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1.
Urolithiasis ; 52(1): 93, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38888601

ABSTRACT

Alexander Randall first published renal papillary tip findings from stone formers in 1937, paving the way for endoscopic assessment to study stone pathogenesis. We performed a literature search to evaluate the safety of papillary tip biopsy and clinical insights gained from modern renal papillary investigations. A search on the topic of renal papillary biopsy provided an overview of Randall's plaques (RP), classification systems for renal papillary grading, and a summary of procedure type, complications, and outcomes. Within 26 identified manuscripts, 660 individuals underwent papillary tip biopsy percutaneously (n = 562), endoscopically (n = 37), or unspecified (n = 23). Post-operative hemoglobin changes were similar to controls. One individual (0.2%) reported fever > 38°, and long-term mean serum creatinine post-biopsy (n = 32) was unchanged. Biopsies during ureteroscopy or PCNL added ~20-30 min of procedure time. Compared to controls, papillary plaque-containing tissue had upregulation in pro-inflammatory genes, immune cells, and cellular apoptosis. Urinary calcium and papillary plaque coverage were found to differ between RP and non-RP stone formers, suggesting differing underlying pathophysiology for these groups. Two renal papillary scoring systems have been externally validated and are used to classify stone formers. Overall, this review shows that renal papillary biopsies have a low complication profile with high potential for further research. Systematic adaption of a papillary grading scale, newer tissue analysis techniques, and the development of animal models of Randall's plaque may allow further exploration of plaque pathogenesis and identify targets for prevention therapies in patients with nephrolithiasis.


Subject(s)
Kidney Calculi , Humans , Kidney Calculi/pathology , Kidney Calculi/surgery , Kidney Calculi/chemistry , Biopsy/adverse effects , Ureteroscopy/adverse effects , Kidney Medulla/pathology , Nephrolithotomy, Percutaneous/adverse effects , Nephrolithotomy, Percutaneous/methods
2.
Asian J Urol ; 10(3): 246-257, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37538166

ABSTRACT

Objective: Prevalence of kidney stone disease continues to increase globally with recurrence rates between 30% and 50% despite technological and scientific advances. Reduction in recurrence would improve patient outcomes and reduce cost and stone morbidities. Our objective was to review results of experimental studies performed to determine the efficacy of readily available compounds that can be used to prevent recurrence. Methods: All relevant literature up to October 2020, listed in PubMed is reviewed. Results: Clinical guidelines endorse the use of evidence-based medications, such as alkaline agents and thiazides, to reduce urinary mineral supersaturation and recurrence. However, there may be additional steps during stone pathogenesis where medications could moderate stone risk. Idiopathic calcium oxalate stones grow attached to Randall's plaques or plugs. Results of clinical and experimental studies suggest involvement of reactive oxygen species and oxidative stress in the formation of both the plaques and plugs. The renin-angiotensin-aldosterone system (RAAS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mitochondria, and NOD-like receptor pyrin domain containing-3 (NLRP3) inflammasome have all been implicated at specific steps during stone pathogenesis in animal models. Conclusion: In addition to supersaturation-reducing therapies, the use of anti-oxidants, free radical scavengers, and inhibitors of NADPH oxidase, NLRP3 inflammasome, and RAAS may prove beneficial for stone prevention. Compounds such as statins and angiotensin converting enzyme inhibitors are already in use as therapeutics for hypertension and cardio-vascular disease and have previously shown to reduce calcium oxalate nephrolithiasis in rats. Although clinical evidence for their use in stone prevention in humans is limited, experimental data support they be considered along with standard evidence-based medications and clinical expertise when patients are being counselled for stone prevention.

3.
Urology ; 180: 278-284, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37467806

ABSTRACT

OBJECTIVE: To conduct the first study examining the accuracy of ChatGPT, an artificial intelligence (AI) chatbot, derived patient counseling responses based on clinical care guidelines in urology using a validated questionnaire. METHODS: We asked ChatGPT a set of 13 urological guideline-based questions three times. Answers were evaluated for appropriateness and using Brief DISCERN (BD), a validated healthcare information assessment questionnaire. Data analysis included descriptive statistics and Student's t test (SAS Studio). RESULTS: 60% (115/195) of ChatGPT responses were deemed appropriate. Variability existed between responses to the same prompt, with 25% of the 13 question sets having discordant appropriateness designations. The average BD score was 16.8 ± 3.59. Only 7 (54%) of 13 topics and 21 (54%) of 39 responses met the BD cut-off score of ≥16 to denote good-quality content. Appropriateness was associated with higher overall and Relevance domain scores (both P < .01). The lowest BD domain scores were for Source categories, since ChatGPT does not provide references by default. With prompting, 92.3% had ≥1 incorrect, misinterpreted, or nonfunctional citations. CONCLUSION: While ChatGPT provides appropriate responses to urological questions more than half of the time, it misinterprets clinical care guidelines, dismisses important contextual information, conceals its sources, and provides inappropriate references. Chatbot models hold great promise, but users should be cautious when interpreting healthcare-related advice from existing AI models. Additional training and modifications are needed before these AI models will be ready for reliable use by patients and providers.


Subject(s)
Artificial Intelligence , Urology , Humans , Software , Data Analysis , Health Facilities
4.
PLoS One ; 18(5): e0285556, 2023.
Article in English | MEDLINE | ID: mdl-37167324

ABSTRACT

Oxalate oxidase is an enzyme that degrades oxalate and is used in commercial urinary assays to measure oxalate levels. The objective of this study was to establish an enhanced expression system for secretion and purification of oxalate oxidase using Pichia pastoris. A codon optimized synthetic oxalate oxidase gene derived from Hordeum vulgare (barley) was generated and cloned into the pPICZα expression vector downstream of the N-terminal alpha factor secretion signal peptide sequence and used for expression in P. pastoris X-33 strain. A novel chimeric signal peptide consisting of the pre-OST1 sequence fused to pro-αpp8 containing several amino acid substitutions was also generated to enhance secretion. Active enzyme was purified to greater than 90% purity using Q-Sepharose anion exchange chromatography. The purified oxalate oxidase enzyme had an estimated Km value of 256µM, and activity was determined to be 10U/mg. We have developed an enhanced oxalate oxidase expression system and method for purification.


Subject(s)
Hordeum , Hordeum/genetics , Pichia/genetics , Pichia/metabolism , Protein Sorting Signals , Oxalates/metabolism , Recombinant Proteins/genetics , Recombinant Proteins/metabolism
5.
Urolithiasis ; 50(3): 239-247, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35294609

ABSTRACT

Existing animal models of renal oxalate excretion utilize either gut or peritoneal cavity for oxalate absorption. Ex vivo renal perfusion is an established tool for graft preservation. We sought to repurpose this concept to study the early pathogenesis of urinary lithiasis. Juvenile female Yorkshire porcine kidneys were removed laparoscopically and placed on an ex vivo cardiopulmonary bypass circuit utilizing whole-blood based perfusate. Pre-defined goals were identified for each attempt (n = 5) with plans to increase physiologic model complexity. Tissue perfusion and oxygenation were monitored by serial perfusate iSTAT testing. Once steady urine production was achieved, aqueous oxalate was injected into the perfusate. Renal outcomes were assessed by histology and blood/urinary assays. After demonstrating proof-of-concept in early trials, normothermic (37 °C) ex vivo whole-blood perfusion with Steen Solution™ was performed exceeding three hours at physiologic mean arterial pressures. Circuit parameters remained in the physiologic range for electrolytes, temperature, mean arterial pressure, lactate, and pH. Urine was produced in three experiments. Urinary filtrate demonstrated consistently higher urine creatinine compared to perfusate, and arterial perfusate oxalate boluses lead to urinary oxalate spikes followed by continuous oxalate clearance. Histopathologic analysis with H&E and Pizzolato's method staining demonstrated formation of calcium oxalate crystals. In light of these promising metabolite clearances, ex vivo porcine renal perfusion appears to be a feasible alternative to study oxalate excretion. Longer validation studies are necessary to establish this technique as a model for kidney stone pathogenesis.


Subject(s)
Organ Preservation , Oxalates , Animals , Calcium Oxalate/metabolism , Female , Humans , Kidney/metabolism , Male , Organ Preservation/methods , Oxalates/metabolism , Perfusion/methods , Swine
6.
J Urol ; 206(6): 1438-1444, 2021 12.
Article in English | MEDLINE | ID: mdl-34288713

ABSTRACT

PURPOSE: In vitro experiments demonstrate calcium oxalate (CaOx) supersaturation (SS) drives CaOx nucleation and growth. We investigated the link between 24-hour urine SS CaOx and in vivo stone growth through a natural history, imaging study. MATERIALS AND METHODS: Using an institutional review board-approved database, we sought >80% CaOx stone formers who prior to stone intervention obtained 2 separate computerized tomography (CT) scans with at least one 24-hour urine collection between scans. Two blinded reviewers calculated bilateral 3-dimensional stone volume using the Visage 7® region of interest pen tool. CT volume difference was divided by time between scans, and SS CaOx was grouped into low (<5), medium (5-10) and high risk (>10). Statistical significance between groups was assessed by Kruskal-Wallis test. RESULTS: We identified 80 individuals with stone growth measured by 3-dimensional CT (mean ∼7 months between studies). Inter-reviewer reliability of CT volume measurement was well correlated (0.98, Gwet's AC2), and an arbitrator was only needed in 13/160 (8%) cases. Median stone volume growth/year was 15%, 71% and 177% for low, medium and high risk groups, respectively (p <0.001). Despite inter-individual variation, best fit of mean SS CaOx vs stone volume growth was moderately correlated (Spearman's rho=0.53, p <0.001). CONCLUSIONS: In a population of pure CaOx stone formers, increased 24-hour SS CaOx risk was associated with increased in vivo stone growth. Further investigations using CT volumetric stone growth may allow for the noninvasive study of stone growth modulators, improved stone risk prediction and development of a kidney stone simulator.


Subject(s)
Calcium Oxalate/urine , Kidney Calculi/diagnostic imaging , Kidney Calculi/urine , Tomography, X-Ray Computed , Adult , Aged , Calcium Oxalate/analysis , Correlation of Data , Female , Humans , Kidney Calculi/chemistry , Male , Middle Aged , Risk Assessment , Time Factors
7.
Pain Med ; 22(6): 1253-1260, 2021 06 04.
Article in English | MEDLINE | ID: mdl-33537703

ABSTRACT

BACKGROUND: The obturator nerve runs along the posterolateral walls of the bladder and electrosurgical stimulation in this region can result in adductor spasm which can occur suddenly and unexpectedly with potentially catastrophic results. METHODS: Sixty patients were prospectively randomized to receive either a single-injection ultrasound-guided obturator nerve block (ONB) or intravenous rocuronium after induction of general anesthesia (i.e., neuromuscular block [NMB]). The primary objective was to compare the incidence of adductor spasm during posterolateral bladder tumor resection when ONB or NMB was used. Secondary objectives included assessment of fall risk and incidence of adverse events. RESULTS: Five patients in the ONB group and six in the NMB group had nonlateral wall lesions. One patient in the ONB group suffered a cardiac arrest after induction of general anesthesia. Of the remaining 48 patients, six (10.2%) experienced adductor spasm. Most of these patients were in the NMB group (5/24, 20.8%), with only one patient (1/24, 4.2%) experiencing obturator reflex in the ONB group; this difference was not statistically significant (P=0.19). Patients in the ONB group had a greater decrease in mean hip adductor strength. Our study population was found to be at high risk of falls before surgery. There were no statistically significant group differences in the Timed Up and Go test, with time to perform the test increasing in both groups. CONCLUSIONS: Both techniques are safe and efficacious for preventing adductor spasm. Our data and experience suggest that the ONB is relatively easy to perform and should be considered in patients with posterolateral bladder tumors.


Subject(s)
Nerve Block , Neuromuscular Blockade , Urinary Bladder Neoplasms , Humans , Nerve Block/adverse effects , Neuromuscular Blockade/adverse effects , Postural Balance , Spasm , Time and Motion Studies , Urinary Bladder Neoplasms/surgery
8.
Nat Rev Nephrol ; 17(6): 417-433, 2021 06.
Article in English | MEDLINE | ID: mdl-33514941

ABSTRACT

Idiopathic calcium oxalate (CaOx) stones often develop attached to Randall's plaque present on kidney papillary surfaces. Similar to the plaques formed during vascular calcification, Randall's plaques consist of calcium phosphate crystals mixed with an organic matrix that is rich in proteins, such as inter-α-trypsin inhibitor, as well as lipids, and includes membrane-bound vesicles or exosomes, collagen fibres and other components of the extracellular matrix. Kidney tissue surrounding Randall's plaques is associated with the presence of classically activated, pro-inflammatory macrophages (also termed M1) and downregulation of alternatively activated, anti-inflammatory macrophages (also termed M2). In animal models, crystal deposition in the kidneys has been associated with the production of reactive oxygen species, inflammasome activation and increased expression of molecules implicated in the inflammatory cascade, including osteopontin, matrix Gla protein and fetuin A (also known as α2-HS-glycoprotein). Many of these molecules, including osteopontin and matrix Gla protein, are well known inhibitors of vascular calcification. We propose that conditions of urine supersaturation promote kidney damage by inducing the production of reactive oxygen species and oxidative stress, and that the ensuing inflammatory immune response promotes Randall's plaque initiation and calcium stone formation.


Subject(s)
Calcium Oxalate/metabolism , Immunity/immunology , Inflammation/metabolism , Kidney Calculi/etiology , Kidney Medulla/pathology , Animals , Calcium Phosphates/metabolism , Humans , Immunity/physiology , Inflammation/immunology , Inflammation/pathology , Kidney Calculi/immunology , Kidney Calculi/metabolism , Kidney Calculi/pathology , Kidney Medulla/immunology , Kidney Medulla/metabolism
9.
Urol Pract ; 8(1): 23-29, 2021 Jan.
Article in English | MEDLINE | ID: mdl-37145433

ABSTRACT

INTRODUCTION: Based on 2010 American Urological Association recommendations our practice transitioned from sterile to high level disinfection flexible cystoscope reprocessing and from sterile to clean handling practices. We examined symptomatic urinary tract infection rate and cost before and after policy implementation. METHODS: We retrospectively reviewed 30-day outcomes following 1,888 simple cystoscopy encounters that occurred from 2007 to 2010 (sterile, 905) and 2012 to 2015 (high level disinfection, 983) at the Malcom Randall Veterans Affairs Medical Center. We excluded veterans who had recent instrumentation, active or recent urinary tract infection, performed intermittent catheterization, or had complicated cystoscopy (dilation, biopsy etc). Patient/procedural factors and cost were collected and compared between groups. RESULTS: Both cohorts had similar age (mean 68 years), race (Caucasian, 82%), comorbidities (cancer history, 62%; diabetes mellitus, 36%; tobacco use, 24.5%), and cystoscopy procedural indications (cancer surveillance, 50%; hematuria, 34%). Urological complication rate was low between groups (1.43%) with no significant difference in symptomatic urinary tract infection events (0.99% sterile vs 0.51% high level disinfection, p=0.29) or unplanned clinic/emergency department visits (0.66% sterile vs 0.71% high level disinfection, p=0.91). Roughly 95% of the cohorts were given prophylactic antibiotics, most commonly fluoroquinolones (91%). High level disinfection was $82 cheaper per procedure than sterile with most cost disparity stemming from reprocessing. Total savings for our facility by switching to high level disinfection was more than $100,000 annually. CONCLUSIONS: In an older, morbid veteran population receiving centralized care and prophylactic antibiotics we found no difference in symptomatic urinary tract infection or unplanned visits between sterile or high level disinfection techniques. However, high level disinfection was associated with a sizable cost savings, improved clinic workflow, and reduced use of personal protective equipment.

11.
Curr Opin Nephrol Hypertens ; 29(4): 400-406, 2020 07.
Article in English | MEDLINE | ID: mdl-32398610

ABSTRACT

PURPOSE OF REVIEW: The aim of the article is to review studies on bone health and oxalate metabolism/therapeutics in the obese rodent model of Roux-en-Y gastric bypass (RYGB) and examine pathways to decrease procedural morbidity. RECENT FINDINGS: Compared with controls, RYGB rodents have up to 40-fold more fat in their stool (steatorrhea) which positively correlates to increased urinary oxalate. These unabsorbed intestinal fatty acids bind calcium and prevent gut calcium oxalate formation, increasing soluble luminal oxalate availability and absorption (enteric hyperoxaluria). When intraluminal fecal fat exceeded about 175 mg/24 h in our model, more paracellular and transcellular oxalate transport across the distal colon occurred. Increasing dietary calcium and colonization with Oxalobacter formigenes reduced hyperoxaluria, whereas vitamin B6 supplementation did not. RYGB animals, when severely calcium deficient, had bone mineral density loss that could not be rescued with vitamin D supplementation. SUMMARY: The findings of hyperoxaluria, steatorrhea, and decreased bone mineral density are seen in both human and rodent RYGB. Our model suggests that a low-fat, low-oxalate diet combined with calcium supplementation can decrease urinary oxalate and improve skeletal bone health. Our model is a useful tool to study renal and bone RYGB effects. Studies of longer duration are required to further evaluate mechanisms of disease and durability of therapeutics.


Subject(s)
Disease Models, Animal , Gastric Bypass , Hyperoxaluria/metabolism , Animals , Bone Density , Humans , Hyperoxaluria/drug therapy , Hyperoxaluria/etiology , Mice , Rats , Steatorrhea/etiology , Steatorrhea/metabolism
12.
Curr Opin Urol ; 30(2): 183-189, 2020 03.
Article in English | MEDLINE | ID: mdl-31913203

ABSTRACT

PURPOSE OF REVIEW: In addition to traditional risk factors such as low urine volume or hypercalciuria, emerging data suggest that calcium oxalate (CaOx), one of the most common mineral complexes in the urine, elicits a strong immunologic response. This review highlights those studies and projects how future therapies may be directed for kidney stone prevention. RECENT FINDINGS: Over the last 2 years, several groups have studied the response of the immune system to CaOx crystals using cell culture and animal models. Dominguez et al. found that CaOx crystals were recognized by monocytes through an lipopolysaccharide-mediated mechanism, leading to M1 'inflammatory' macrophage phenotype. Patel et al. proposed excessive oxalate-mediated reactive oxygen species within macrophage mitochondria may impair their ability to properly clear stones. Two other groups developed mouse models (an androgen receptor knock-out and an overexpression of Sirtuin 3 protein) and demonstrated increased renal anti-inflammatory macrophage differentiation and decreased CaOx deposition in experimental compared with controls. Anders et al. fed hyperoxaluric mice 1,3-butanediol, which blocks an inflammatory form of cell death called NLRP3 inflammasome and found less intrarenal oxidative damage and higher anti-inflammatory renal infiltrates in experimentals. Finally, monocytes exposed to CaOx crystals followed by hydroxyapatite had reduced inflammatory cytokine and chemokine production compared with those without hydroxyapatite, suggesting that Randall's plaque may play a role in dampening M1-mediatiated CaOx inflammation. SUMMARY: By modulating the immune response, immunotherapy could provide the means to prevent stone recurrences in certain individuals. The promotion of M2 over M1 macrophages and inhibition of inflammation could prevent the cascade that leads to CaOx nucleation. Future therapies may target the ability of macrophages to degrade CaOx crystals to prevent stones.


Subject(s)
Calcium Oxalate/immunology , Immunotherapy/methods , Macrophages/immunology , Nephrolithiasis/immunology , Nephrolithiasis/prevention & control , Animals , Calcium Oxalate/adverse effects , Disease Models, Animal , Humans , Inflammation/immunology , Kidney/immunology , Kidney Calculi/etiology , Kidney Calculi/immunology , Kidney Calculi/prevention & control , Mice , Mitochondria/immunology , Monocytes/immunology , Nephrolithiasis/etiology , Rats , Recurrence , Risk Factors
16.
Urology ; 131: 46-52, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31158354

ABSTRACT

OBJECTIVE: To determine if medical therapy affects long-term clinical outcomes in uric acid stone formers (UASF). METHODS: We identified 53 UASF who had complete stone clearance following stone procedure by computed tomography (CT) and had ≥1 postoperative 24-hour urine collection and a clinical follow-up ≥6 months with a surveillance CT scan. Patients were divided into "adherent to medical therapy" (compliance with potassium citrate ± allopurinol verified by computerized pharmacy data) or nonadherent groups. Primary outcomes were CT stone recurrence rate and need for surgical stone intervention. RESULTS: We found 28 of 53 (53%) adherent and 25 of 53 (47%) nonadherent individuals (14 declined medication, 11 intolerant). With median follow-up of 24 months, no significant differences were noted between groups in regards to stone recurrence (32%; P = .99) or in 24-hour urine pH compared to baseline or follow-up (range 5.46-5.62; P = 0.06). Adherent patients, however, had smaller CT stone recurrence sizes (6.3 ± 3.8 vs 11.8 ± 6.2 mm, P = .02), were 28% less likely to require stone surgery compared to those without therapy (P <.01), and trended toward longer time intervals without recurrence (23.1 ± 18.8 vs 10.5 ± 7.5 months, P = .10) compared to nonadherents. Study confounders included a variety of medication dosages and adherences, limited nonadherent follow-up, and small study number. CONCLUSION: UASF adherent to medical therapy had smaller recurrence sizes and fewer surgical interventions vs nonadherent, highlighting the protective role of potassium citrate in UA stone disease. The comparable urine pH and stone recurrence rates between groups, however, underscore areas for improvement in future UA stone prevention strategies.


Subject(s)
Kidney Calculi/drug therapy , Aged , Female , Humans , Kidney Calculi/chemistry , Male , Medication Adherence/statistics & numerical data , Middle Aged , Recurrence , Retrospective Studies , Time Factors , Treatment Outcome , Uric Acid/analysis
17.
Bone ; 127: 172-180, 2019 10.
Article in English | MEDLINE | ID: mdl-31226531

ABSTRACT

Postoperative bone loss and increased fracture risk associated with Roux-en-Y gastric bypass (RYGB) have been attributed to vitamin D/calcium malabsorption and resultant secondary hyperparathyroidism (HPT). Adequate vitamin D supplementation (VDS), particularly in an older female population, reduces incidence of secondary HPT but the effect on bone loss and fracture risk remains unclear. To investigate whether VDS corrects the RYGB bone phenotype, 41 obese adult female rats were randomized to RYGB with 1000 IU (R1000) or 5000 IU (R5000) vitamin D/kg food or a sham surgical procedure with either paired (PF) or ad libitum (AL) feeding. Bone turnover markers, urinary calcium/creatinine ratio (CCR), and serum calciotropic and gut hormones were assessed throughout a 14-week postoperative period. Femurs were analyzed by micro-computed tomography (µCT), three-point bending test, and histomorphometry. 1000 IU animals had low 25­hydroxyvitamin D (25(OH)D), high serum parathyroid hormone (PTH), and very low urine CCR levels. 5000 IU corrected the 25(OH)D and secondary HPT but did not increase urine CCR or serum levels of 1,25­dihydroxyvitamin D (1,25(OH)D) significantly between RYGB groups. Compared to sham animals at 14 weeks, RYGB animals had significantly higher serum osteocalcin (OCN) and C-terminal telopeptide (CTX) levels. The gut hormone peptide tyrosine tyrosine hormone (PYY) was higher in the RYGB groups, and leptin was lower. µCT and biomechanical testing revealed RYGB females had decreased cortical and trabecular bone volume and weaker, stiffer bone than controls. Histomorphometry showed decreased bone volume and increased osteoid volume with increased mineral apposition rate in RYGB compared to controls. No differences in bone phenotype were identified between 1000 IU and 5000 IU groups, and osteoclast numbers were comparable across all four groups. Thus, in our model, 5000 IU VDS corrected vitamin D deficiency and secondary HPT but did not rescue RYGB mineralization rate nor the osteomalacia phenotype. Longer studies in this model are required to evaluate durability of these detrimental effects. Our findings not only underscore the importance of lifelong repletion of both calcium and vitamin D but also suggest that additional factors affect skeletal health in this population.


Subject(s)
Bone Resorption/drug therapy , Bone Resorption/etiology , Dietary Supplements , Gastric Bypass/adverse effects , Vitamin D/therapeutic use , Animals , Biomarkers/metabolism , Biomechanical Phenomena/drug effects , Body Weight , Bone Remodeling/drug effects , Bone Resorption/blood , Bone Resorption/diagnostic imaging , Calcium/metabolism , Dose-Response Relationship, Drug , Feeding Behavior , Female , Femur/diagnostic imaging , Femur/drug effects , Femur/physiopathology , Hormones/metabolism , Rats, Sprague-Dawley , Vitamin D/pharmacology , X-Ray Microtomography
18.
Urolithiasis ; 47(4): 335-346, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30218116

ABSTRACT

Idiopathic stone formers often form calcium oxalate (CaOx) stones that are attached to calcium phosphate (CaP) deposits in the renal tissue, known as Randall's plaques (RP). Plaques are suggested to originate in the renal tubular basement membrane and spread into the interstitial regions where collagen fibrils and vesicles become mineralized; if the epithelium is breached, the RP becomes overgrown with CaOx upon exposure to urine. We have developed a two-stage model system of CaP-CaOx composite stones, consisting of Stage (1) CaP mineralized plaque, followed by Stage (2) CaOx overgrowth into a stone. In our first paper in this series (Stage 1), osteopontin (and polyaspartate) were found to induce a non-classical mineralization of porcine kidney tissues, producing features that resemble RP. For the Stage 2 studies presented here, biomimetic RPs from Stage 1 were implanted into the bladders of rats. Hyperoxaluria was induced with ethylene glycol for comparison to controls (water). After 4 weeks, rats were sacrificed and the implants were analyzed using electron microscopy and X-ray microanalyses. Differences in crystal phase and morphologies based upon the macromolecules present in the biomimetic plaques suggest that the plaques have the capacity to modulate the crystallization reactions. As expected, mineral overgrowths on the implants switched from CaP (water) to CaOx (hyperoxaluric). The CaOx crystals were aggregated and mixed with organic material from the biomimetic RP, along with some amorphous and spherulitic CaOx near the "stone" surfaces, which seemed to have become compact and organized towards the periphery. This system was successful at inducing "stones" more similar to human idiopathic kidney stones than other published models.


Subject(s)
Calcium Oxalate/chemistry , Calcium Phosphates/chemistry , Kidney Calculi/pathology , Kidney/pathology , Animals , Biomimetics , Disease Models, Animal , Humans , Male , Rats , Swine
19.
Urology ; 124: 310.e9-310.e14, 2019 02.
Article in English | MEDLINE | ID: mdl-30412704

ABSTRACT

OBJECTIVE: To test the effect of calcium and vitamin B6 therapies on urinary oxalate excretion in a rodent model of enteric hyperoxaluria after Roux-en Y gastric bypass (RYGB) surgery. METHODS: Obese male Sprague-Dawley rats underwent sham (n = 7) or RYGB (n = 10). Animals were maintained on low oxalate (1.5%) and fat (10%; LOF), normal calcium (0.6 %) diet for 8 weeks and then completed a 2-phase crossover metabolic study. In the first 2-week phase, animals were fed a Low oxalate and fat (LOF), high calcium (2.4%; HC) diet. After a 2-week washout, rats were fed a LOF/normal calcium diet highly enriched with vitamin B6. Urine was collected before and after each intervention. Plasma pyridoxal 5'-phosphate (PLP) and metabolites were measured baseline and 11 weeks after sham or RYGB. RESULTS: Compared to baseline, sham animals on LOF/HC diet doubled their urinary calcium excretion but not oxalate. RYGB animals on LOF/HC diet decreased urinary oxalate excretion 28% (P = .001) without a significant rise in urinary calcium. Vitamin B6 supplementation decreased RYGB urinary oxalate by approximately 15% (P = .06), and serum PLP explained 63% of urinary oxalate variability. CONCLUSION: Based on the findings in this model, calcium supplementation appears to be a reasonable therapy to decrease urinary oxalate in RYGB patients who maintain a low fat and oxalate diet. Serum PLP had a fair correlation to urinary oxalate excretion and may be a useful screening tool in hyperoxaluric RYGB patients. Further experimental human studies after RYGB are necessary to determine whether these commonly employed supplements truly provide a benefit in enteric hyperoxaluria.


Subject(s)
Calcium/therapeutic use , Dietary Supplements , Gastric Bypass , Hyperoxaluria/drug therapy , Hyperoxaluria/urine , Oxalates/urine , Postoperative Complications/drug therapy , Postoperative Complications/urine , Vitamin B 6/therapeutic use , Vitamin B Complex/therapeutic use , Animals , Disease Models, Animal , Gastric Bypass/adverse effects , Hyperoxaluria/etiology , Male , Postoperative Complications/etiology , Rats , Rats, Sprague-Dawley
20.
Biomed Res Int ; 2018: 5120974, 2018.
Article in English | MEDLINE | ID: mdl-30363655

ABSTRACT

OBJECTIVE: To compare organ specific radiation dose and image quality in kidney stone patients scanned with standard CT reconstructed with filtered back projection (FBP-CT) to those scanned with low dose CT reconstructed with iterative techniques (IR-CT). MATERIALS AND METHODS: Over a one-year study period, adult kidney stone patients were retrospectively netted to capture the use of noncontrasted, stone protocol CT in one of six institutional scanners (four FBP and two IR). To limit potential CT-unit use bias, scans were included only from days when all six scanners were functioning. Organ dose was calculated using volumetric CT dose index and patient effective body diameter through validated conversion equations derived from previous cadaveric, dosimetry studies. Board-certified radiologists, blinded to CT algorithm type, assessed stone characteristics, study noise, and image quality of both techniques. RESULTS: FBP-CT (n=250) and IR-CT (n=90) groups were similar in regard to gender, race, body mass index (mean BMI = 30.3), and stone burden detected (mean size 5.4 ± 1.2 mm). Mean organ-specific dose (OSD) was 54-62% lower across all organs for IR-CT compared to FBP-CT with particularly reduced doses (up to 4.6-fold) noted in patients with normal BMI range. No differences were noted in radiological assessment of image quality or noise between the cohorts, and intrarater agreement was highly correlated for noise (AC2=0.873) and quality (AC2=0.874) between blinded radiologists. CONCLUSIONS: Image quality and stone burden assessment were maintained between standard FBP and low dose IR groups, but IR-CT decreased mean OSD by 50%. Both urologists and radiologists should advocate for low dose CT, utilizing reconstructive protocols like IR, to reduce radiation exposure in their stone formers who undergo multiple CTs.


Subject(s)
Kidney Calculi/diagnostic imaging , Radiographic Image Interpretation, Computer-Assisted/methods , Tomography, X-Ray Computed/methods , Adolescent , Adult , Aged , Aged, 80 and over , Algorithms , Female , Humans , Image Processing, Computer-Assisted/methods , Male , Middle Aged , Phantoms, Imaging , Radiation Dosage , Radiometry/methods , Retrospective Studies , Young Adult
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