Urinary Ca Excretion Research Articles

#370 Macroscopic hematuria-associated severe acute kidney injury from thin basement membrane disease

Abstract Background Macroscopic hematuria-associated acute kidney injury (MH-AKI) is a rare condition reported in IgA nephropathy and others, and the mechanism of renal tubular damage caused by red blood cells in the tubules appears to be similar to that of anticoagulant nephropathy. Case presentation A 66-year-old Japanese woman with no previous medical history was referred to our hospital with anuric severe kidney injury. Seven days earlier, she had transient acute lumbar back pain, which was followed by gradual worsening of malaise and loss of appetite. On admission, her serum BUN was 147.8 mg/dL, serum Cr 18.57 mg/dL, hemoglobin 11.2 g/dL, urinary red blood cells> 100/HPF, urinary protein 28.8 g/gCr, no hydronephrosis in either kidney, but a small stone in the right kidney. After admission, while starting hemodialysis, she was treated with methylprednisone 1000 mg for 3 days followed by prednisone 40 mg/day because of suspected rapidly progressive glomerulonephritis, but both MPO-/PR3-ANCA and anti-GBM antibodies were negative. Renal biopsy from left kidney showed acute tubular injury with large amounts of red blood cells and red blood cell casts filling the distal tubules (Figure), and prednisone was discontinued. Subsequently, urine flowed out with gross hematuria, and her hematuria and renal function improved with increased urine output, and she was weaned from hemodialysis. Electron microscopy showed glomerular thin basement membrane (TBMD) (Figure). Her renal function and hematuria slowly improved and the right kidney stone disappeared. Microscopic hematuria eventually disappeared, and her serum Cr level was 1.1 mg/dL one year after onset. Conclusions This is the first report of MH-AKI in TBMD without a background of anticoagulation, severe thrombocytopaenia, or iron overload. In one report, compared to IgA nephropathy, TBMD is associated with increased urinary Ca and uric acid excretion, which is associated with gross hematuria and back pain [1]. In this case of MH-AKI from TBMD, both red blood cells and crystal formation in the tubular lumens may have transiently and synergistically caused renal tubular obstruction and heme iron-induced tubular damage.

Urinary Silicon Excretion in Relation to Lactation and Bone Mineral Density - a Longitudinal Study Post-partum.

Silicon (Si) may be a mineral beneficial for bone health. Pregnancy and lactation have major impacts on maternal bone metabolism as bone minerals, including calcium (Ca), are required for growth of the foetus and for milk production. Like urinary Ca excretion, Si excretion has been reported to be high in pregnant women, but there are no data post-partum and during lactation. The aim of the present study was to investigate the urinary excretion of Si (U-Si), from the third trimester of pregnancy until 18 months post-partum, and in relation to the length of lactation, to determine if changes in U-Si are associated with changes in areal bone mineral density (aBMD). This longitudinal study included 81 pregnant women, of whom 56 completed the study. Spot urine samples were collected at the third trimester and at 0.5, 4, 12, and 18 months post-partum and were analysed for Si and Ca by ICP-OES. The aBMD was measured post-partum at lumbar spine and femoral neck by dual-energy x-ray absorptiometry. Women lactating for 4-8.9 and ≥ 9 months had significantly higher U-Si at 4 months post-partum, compared with the third trimester. No significant longitudinal differences in U-Si were found after correcting for creatinine. Changes in U-Si and in aBMD were not correlated, except at the lumbar spine from 0.5 to 12 months post-partum in the women lactating for 4-8.9 months. Taken together, our results suggest that there is a possibility that U-Si increases post-partum in women lactating for 4 months or longer, although it is not related to changes in aBMD.

Effect of different selenium sources on nutrient digestibility, performance and antioxidant status in Mecheri lambs

An experiment was conducted to determine the effect of different selenium sources on nutrient digestibility, performance and antioxidant status in Mecheri lambs. Mecheri lambs (30) were distributed randomly into five equal groups (Control, T1, T2, T3 and T4) with six lambs in each, on the basis of average body weight (14.1±1.1 kg). The animals in T1, T2, T3 and T4 were given sodium selenite (0.30 ppm), selenocysteine (0.30 ppm), nano selenium (0.30 ppm) and nano selenium (0.15 ppm), respectively for 120 days. The result revealed that DM, OM, CP, EE, CF, NDF, ADF and NFE digestibility were significantly higher for lambs in group T2 and T3 than other groups. T3 group showed highest nitrogen intake, retention and balance. There was no difference in daily intake, faecal and urinary excretion and balance of Ca and P. There was no effect on DM intake but T3 and T4 group showed significant difference in body weight gain, average daily gain and feed conversion ratio between the experimental groups. All sources of Se showed no effect on biochemical parameters. However, T3 group showed significantly lower MDA content in blood and significantly higher activity of GSH-Px and SOD compared to other groups. In conclusion, dietary supplementation of Nano-Se at 0.30 ppm can be used more efficiently to improve the nutrient digestibility, growth performance and antioxidant status in Mecheri lambs.

SAT237 AZP-3601, A Novel PTH 1 Receptor Agonist, Induces Rapid Reduction And Normalization Of Urinary Calcium In Chronic Hypoparathyroid Patients

Abstract Disclosure: L. Figueres: None. I. Takacs: None. E. Mezosi: None. A. Soto: None. P. Kamenicky: None. S. Lemoine: None. F. Borson-Chazot: None. I. Capel: None. M.A. Galvez moreno: None. M. Ovize: Employee; Self; employee. T. OuldRouis: Employee; Self; employee. S. allas: Employee; Self; employee. M. Sumeray: Employee; Self; employee. M. Mannstadt: Consulting Fee; Self; consultant. Background: Conventional therapy with oral calcium (Ca) and active vitamin D (vitD) supplementation for chronic hypoparathyroidism (cHP) can induce or aggravate hypercalciuria and may lead to detrimental long-term renal complications. AZP-3601 is a novel 36-amino-acid peptide designed to activate the R0 conformation of the PTH 1 receptor which produces a prolonged calcemic response despite a short half-life. This phase 2 study examined the effects of AZP-3601 on urinary Ca (uCa) excretion in two consecutive cohorts (C1 and C2) of cHP patients. Methods: Following an optimization period, during which Ca and active vitD doses were adjusted to achieve baseline albumin-adjusted serum calcium within the target range of 7.8 to 9.0 mg/dL, patients received a daily sc. injection of AZP-3601 at initial doses of 20 µg/day (C1) or 10 µg/day (d) (C2), while simultaneously reducing their Ca and active vitD . Subsequent up-titration to a maximum daily dose of 60 µg (C1) or 80 µg(C2) was allowed. Twenty-four-hour urinary Ca excretion (24h-uCa), fractional excretion of Ca (FECa), 24h-urinary phosphate (24h-uP), serum phosphate (sP) were assessed at baseline and at D84. Pooled data from 24 patients who completed the study are presented here. Results: Twenty-four patients (18 women) aged (SD) 56(11) years were taking 0.61(0.26) µg/d active vitD and 1733(1442) mg oral Ca at baseline. At D84 , active vitD and oral Ca were each discontinued in 88% of patients, while mean albumin-adjusted serum calcium remained within the target range. Mean 24h-uCa decreased from 325(172) mg/24h to 207(107) mg/24h and 130(91) mg/24h at D14 and D84, respectively. In 13 patients with hypercalciuria at baseline, we observed a 67% reduction of 24h-uCa at D84 and a normalization of 24h-uCa in 92% of them. From baseline to D84, mean FECa decreased in the entire population and in patients with hypercalciuria. Between baseline to D84, 24h-uP excretion increased from 721(331) mg/24h to 794(238) mg/24h while mean sP decreased from 4.3(0.8) mg/dL to 3.7(0.6) mg/dL. Conclusion: These data demonstrate that AZP-3601 treatment maintained sCa within the target range after withdrawal of conventional therapy likely acting via a potent effect on the tubular reabsorption of calcium. The observed significant improvement in both uCa and sP is expected to translate to a clinically meaningful benefit for cHP patients in the long-term. Presentation: Saturday, June 17, 2023

FRI687 Clinical Relevance Of 24-hour Urine Calcium Measurement In Patients With Primary Hyperparathyroidism (PHPT)

Abstract Disclosure: A. Bhan: None. R. Simon: None. G. Jacobsen: None. A. Yaseen: None. P. Navaratnarajah: None. A. Sweidan: None. S.D. Rao: None. Introduction: PHPT is the third most common endocrine disease and the most common cause of hypercalcemia in outpatient setting, presents with mild to moderate hypercalcemia with unsuppressed or elevated serum PTH levels, and most patients are asymptomatic. A 24-hour urine Ca measurement to exclude both hypo- and hypercalciuria is used to recommend parathyroidectomy. The purpose of our study is to evaluate the clinical relevance of urine Ca measurement in evaluating patients with PHPT. Methods: A retrospective electronic medical record review was performed on all adult patients with PHPT in whom a 24-hour urine Ca was measured between 2015-2019. Patients with secondary HPT, those without a 24-hour urine Ca measurement, and patients with serum Cr >1.5 mg/dl were excluded. Results: 393 patients met inclusion criteria for subsequent analyses. For the entire cohort, mean serum Ca was 10.9 ± 0.6 mg/dl, Cr 0.9 ± 0.2 mg/dl and PTH 111± 65 pg/ml with no significant difference between groups by gender, race, or stone history. Mean urine Ca for the entire cohort was 254 ± 170 mg/day. 46% and 35% had urine Ca >250 or >300 mg/d respectively. Multiple linear regression results indicated that higher serum Ca (p=0.004), lower serum Cr (p<0.001), white race (p<0.001), and higher urine sodium (p<0.001) were all significantly predictive of higher UCa. However, the mean urine Ca did not differ between patients with and without nephrolithiasis (276 ± 182 Vs. 280 ± 247 mg/d; p=0.174). Discussion: The most recent guidelines for the management of asymptomatic PHPT recommend measurement of 24-hour urine Ca in all PHPT patients. However, the validity, sensitivity and specificity of such an approach has never been formally evaluated, considering wide variability of urine Ca excretion in the population and lack of difference in urine Ca between patients with and without nephrolithiasis. Previous guidelines discussed this issue and determined that measurement of a 24-hour urine collection is cumbersome and adds very little to patient management. Our study questions the clinical relevance of re-including 24-hour urine Ca in the latest guidelines. Conclusions: Our study suggests that measurement of 24-hour urine Ca in the routine evaluation of patients with PHPT is unhelpful. Presentation: Friday, June 16, 2023

Negative dietary cation-anion difference and amount of calcium in prepartum diets: Effects on urine and serum minerals

Negative dietary cation-anion difference (DCAD) diets fed prepartum induce a compensated metabolic acidosis, which stimulates metabolic Ca flux before calving and decreases clinical and subclinical hypocalcemia after calving. Effects of low or high dietary Ca in these diets are unclear. Our objective was to determine the effects of inducing a prepartum metabolic acidosis and the amount of dietary Ca on urinary mineral excretion and serum mineral concentrations during the transition period in multiparous Holstein cows (n = 81). Treatment diets fed during the last 28 d before calving were (1) positive DCAD, +6 mEq/100 g of dry matter (DM), target urine pH >7.5, low dietary Ca (0.40% DM; CON); (2) negative DCAD, −24 mEq/100 g of DM, target urine pH 5.5 to 6.0, low dietary Ca (0.40% DM; ND); or (3) negative DCAD, −24 mEq/100 g of DM, target urine pH 5.5 to 6.0, high dietary Ca (2.0% DM; NDCA). Urine was sampled on −21, −14, −7, +1, +2, and +7 d relative to calving. Blood samples were collected on d −30, −21, −14, −7, −4, −2, −1, 0, 1, 2, and 4 relative to parturition. Preplanned treatment contrasts were (1) CON versus ND and NDCA, and (2) ND versus NDCA. Cows fed ND or NDCA had increased urinary volume and excretion of Ca, Cl, and SO4−2, along with decreased excretion of K. Supplementation of Ca to the acidogenic diet increased urinary excretion of Ca at d −21, but this difference lessened as cows approached parturition. Additional Ca increased prepartum urinary excretion of K and Cl. Differences in excretion decreased quickly after parturition, although urinary excretion of Cl remained greater for cows previously fed negative DCAD diets. Acidogenic diets increased serum K and Cl concentrations prepartum. Supplemental Ca decreased serum P relative to ND. During d 0 to 4, serum P and K were greater for cows fed ND or NDCA than for cows fed CON; these differences disappeared by d 4. Acidogenic diets increased serum Ca by increasing Ca flux and excretion in urine. Supplemental Ca in the acidogenic diet modestly increased Ca excretion early in the close-up period.

Macroelement and Microelement Levels in the Urine in Experimental Acanthamoebiasis.

Free-living amoebas can impact the excretion of macroelements and microelements in urine. The aim of the present study was to examine the concentrations of macroelements, including calcium (Ca), phosphorus (P), sodium (Na), potassium (K), and magnesium (Mg), as well as microelements such as manganese (Mn), zinc (Zn), copper (Cu), iron (Fe), and chromium (Cr), in the urine during acanthamoebiasis while considering the host's immunological status. This is the first study to show an increase in urinary excretion of Ca, Mn, Cu, Fe, Na, and Cr, along with a decreased excretion of K, in immunocompetent mice 16 days post Acanthamoeba sp. infection. In the final phase of infection (24 dpi), there was a further decrease in urinary K excretion and a lower level of P in Acanthamoeba sp. infected immunocompetent hosts. During acanthamoebiasis in immunosuppressed hosts, increased excretion of Zn, Fe, and Cr was observed at the beginning of the infection, and increased Na excretion only at 16 days post Acanthamoeba sp. infection. Additionally, host immunosuppression affected the concentration of Fe, Cr, Zn, Cu, Mn, and Ca in urine.

Eucalcemia during lipopolysaccharide challenge in postpartum dairy cows: II. Calcium dynamics

Hypocalcemia induced by immune activation is a conserved response among mammals. Early postpartum cows will experience decreased circulating Ca concentrations following acute immune activation; however, the cause for decreased Ca concentration is unknown. Our objectives were to (1) describe Ca dynamics following an intravenous (IV) LPS challenge in early postpartum cows, and (2) compare inflammatory-induced changes in Ca dynamics between IV Ca-treated cows and control cows. Cows (n = 14, 8 ± 1 d in milk) were enrolled in a matched-pair randomized controlled design to receive IV Ca (IVCa) in a eucalcemic clamp for 12 h, or 0.9% NaCl (CTRL) following an IV LPS infusion (0.040 or 0.045 µg of LPS/kg of body weight over 1 h). During the 24 h following LPS infusion, circulating concentrations of parathyroid hormone and serotonin were measured, serum and urine samples were collected to calculate urinary fractional excretion of Ca (FECa), and fecal samples were collected to calculate Ca apparent digestibility (ADCa) using amylase-treated and ash-corrected undigested neutral detergent fiber after 240 h (uNDFom240) as an internal marker. Changes in Ca intake and milk Ca secretion were also quantified and compared with baseline values. Cows were fasted during challenge and dry matter intake was 20 ± 5% less than baseline values on the day of challenge and did not differ between groups. On the day of challenge, milk Ca concentration increased, but milk yield decreased such that total Ca secreted in milk did not change from baseline. Urine FECa was low overall, but an interaction of treatment and time was identified such that FECa increased in IVCa but decreased in CTRL. Concentrations of parathyroid hormone increased and serotonin decreased following challenge. Fecal dry matter decreased from baseline, but did not differ between 6, 12, and 24 h, and did not differ between groups. An interaction of treatment and time was identified for ADCa and apparent digestibility of dry matter such that digestibility was decreased in CTRL but not IVCa at 6 h. Acute immune activation induced hypocalcemia in CTRL, and although urinary Ca excretion was not a primary cause, it is unclear to what degree hypocalcemia was due to altered ADCa. Eucalcemia appeared to alter adaptations in Ca homeostasis during immune activation as FECa was increased in IVCa animals.

A simple assessment of the effect of strontium on the urinary excretion of calcium in Sprague Dawley rats.

This study was aimed at investigating the impact of varying concentrations of strontium (Sr) on calcium (Ca) excretion via the urine and determine its impact on kidney stone formation. Twenty adult male Sprague Dawley rats weighing between 200 and 300g were selected. The rats were randomly divided into four groups of five. One group was used as a control group while the other three groups were experimental. The diet of the rats was modulated over a 12week period to investigate the impact of Sr on the urinary excretion of Ca. Urinary samples were collected every 2weeks from the rats. The rats were fed water ad libitum. After the study the rats were euthanised and their kidneys harvested. Urine and kidney samples from the rats were analysed using Total Reflection X-Ray Fluorescence (TXRF). In the urine excretion of Ca increased with increased intake of Sr in the diet. Sr excretion via the urine also increased with increased dietary intake. There was a correlation of 0.835 at the significance level of 0.01 between Ca and Sr in the urine. However, for the kidneys, the varying concentration of Sr did not impact the retention of Ca in the kidneys. There was increased retention of Sr in the kidneys with increased dietary intake. In this study an increase of Sr in the diet resulted in an increase in urinary excretion of Ca.

Evaluation of management of patients with postoperative permanent hypoparathyroidism. How close are we to the targets?

Postoperative hypoparathyroidism (PO-HypoPT) is a complication usually seen after thyroid surgery. PO-HypoPT, which lasts longer than 6 months is defined permanently. The aim of this study was to evaluate how close permanent PO-HypoPT patients can approach target values. One hundred seven patients who were followed-up with permanent diagnosis of PO-HypoPT between 2016-2020 were included in the study. The study protocol includes serum albumin corrected total calcium (Alb-sCa), phosphate (P), Ca-P product, and 24 h urine calcium measurements. Laboratory measurements of the patients include the values recorded in 4-year visits and in the last visit. In addition, radiological reports of renal/abdominal ultrasound and cranial tomography examinations performed in our hospital for any reason during this period were also reviewed. When looking at the total measurements in the 4-year period, the Alb-sCa level was below the target in most of the measurements (68.1%). P level was higher than normal in 296 (46.2%) measurements. Twenty-four h urine ca excretion was measured 185 times in total visits, and 81 (43.7%) of these measurements showed hypercalciuric values. The patient's latest visit measurements were evaluated on 4 targets (Alb-sCa, P, Ca-P product and 24 h urine Ca excretion). The number of patients meeting all four targets was only 21 (19.6%). Six (7.5%) patients had kidney stones or nephrocalcinosis. Three (0.09%) patients with imaging had calcification in the basal ganglia. Our study shows that the management of the patients with PO-HypoPT is suboptimal with active vitamin D and cholecalciferol treatment.

Influence of glycoprotein MUC1 on trafficking of the Ca2+-selective ion channels, TRPV5 and TRPV6, and on in vivo calcium homeostasis

Polymorphism of the gene encoding mucin 1 (MUC1) is associated with skeletal and dental phenotypes in human genomic studies. Animals lacking MUC1 exhibit mild reduction in bone density. These phenotypes could be a consequence of modulation of bodily Ca homeostasis by MUC1, as suggested by the previous observation that MUC1 enhances cell surface expression of the Ca2+-selective channel, TRPV5, in cultured unpolarized cells. Using biotinylation of cell surface proteins, we asked whether MUC1 influences endocytosis of TRPV5 and another Ca2+-selective TRP channel, TRPV6, in cultured polarized epithelial cells. Our results indicate that MUC1 reduces endocytosis of both channels, enhancing cell surface expression. Further, we found that mice lacking MUC1 lose apical localization of TRPV5 and TRPV6 in the renal tubular and duodenal epithelium. Females, but not males, lacking MUC1 exhibit reduced blood Ca2+. However, mice lacking MUC1 exhibited no differences in basal urinary Ca excretion or Ca retention in response to PTH receptor signaling, suggesting compensation by transport mechanisms independent of TRPV5 and TRPV6. Finally, humans with autosomal dominant tubulointerstitial kidney disease due to frame-shift mutation of MUC1 (ADTKD-MUC1) exhibit reduced plasma Ca concentrations compared to control individuals with mutations in the gene encoding uromodulin (ADTKD-UMOD), consistent with MUC1 haploinsufficiency causing reduced bodily Ca2+. In summary, our results provide further insight into the role of MUC1 in Ca2+-selective TRP channel endocytosis and the overall effects on Ca concentrations.

Effect of source and amount of vitamin D on serum concentrations and retention of calcium, magnesium, and phosphorus in dairy cows

The objectives of the experiment were to determine the effects of supplementing 2 amounts of 25-hydroxyvitamin D3 (calcidiol; CAL) compared with equal amounts of vitamin D3 (cholecalciferol; CHOL) on serum concentrations, absorptions, and retentions of Ca, Mg, and P in periparturient dairy cows. One hundred seventy-seven (133 parous and 44 nulliparous) pregnant Holstein cows were enrolled in the experiment. Cows were blocked by parity and previous lactation milk yield (parous) or genetic merit for energy-corrected milk yield (nulliparous) and assigned randomly to receive 1 or 3 mg/d of CAL or CHOL in a 2 × 2 factorial arrangement of treatments. Treatments were provided to individual cows as a top-dress to the prepartum diet from 250 d gestation until parturition. The prepartum diet had a dietary cation-anion difference of -128 mEq/kg of dry matter. All cows were fed a common postpartum diet containing 46 μg of vitamin D3/kg of dry matter without further supplementation of treatments. Concentrations of vitamin D metabolites, Ca, Mg, and P in serum were measured pre- and postpartum, in addition to total-tract digestibility and urinary excretion of Ca, Mg, and P in the prepartum period. Feeding 3 mg compared with 1 mg of CAL increased serum 25-hydroxyvitamin D3 (CAL1 = 94 vs. CAL3 = 173 ± 3 ng/mL). In comparison, the increment in serum 25-hydroxyvitamin D3 from feeding 3 mg compared with 1 mg of CHOL was small (CHOL1 = 58 vs. CHOL3 = 64 ± 3 ng/mL). Feeding CAL increased prepartum concentration of P in serum compared with CHOL (CHOL = 1.87 vs. CAL = 2.01 ± 0.02 mM), regardless of the amount fed, but neither source nor amount affected prepartum Ca or Mg in serum. Feeding CAL increased serum Ca and P for the first 11 d postpartum compared with CHOL (CHOL = 2.12 vs. CAL = 2.16 ± 0.01 mM serum Ca; CHOL = 1.70 vs. CAL = 1.78 ± 0.02 mM serum P) but the amount of vitamin D did not affect postpartum concentrations of Ca, Mg, and P in serum. Feeding CAL increased prepartum apparent digestibility of Ca compared with CHOL (CHOL = 26.6 vs. CAL = 33.5 ± 2.8%) but treatments did not affect Ca retention prepartum. Neither source nor amount of vitamin D affected Mg and P apparent digestibility, but CAL decreased the concentration of P excreted in urine during the prepartum period (CHOL = 1.8 vs. CAL = 0.8 ± 0.3 g/d). Calcidiol tended to increase the amount of Ca secreted in colostrum (CHOL = 9.1 vs. CAL = 11.2 ± 0.9 g/d) and Ca excreted in urine postpartum (CHOL = 0.4 vs. CAL = 0.6 ± 0.1 g/d) compared with CHOL. Collectively, feeding CAL at 1 or 3 mg/d compared with CHOL in the last 24 d of gestation is an effective way to increase periparturient serum P concentration and postpartum serum Ca of dairy cows fed a prepartum diet with negative DCAD.

Production, physiological response, and calcium and magnesium balance of lactating Holstein cows fed different sources of supplemental magnesium with or without ruminal buffer

The objective of this study was to evaluate the effects of dietary replacement of magnesium oxide (MgO) with calcium-magnesium hydroxide [CaMg(OH)2] and its interaction with ruminal buffer (sodium sesquicarbonate) supplementation on production, Ca and Mg balance, and overall physiological response of mid-lactation Holstein dairy cows. Sixty cows averaging 40.5 ± 7.0 kg of milk/d were used. Treatments were assigned following a 2 × 2 factorial arrangement: (1) MgO, (2) MgO + buffer, (3) CaMg(OH)2, or (4) CaMg(OH)2 + buffer. Diets were formulated to have 16.5% of crude protein, 1.82 Mcal/kg of net energy for lactation, 0.67% Ca, 0.39% P, and 0.25% Mg, all on a dry matter (DM) basis. Treatments were individually top dressed. Milk production, composition, and DM intake were evaluated. A subsample of 20 cows were randomly selected for the evaluation of Ca and Mg balance, blood gases, and electrolytes. Ruminal fluid was also collected for evaluation of pH and Ca and Mg solubility. Effects of Mg source, buffer, and the interaction Mg source × buffer were analyzed through orthogonal contrasts. An interaction of Mg source × buffer was found for DM intake and feed efficiency, in which cows fed CaMg(OH)2 had a similar feed efficiency regardless of ruminal buffer inclusion; however, when cows were fed MgO, the inclusion of buffer reduced feed efficiency. No effects on body weight and milk yield were observed. Buffer addition tended to increase the concentrations of fat, protein, and solids-not-fat, without affecting the yields of these milk components. Magnesium source and buffer did not affect ruminal fluid, blood, urine, or fecal pH; however, buffer supplementation increased urinary pH. Treatment with CaMg(OH)2 increased blood concentration of HCO3-, total CO2, and base excess compared with cows fed MgO. No differences were observed in the ruminal solubility of Ca and Mg or on milk or urinary Ca and Mg excretion. Greater plasma Mg concentration was observed for animals fed MgO compared with cows fed CaMg(OH)2; however, both sources were above the threshold recommended in the literature for dairy cows. Also, a reduction in fecal Mg excretion was observed in animals fed CaMg(OH)2. In summary, we provide evidence that CaMg(OH)2 could replace MgO without affecting performance, overall physiological response, or Ca and Mg balance of mid-lactating dairy Holstein cows.

Case Report: Hypercalcaemia due to Primary Hyperparathyroidism in Pregnancy

A 34-year-old pregnant patient presented at 6 weeks gestation for routine biochemistry tests with elevated serum calcium levels (measured Ca 2.78 mmol/L and calculated Ca 2.64 mmol/L; RI 2.10 to 2.60 mmol/L) with normal serum albumin (47 g/L; RI 37 – 48 g/L). Subsequent presentations showed persisting high Ca and ionised Ca, with normal serum parathyroid hormone (PTH) (2.7 pmol/L; RI 1.5 – 7.5 pmol/L), serum PO4, vitamin D and normal renal markers. Urine Ca excretion was within reference limits. Following an early miscarriage serum Ca levels normalised while PTH progressively increased. (5.6 at 9 weeks gestation and 7.7 at 13 weeks gestation (1.5 – 75 pmol/L). A parathyroid adenoma was diagnosed on imaging and a left superior parathyroidectomy was performed. Post-operative blood results suggested resolution of hyperparathyroidism. Her second pregnancy too, spontaneously aborted after 6 weeks of gestation despite Ca remaining within normal limits. Thyroid function remained normal, and there was no clinical suspicion of MEN. All other major causes of early pregnancy loss were screened for and excluded. The patient presented again in early pregnancy with no known complication and normal serum PTH (2.1 pmol/L; RI 1.5 – 7.5 pmol/L) and progressed to full term. (Figure 1) shows the measured and calculated serum Ca and PTH levels during the period of testing.

Relationship between Urinary Calcium Excretion and Lower Urinary Tract Symptoms.

To date, few detailed studies have been conducted on the convenient and useful markers for the prevalence of lower urinary tract symptoms (LUTS), including overactive bladder (OAB) and nocturia. A high level of calcium (Ca) excretion (hypercalciuria) is indicative of lifestyle-related diseases such as hypertension, which are associated with the onset of LUTS. Hence, in this study we attempted to clarify the relationship between urinary Ca excretion and OAB, nocturia, and nocturnal polyuria in adults. The present study showed that patients with hypercalciuria frequently experienced OAB, nocturia, and nocturnal polyuria. In addition, this study revealed that the severity of LUTS is significantly associated with urinary Ca excretion and that hypercalciuria is an important risk factor for OAB, nocturia, and nocturnal polyuria.

Effect of vitamin D source and dietary cation-anion difference in peripartum dairy cows on calcium homeostasis and milk production.

The objective of this experiment was to determine the effects of dietary vitamin D source on serum calcium (Ca), urinary Ca excretion, and milk production when fed in combination with a prepartum acidogenic negative dietary cation–anion difference (DCAD) diet. Nonlactating, pregnant multiparous cows (n = 15), balanced for breed (Holstein n = 9 and Jersey n = 6), and previous mature equivalent milk production, were assigned to one of three treatments (five cows/treatment), consisting of a control (PCH; positive DCAD, 8.9 mEq/100 g DM) and two negative DCAD diets (−15.4 mEq/100 g DM), one with vitamin D3 (cholecalciferol; NCH) and one with 25-hydroxyvitamin D3 (calcidiol; NCA; DSM nutritional products). The treatments were formulated to provide 1.95 mg/d of vitamin D and were fed 28 d prior to expected calving date. Delivery of vitamin D sources was accomplished by manufacture of a pellet and 2 kg of these pellets were individually fed simultaneously each day along with 2 kg of ground corn daily at 0800 hours. Negative DCAD treatments were formulated to provide 0.46 kg/d of Animate (Phibro Animal Health) and, if needed, additional Animate was top-dressed at each feeding to achieve a urine pH between 5.5 and 6.0 based on the previous day’s urine pH. Close-up cows had ad libitum access to chopped bermudagrass (Cynodon dactylon L.) hay and hay intake was measured using SmartFeed Pro systems (C-Lock Inc.; Rapid City, SD). Prepartum urine and serum samples were collected weekly and serum was collected 36, 48, and 72 h post-calving. Prepartum dry matter intake (DMI) as a percent of body weight was not (P = 0.66) affected by treatments. Cows fed NCH and NCA had greater (P = 0.02) prepartum serum Ca than PCH and tended to have greater urinary Ca excretions (P = 0.10). Average postpartum serum Ca (mg/dL) was greater (P = 0.05) for cows fed NCH (8.8) compared with PCH (7.8), whereas NCA (8.4) was numerically intermediate and not (P > 0.05) different from either of the other treatments. Postpartum DMI was not affected by treatment (P = 0.39). Daily milk yield (MY) (kg/d) was greatest (P < 0.01) for NCA (37.5) compared with the other treatments and NCH (34.1) was intermediate and greater than PCH (29.9). These results suggest that an acidogenic prepartum diet in combination with vitamin D was effective in maintaining peripartum serum Ca and the 25-hydroxy form of vitamin D improved MY compared with NCH in early lactation.

Novel mutations of the calcium-sensing receptor impede differential diagnosis of primary hyperparathyroidism and familial hypocalciuric hypercalcemia.

Familial hypocalciuric hypercalcemia 1 (FHH1) is an autosomal dominant disorder caused by inactivating mutations in the calcium-sensing receptor (CaSR) gene, commonly leading-in contrast to primary hyperparathyroidism (PHPT)-to asymptomatic hypercalcemia. It is important to establish the correct diagnosis, as surgery may be curative in PHPT, but most likely ineffective in FHH. The study aims to evaluate patients with FHH1, initially misinterpreted as PHPT and some even undergone surgery. CaSR-genotyping was conducted, various biochemical parameters including twenty-four-hour urinary Ca excretion (24hU CE) and the calculated relation of urinary Ca clearance to creatinine clearance (CCCR), type of surgery and 1-year follow-up data of fourteen patients with proven FHH1 were evaluated retrospectively. Genetic analysis revealed a total of nine novel heterozygous variants in the CaSR gene in our study population. Six of fourteen patients (42.9%) underwent surgery for initially suspected PHPT, showing normalized biochemical parameters immediately after surgery. In 1-year follow-up, however, five of six operated patients (83.3%) showed normal parathyroid hormone (PTH), but elevated serum calcium levels. In contrast, only one of the operated patients (16.7%) presented both PTH and serum calcium in the normal range. Histology showed adenoma in three (50%), hyperplasia in two (33.3%), and normal parathyroid tissue in one (16.7%) of the patients. We discovered novel heterozygous variants in the CaSR gene, which considerably impede differential diagnosis of PHPT and FHH1. Furthermore, our results indicate that parathyroid surgery fails to provide long-term benefits for patients with FHH1 and suspected PHPT, even though this coincidence seems to exist.

Short-Term Supplemental Dietary Potassium from Potato and Potassium Gluconate: Effect on Calcium Retention and Urinary pH in Pre-Hypertensive-to-Hypertensive Adults.

Potassium supplementation has been associated with reduced urinary calcium (Ca) excretion and increased Ca balance. Dietary interventions assessing the impact of potassium on bone are lacking. In this secondary analysis of a study designed primarily to determine blood pressure effects, we assessed the effects of potassium intake from potato sources and a potassium supplement on urinary Ca, urine pH, and Ca balance. Thirty men (n = 15) and women (n = 15) with a mean ± SD age and BMI of 48.2 ± 15 years and 31.4 ± 6.1 kg/m2, respectively, were enrolled in a cross-over, randomized control feeding trial. Participants were assigned to a random order of four 16-day dietary potassium interventions including a basal diet (control) of 2300 mg/day (~60 mmol/day) of potassium, and three phases of an additional 1000 mg/day (3300 mg/day(~85 mmol/day) total) of potassium in the form of potatoes (baked, boiled, or pan-heated), French fries (FF), or a potassium (K)-gluconate supplement. Calcium intake for all diets was approximately 700–800 mg/day. Using a mixed model ANOVA there was a significantly lower urinary Ca excretion in the K-gluconate phase (96 ± 10 mg/day) compared to the control (115 ± 10 mg/day; p = 0.027) and potato (114 ± 10 mg/day; p = 0.033). In addition, there was a significant difference in urinary pH between the supplement and control phases (6.54 ± 0.16 vs. 6.08 ± 0.18; p = 0.0036). There were no significant differences in Ca retention. An increased potassium intake via K-gluconate supplementation may favorably influence urinary Ca excretion and urine pH. This trial was registered at ClinicalTrials.gov as NCT02697708.

Effects of Postpartum Supplemental Oral Ca for Dairy Cows Fed Prepartum Dietary Acidogenic Salts

Simple SummaryLow blood calcium after calving is problematic in dairy cows, particularly for older cows and for Jerseys vs. Holsteins. Feeding acidogenic salts before calving and oral Ca supplementation post-calving help mitigate this. We evaluated: (1) a novel approach to delivering acidogenic salts prepartum applicable to small dairies and (2) the combined effects of prepartum acidogenic salts and postpartum oral Ca supplementation for both Holsteins and Jerseys of varying parity. We found this novel approach to providing acidogenic salts to be effective. We also found preliminary evidence that shortening the time of application of this technology may enhance its beneficial effects. Responses to prepartum acidogenic salts and postpartum oral calcium supplementation were very different for second vs. greater than second parity cows. Finally, we found an increased risk of low blood calcium, particularly in older Jersey cows, when either prepartum urinary calcium excretion was low or colostrum production was high.Postpartum hypocalcemia is a problem in dairy cows. Both the Jersey vs. Holstein breed and increasing parity are known risk factors. Our objectives were: (1) to evaluate a simple approach to provide dietary acidogenic salts suitable for application on small dairies and (2) to evaluate the combined effects of degree of acidification and oral Ca supplementation along with breed and parity group on periparturient Ca status of Holstein and Jersey cows. Cows were moved weekly from the far-off dry pen at 260 days pregnant to the close-up pen, where all cows received the acidogenic diets. The diet was offered as a total mixed ration and CaCl2, and our source of acidogenic salts was top-dressed in liquid form and mixed in by hand. Thirty-six cows were blocked by parity group (parity = 2 vs. parity ≥ 3) and breed (Holstein vs. Jersey) and assigned to one of two treatments (no intervention or postpartum oral Ca bolus supplementation) in an alternating fashion, based on expected date of parturition. Urinary acidification appeared complete within 3–4 days. Increased urinary Ca excretion was >93% of maximum from 7–21 days before falling to <5% of maximum by 28 days. Serum Ca concentrations 12–24 h postpartum were lower for Jerseys vs. Holsteins and for parity ≥ 3 vs. parity = 2 cows. Serum Ca over 6–48 h postpartum decreased and increased, respectively, with oral Ca supplementation for parity = 2 and parity ≥ 3 cows. Decreased prepartum urinary Ca excretion and increased colostrum yield appear to be independent risk factors of hypocalcemia for parity ≥ 3 Jerseys.

Tubular calcium, magnesium, and phosphate excretion during therapeutic hypothermia for neonatal hypoxic–ischemic encephalopathy: A prospective study

ObjectivesHypocalcemia, hypomagnesemia, and hyperphosphatemia are common electrolyte disturbances in perinatal asphyxia (PA). Different reasons have been proposed for these electrolyte disturbances. This study investigated the effect of the urinary excretion of calcium (Ca), magnesium (Mg), and phosphorus (P) on the serum levels of these substances in babies who were treated using therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) caused by PA. This study sheds light on the pathophysiology that may cause changes in the serum values of these electrolytes. MethodsThis study included 21 healthy newborns (control group) and 38 patients (HIE group) who had undergone therapeutic hypothermia due to HIE. Only infants with a gestational age of 36 weeks and above and a birth weight of 2000 g and above were evaluated. The urine and serum Ca, Mg, P, and creatinine levels of all infants were evaluated at 24, 48, and 72 h. ResultsThe lower serum Ca value and the higher serum P value of the HIE group were found to be statistically significant compared to the control group (p<0.05). There was no significant difference in serum Mg values between the groups. However, hypomagnesemia was detected in five patients from the HIE group. The urine excretion of FeCa and FeMg at 24 h, and FeP excretion at 48 and 72 h were found to be significantly higher in the HIE group compared to the control group. ConclusionsThis study determined that the urinary excretion of Ca, Mg, and P has an effect on the serum Ca, Mg, and P levels of infants with HIE.