Contrasting Response of Urine Stone Risk to Medical Treatment in Calcium Oxalate versus Calcium Phosphate Stone Formers.
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ABSTRACT:
SUBMITTER: Steely A
PROVIDER: S-EPMC10914189 | biostudies-literature | 2024 Feb
REPOSITORIES: biostudies-literature
Publications
Contrasting Response of Urine Stone Risk to Medical Treatment in Calcium Oxalate versus Calcium Phosphate Stone Formers.
Steely Audrey A Worcester Elaine E Prochaska Megan M
Kidney360 20240122 2
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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: Not available
| S-EPMC10927472 | biostudies-literature
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:BackgroundAnimal models have demonstrated an interactive relationship between the epithelial anion exchanger SLC26A6 and transporter NaDC-1 that regulates citrate and oxalate homeostasis. This relationship is a potential mechanism to protect against kidney stones as higher urine oxalate is accompanied by higher urine citrate but it has not been explored in humans.MethodsWe examined 24-h urine data on 13,155 kidney stone forming patients (SF) from separate datasets at the University of Chicago and Litholink, a national laboratory, and 143 non-kidney stone forming participants (NSF) to examine this relationship in humans. We used multivariate linear regression models to examine the association between oxalate and citrate in all study participants and separately in SF and NSF.ResultsHigher urinary oxalate was associated with higher urinary citrate in both SF and NSF. In NSF, the multivariate adjusted urine citrate excretion was 3.0 (1.5-4.6) (mmol)/creatinine (mmol) per oxalate (mmol)/creatinine (mmol). In SF, the multivariate adjusted urine citrate excretion was 0.3 (0.2-0.4) (mmol)/creatinine (mmol) per oxalate (mmol)/creatinine (mmol).ConclusionsHigher urinary oxalate excretion was associated with higher urinary citrate excretion and this effect was larger in non-kidney stone forming participants compared with those who form kidney stones.
| S-EPMC9814525 | 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: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 characterize the endoscopic and histologic renal papillary lesions in a cohort of uric acid (UA) stone formers (SF).MethodsData were prospectively obtained during percutaneous nephrolithotomy between 2009 and 2013. Renal papillae were endoscopically analyzed to quantitate surface area occupied by plaque or plug, and biopsies were obtained. UA SF were compared with non-SF controls and patients with >50% calcium oxalate (CaOx) in the absence of UA.ResultsThere were 23 UA SF; of which 19 stones (83%) were admixed with CaOx and 4 (17%) were pure. Compared with CaOx SF and controls, UA SF had a higher prevalence of diabetes and obesity, greater serum creatinine and UA levels, lower estimated glomerular filtration rate and urine pH, and elevated UA supersaturation. Characteristics of UA SF were compared with 95 CaOx SF and 19 controls. Overall, 23 (100%) UA SF had endoscopic plaque and 13 (57%) plugs. Endoscopically, UA SF displayed a greater incidence of plugging (57% vs 45% vs 11%; P = .006) relative to CaOx SF and controls. Likewise, UA SF had a greater percentage surface area of plugging (0.1 vs 0.0; P = .002) and plaque (2.0 vs 0.9; P = .006) than controls but similar amounts to CaOx SF. Histologic plugs were similar in UA and CaOx SF, although CaOx SF demonstrated greater interstitial inflammation on endoscopic biopsy.ConclusionUA and CaOx SF have similar amounts of plaque, whereas UA SF have more endoscopic but not histologic collecting duct plugs. These data suggest an overlap between the pathogenesis of UA and CaOx stones. The anchoring site for UA stones remains uncertain.
| S-EPMC4380657 | 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:BackgroundTo explore long-non-coding RNA (lncRNA), microRNA (miRNA) and messenger RNA (mRNA) expression profiles and their biological functions in the urine samples in calcium oxalate (CaOx) patients.MethodsFive CaOx kidney stone patients were recruited in CaOx stone group and six healthy people were included as control group, whose midstream morning urine was collected before the patients were given any medicine on admission. After total RNA was extracted from urine, microarray of miRNA, mRNA and lncRNA were applied to explore their expression variation. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to reveal the gene functions of the dysregulated lncRNA-associated competing endogenous RNA (ceRNA) network. Quantitative real-time PCR were performed on HK-2 cells treated with sodium oxalate (NaOx) to further screen out the differentially expression profiles of these RNAs.ResultsA total of nine miRNAs, 883 mRNAs and 1002 lncRNAs were differentially expressed in urine of CaOx patients compared with normal population. GO analysis revealed that most of mRNAs from ceRNA network were enriched in terms of respiratory burst, regulation of mitophagy, and protein kinase regulator activity. KEGG pathway analysis of these genes related to ceRNA network highlight their critical role in pentose phosphate pathway, glyoxylate and dicarboxylate metabolism, and Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling pathway. Five miRNAs (miR-6796-3p, miR-30d-5p, miR-3192-3p, miR-518b and miR-6776-3p), four mRNAs (NT5E, CDH4, CLEC14A, CCNL1) and six lncRNAs (lnc-TIGD1L2-3, lnc-KIN-1, lnc-FAM72B-4, lnc-EVI5L-1, lnc-SERPINI1-2, lnc-MB-6) from the HK-2 cells induced by NaOx were consistent with the expression changes of microarray results.ConclusionThe differential expressed miRNAs, mRNAs and lncRNAs may be associated with numerous variations of the signaling pathways or regulation of metabolism and kinase activity, providing potential biomarkers for early diagnosis of urolithiasis and new basis for further research of urolithiasis mechanism.
| S-EPMC6489260 | biostudies-literature
Project description: Not available
| S-EPMC10476682 | biostudies-literature