The Conundrum of Alkali Therapy in Calcium Phosphate Stone Formers.
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ABSTRACT:
SUBMITTER: Yau AA
PROVIDER: S-EPMC10927472 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
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The Conundrum of Alkali Therapy in Calcium Phosphate Stone Formers.
Kidney international reports 20231226 3
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Project description: Not available
| S-EPMC10914189 | biostudies-literature
Project description:PurposeTo our knowledge no medication has been shown to be effective for preventing recurrent calcium phosphate urinary stones. Potassium citrate may protect against calcium phosphate stones by enhancing urine citrate excretion and lowering urine calcium but it raises urine pH, which increases calcium phosphate saturation and may negate the beneficial effects. Citric acid can potentially raise urine citrate but not pH and, thus, it may be a useful countermeasure against calcium phosphate stones. We assessed whether these 2 agents could significantly alter urine composition and reduce calcium phosphate saturation.Materials and methodsIn a crossover metabolic study 13 recurrent calcium phosphate stone formers without hypercalciuria were evaluated at the end of 3, 1-week study phases during which they consumed a fixed metabolic diet and received assigned study medications, including citric acid 30 mEq twice daily, potassium citrate 20 mEq twice daily or matching placebo. We collected 24-hour urine specimens to perform urine chemistry studies and calculate calcium phosphate saturation indexes.ResultsUrine parameters did not significantly differ between the citric acid and placebo phases. Potassium citrate significantly increased urine pH, potassium and citrate compared to citric acid and placebo (p <0.01) with a trend toward lower urine calcium (p = 0.062). Brushite saturation was increased by potassium citrate when calculated by the relative supersaturation ratio but not by the saturation index.ConclusionsCitric acid at a dose of 60 mEq per day did not significantly alter urine composition in calcium phosphate stone formers. The long-term impact of potassium citrate on calcium phosphate stone recurrence needs to be studied further.
| S-EPMC6300162 | biostudies-literature
Project description:BackgroundPrevious studies have shown that, compared with non-stone formers, stone formers have a higher papillary density measured with computer tomography (CT) scan. The effect of increased hydration on such papillary density in idiopathic calcium stone formers is not known.MethodsPatients with recurrent calcium oxalate stones undergoing endourological procedures for renal stones at our Institution from June 2013 to June 2014 were considered eligible for enrolment. Enrolled patients underwent a baseline unenhanced CT scan before the urological procedure; after endoscopic removal of their stones, the patients were instructed to drink at least 2 L/day of a hypotonic, oligomineral water low in sodium and minerals (fixed residue at 180 °C < 200 mg/L) for at least 12 months. Finally, the patients underwent a follow-up unenhanced CT scan during hydration regimen.ResultsTwenty-five patients were prospectively enrolled and underwent baseline and follow-up CT scans. At baseline, mean papillary density was 43.2 ± 6.6 Hounsfield Units (HU) (43.2 ± 6.7 for the left kidney and 42.8 ± 7.1 HU for the right kidney). At follow-up and after at least 12 months of hydration regimen, mean papillary density was significantly reduced at 35.4 ± 4.2 HU (35.8 ± 5.0 for the left kidney and 35.1 ± 4.2 HU for the right kidney); the mean difference between baseline and follow-up was - 7.8 HU (95% confidence interval - 10.6 to - 5.1 HU, p < 0.001).ConclusionsIncreased fluid intake in patients with recurrent calcium oxalate stones was associated with a significant reduction in renal papillary density.Trial registrationNCT03343743 , 15/11/2017 (Retrospectively registered).
| S-EPMC6233505 | 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:BackgroundKidney stone formers (SFs) are at increased risk of stroke, myocardial infarction, and atherosclerosis of the carotid and coronary arteries. These cardiovascular and urologic pathologies can result from ectopic biomineral deposition. The objectives of this study are: (I) to evaluate risk factors for ectopic biomineralization, and (II) to characterize the overall burden of ectopic minerals in known SFs compared to non-stone formers (NSFs) matched for these risk factors.MethodsPresence and quantity of biominerals at eight anatomic locations (abdominal aorta, common iliac arteries, pelvic veins, prostate or uterus, mesentery, pancreas, and spleen) were determined in a case control study by retrospective analysis of clinical non-contrast computed tomography scans obtained from 190 SFs and 190 gender- and age-matched NSFs (renal transplant donors). Predictors of biomineralization were determined using negative binomial regression. A subgroup of 140 SFs and 140 NSFs were matched for risk factors for systemic biomineralization, and mineralization was compared between these matched SFs and NSFs using ordinal logistic regression.ResultsHypertension, hyperlipidemia, diabetes mellitus, and smoking were more common amongst SFs. Risk factors for increased systemic biomineralization included history of nephrolithiasis, male gender, older age, and history of hyperlipidemia. When controlling for these comorbidities, SFs had significantly increased biomineralization systemically and at the abdominal aorta, iliac arteries, prostate, mesentery, pancreas, and spleen compared to NSFs.ConclusionsThe current study provides evidence that SFs are at increased risk of biomineralization systemically, independent of common risk factors of atherosclerosis.
| S-EPMC7658123 | biostudies-literature
Project description:BackgroundAccumulated evidences indicate that dysbiosis of the urinary microbiota is associated with kidney stone formation. In the present study, we aimed to investigate the urinary microbiota composition and functionality of patients with calcium oxalate stones and compare it with those of healthy individuals.MethodWe collected bladder urine samples from 68 adult patients with calcium oxalate stones and 54 age-matched healthy controls by transurethral catheterization. 16S rRNA gene and shotgun sequencing were utilized to characterize the urinary microbiota and functionality associated with calcium oxalate stones.ResultsAfter further exclusion, a total of 100 subjects was finally included and analyzed. The diversity of the urinary microbiota in calcium oxalate stone patients was not significantly different from that of healthy controls. However, the urinary microbiota structure of calcium oxalate stone formers significantly differed from that of healthy controls (PERMANOVA, r = 0.026, P = 0.019). Differential representation of bacteria (e.g., Bifidobacterium) and several enriched functional pathways (e.g., threonine biosynthesis) were identified in the urine of calcium oxalate stone patients.ConclusionOur results showed significantly different urinary microbiota structure and several enriched functional pathways in calcium oxalate stone patients, which provide new insight into the pathogenesis of calcium oxalate stones.
| S-EPMC11190077 | biostudies-literature
Project description:Elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D) concentrations have been reported among cohorts of recurrent calcium (Ca) kidney stone-formers and implicated in the pathogenesis of hypercalciuria. Variations in Ca and vitamin D metabolism, and excretion of urinary solutes among first-time male and female Ca stone-formers in the community, however, have not been defined.In a 4-year community-based study we measured serum Ca, phosphorus (P), 25-hydroxyvitamin D (25(OH)D), 1,25(OH)2D, 24,25-dihydroxyvitamin D (24,25(OH)2D), parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF-23) concentrations in first-time Ca stone-formers and age- and gender frequency-matched controls.Serum Ca and 1,25(OH)2D were increased in Ca stone-formers compared to controls (P = 0.01 and P = 0.001). Stone-formers had a lower serum 24,25(OH)2D/25(OH)D ratio compared to controls (P = 0.008). Serum PTH and FGF-23 concentrations were similar in the groups. Urine Ca excretion was similar in the two groups (P = 0.82). In controls, positive associations between serum 25(OH)D and 24,25(OH)2D, FGF-23 and fractional phosphate excretion, and negative associations between serum Ca and PTH, and FGF-23 and 1,25(OH)2D were observed. In SF associations between FGF-23 and fractional phosphate excretion, and FGF-23 and 1,25(OH)2D, were not observed. 1,25(OH)2D concentrations associated more weakly with FGF-23 in SF compared with C (P <0.05).Quantitative differences in serum Ca and 1,25(OH)2D and reductions in 24-hydroxylation of vitamin D metabolites are present in first-time SF and might contribute to first-time stone risk.
| S-EPMC4558059 | biostudies-other
Project description:Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogen-activated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.
| S-EPMC5198277 | biostudies-literature
Project description:ObjectiveTo study the prevalence of, risk factors for, and renal functional consequences of ductal plug formation in idiopathic calcium oxalate (iCaOx) stone formers (SF).Patients and methodsAccessible renal papillae were videotaped to determine the percent surface area (SA) occupied by plaque and ductal plug in a consecutive cohort of iCaOx SF undergoing percutaneous nephrolithotomy for stone removal.ResultsBetween 2009 and 2014, iCaOx SF comprised 96 of 240 enrolled patients. Of these, 41 (43%) had ductal plugs. Mean plaque SA did not differ between the low and high % plug groups (2.1% vs 3.4%, respectively). The amounts of mean % SA plaque and ductal plug were not strongly correlated (Spearman's ρ = 0.12, P = .3). Patients with >1% mean SA plug had a higher urinary pH (median 6.5 vs 6.0, P = .02) and elevated urinary hydroxyapatite supersaturation (median 5.4 vs 3.7 delta G; P = .04). Those with >1% plugging had more extensive ductal dilation (P = .002) compared to those with ≤1%. However, estimated glomerular filtration rate was the same (median 75.4 mL/min/1.73 m(2) vs 74.7 mL/min/1.73 m(2)). Number of prior stone events was associated with mean and maximum papillary SA occupied by plug (P < .05 for both), but not plaque (P = .3 and p = .5, respectively).ConclusionWithin a cohort of iCaOx SF, macroscopic plaque and ductal plugs often coexist. Intraluminal features known to favor calcium phosphate crystallization appear to play a role in plug formation. The pathogenic significance of these plugs remains to be established, although their extent appears to correlate with stone burden.
| S-EPMC5492383 | biostudies-literature
Project description:Here we define precision medicine approaches and discuss how these may be applied to renal stone-formers to optimise diagnosis and a management. Using the gene discovery of monogenic stone disorders as examples, we discuss the benefits of personalising therapies for renal stone-formers to provide improved prevention and treatment of these disorders.
| S-EPMC6373186 | biostudies-literature