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Urinary calcium/creatinine ratio (UCa/Cr) on a single spot urine sample is frequently used in children to evaluate calciuria, but its accuracy to estimate 24-h urinary calcium excretion (24hUCa) has not been properly assessed. We analyzed the correlation between UCa/Cr in various spot samples and 24hUCa among healthy children. A 24-h urine specimen and three spot urine samples (evening, first, and second morning) were collected in a convenience sample of children aged 6 to 16 years (n = 101). Measured 24hUCa was compared with UCa/Cr in each of the three spot samples. The ability of UCa/Cr to discriminate between children with and without hypercalciuria (calciuria > 4 mg/kg/24 h, 1 mmol/kg/24 h) and optimal timing of the spot sample were determined. Eighty-five children completed an adequate 24-h urine collection. Pearson correlation coefficients between the UCa/Cr on the spot sample and 24hUCa were 0.64, 0.71, and 0.52 for the evening, first, and second morning spot samples, respectively. Areas under the ROC curve were 0.90, 0.82, and 0.75, respectively, for the corresponding spot samples.Conclusion: The relatively strong correlation between 24hUCa and UCa/Cr in evening and first morning spot urine samples suggests that these spots could be preferred in clinical practice.Trial registration:ClinicalTrials.gov, NCT02900261, date of trial registration 14 September 2016.What is Known:•Urinary calcium/creatinine ratio on a single spot urine sample is frequently used as a proxy for 24-h urinary calcium excretion.•Correlation of these indicators, including the best timing for spot urine sampling, has not been properly assessed.What is New:•Relatively strong correlations were found between the calcium/creatinine ratio on a single spot urine sample and 24-h urinary calcium excretion in healthy children.•Evening and first morning spot samples had the highest correlation.

Summary The impact of urine calcium on kidney, bone, and cardiovascular systems in osteoporosis is not well-known. In this 7-year-follow-up study, high urine calcium did not affect kidney function but increased risk of kidney stones, while low urine calcium increased cardiovascular diseases. Maintaining normal urine calcium is beneficial for bone health. Purpose Hypercalciuria is common in patients with osteoporosis. However, the long-term effect of urinary calcium excretion (UCaE) on patients’ health is not well-examined. The current study aims to assess the impact of UCaE on kidney, bone, and cardiovascular outcomes in patients with bone biopsy proven osteoporosis. Methods Longitudinal study of all patients with osteoporosis who underwent bone biopsy and 24-h urine collection between 2008 and 2015 in the University of Kentucky. DXA scans, serum markers, kidney function, and cardiovascular events were recorded until last clinic visit in 2021. Exclusion criteria were secondary osteoporosis or conditions that might substantially impact UCaE. The significant results in univariate analysis were confirmed in multi-variable regression models involving clinically important covariates that might impact patients’ outcomes. Results Study included 230 patients with mean follow-up of 7.2 ± 2.9 years. The mean age was 61 years, and the mean eGFR at baseline was 85 ± 19 ml/min/1.73 m 2 . Low bone turnover (LBT) was present in 57% and high bone turnover (HBT) in 43% of patients. Hypercalciuria was found in one-third of patients with no difference between LTB and HTB. UCaE correlated positively with eGFR but did not affect the rate of eGFR decline over time. Higher UCaE predicted kidney stones development. We observed U-shaped effect of UCaE on bone health. Hypercalciuria predicted loss of BMD at all sites, but also hypocalciuria was associated with higher loss in total hip BMD. Upper limb fractures were the most observed fractures, and their incidence was higher in patients with hyper- or hypo-calciuria. Lower UCaE independently predicted development of major adverse cardiac events (MACE) and cardiovascular disease (CVD). Conclusion UCaE correlated with eGFR but it did not affect the change of eGFR over time. Patients with normal UCaE had lower incidence of upper limb fractures and less reduction in BMD. Low UCaE predicted MACE and CVD.

In this single-center, randomized, placebo-controlled, single-blinded, crossover trial (Clinical Trial Registry-India: CTRI/2024/08/090041), we evaluated the efficacy and safety of low-dose hydrochlorothiazide (HCTZ) in adults with nonsurgical hypoparathyroidism (excluding autoimmune and obvious syndromic forms). After stabilization on fixed doses of calcium carbonate and calcitriol under a controlled low-sodium diet, 26 participants received HCTZ (12.5-25 mg/d) or placebo for 7 d, with a 15-d washout before crossover, followed by an optional 4-wk open-label HCTZ extension. The primary outcome was change in serum calcium; secondary outcomes included change in 24-h urinary calcium (UCa), fractional calcium excretion, urinary sodium, and bone turnover markers (β-CTX and P1NP). Compared to baseline (8.61 ± 0.32 mg/dL), serum calcium increased significantly with HCTZ at day 5 (9.01 ± 0.46 mg/dL) and day 8 (9.04 ± 0.52 mg/dL; p < .001), while no significant change occurred with placebo. Hydrochlorothiazide reduced 24-h UCa by −26.3% at day 8 (vs +4.7% with placebo; p < .001). These effects remained robust in sensitivity analyses adjusting for urinary sodium and when expressed per kg body weight. Fractional calcium excretion fell by 29.9% with HCTZ (p < .001). A small but statistically significant decline in serum potassium was observed at day 8 (from 4.18 to 3.95 mEq/L; p < .001), though values remained within the normal range, no participants developed hypokalemia; renal function and intact PTH (iPTH) were stable. During the extension phase, serum calcium levels rose while UCa excretion declined significantly, without any reported adverse effects. These findings indicate that low-dose HCTZ with sodium restriction safely improves calcium homeostasis in nonsurgical hypoparathyroidism—raising serum calcium and reducing calciuria—with good tolerability. Hydrochlorothiazide offers a cost-effective adjunct to standard therapy and warrants further investigation for long-term outcomes.

Primary hyperparathyroidism (PHPT) is characterized by inappropriate secretion of parathyroid hormone, causing hypercalcemia and hypercalciuria, leading to renal stone diseases and nephrocalcinosis. The frequency, risk factors, and curative effect on nephrocalcinosis in post-parathyroidectomy have not been identified yet. Therefore, the present study evaluated the clinico-biochemical, radiological parameters and curative effect on nephrocalcinosis. A total of 583 PHPT patients were analysed in four groups viz. Group 1 (PHPT with nephrocalcinosis-98; 16.8%); Group 2 (PHPT with nephrolithiasis-227; 38.9%); Group 3 (PHPT with both nephrolithiasis and nephrocalcinosis-59; 10.1%); and Group 4 (PHPT without renal diseases-199, 34.1%). In the sub-group analysis, younger age ( p  ≤ 0.05), male gender ( p  ≤ 0.05), and hematuria ( p  ≤ 0.005) were significant in Group 1 vs. Group 4. Dysuria and low eGFR were significant in Group 1 vs. Group 2 ( p  ≤ 0.0005; p  ≤ 0.05) and Group 1 vs. Group 4 ( p  ≤ 0.0005; p  ≤ 0.0005). Polyuria ( p  ≤ 0.05; p  ≤ 0.05, p  ≤ 0.005), and gravluria ( p  ≤ 0.05; p  ≤ 0.0005, p  ≤ 0.005) were frequent in Group 1 vs. other groups. A significant difference was observed in S.Ca and, 24-hrs U.Ca in Group 1 vs. Group 2 {(12.2 (10.8-13.4) vs. 11.2 (10.7–12.4), p  ≤ 0.05; 301 (189.5–465) vs. 180 (92.5-323.1), p  ≤ 0.05} and Group 1 vs. Group 4 {(12.2 (10.8–13.4) vs. 11.4 (10.7–12.5), p  ≤ 0.05 ; 301 (189.5–465) vs. 213 (110-360), p  ≤ 0.0005}. Multivariate logistic regression showed gravluria [aOR = 9.2, p  = 0.0001], S.Ca (aOR = 1.30, p  = 0.003) and, 24-hrs U.Ca (aOR = 1.02, p  = 0.042) to be independent predictors of nephrocalcinosis. Pre and post-operative assessment revealed decreased S. Ca levels [(11.9 ± 1.9) vs. (10.5 ± 1.0) mg/dL; p  = 0.04] and complete radiological resolution (10.4%) in PHPT with nephrocalcinosis. Therefore, serum calcium, 24-hrs Urinary calcium, and gravluria were independent predictors of nephrocalcinosis with 10.4% showing complete radiological resolution post-operatively.

Purpose Herein, we investigated the correlation between urinary calcium excretion (UCaE) and chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). Methods From August 2018 to January 2023, a total of 2031 T2DM patients providing 24-h urine samples were included in the final analyses. Patients were separated into four cohorts, based on the UCaE quartiles. We then analyzed renal functional indicators like estimated glomerular filtration rate (eGFR) and urinary albumin excretion (UAE) among the four groups. Lastly, we utilized multivariable logistic regression models to investigate the correlation between UCaE and CKD. Results After adjusting for confounding factors, we observed a decreasing trend in CKD prevalence (36.3%, 13.0%, 7.5%, and 6.6%, respectively, P  < 0.001) across the UCaE quartiles. Albuminuria (55.5% vs. 40.0%, 36.5%, 37.4%) and macroalbuminuria prevalence (20.0% vs. 9.3%, 5.2%, 5.7%) in the lowest quartile were markedly elevated, compared to the remaining three quartiles ( P  < 0.001). Meanwhile, the eGFR level ( P  < 0.001) showed a clearly increasing trend across the UCaE quartiles, and patients with moderate-to-severe decreases in eGFR levels (with cutoff limits at 30–59, 15–30, and < 15 mL/min/1.73m2) were mostly found in the lowest quartile ( P  < 0.001). Logistic regression analysis revealed that patients in the lowest quartile experienced an enhanced prevalence of CKD, relative to those in the highest quartile (odds ratio: 5.90, 95% confidence interval: 3.60–9.67, P  < 0.001). Conclusion Decreased UCaE was independently associated with the CKD prevalence in T2DM patients.

Abstract The potential of Alhagi maurorum (Boiss.) aqueous extract (AME), used in traditional medicine for treatment or prevention of urolithiasis, to dissolve calcium oxalate stones in vitro was evaluated. In order to determine the litholytic potential of the extract, Calcium oxalate urinary stones were incubated during 12 weeks under continuous shaking in the presence of AME, Rowanix or NaCl 9 g/mL solution were used as controls. After the incubation period, the residual weight of the treated calculi was determined and the rate of dissolution was calculated. The medium pH variation was measured and changes in the calcium oxalate crystals at the stone surface were assessed using a scanning electron microscope (SEM). The results showed a significant dissolution effect for the extract on the kidney calculi during the experimentation period. At the end of the experiment, the percentages of calculi weight decrease were 41.23, 4.97 and 55.67% for the extract, NaCl solution and Rowanix, respectively. Gas Chromatography analysis revealed mainly the presence of the following phyto-compounds: Cyclopropenone, 2,3-diphenyl; 1-Nonadecanol; methyl-alpha-D-mannopyranoside; cis-9-Hexadecenal. These compounds unarguably play crucial roles in the health care system especially in cancer treatment and many other diseases including urolithiasis. The urinary stone dissolution, independent of medium pH, could be attributed to formation of complexes between the phytochemical compounds in the extract and the calculi. Resumo Foi avaliado o potencial do extrato aquoso (AME) de Alhagi maurorum (Boiss.), usado na medicina tradicional para tratamento ou prevenção de urolitíase, para dissolver cálculos de oxalato de cálcio in vitro. Para determinar o potencial litolítico do extrato, cálculos urinários de oxalato de cálcio foram incubados durante 12 semanas sob agitação contínua na presença de AME, Rowanix ou solução de NaCl 9 g/mL foram usados como controles. Após o período de incubação, o peso residual dos cálculos tratados foi determinado e a taxa de dissolução foi calculada. A variação do pH médio foi medida e as alterações nos cristais de oxalato de cálcio na superfície da pedra foram avaliadas usando um microscópio eletrônico de varredura (MEV). Os resultados mostraram um efeito de dissolução significativo para o extrato sobre os cálculos renais durante o período de experimentação. Ao final do experimento, os percentuais de diminuição do peso dos cálculos foram de 41,23, 4,97 e 55,67% para o extrato, solução de NaCl e Rowanix, respectivamente. A análise por cromatografia gasosa revelou principalmente a presença dos seguintes fitocompostos: Ciclopropenona, 2,3-difenil; 1-Nonadecanol; metil-alfa-D-manopiranosídeo; cis-9-hexadecenal. Esses compostos indiscutivelmente desempenham papéis cruciais no sistema de saúde, especialmente no tratamento do câncer e de muitas outras doenças, incluindo urolitíase. A dissolução do cálculo urinário, independente do pH médio, pode ser atribuída à formação de complexos entre os compostos fitoquímicos do extrato e os cálculos.

Background Gitelman Syndrome (GS) is a hereditary tubulopathy associated with a biallelic inactivating mutations of the SLC12A3 gene encoding the thiazide-sensitive sodium-chloride cotransporter (NCCT). The typical clinical manifestation is a hypokalemic metabolic alkalosis with significant hypomagnesemia, and low urinary calcium excretion. Hypocalciuria is widely believed to be a hallmark of GS that distinguishes it from Barter’s syndrome, presenting as hypercalciuria. The pathomechanism of hypocalciuria in GS is not fully elucidated. Up to date, a clinical course of GS with normocalciuria has been reported only in men, while women have a milder course of the disease with typical hypocalciuria, which is believed as the result of sex hormone. Additionally, there is a growing evidence that calcium channels of the distal nephron could be regulated by a variety of hormones, including aldosterone (Aldo). Case presentation We present the case of a 28-year-old Caucasian woman with asymptomatic, chronic hypokalemia, hypomagnesemia, hypochloremic alkalosis and normal urinary calcium excretion. A high renin levels with normal concentration of Aldo in serum have also been found. The values of blood pressure were low. Based on genetic studies, two heterozygous mutations in the trans position were confirmed: c.2186G>T (p.Gly729Val) and c.1247G>C (p.Cys416Ser) in the SLC12A3 gene, which ultimately confirmed the diagnosis of GS. Conclusions We report here the first case of genetically confirmed GS manifested as normocalciuria in a Caucasian woman. Thus, our result does not confirm a role of sex hormones on the level of calciuria. Based on the results of normal Aldo concentration despite high renin level in our patient, we hypothesized that Aldo may be connecting with the level of urinary calcium excretion in patients with the GS.

Osteoporosis is the most common metabolic bone disease and a major public health problem worldwide. Thiazides are widely used as antihypertensive agents with good tolerability and efficacy. Furthermore, thiazides have long been regarded as candidates for the prevention of postmenopausal bone loss. However, there is insufficient evidence that thiazides have a sustained beneficial effect on preserving bone mass and preventing osteoporosis to date. We searched the PubMed, the Cochrane Library, and Embase in June 2018 for randomized controlled trials on the use of thiazides to treat osteoporosis. Continuous outcomes are presented as the standardized mean difference (SMD) and 95% CI. Furthermore, -values <0.05 were considered significant. Five trials with 756 patients were randomly assigned in the five trials included in this meta-analysis. Serum calcium level was higher in the thiazide group than in the control group (SMD 0.33, 95% CI [0.16, 0.50]), and urinary calcium level was significantly lower in the thiazide group (SMD -0.35, 95% CI [-0.52, -0.17]). There was no significant difference in bone mineral density between the two groups (SMD 0.19, 95% CI [-0.16, 0.54]). Thiazides might play a role in preserving bone mass and be effective in the prevention and treatment of osteoporosis. Future high-quality trials are needed to confirm our findings in the future.

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.

PurposeThe recent observation that urinary calcium excretion (UCE) drops considerably with CKD and that this effect may occur beyond compensation for reduced intestinal calcium absorption suggests that CKD per se is a state of sustained positive calcium balance, a mechanism likely to contribute to vascular calcification and CVD in CKD. However, the determinants of UCE reduction in CKD are not well understood and there is a lack of clinical studies, particularly in the CKD population. Therefore, in this study, we aimed to evaluate variables associated with UCE in a CKD cohort.MethodsBaseline data on 356 participants of the Progredir Study, Sao Paulo, Brazil, essentially composed of CKD G3a–G4, were analyzed according to UCE (24 h urine collection).ResultsMedian 24 h UCE was 38 mg/day (IQR 21–68 mg/day) and 0.48 mg/kg/day (IQR 0.28–0.82 mg/kg/day). In univariate analysis, UCE was inversely related to age, phosphorus, 1-84 PTH, FGF-23 and sclerostin, and positively associated with eGFR, DBP, 1,25(OH)2-vitamin D, calcium, bicarbonate, total calorie intake and spironolactone use. After adjustments for age, sex and eGFR, only 1,25(OH)2-vitamin D, calcium, FGF-23, bicarbonate and total calorie intake remained associated with it, but not PTH nor sclerostin. Lastly, in a multivariable model, eGFR, serum 1,25(OH)2-vitamin D, calcium, and FGF-23 remained associated with UCE. Similar results were observed when calcium fractional excretion was used instead of UCE, with eGFR, 1-25-vitamin D and FGF-23 remaining as independent associations.ConclusionOur results showed that CKD is associated with very low levels of UCE and that 1,25(OH)2-vitamin D, serum calcium and FGF-23 were independently associated with UCE in this population, raising the question whether these factors are modulators of the tubular handling of calcium in CKD.