Thiazide Dose, Urine Calcium, and Symptomatic Kidney Stone Events.
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ABSTRACT:
SUBMITTER: Hsi RS
PROVIDER: S-EPMC11342138 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
Publications
Thiazide Dose, Urine Calcium, and Symptomatic Kidney Stone Events.
Hsi Ryan S RS Yan Phyllis L PL Maalouf Naim M NM Best Sara L SL Asplin John R JR Shahinian Vahakn V Hollingsworth John M JM
JAMA network open 20240801 8
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Project description:ObjectiveTo find the optimal characterization of asymptomatic radiographic stone burden on computed tomography (CT) scans.MethodsA survey was sent to stone formers who underwent a CT scan while asymptomatic during a stone clinic evaluation. Symptomatic stone passage events after CT scan were detected by survey and medical record review. Radiographic stone burden was quantified by number of stones, largest stone diameter, automated total stone volume (TSV), and bilateral stones and then compared as predictors of stone events.ResultsThere were 550 stone formers; 43% had a stone event for a median of 4.7 years after the CT scan. Stone burden by quartiles was 0-1, 2-3, 4-6, and ≥7 for number of stones; 0-2, 3-4, 5-7, and ≥8 mm for largest stone diameter; and 0-8, 9-78, 79-280, and ≥281 mm(3) for TSV; 48% had bilateral stones. The hazard ratios (HRs) for symptomatic event was 1.30 (P <.001) for the number of stones per quartile, 1.26 (P <.001) for largest stone diameter per quartile, 1.38 (P <.001) for TSV per quartile, and 1.80 (P <.001) for bilateral stones. On multivariate analysis, only TSV was an independent predictor of symptomatic events (HR, 1.35 per quartile; P = .01). This risk of events with TSV was also independent of demographics, urine chemistries, and stone composition. Among the 53 patients with interim events between CT scans, a rapid increase in TSV between CT scans (>570 mm(3) per year) predicted subsequent events (HR, 2.8; P = .05).ConclusionAutomated TSV is more predictive of symptomatic events than manual methods for quantifying stone burden on CT scan.
| S-EPMC4275381 | biostudies-literature
Project description:BackgroundsPrevious studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs).MethodsBiobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry.ResultsUrine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies.ConclusionsUrinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.
| S-EPMC8170929 | biostudies-literature
Project description:ObjectiveTo determine the variation in kidney stone composition and its association with risk factors and recurrence among first-time stone formers in the general population.Patients and methodsMedical records were manually reviewed and validated for symptomatic kidney stone episodes among Olmsted County, Minnesota, residents from January 1, 1984, through December 31, 2012. Clinical and laboratory characteristics and the risk of symptomatic recurrence were compared between stone compositions.ResultsThere were 2961 validated first-time symptomatic kidney stone formers. Stone composition analysis was obtained in 1508 (51%) at the first episode. Stone formers were divided into the following mutually exclusive groups: any brushite (0.9%), any struvite (0.9%), any uric acid (4.8%), and majority calcium oxalate (76%) or majority hydroxyapatite (18%). Stone composition varied with clinical characteristics. A multivariable model had a 69% probability of correctly estimating stone composition but assuming calcium oxalate monohydrate stone was correct 65% of the time. Symptomatic recurrence at 10 years was approximately 50% for brushite, struvite, and uric acid but approximately 30% for calcium oxalate and hydroxyapatite stones (P<.001). Recurrence was similar across different proportions of calcium oxalate and hydroxyapatite (P for trend=.10). However, among calcium oxalate stones, 10-year recurrence rate ranged from 38% for 100% calcium oxalate dihydrate to 26% for 100% calcium oxalate monohydrate (P for trend=.007).ConclusionCalcium stones are more common (93.5% of stone formers) than has been previously reported. Although clinical and laboratory factors associate with the stone composition, they are of limited utility for estimating stone composition. Rarer stone compositions are more likely to recur.
| S-EPMC4593754 | biostudies-literature
Project description: Not available
| S-EPMC10914189 | biostudies-literature
Project description:Background and objectivesPrior work has suggested a higher risk of hypertension in kidney stone formers but lacked disease validation and adjustment for potential confounders. Certain types of stone formers may also be at higher risk of hypertension.Design, setting, participants, & measurementsIn our study, incident symptomatic stone formers in Olmsted County from 2000 to 2011 were manually validated by chart review and age and sex matched to Olmsted County controls. We followed up patients through November 20, 2015. Hypertension was also validated by manual chart review, and the risk of hypertension in stone formers compared with controls was assessed both univariately and after adjusting for comorbidities. The risk of hypertension among different subtypes of stone formers was also evaluated.ResultsAmong 3023 coded stone formers from 2000 to 2011, a total of 1515 were validated and matched to 1515 controls (mean age was 45 years old, and 56% were men). After excluding those with baseline hypertension (20% of stone formers and 18% of controls), 154 stone formers and 110 controls developed hypertension. Median follow-up time was 7.8 years in stone formers and 9.6 years in controls. Stone formers were found to have a higher risk of hypertension compared with controls (hazard ratio, 1.50; 95% confidence interval, 1.18 to 1.92), even after adjusting for age, sex, body mass index, serum creatinine, CKD, diabetes, gout, coronary artery disease, dyslipidemia, tobacco use, and alcohol abuse (hazard ratio, 1.58; 95% confidence interval, 1.12 to 2.21). Results were similar after excluding patients who were ever on a thiazide diuretic (hazard ratio, 1.65; 95% confidence interval, 1.16 to 2.38). Stone composition, radiographic stone burden, number of subsequent stone events, and stone removal surgeries were not associated with hypertension (P>0.05 for all).ConclusionsThe risk of hypertension was higher after the first symptomatic kidney stone event. However, kidney stone severity, type, and treatment did not associate with hypertension.
| S-EPMC5338710 | biostudies-literature
Project description: Not available
| S-EPMC10476682 | biostudies-literature
Project description:Rational & objectiveDiabetes and uric acid kidney stones are strongly associated. Patients with calcium kidney stones also have higher risk of developing diabetes compared with nonkidney stone patients yet this has not been further investigated. We aimed to characterize insulin resistance in calcium kidney stone patients.Study designObservational.Setting & populationThis study was performed in the University of Chicago Clinical Research Center. Kidney stone patients (N = 42) were selected for having idiopathic hypercalciuria and calcium stones with no other medical conditions, and controls (N = 27) were healthy.ExposuresAll participants presented to the Clinical Research Center in a fasting state and at least 2 timed fasting blood and urine collections were collected before a fixed breakfast. Six additional timed blood and urine collections were performed after breakfast.OutcomesWe compared fasting and fed indices of insulin resistance between the groups.Analytic approachWe used t tests and multivariable linear regression models. A sensitivity analysis removing all patients who had ever been on a thiazide diuretic was also performed.ResultsIn separate multivariable linear models, kidney stone patients had higher fasting serum insulin levels (24 (3-46 pmol/L), P = 0.03) and higher homeostatic model of insulin resistance (HOMA-IR) (1.0 (0.2-1.8), P = 0.02). In separate multivariable linear models, kidney stone patients had higher fed serum glucose levels (10 (2-18 mg/dL), P = 0.01). Results were similar in a sensitivity analysis removing all patients who had ever been on a thiazide diuretic. There were no differences in urine composition based on HOMA-IR levels.LimitationsSingle institution. Small sample size limited subanalyses by different calcium stone types.ConclusionsCalcium kidney stone patients without diabetes or other medical conditions demonstrated signs of insulin resistance compared with healthy matched controls.
| S-EPMC11615144 | biostudies-literature
Project description:ImportanceClinical trial data have called into question the efficacy of thiazide diuretics for the prevention of kidney stones.ObjectiveTo identify whether there is an association between genetic proxies of thiazide diuretics and the risk of kidney stones.Design, setting, and participantsThis genetic association study undertook a mendelian randomization analysis of derived exposures and outcomes from genome-wide association study summary statistics. Genetic proxies of thiazide diuretics were derived from the International Consortium for Blood Pressure. Kidney stone cases and controls were derived from the Million Veteran Program, UK Biobank, and the FinnGen study. These cross-sectional designs do not report a duration of follow-up. Data analysis was performed in May 2023.ExposureGenetic proxies of thiazide diuretics were genetic variants in the thiazide-sensitive sodium chloride cotransporter gene associated with systolic blood pressure. Genetic proxies of β-blockers and systolic blood pressure served as negative controls.Main outcomes and measuresThe main outcome was the odds of kidney stones. The secondary outcomes were serum laboratory values relevant to the treatment of kidney stones.ResultsThe main analysis included up to 1 079 657 individuals, including 50 832 kidney stone cases and 1 028 825 controls. In a meta-analysis of all cohorts, genetic proxies of thiazide diuretics were associated with a lower odds of kidney stones (OR, 0.85; 95% CI, 0.81-0.89; P < .001). Genetic proxies of β-blockers (OR, 1.02; 95% CI, 0.96-1.07; P = .52) and systolic blood pressure (OR, 1.00; 95% CI, 1.00-1.01; P = .49) were not associated with kidney stones. Genetic proxies of thiazide diuretics were associated with higher serum calcium (β [SE], 0.051 [0.0092]; P < .001) and total cholesterol (β [SE], 0.065 [0.015]; P < .001), but lower serum potassium (β [SE], -0.073 [0.022]; P < .001).Conclusions and relevanceIn this genetic association study, genetic proxies of thiazide diuretics were associated with reduced kidney stone risk. This finding reflects a drug effect over the course of a lifetime, unconstrained by the limited follow-up period of clinical trials.
| S-EPMC10646726 | biostudies-literature
Project description:Escherichia coli is the most common bacterium isolated from urine and stone matrix of calcium oxalate (CaOx) stone formers. Whether it has pathogenic role(s) in kidney stone formation or is only entrapped inside the stone remains unclear. We thus evaluated differences between E. coli isolated from urine of patients with kidney stone (EUK) and that from patients with urinary tract infection (UTI) without stone (EUU). From 100 stone formers and 200 UTI patients, only four pairs of EUK/EUU isolates had identical antimicrobial susceptibility patterns. Proteomic analysis revealed nine common differentially expressed proteins. Among these, the greater level of elongation factor Tu (EF-Tu) in EUK was validated by Western blotting. Outer membrane vesicles (OMVs) derived from EUK had greater promoting activities on CaOx crystallization, crystal growth and aggregation as compared to those derived from EUU. Neutralizing the OMVs of EUK with monoclonal anti-EF-Tu antibody, not with an isotype antibody, significantly reduced all these OMVs-induced promoting effects. Moreover, immunofluorescence staining of EF-Tu on bacterial cell surface confirmed the greater expression of surface EF-Tu on EUK (vs. EUU). Our data indicate that surface EF-Tu and OMVs play significant roles in promoting activities of E. coli on CaOx crystallization, crystal growth and aggregation.
| S-EPMC5462744 | biostudies-literature
Project description:PurposeThis study aimed to assess whether kidney stone burden and risk factors at the time of kidney donor evaluation were associated with a symptomatic stone event post-donor evaluation.MethodsWe identified adults evaluated at Mayo Clinic (two sites) (2000-2011) for living kidney donation and had either a personal history or radiological evidence of kidney stone disease. We analyzed demographics, stone risk factors, stone number/size, and the committee's donation decision and reasons. A follow-up survey (2022-2023) assessed post-evaluation symptomatic kidney stones and related morbidity.ResultsAmong 412 potential donors with kidney stone disease, 258 donated, 75 did not donate due to kidney stones, and 79 did not donate for other reasons. Multivariable analysis showed that candidates not donating due to stones had higher body mass index (BMI), prior symptomatic kidney stones, multiple stones on imaging, bilateral kidney stones, and diameter of largest stone ≥3 mm. Of 147 who completed the survey, 26 (18%) had a symptomatic kidney stone post-donor evaluation. Younger age (p = 0.031) and multiple stones on imaging (p = 0.02) were significant predictors of post-evaluation symptomatic stones regardless of donation status (p = 0.41).ConclusionsStone burden on imaging and prior symptomatic stone events were associated with not donating. Younger age and stone burden on imaging were the primary risk factors for a symptomatic kidney stone event after donor evaluation.
| S-EPMC11687201 | biostudies-literature