function has not been tested. Based on in vitro IC50 concentrations, we chose to study 30 mg/kg (oral gavage, 1% of body weight) in short‐term (3 hours) metabolic cage experiments in C57BL/6J mice. Compared to vehicle (n=14), bolus administration of Npt2a‐I (n=12) caused significantly higher (~4‐fold) urinary phosphate excretion (104±8 vs 27±6 μmol*min−1, P&lt;0.05). Similarly, urinary phosphate/creatinine ratios were also significantly higher (32±2 vs 8±2 mmol*mmol−1, P&lt;0.05). In addition, Npt2a‐I caused higher urinary excretion of calcium (9±1 vs 3±1 μmol*min−1, P&lt;0.05), sodium (316±37 vs 113±24 μmol*min−1, P&lt;0.05), and chloride (277±31 vs 91±24 μmol*min−1, P&lt;0.05), as well as their respective creatinine ratios (Ca2+: 2.5±0.2 vs 0.8±0.1; Na+: 92±9 vs 31±6; Cl−: 81±8 vs 25±6 mmol*mmol−1; all P&lt;0.05). In contrast, urinary flow rate, urinary potassium excretion, potassium/creatinine ratio, and urinary pH were not significantly different between vehicle and Npt2a‐I. In a different set of mice, we studied the effect of Npt2a‐I on plasma phosphate and calcium. Under baseline conditions, plasma phosphate and calcium levels were not significantly different between the vehicle and Npt2a‐I groups. Oral bolus administration of vehicle did not significantly change plasma phosphate (Δ 0.06±0.08 mmol/L, NS) or calcium (Δ −0.04±0.02 mmol/L, NS) 3 hours after application. In contrast, administration of Npt2a‐I caused a significant decrease in plasma phosphate (Δ −0.5±0.05 mmol/L, P&lt;0.05) without affecting plasma calcium (Δ 0.01±0.03 mmol/L, NS). In summary, our study demonstrates for the first time that in vivo application of a novel Npt2a inhibitor efficiently increases urinary phosphate excretion leading to a decrease in plasma phosphate levels. Thus, inhibiting Npt2a might be a useful treatment strategy for hyperphosphatemia.Support or Funding InformationTR is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK110621). JX was supported by an American Heart Association Predoctoral Fellowship (18PRE33990236) and LT by a Postdoctoral Fellowship (19POST34400026).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A15382 Primary Hyperparathyroidism in a Patient with Primary Aldosteronism

Objectives: Primary aldosteronism is sometimes complicated with hyperparathyroidism, which can be classified into secondary hyperparathyroidism due to increased urinary calcium excretion. Low calcium intake has been reported to be a risk of primary hyperparathyroidism, however, it is unclear whether primary aldosteronism is causally related to the occurrence of primary hyperparathyroidism. Herein, we report an interesting case of primary aldosteronism complicated with primary hyperparathyroidism. Methods: This is a case report. Results: A 58-year-old woman, who had a history of parathyroidectomy for primary hyperparathyroidism due to parathyroid adenoma at the age of 43, was admitted for 20-years history of hypertension without remarkable family histories including hypertension. Her hypertension had been gradually worsening and was not improved by the parathyroidectomy. The laboratory findings were as follows: creatinine, 0.61 mg/dL; potassium, 4.0 mEq/L; corrected alcium, 8.9 mg/dL; plasma aldosterone concentration, 156 pg/mL; plasma renin activity, < 0.1 ng/mL/h; intact PTH, 73 pg/mL. Confirmatory tests and adrenal venous sampling revealed idiopathic hyperaldosteronism. Conclusion: We presented a case of primary aldosteronism, who experienced primary hyperparathyroidism. Her hyperaldosteronism might have contributed to the development of primary hyperparathyroidism through high urinary calcium excretion. We may need to carefully consider a possible complication of not only secondary but also primary hyperparathyroidism in patients with primary aldosteronism.

Distinct phenotype of kidney stone formers with renal phosphate leak.

Hypercalciuria is the most frequent metabolic disorder encountered in kidney stone formers (SF). Reduced renal phosphate reabsorption (i.e. renal phosphate leak) was proposed to be a driver of hypercalciuria in calcium SF. However, the phenotype of SF with renal phosphate leak remains poorly defined and the association of renal phosphate leak with stone history, stone composition and bone mineral density (BMD) has not been studied. To fill these knowledge gaps, we conducted a cross-sectional analysis in a cohort of 555 idiopathic calcareous SF. The ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate (TmP/GFR) was used to evaluate renal phosphate transport. Multivariable regression analyses revealed a negative association of parathyroid hormone (PTH), a positive association of 25-hydroxy vitamin D (25(OH)D) and 1,25-dihydroxy vitamin D (1,25(OH)2D) but no association of fibroblast growth factor 23 (FGF23) with TmP/GFR. SF with low TmP/GFR had their first stone event at a younger age and were more likely to have a positive family history of kidney stones. In addition, urinary calcium excretion and prevalence of brushite stones were significantly higher in SF with low TmP/GFR. However, BMD, measured by dual-energy X-ray absorptiometry, was not associated with TmP/GFR in SF. Renal phosphate handling has a strong heritable component in SF and correlates with PTH, 25(OH)D and 1,25(OH)2D, but not with FGF23 levels. Furthermore, a low TmP/GFR (i.e. a renal phosphate leak) is associated with higher urinary calcium excretion and an increased prevalence of brushite stones.

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.

Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria.

Background. Skeletal fragility is a complication of phenylketonuria (PKU). A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF) provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF). Design. In a crossover design, 8 participants with PKU (16–35 y) provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL) of AA-MF and GMP-MF and determined bone mineral density (BMD) measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p = 0.002). Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p = 0.012) and magnesium by 30% (p = 0.029). Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258.

Urinary Calcium Excretion and Risk of Chronic Kidney Disease in the General Population

IntroductionHigh urinary calcium excretion (UCaE) has been shown to lead to accelerated renal function decline in individuals with renal tubular diseases. It is not known whether this association also exists in the general population. Therefore, we investigated whether high UCaE is associated with risk of developing chronic kidney disease (CKD) in community-dwelling subjects.MethodsUrine samples of 5491 subjects who were free of CKD at baseline and participated in the Prevention of Renal and Vascular End-Stage Disease study (a prospective, observational, general population-based cohort of Dutch men and women aged 28–75 years) were examined for UCaE. UCa concentration was measured in two 24-hour urine samples at baseline (1997–1998) by indirect potentiometry. UCaE was treated as a continuous variable and a categorical variable grouped according to sex-specific quintiles for UCaE. UCaE was compared with de novo development of estimated glomerular filtration rate <60 ml/min per 1.73 m2 and/or albuminuria >30 mg/24 h.ResultsBaseline median UCaE was 4.13 mmol/24 h for men and 3.52 mmol/24 h for women. During a median follow-up of 10.3 years, 899 subjects developed CKD. After multivariable adjustment, every 1 mmol/24 h higher baseline UCaE was associated with a 6% lower risk for incident CKD during follow-up (hazard ratio: 0.94 [0.88–0.99], P = 0.02). The association was shown to be significantly nonlinear, with highest risk of CKD in the lowest quintile for UCaE (hazard ratio: 1.28 [0.97–1.68], P = 0.09). There was no association between UCaE and mortality or cardiovascular health during follow-up, suggesting that this association was not a reflection of poor nutritional intake due to bad health.DiscussionThese findings indicate that high UCaE does not increase risk of CKD, but rather that low UCaE may be harmful.

Reduction of Senescence Marker Protein-30 (SMP30) in Male Aging Rats with High Urinary Calcium Excretion by Testosterone Deficiency

Reduction of Senescence Marker Protein-30 (SMP30) in Male Aging Rats with High Urinary Calcium Excretion by Testosterone Deficiency

Hypoparathyroidism and pseudohypoparathyroidism: etiology, laboratory features and complications.

To identify a clinical profile and laboratory findings of a cohort of hypoparathyroidism patients and determine the prevalence and predictors for renal abnormalities. Data from medical records of five different visits were obtained, focusing on therapeutic doses of calcium and vitamin D, on laboratory tests and renal ultrasonography (USG). Fifty-five patients were identified, 42 females and 13 males; mean age of 44.5 and average time of the disease of 11.2 years. The most frequent etiology was post-surgical. Levels of serum calcium and creatinine increased between the first and last visits (p < 0.001 and p < 0.05, respectively); and serum levels of phosphate decreased during the same period (p < 0.001). Out of the 55 patients, 40 had USG, and 10 (25%) presented with kidney calcifications. There was no significant difference in the amount of calcium and vitamin D doses among patients with kidney calcifications and others. No correlation between serum and urinary levels of calcium and the presence of calcification was found. Urinary calcium excretion in 24h was significantly higher in patients with kidney calcification (3.3 mg/kg/d) than in those without calcification (1.8 mg/kg/d) (p < 0.05). The reduction of hypocalcemia and hyperphosphatemia suggest an effectiveness of the treatment, and the increase in serum creatinine demonstrates an impairment of renal function during follow-up. Kidney calcifications were prevalent in this cohort, and higher urinary calcium excretion, even if still within the normal range, was associated with development of calcification. These findings suggest that lower rates of urinary calcium excretion should be aimed for in the management of hypoparathyroidism.

USE OF TERIPARATIDE IN A FOUR YEAR OLD PATIENT WITH AUTOSOMAL DOMINANT HYPOCALCAEMIA

AimWe report the effective use of the synthetic parathyroid hormone (PTH) teriparatide to treat a 4 year old boy with autosomal dominant hypocalcaemia.BackgroundAutosomal Dominant hypocalcaemia is characterised by hypocalcaemia with...

Vitamin-D status and mineral metabolism in two ethnic populations with sarcoidosis

Vitamin-D insufficiency and sarcoidosis are more common and severe in African Americans (AA) than Caucasians. In sarcoidosis, substrate-dependent extrarenal 1,25-dihydroxyvitamin-D (1,25-(OH)2D) production is thought to contribute to hypercalciuria and hypercalcemia,...

Altered TRPV5 Expression in Dahl Salt‐sensitive Rats (LB728)

We have previously shown that urinary calcium excretion is increased in Dahl salt‐sensitive (DS) rats following a high salt diet and this higher urinary calcium excretion is associated with the elevated blood pressure observed in DS following a high salt diet. The mechanism of the calcium loss following a high salt diet is undefined. In this report we investigate whether the transient receptor potential cation channel subfamily V member 5 (TRPV5), a calcium channel protein expressed on the luminal surface of the thick ascending loop and distal tubule and involved in transcellular calcium reabsorption, expression is altered in DS rats. Dahl DS and salt‐resistant (DR) rats were placed on a high (8%) salt diet for one week. At the end of the treatment period kidneys were collected for performing western analysis for TRPV5 protein expression in renal cortical and medullary tissue. Renal medullary TRPV5 protein levels were higher in DS rats (n=3) compared to DR rats (n=3) (1.4 ± 0.3 vs. 0.03 ± 0.03 arbitrary units; p&lt;0.05). There was no difference in renal cortical TRPV5 expression between DS and DR rats. Higher medullary TRPV5 expression in DS rats on a high salt diet suggests that there is a compensatory attempt to increase calcium reabsorption. However, the compensatory increase in TRPV5 does not appear to prevent the increased urinary calcium excretion in DS rats following a high salt diet. Further studies are needed to investigate other renal calcium transporters involved in calcium reabsorption to explain the urinary calcium loss in hypertensive DS rats.Grant Funding Source: Supported by 2P20MD000175 and APS Frontiers in Physiology

Frequency of rare allelic variation in candidate genes among individuals with low and high urinary calcium excretion.

Our study investigated the association of rare allelic variants with extremes of 24-hour urinary calcium excretion because higher urinary calcium excretion is a dominant risk factor for calcium-based kidney stone formation. We resequenced 40 candidate genes potentially related to urinary calcium excretion in individuals from the Nurses' Health Studies I & II and the Health Professionals Follow-up Study. A total of 960 participants were selected based on availability of 24-hour urine collection data and level of urinary calcium excretion (low vs. high). We utilized DNA sample pooling, droplet-based target gene enrichment, multiplexing, and high-throughput sequencing. Approximately 64% of samples (n = 615) showed both successful target enrichment and sequencing data with >20-fold deep coverage. A total of 259 novel allelic variants were identified. None of the rare gene variants (allele frequencies <2%) were found with increased frequency in the low vs. high urinary calcium groups; most of these variants were only observed in single individuals. Unadjusted analysis of variants with allele frequencies ≥2% suggested an association of the Claudin14 SNP rs113831133 with lower urinary calcium excretion (6/520 versus 29/710 haplotypes, P value = 0.003). Our data, together with previous human and animal studies, suggest a possible role for Claudin14 in urinary calcium excretion. Genetic validation studies in larger sample sets will be necessary to confirm our findings for rs113831133. In the tested set of candidate genes, rare allelic variants do not appear to contribute significantly to differences in urinary calcium excretion between individuals.

Differences in 24-Hour Urine Composition Between Apatite and Brushite Stone Formers

To determine the differences in 24-hour urine composition between apatite and brushite stone formers. We conducted a retrospective review of 110 calcium phosphate (CaP) stone formers with both stone composition analysis and 24-hour urinalysis available. Analysis of 24-hour urine constituents between apatite and brushite stone formers was performed using univariable t test and multivariable linear regression models, adjusting for clinical and demographic factors. A total of 97 patients (88%) had predominantly apatite stones and 13 patients (12%) had predominantly brushite stones. In univariable analysis, brushite stone formers had significantly higher mean 24-hour urinary calcium excretion (apatite= 204.8 ± 103.5 mg vs brushite= 329.7± 136.6 mg, P= .007), higher mean super saturation (SS) CaP (apatite= 1.423 ± 0.867 vs brushite= 2.576 ± 0.171, P= .004) and lower mean SS uric acid (apatite= 0.688 ± 0.796 vs brushite= 0.345 ± 0.190, P<.001). Similarly in multivariable analysis, brushite stone formers had significantly higher mean 24-hour urinary calcium excretion (mean difference= 135.1 mg, P<.001) and higher mean SS CaP (mean difference= 1.14, P<.001) but similar mean SS uric acid (mean difference=-0.37, P= .103). All other factors analyzed including body-mass index, urinary pH, volume, oxalate, citrate, sodium, potassium, magnesium, phosphate, chloride, ammonium, sulfate, uric acid, and SS calcium oxalate were similar between both stone groups. In a cohort of CaP stone formers, brushite stones were associated with higher urinary calciumexcretion and higher urinary SS CaP when compared to apatite stones. Aggressive measures toreduce urinary calcium may be particularly helpful to prevent brushite stone formation.

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.

Hypercalciuria and kidney function in children with haemophilia

Adults with haemophilia have a higher incidence of chronic kidney disease than general male population. We recently showed that children with haemophilia have higher urinary calcium excretion and lower whole body bone mineral density than controls in spite of prophylaxis with the deficient coagulation factor concentrate, serum vitamin D concentrations comparable to those of healthy children and physically active lifestyle. Persistent hypercalciuria may result in nephrocalcinosis and impact renal function. This study sought to assess persistence of urinary calcium excretion and kidney function in children with haemophilia. We investigated retrospectively urinary calcium excretion in 30 children with haemophilia (mean age 12.5years) from consecutive urine samples over a 2-year period. Renal evaluation included blood and urine specimen, blood pressure, and renal ultrasound. High number of children with haemophilia had intermittent hypercalciuria. Hypercalciuria was not associated with age, severity of haemophilia or previous hypercalciuria. Kidney function and renal ultrasound were normal with the exception of suspected kidney stone in one patient with haemophilia and transient hypercalciuria. Vitamin D concentrations improved after the families had received information and recommendations concerning vitamin D substitution. Our findings indicate that haemophilia per se predisposes to hypercalciuria which may in turn affect bone mineral content and kidney function. Whether childhood-onset intermittent hypercalciuria contributes to hypertension and renal complications in adulthood remains to be elucidated in future studies.

Evidence in Favor of a Severely Impaired Net Intestinal Calcium Absorption in Patients with (Early-Stage) Chronic Kidney Disease

Introduction: Calcium and phosphorus are essential to many vital physiological processes. Little is known about the net and fractional intestinal absorption of calcium and phosphorus in patients with chronic kidney disease (CKD) and their clinical and hormonal determinants. Methods: Blood and 24-hour urine samples were collected in 20 healthy volunteers (HV) and 72 stable CKD stage 1–4 patients and analyzed for parameters of mineral metabolism including calcidiol, calcitriol, and parathyroid hormone (PTH). Dietary intake was assessed by dietary history. Results: The 24-hour urinary calcium excretion, as opposed to the phosphorus excretion, showed a stepwise decrease across CKD stages (median of 219, 84, 40, and 22 mg/day in HV and patients with CKD stages 1–2, 3 and 4, respectively). Younger age, high serum calcitriol, and high estimated GFR were associated with a high 24-hour urinary calcium excretion. High serum calcitriol levels and dietary phosphorus intake were associated with a high 24-hour urinary phosphorus excretion. The fractional intestinal calcium absorption, as estimated by the urinary-to-ingested calcium ratio, decreased across CKD stages. Conclusions: The 24-hour urinary excretion of calcium, as opposed to phosphorus, is markedly decreased in CKD, even in early-stage disease. This is partly explained by low calcitriol levels and older age. Assuming a neutral calcium balance at the time of urine collection, we infer that net intestinal calcium absorption may be severely impaired in CKD.

Urinary Parameters as Predictors of Primary Hyperparathyroidism in Patients With Nephrolithiasis

Serum calcium and parathyroid hormone levels are the primary means of evaluating patients for hyperparathyroidism. Whether there are differences in urinary parameters between stone formers with and those without hyperparathyroidism is controversial. In this study we identify urinary parameters that predict primary hyperparathyroidism. From 2001 to 2010 a total of 1,190 adult, noncystine stone forming patients underwent urinary metabolic stone evaluation. Of these patients 34 (3%) underwent parathyroidectomy for primary hyperparathyroidism. Urinary parameters were evaluated as predictors of primary hyperparathyroidism. The most accurate combination of serum and urinary tests and their cutoffs were determined. Stone forming patients with primary hyperparathyroidism were more likely to be women and had higher urinary calcium excretion. Hypercalciuria (aOR 4.38), supersaturation calcium oxalate greater than 10 (aOR 4.27), supersaturation calcium phosphate greater than 2 (aOR 3.64), calcium per kg greater than 4 mg/kg (aOR 8.03) and calcium-to-creatinine ratio greater than 150 mg/gm (aOR 7.07) were significant predictors of primary hyperparathyroidism in separate multivariate models after adjustment. The best accuracy was determined using serum calcium and parathyroid hormone levels with our laboratory cutoffs (AUC 0.984) with a sensitivity of 87%, specificity of 99%, positive predictive value of 79% and negative predictive value of 99.5%. No other factor(s) improved diagnostic accuracy or could replace parathyroid hormone level. Greater urinary calcium excretion predicted primary hyperparathyroidism. Serum calcium with parathyroid hormone level was the most accurate test for primary hyperparathyroidism. No other serum or urinary parameter improved diagnostic accuracy or could replace parathyroid hormone. There were no obvious cutoffs for any of the urinary parameters that reliably differentiated cases of hyperparathyroidism.