Urinary Calcium Levels Research Articles

O-12 A rare cause of parathyroid hormone independent hypercalcemia: 1,25-(OH)2D-24 Hydroxylase (CYP24A1) deficiency

Abstract Background Common causes of parathyroid hormon (PTH)-independent hypercalcemia in adulthood are malignancy, granulomatous diseases, and endocrinopathies. Loss-of-function mutations of CYP24A1 gene, encoding for 1,25-dihydroxyvitamin D3 24-hydroxylase, can also be a rare cause of supressed intact PTH levels, usually associated with, nephrolithiasis and nephrocalcinosis. This disease, defined as idiopathic infantile hypercalcemia, classically presents with hypercalcemia in infants. However, some individuals have also been reported with late-onset clinical manifestation or late diagnosis in adulthood. Clinical Case A 59-year-old male patient with a known diagnosis of type 2 diabetes mellitus for 30 years. He had a history of recurrent kidney stones since 2006. His blood and urine tests revealed elevated creatinine level, hypercalcemia with normal phosphorus levels, normal 25-hydroxycholecalciferol levels, suppressed intact PTH level and normal 24-hour urinary calcium level (Table 1). Urinary ultrasonography was consisted with medullary nephrocalcinosis and chronic kidney disease. PTH-independent causes of hypercalcemia were investigated. Malignancies, granulomatous diseases and endocrinopathies were ruled out. The 1,25-dihydroxycholecalciferol level was within the normal range. Parathormone related peptide level was determined as 1.60 pmol/L (normal value <4.2). Genetic workup revealed a homozygous loss-of-function mutation p.E143del in the CYP24A1 gene. Thereupon, genetic screening started on the siblings of the patient which not been finalized yet. However, none of them were found to have hypercalcemia in the laboratory evaluation. Treatment was started with low-dose fluconazole, which inhibits enzymes (including 25-hydroxylases and 1-α-hydroxylase) synthesizing vitamin D. After a month of treatment at a dose of 50 mg/day, no change was observed in the patient's calcium values. Follow-up with calcium-restricted diet and adequate oral hydration therapy was planned. Conclusion Idiopathic infantile hypercalcemia may manifest later or diagnosed later in adulthood. Genetic examination should be considered in adult patients in whom other causes of PTH-independent hypercalcemia have been excluded.Table 1.Patient's laboratory parameters

Effects of Klotho protein, vitamin D, and oxidative stress parameters on urinary stone formation and recurrence.

The present study aimed to investigate the effects of α-Klotho and oxidative stress markers on urinary stone disease (USD) and demonstrate their use as biochemical markers in USD. Among the 90 individuals included, 30 individuals were healthy controls (Group 1), 30 individuals presented with USD for the first time (Group 2), and 30 individuals demonstrated recurrent USD (Group 3). Serum levels of α-Klotho, vitamin D, malondialdehyde (MDA), total oxidant status, and total antioxidant status were determined using spectrophotometry analysis. Serum calcium and parathormone levels and 24-h urine calcium levels were measured via biochemical analysis. No significant intergroup difference was noted in terms of age and sex. The groups had significant differences regarding α-Klotho, oxidative stress index (OSI), MDA, and 24-h urine calcium levels. α-Klotho was a determinant of 24-h urine calcium level and OSI. An increase of 1pg/mL in α-Klotho level appeared to result in a decrease of 8.55mg in 24-h urine calcium level and a decrease of 0.04 Arbitrary Unit in OSI. In patients experiencing USD for the first time, α-Klotho values were < 21.83pg/mL and showed 66% sensitivity and 64% specificity. In individuals with recurrent stone formation, α-Klotho values below 19.41pg/mL had 60% sensitivity and 77% specificity. The biochemical markers investigated herein, i.e., α-Klotho, OSI, and MDA, were involved in the pathogenesis of stone formation and can be used in day-to-day clinical practices of urology clinics to identify patients at risk for both first time and recurrent USD.

A prospective case-control study on the evaluation of oxidative stress in renal stone formers.

Association of increased oxidative stress (OS) with the pathophysiology of renal stone formation has not been explored greatly in the field of urolithiasis. In this prospective case-control study, we measured 24-h urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in patients with urolithiasis and compared them with matched healthy controls. We also measured 24-h urinary uric acid, calcium, oxalate, and citrate levels in patients with renal stone disease and studied their relation with urinary 8-OHdG levels. Seventy-five cases of renal stone disease and 75 well-matched controls were included. Median 24-h urinary 8-OHdG levels were significantly higher in cases compared to controls (7.6 vs. 3.7µg/g of creatinine; p < 0.000). Receiver-operating curve (ROC) analysis for 8-OHdG between cases and controls revealed an area under the curve of 0.90. At 8-OHdG (µg/g of creatinine) value of 5 or more, a sensitivity and a specificity of 84% each were obtained. A positive correlation between 8-OHdG (µg/g of creatinine) and 24-h urinary oxalate level was noted (r = 0.461, p = 0.000). No correlation between 8-OHdG (µg/g of creatinine) and other variables was noted. On multivariate linear regression analysis, we noted 24-h urinary oxalate levels to be an independent predictor of urinary 8-OHdG levels. OS is significantly higher in patients with renal stone diseases compared to healthy controls. Urinary oxalate levels were significantly correlated with urinary 8-OHdG levels.

Molecular docking and in vivo protective effects of okra (Abelmoschus esculentus) against metabolic dysfunction in high-fat, high-sodium diet-fed rats.

Okra pods (Abelmoschus esculentus L. Moench) have been used as a functional vegetable as they contain polysaccharides, flavonoids, and other bioactive molecules that protect the body from several chronic diseases. The purpose of this study was to look at the involvement of okra constituents (mucilage and flesh) in the prevention of metabolic dysfunctions induced in a rat model by a high-fat, high-salt (HF/NaCl) diet. Okra mucilage was extracted using an ultrasonic method, freeze-dried, characterized using Fourier transform infrared (FTIR) and scanning electron microscopy (SEM), and tested for swelling ratio and radical scavenging activity. Okra flesh (skin and seeds) was separated from pods; characterized using SEM; and tested for dietary fiber content, phenolic profile, and radical scavenging activity. The significance of okra bioactive compounds in inhibiting human salivary amylase, glutamine : fructose-6-phosphate amidotransferase (GFAT), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) was investigated using molecular docking. Rats were fed an HF/NaCl diet and orally treated daily with freeze-dried okra mucilage or flesh (100 mg per kg body weight) for 8 weeks. Glucose, insulin, inflammatory indicators (CRP, TNF-α, and interleukin 6), oxidative markers (red blood cell lipid peroxidation, glutathione peroxidase, nitric oxide, and superoxide dismutase), lipid profile, estradiol, feces lipids as well as femur and urine calcium were measured. The molecular docking findings showed the interaction of quercetin and chlorogenic acid, which are the most abundant phenolic compounds in okra pods, with the studied proteins, which gives an indication of the mechanism of okra's anti-diabetic, anti-oxidant, and anti-inflammatory effects. Okra mucilage and flesh significantly reduced glucose, insulin, cholesterol, lipid peroxidation, CRP, TNF-α, IL-6, and urine calcium levels while significantly increasing feces lipid and femur calcium levels. The findings suggested that okra mucilage and flesh seem to be promising candidates for protection against metabolic dysfunction.

Correlation of Calcium, Magnesium, Uric Acid and Phosphate Levels in Serum, 24-Hour Urine, and Stone Components in Patients with Urolithiasis: A Cross-sectional Study

Introduction: Urolithiasis is the formation of stony concretions in the bladder or urinary tract. Nearly 10% of the population suffers from urolithiasis, which has a high chance of recurring. Many resources are used to treat urinary stones globally, but the need for prevention has been neglected. Aim: To determine the levels of Calcium (Ca), Phosphorus (P), Uric Acid (UA) and Magnesium (Mg) in the blood and urine of patients with urolithiasis, as well as in urinary stones post-procedure. Materials and Methods: This cross-sectional study was conducted at the Department of General Surgery at the Himalayan Institute of Medical Sciences (HIMS), Swami Ram Nagar, Dehradun, Uttarakhand, India, from November 2021 to October 2022. A total of 80 patients suffering from urolithiasis were involved in the study. Serum and 24-hour urinary samples were collected for quantitative analysis of Mg, Ca, UA and Phosphate (Ph) levels. Urinary stones postsurgery were sent to the biochemistry section of the reference laboratory for semi- quantitative colorimetric determination and morphological analysis. Spearman’s Rank correlation coefficient was used to correlate two quantitative variables and a p-value of &lt;0.05 was considered statistically significant. Results: In the study, 77.5% of the patients were males and 22.5% were females. Based on their fundamental components, a single calcium oxalate calculus was found in 39 patients. The levels of biochemical parameters associated with urinary stones were as follows: Ca component= 38.13±5.53 mg/dL; Mg component= 10.33±4.94 mg/dL; UA= 10.13±9.04 mg/dL; and Ph= 4.55±1.08 mg/dL. A strong positive correlation was observed between serum calcium and stone calcium (r=0.747, p=0.001) and between stone calcium and urine uric acid (r=0.813, p=0.001). Conclusion: A significant relationship was observed between stone calcium and serum calcium.

Correlation of Calcium, Magnesium, Uric Acid and Phosphate Levels in Serum, 24-Hour Urine, and Stone Components in Patients with Urolithiasis: A Cross-sectional Study

Introduction: Urolithiasis is the formation of stony concretions in the bladder or urinary tract. Nearly 10% of the population suffers from urolithiasis, which has a high chance of recurring. Many resources are used to treat urinary stones globally, but the need for prevention has been neglected. Aim: To determine the levels of Calcium (Ca), Phosphorus (P), Uric Acid (UA) and Magnesium (Mg) in the blood and urine of patients with urolithiasis, as well as in urinary stones post-procedure. Materials and Methods: This cross-sectional study was conducted at the Department of General Surgery at the Himalayan Institute of Medical Sciences (HIMS), Swami Ram Nagar, Dehradun, Uttarakhand, India, from November 2021 to October 2022. A total of 80 patients suffering from urolithiasis were involved in the study. Serum and 24-hour urinary samples were collected for quantitative analysis of Mg, Ca, UA and Phosphate (Ph) levels. Urinary stones postsurgery were sent to the biochemistry section of the reference laboratory for semi- quantitative colorimetric determination and morphological analysis. Spearman’s Rank correlation coefficient was used to correlate two quantitative variables and a p-value of &lt;0.05 was considered statistically significant. Results: In the study, 77.5% of the patients were males and 22.5% were females. Based on their fundamental components, a single calcium oxalate calculus was found in 39 patients. The levels of biochemical parameters associated with urinary stones were as follows: Ca component= 38.13±5.53 mg/dL; Mg component= 10.33±4.94 mg/dL; UA= 10.13±9.04 mg/dL; and Ph= 4.55±1.08 mg/dL. A strong positive correlation was observed between serum calcium and stone calcium (r=0.747, p=0.001) and between stone calcium and urine uric acid (r=0.813, p=0.001). Conclusion: A significant relationship was observed between stone calcium and serum calcium.

Abstract B119: First-in-class orally active pharmacological inhibitors of TRPV6 for the treatment of advanced prostate cancer

Abstract The highly calcium selective ion channel TRPV6, has pronouced overexpression in many prostate cancers, is a promotor of prostate cancer growth and has been proposed as a prognostic marker in prostate cancer. A novel series of first-in-class TRPV6 inhibitors has been developed by the Queensland Emory Drug Discovery Initiative (QEDDI), a drug discovery and development group aiming to collaborativey translate academic biomedical research into new medicines. The preclinical lead drug candidate QED-203, is orally active and potently inhibits (low nM) calcium influx mediated by TRPV6 as assessed by both Ca2+ probe and electrophysiology assays, and TRPV6-driven NFAT activation as assessed by a luciferase reporter assay. Using RNAseq and qPCR analysis TRPV6 pharmacological inhibition and/or siRNA-mediated silencing was shown to remodel the expression of genes related to both NFAT and WNT signalling, as well as ER stress and the cell cycle. In prostate cancer cell lines that had increased levels of TRPV6, TRPV6 inhibition promoted cell cycle arrest, decreased proliferation and promoted apoptosis. Proliferation of enzalutamide resistant prostate cancer cell lines was also inhibited by QED-203. QED-203 exhibited greater potency over enzalutamide, darolutamide and apalutamide [androgen receptor targeting agents (ARTA)] in prostate cancer cell lines with clinically relevant AR mutations or those with the ARV7 splice variant. QED-203 appeared well suited to once-a-day oral dosing with a high bioavailability and an advantageous pharmacokinetic profile. In preclinical models, QED-203 was well tolerated in rodents and had similar in vivo efficacy to enzalutamide in a castrated LNCaP mouse model of prostate cancer as assessed by tumour growth and PSA levels. Increases in urine calcium levels and gene expression changes consistent with TRPV6 inhibition in isolated xenograft tumours, confirmed QED-203 TRPV6 target engagement in vivo. These studies suggest that the orally active TRPV6 inhibitor QED-203 represents a first-in-class mechanism to treat prostate cancer patients whose tumours have become resistant to current ARTA therapies. Pharmacological inhibitors of TRPV6, could be particularly valuable during the advanced stages of prostate cancer, where there is a clear unmet clinical need. Citation Format: Gregory Monteith, Kimberley Beaumont, Rebecca Pouwer, Rebecca Farrow, Matthew McLachlan, Mei Yeh, Therese Johnson, Raphael Rahmani, Claire Levrier, Hasanthi Wijesekera, Malika Kumarasiri, Grant Stuchbury, Terrie-Anne Cock, Andrew Harvey, Brian Dymock. First-in-class orally active pharmacological inhibitors of TRPV6 for the treatment of advanced prostate cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B119.

Evaluation of Effect of Rosmarinus officinalis L. on Ethylene Glycol Induced Kidney Stone in Rats

The present study evaluation of effect of Rosmarinus officinalis L. on ethylene glycol induced kidney stone in rats showed that the ethanolic extract of Rosmarinus officinalis possess the diuretic activity and effective in the treatment of kidney stone. The activity was evaluated against ethylene glycol (0.75%) induced kidney stone in albino rats. Animals were divided into five groups, containing six animals in each. Group I serve as normal control and received regular rat food and drinking water ad libitum. Ethylene glycol (0.75%) in drinking water was feed to Groups II to V for induction of renal calculi for 28 days. Group III received standard anti-urolithiasis drug, cystone (750mg/kg body weight) from 15th to till 35th day. Group IV and V received ethanolic extract of Rosmarinus officinalis at dose of 100mg/kg and 200mg/kg respectively from 15th to till 35th day.&#x0D; The serum creatinine level, serum urea level, urine calcium level, protein level in urine, serum uric acid was increased and serum calcium level, protein level in serum was decreased in all experimental groups except normal control group after ethylene glycol administration till day 14.&#x0D; The animals treated on the day 14th with standard drug (Cystone 750mg/kg) and Rosmarinus officinalis extract (100mg/kg and 200mg/kg), were observed significant decreased serum creatinine level, serum urea level, urine calcium level, protein level in urine and serum uric acid and increased serum calcium level, protein level in serum compared to normal control group on the day 28th and 35th.&#x0D; This indicates that the ethanolic extract of Rosmarinus officinalis (200mg/kg) have protective role against kidney stone.&#x0D; Keywords: Kidney Stone, Ethanolic extract, Rosmarinus officinalis, Ethylene glycol, uric acid, creatinine.

THU439 Baby's Coming, Break A Leg! A Case Of Transient Osteoporosis Of The Hip

Abstract Disclosure: A. Khan: None. A. Syeda: None. H.B. Aftab: None. Introduction: Pregnancy-associated osteoporosis (PAO) is a rare condition presenting as fragility fractures usually in the latter part of pregnancy or immediate postpartum period. Vertebral fractures are more commonly reported but femoral fractures have also been described in the literature as a distinct entity: transient osteoporosis of the hip (TOH). We present a case of bilateral (B/L) femoral fractures in a woman during pregnancy and in the postpartum period. Case: A 31-year-old, gravida 1 female developed left leg pain at 26 weeks of gestation. The pain radiated from her left lower back to her left knee. It was severe in intensity resulting in her walking with crutches. Subsequent MRI of the left hip showed subchondral insufficiency fracture of the femoral head with prominent bone marrow edema extending from the head into the femoral neck. She was managed conservatively with non-weight bearing status and oral analgesics. She had an uncomplicated vaginal delivery at 39 weeks of gestation. During the first postpartum week she developed right hip pain. MRI of right hip revealed nondisplaced right femoral head subchondral insufficiency fracture with associated effusion and synovitis. She recovered within the next 3 months with resolution of her pain with conservative management. Other than limited calcium intake in childhood, there were no other identifiable risk factors for osteoporosis. Bone density scan revealed normal Z-scores at the lumbar spine and non-dominant wrist. The hips were not evaluated. Workup for secondary causes of osteoporosis was unremarkable including normal serum calcium, PTH, phosphorus, magnesium, SPEP, tissue transglutaminase antibodies, estradiol, LH, FSH, prolactin levels. However, 24-hour urine calcium level was low at 11 (35-250) mg/24hr. Elevated levels of bone specific alkaline phosphatase and urine N-telopeptide (NTX) were noted at 19.9 (5.3-19.5) mcg/L and 110 (4-64) nM BCE/mM creatinine, respectively. Patient was continued on vitamin D and calcium supplements. She breastfed for the initial 2 months but was advised to stop. At her most recent follow up visit 4 months postpartum patient was doing well. Discussion: TOH is a rare entity, and presentation as B/L femoral fractures is exceedingly rare. During pregnancy and lactation, the skeletal system undergoes bone loss to compensate for the calcium demand of the fetal skeletal system. In TOH, venous stasis from the gravid uterus resulting in bone marrow edema is the proposed mechanism in addition to pregnancy associated bone loss. In our patient, a low 24-hr urine calcium could suggest low calcium intake which could have contributed to the fracture as well. While recurrence of PAO has been described, no recurrence of TOH has been reported in subsequent pregnancies. Our case highlights the importance of keeping this rare entity on the differential in pregnant women presenting with back or hip pain. Presentation: Thursday, June 15, 2023

The effects of Portulaca oleracea extract on 24-hour urine indices in patients with renal stone: A double-blind randomized placebo-controlled clinical trial

Introduction: Portulaca oleracea, or purslane, is a medicinal plant used in traditional medicine, according to its various medical properties, as well as its potential antioxidant and anti-inflammatory properties. Objectives: The present study aimed to investigate the efficacy of P. oleracea powder on 24-hour urine indices in patients with nephrolithiasis and normal kidney function. Patients and Methods: In this randomized clinical trial, eligible patients with nephrolithiasis were randomly assigned to receive P. oleracea or placebo capsules once daily for eight weeks. Twenty-four-hour urine indices, along with serum electrolytes, inflammatory and lipid components were measured, then compared between the two groups at baseline and the end of the trial. Results: A total of 54 patients, including 28 in P. oleracea and 26 in the control groups, were assigned. Their mean age was 42.2±9.8 years; there was no statistically significant difference between the mean age of the P. oleracea and placebo groups (42.1years versus 42.2 years, respectively; P&gt;0.05). After eight weeks, the mean urine citrate level in the Portulaca oleracea subjects (674.82±94.56 mg/24 h) was significantly higher than placebo group subjects (579.19±85.06 mg/24 h; P&lt;0.01). In addition, the mean urine calcium level in the P. oleracea group (176.32±27.40 mg/24 h) was significantly lower compared to the control group (194.26±25.17 mg/24 h; P=0.016). Within the groups, analysis revealed that in subjects in P. oleracea and control groups, mean serum triglyceride (TG) decreased after intervention (P=0.01 and P=0.02, respectively), as well as mean urine citrate level (P&lt;0.01, P=0.01, respectively). Conclusion: The findings show that P. oleracea may be proposed as a medicinal plant that has a preventive effect on kidney stone formation by increasing urine citrate and decreasing urine calcium level. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (identifier: IRCT20170725035305N4; https://en.irct.ir/trial/42388, ethical code; IR.SBMU.MSP. REC.1398.538).

Urinary Calcium Is Associated with Serum Sclerostin among Stone Formers.

Sclerostin plays an important role in bone metabolism and adipose tissue. Animal studies suggest that sclerostin influences urinary calcium (UCa), but this relationship has not been evaluated in stone formers (SFs). We aimed to investigate the association of UCa with serum sclerostin, bone mineral density (BMD), and body composition among SFs. Clinical and laboratorial data were retrieved from medical records. Determinants of UCa were studied using linear regression. A total of 107 SFs (35.8 ± 9.3 years, 54% male) with eGFR 99.8 ± 14.5 mL/min/1.73 were studied. Subjects were split by sex and grouped into tertiles of UCa levels. Men in the highest UCa tertile had higher body mass index (BMI) and serum sclerostin, lower lean mass, and a trend towards higher fat mass. Women in the highest tertile had higher BMI and a trend towards higher serum sclerostin. Hypertension and metabolic syndrome, but not lower BMD, were more prevalent in the highest UCa tertile for both sexes. Sclerostin was positively correlated with fat mass and inversely correlated with lean mass among men, but not among women. BMD corrected for BMI at lumbar spine was inversely associated with UCa in a univariate analysis, but only serum sclerostin, hypertension, and NaCl intake were independent determinants of UCa in the multivariate model. The present findings disclose that in addition to hypertension and salt intake, serum sclerostin is associated with urinary calcium in stone formers, suggesting that in addition to the hormones traditionally thought to alter calcium reabsorption in the kidney, sclerostin may play a significant additional role, warranting further investigation.

Assessment of metabolic risk factors for nephrolithiasis in patients with autosomal dominant polycystic kidney disease: a cross-sectional study.

Nephrolithiasis is more common in autosomal dominant polycystic kidney disease (ADPKD) than in the normal population. We aimed to investigate the anatomical and metabolic factors that may be associated with nephrolithiasis in patients with ADPKD METHODS: In this cross-sectional study, a total of 180 participants were included. Eighty-five patients with ADPKD [42 patients with nephrolithiasis (PKD N +) and 43 without nephrolithiasis (PKD N -)] were recruited. Forty-seven nephrolithiasis patients without ADPKD (N) and 48 healthy controls (HC) were selected as control groups. 24-h urine collections were measured in all participants. 24-h urine citrate, calcium, urate, oxalate, magnesium and sodium, serum electrolytes, and eGFRs were compared. Total kidney volumes were not different between patients with PKD N + and PKD N -. Hypocitraturia was common in all patients with ADPKD (69.4%), and it was not different between PKD N + (76.2%) and PKD N- (62.8%). However, hypocitraturia was statistically higher in PKD N + and PKD N - than in N (38.3%) and HC (12.5%) (p<0.05). 24-h urine calcium, urate, and oxalate levels were similar between PKD N + and PKD N - CONCLUSIONS: Hypocitraturia was found to be significantly higher in patients with ADPKD than in healthy adults and other kidney stone patients.

Ovarian cancer G protein-coupled receptor 1 deficiency exacerbates crystal deposition and kidney injury in oxalate nephropathy in female mice.

Ovarian cancer G protein-coupled receptor 1 (OGR1) (Gpr68) and G protein-coupled receptor 4 (GPR4) (Gpr4) are proton-activated G protein-coupled receptors that are stimulated upon increased extracellular acidity. These receptors have various physiological and pathophysiological roles in renal acid-base physiology, tissue inflammation, and fibrosis among others. Their function in injured renal tissue, however, remains mostly unclear. To address this, we investigated their role in crystalline nephropathy by increasing the oxalate intake of GPR4 KO and OGR1 KO mice. After 10 days of high-oxalate intake and 4 days of recovery, renal crystal content, histopathology, filtration function, and inflammation were assessed. While GPR4 deficiency did not show major alterations in disease progression, OGR1 KO mice had higher urinary calcium levels and exacerbated crystal accumulation accompanied by decreased creatinine clearance and urea excretion and a decreased presence of regulatory T (Treg) cells in kidney tissue. When lowering the severity of the kidney injury, OGR1 KO mice were more prone to develop crystalline nephropathy. In this setting, OGR1 KO mice displayed an increased activation of the immune system and a higher production of proinflammatory cytokines by T cells and macrophages. Taken together, in the acute setting of oxalate-induced nephropathy, the lack of the proton-activated G protein-coupled receptor (GPCR) GPR4 does not influence disease. OGR1 deficiency, however, increases crystal deposition leading to impaired kidney function. Thus, OGR1 may be important to limit kidney crystal deposition, which might subsequently be relevant for the pathophysiology of oxalate kidney stones or other crystallopathies.

Abstract #1407986: Abaloparatide Administration Through the Simplicity Patch: A Therapeutic Option for Refractory Hypoparathyroidism Post-thyroidectomy

Hypoparathyroidism (HPT), characterized by hypocalcemia is typically managed with oral replacement of calcium and vitamin D. Some fail to achieve normocalcemia despite high doses. Such refractory HPT cases have benefited from recombinant PTH (rPTH). Abaloparatide, initially approved for the treatment of osteoporosis, has never been used for refractory HPT. Our case report discusses its administration in refractory HPT through the Simplicity patch. 39 y/o female with iatrogenic HPT failed to achieve normocalcemia despite high doses of vitamin D, calcium supplementation, and rPTH injection. Due to the patient’s recurrent hypocalcemia episodes requiring frequent hospitalizations, we elected to attempt controlling the refractory HPT with a subcutaneous administration of Abaloparatide. A review of the cases that used teriparatide administration through insulin delivery mechanisms was studied meticulously. We opted for Abaloparatide administration via the Simplicity patch. 1mL of Abaloparatide (equivalent to 2000mcg) was transferred to the Simplicity patch so that each click administered a 20mcg dose of Abaloparatide. The patient was closely monitored for 5 days. On day 1, we administered 1 to 2 clicks, spaced 2 hours apart. The patient’s serum calcium levels were carefully monitored with serial calcium profile testing. Over the next 4 days, based on the patient’s response and calcium levels, we created a click-dosing schedule. Her calcium levels were then closely followed weekly for 4 weeks, and monthly thereafter. Two months after the initiation of the therapy, she was able to maintain her calcium levels at 9mg/dl. Follow-up labs indicated better control of the calcium status and we were able to wean off the oral calcium and vitamin D supplementation by end of 4 months. Four months after initiation of Abaloparatide with the Simplicity patch, she was able to sustain normal calcium levels and reported no hypocalcemic events. rPTH(1-84) has been approved for the treatment of chronic refractory HPT since 2015. Studies have compared the use of teriparatide for refractory HPT. Administration of teriparatide as divided doses were associated with better control of calcium levels when compared to once-a-day dosing. Higher calcium levels with fewer fluctuations and normal urinary calcium levels were noted in twice-a-day dosing. Several studies have also explored utilizing insulin pumps to administer continuous infusion of rPTH and noted that it was associated with less fluctuation in their serum calcium levels. Abaloparatide is available as a subcutaneous injection, just like teriparatide. It has never been used for refractory HPT. They have a similar mechanism of action and pharmacokinetics. The ease of using the Simplicity patch, allowed us to divide the doses into a customizable click-dosing schedule. Our patient demonstrated a good response to the click-dosing, without any side effects. With the increasing availability of different insulin delivery mechanisms and newer rPTH, there is a need for large-scale trials to further explore the role of Abaloparatide in the management of chronic HPT, using insulin delivery systems.

Bioactivity of Falkenbergia rufolanosa Methanolic Extract: Assessment of Its Effect on Methyl-Thiophanate Induced Bone and Blood Disorders.

This study aimed to evaluate the potentiality of a mineral and antioxidant-rich methanolic extract of the red marine alga Falkenbergia rufolanosa (FRE) against methyl-thiophanate (MT)-induced toxicity in adult rats. The animals were allocated into four groups: controls, MT (300 mg/kg), MT + FRE, and FRE-treated group for 7 days. Our results demonstrated severe mineral perturbations due to MT treatment, especially in calcium and phosphorus levels in plasma, urine, and bone. Similarly, the hematological analysis revealed increased red blood cells, platelets, and white blood cells associated with striking genotoxicity. Interestingly, a significant rise in lipid peroxidation and advanced oxidation protein products level in erythrocytes and bone were noted. Meanwhile, a depletion of the antioxidant status in both tissues occurred. These biochemical alterations were in harmony with DNA degradation and histological variation in bone and blood. In the other trend, data showed that treatment with alga improved MT-induced hematotoxicity, genotoxicity, and oxidative stress in the blood and bone. Osteo-mineral metabolism and bone histo-architecture were also noted. In conclusion, these findings demonstrated that the red alga Falkenbergia rufolanosa is a potent source of antioxidant and antibacterial agents, as revealed by the in vitro analysis.

The importance of hypophosphatemia in the clinical management of primary hyperparathyroidism.

The levels of serum phosphorus (P) are low or low-normal in primary hyperparathyroidism (PHPT), and there is an inverse relationship between the levels of parathormone (PTH) and P. However, when considering the diagnostic and surgical indication criteria of PHPT, serum P levels are generally ignored. The aim of this study was to retrospectively evaluate the association of serum P levels with the clinical outcomes of PHPT. A retrospective evaluation was made of the data of 424 consecutive patients (370 females, 54 males) with PHPT who presented at our centre. The mean age of the study population was 57 ± 11.68years. The mean P was 2.57 ± 0.53mg/dl. Asymptomatic disease was determined in 199 (47%) patients. Male patients had significantly lower levels of P. Symptomatic patients and patients with renal stones, vitamin D < 20µg/l, calcium level ≥ 11.2mg/dl, 24h urinary calcium > 400mg/day, or hypomagnesemia, were seen to have significantly lower levels of P (p < 0.05). Hypophosphatemia (hypoP) was found in 202 of 424 patients (47%), and these patients had a higher rate of symptomatic disease (63% to 44%, p < .0001). Of the 61 (88%) patients with moderate hypoP, 54 (88%) had at least one of the surgical criteria. A statistically significant increase in the incidence of hypoP was determined in symptomatic and male patients. In the patients with hypoP, serum PTH and urine calcium levels were found to be higher, and lumbar T-scores and serum vitamin D levels were lower. The patients with hypoP had higher rates of renal stones and osteoporosis (p < 0.05). The current study results show that hypoP is associated with a higher risk of osteoporosis and renal stones in PHPT patients. Even if patients are asymptomatic, moderate hypoP may be associated with poor outcomes of PHPT. Therefore, moderate hypoP may be a new criterion for parathyroidectomy, regardless of hypercalcemia level.

Anti-urolithiatic effect of Cucumis melo L. var inodorous in male rats with kidney stones.

Melon seed extracts have high antioxidant activities and are effective against a variety of diseases, including kidney stones. In kidney stone model rats, the anti-urolithiatic effects of the hydro-ethanolic extract of melon seed and potassium citrate were studied and compared. After urolithiasis induction by ethylene glycol, the extract and potassium citrate were treated orally for 38days concurrent with ethylene glycol. Then, urine and kidney sampling were done, and the urinary parameter levels were measured. The melon and potassium citrate treatments reduced the kidney index, the levels of urinary calcium and oxalate, calcium oxalate deposit numbers, the score of crystal deposits, histo-pathological damages, and the score of inflammation in the kidney sections, while elevating the urinary pH, magnesium, and citrate levels, and also the expression of the UMOD, spp1, and reg1 genes in the kidney of treated animals. The effect of potassium citrate is the same as the effect of melon in treated animals. So, their effects could be by normalizing urinary parameters, reducing crystal deposits, excreting small deposits from the kidney, reducing the chance of them being retained in the urinary tract, and elevating the expression of the UMOD, spp1, and reg1 genes, which are involved in kidney stone formation.

Bone turnover markers and bone mineral density in patients with type 2 diabetes

Background: This study was designed in order to evaluate bone and mineral metabolism in type 2 diabetic patients and its relationship with bone mineral density and diabetic microvascular complications. Methods: Forty two type 2 diabetic patients and 23 healthy cases were included in the study. Serum osteocalcin, procollagen type 1 – C peptide (PICP), total and bone specific alkaline phosphatase (bone ALP), urinary deoxypyridinoline (free DPD), parathormone (PTH), serum and urinary calcium and phosphorus levels were measured. Bone mineral densities of all subjects were studied in lumbar vertebra and femur region using dual X-ray absorptiometry (DXA). Results: Serum osteocalcin and bone ALP levels of the diabetics were found to be significantly lower and total alkaline phosphatase and calcium levels were higher in diabetic patients compared to healthy controls, but PICP and free DPD levels were not different between these two groups. There was a positive correlation between PTH levels and urinary DPD excretion. Among diabetics, serum osteocalcin levels increased with the impairment of renal functions. Bone mineral densities were lower in diabetics with worse renal functions. Conclusion: Bone turnover is slow in type 2 diabetes and there is no prominent bone loss related to this condition. PTH is an important factor determining the rate of bone resorption in diabetics. Renal functional impairment is the most important factor affecting the bone mass in type 2 diabetic patients.

Comparison of 24-hour urine composition prior to and after stone removal in nephrolithiasis: a prospective observational study.

To evaluate 24-hour urine composition prior to and after complete stone removal in nephrolithiasis patients to determine potential relationship between kidney stones and patient metabolic status. A prospective observational study was performed with patient enrollment from March 2019 to August 2020. 24-hour urine samples were collected prior to stone removal and 4 weeks after double-J stent removal, and examined the following urinary parameters: volume, creatinine, sodium, calcium, uric acid, citrate, oxalate, potassium, phosphorous, magnesium, and pH value. For each parameter, pairwise t test was performed to compare samples prior to and after stone removal. The number of cases that changed from normal to abnormal or vice versa was also evaluated for each parameter. The study was registered at http://clinicaltrials.gov/ (NCT03846011). A total of 109 patients completed 24-hour urine collections prior to and after stone removal. The urinary calcium and phosphate levels increased significantly after stone removal, showing a mean difference of 0.55 mmol (P=0.015) and 2.35 mmol (P=0.001) respectively. None of the other urinary parameters demonstrated a statistically significant difference when means were compared. The percentage differences for all urinary parameters ranged from 5.4% to 14.1%. The percentages of patients that presented clinically significant changes in urinary parameter values from normal to abnormal or vice versa ranged from 4.6% to 20.1%. Ideally, evaluation of 24-hour urine compositions should be undertaken after total stone removal, especially for patients with calcium stones. For patients who cannot achieve total stone removal, 24-hour urine samples should be thoroughly interpreted as urinary calcium and phosphate levels might be depleted in the presence of urinary stones.

Generation of an induced pluripotent stem cell line CSSi015-A (9553), carrying a point mutation c.2915C > T in the human calcium sensing receptor (CasR) gene

Familial Hypocalciuric Hypercalcemia (FHH1) is a rare autosomal dominant disease with low penetrance, caused by inactivating mutations of the calcium-sensing receptor (CaSR) gene, characterized by significant hypercalcemia, inappropriately normal serum PTH levels and a low urinary calcium level. Human induced pluripotent stem cells (hiPSCs) from a patient carrying a previously identified heterozygous mutation, a p.T972M amino acid substitution in cytoplasmic tail of CasR, were produced using a virus, xeno-free and non-integrative protocol.