Publications by authors named "Benjamin K Canales"

77 Publications

Obturator Nerve Blockade vs. Neuromuscular Blockade for the Prevention of Adductor Spasm in Patients Undergoing Transurethral Resection of Bladder Tumors: A Randomized Controlled Trial.

Pain Med 2021 Jan 4. Epub 2021 Jan 4.

Department of Urology, University of Florida, Gainesville, Florida.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/pm/pnaa448DOI Listing
January 2021

Randall's plaque and calcium oxalate stone formation: role for immunity and inflammation.

Nat Rev Nephrol 2021 Jan 29. Epub 2021 Jan 29.

Department of Urology, University of Florida, Gainesville, FL, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41581-020-00392-1DOI Listing
January 2021

Gross Hematuria Eight Years Following Nephrectomy for Renal Cell Cancer.

Urology 2020 Sep 5;143:1-4. Epub 2020 Jun 5.

Department of Urology, University of Florida, Gainesville, FL. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2020.05.048DOI Listing
September 2020

Lessons from rodent gastric bypass model of enteric hyperoxaluria.

Curr Opin Nephrol Hypertens 2020 07;29(4):400-406

Department of Urology, College of Medicine, University of Florida, Gainesville, Florida, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MNH.0000000000000613DOI Listing
July 2020

Immunotherapy for stone disease.

Curr Opin Urol 2020 03;30(2):183-189

Department of Urology, University of Florida, Gainesville, Florida, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOU.0000000000000729DOI Listing
March 2020

Editorial: Kidney stone prevention.

Curr Opin Urol 2020 03;30(2):157-158

Urology, University of Florida, Gainesville, Florida, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOU.0000000000000731DOI Listing
March 2020

Improving care to decrease stone recurrence and opioid use.

Nat Rev Urol 2020 02;17(2):75-76

University of Florida Department of Urology, Gainesville, FL, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41585-019-0275-2DOI Listing
February 2020

"Alkalinizing Agents: A Review of Prescription, Over-the-Counter, and Medical Food Supplements" by Stern et al. (J Endourol 2020;34(1):1-6; DOI: 10.1089/end.2019.0292).

J Endourol 2020 05 9;34(5):639. Epub 2019 Oct 9.

Department of Urology, University of Florida, Gainesville, Florida, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/end.2019.0666DOI Listing
May 2020

High dose vitamin D supplementation does not rescue bone loss following Roux-en-Y gastric bypass in female rats.

Bone 2019 10 19;127:172-180. Epub 2019 Jun 19.

Department of Urology, North Florida/South Georgia Veterans Affairs Medical Center and University of Florida, Gainesville, FL, United States of America. Electronic address:

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 25‑hydroxyvitamin 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 1,25‑dihydroxyvitamin 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2019.06.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708762PMC
October 2019

Long-term Recurrence Rates in Uric Acid Stone Formers With or Without Medical Management.

Urology 2019 Sep 31;131:46-52. Epub 2019 May 31.

Department of Urology, University of Florida, Gainesville, FL.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2019.05.023DOI Listing
September 2019

The Effect of Calcium and Vitamin B6 Supplementation on Oxalate Excretion in a Rodent Gastric Bypass Model of Enteric Hyperoxaluria.

Urology 2019 02 7;124:310.e9-310.e14. Epub 2018 Nov 7.

Department of Urology, University of Florida, Gainesville, FL. Electronic address:

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2018.06.061DOI Listing
February 2019

Image Quality and Patient-Specific Organ Doses in Stone Protocol CT: A Comparison of Traditional CT to Low Dose CT with Iterative Reconstruction.

Biomed Res Int 2018 27;2018:5120974. Epub 2018 Sep 27.

Department of Urology, University of Florida, Gainesville, FL, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/5120974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181004PMC
February 2019

Development of a two-stage model system to investigate the mineralization mechanisms involved in idiopathic stone formation: stage 2 in vivo studies of stone growth on biomimetic Randall's plaque.

Urolithiasis 2019 Aug 14;47(4):335-346. Epub 2018 Sep 14.

Department of Urology, College of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, FL, 32610-0247, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00240-018-1079-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417989PMC
August 2019

Calcium Oxalate Differentiates Human Monocytes Into Inflammatory M1 Macrophages.

Front Immunol 2018 22;9:1863. Epub 2018 Aug 22.

Department of Urology, University of Florida, Gainesville, FL, United States.

Purpose: A number of hyperoxaluric states have been associated with calcium oxalate (CaOx) deposits in the kidneys. In animal models of stone disease, these crystals interact with circulating monocytes that have migrated into the kidney as part of innate immunity. Similarly, macrophages surround CaOx crystals in kidneys of patients excreting high levels of oxalate. We investigate the effect of this exposure and subsequent human immunological response .

Materials And Methods: Primary human monocytes were collected from healthy donors and exposed to CaOx, potassium oxalate, and zinc oxalate (ZnOx). Cytokine production was measured with a multiplex ELISA. Quantitative reverse transcription-polymerase chain reaction was done to validate the mRNA profile expression. M1 macrophage phenotype was confirmed with immunofluorescence microscopy.

Results: Both primary monocytes and THP-1 cells, a human monocytic cell line, respond strongly to CaOx crystals in a dose-dependent manner producing TNF-α, IL-1β, IL-8, and IL-10 transcripts. Exposure to CaOx followed by 1 h with LPS had an additive effect for cytokine production compared to LPS alone, however, LPS followed by CaOx led to significant decrease in cytokine production. Supernatants taken from monocytes were previously exposed to CaOx crystals enhance M2 macrophage crystal phagocytosis. CaOx, but not potassium or ZnOx, promotes monocyte differentiation into inflammatory M1-like macrophages.

Conclusion: In our experiment, human monocytes were activated by CaOx and produced inflammatory cytokines. Monocytes recognized CaOx crystals through a specific mechanism that can enhance or decrease the innate immune response to LPS. CaOx promoted M1 macrophage development. These results suggest that monocytes have an important role promoting CaOx-induced inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2018.01863DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113402PMC
September 2019

Polymorphisms in Renal Ammonia Metabolism Genes Correlate With 24-Hour Urine pH.

Kidney Int Rep 2017 Nov 21;2(6):1111-1121. Epub 2017 Jun 21.

Division of Nephrology and Hypertension, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Introduction: Urine pH is critical for net acid and solute excretion, but the genetic factors that contribute to its regulation are incompletely understood.

Methods: We tested the association of single nucleotide polymorphisms (SNPs) from 16 genes related to ammonia (NH) metabolism (15 biological candidates selected , 1 selected from a previous genome-wide association study analysis) to that of 24-hour urine pH in 2493 individuals of European descent across 2 different cohorts using linear regression, adjusting for age, sex, and body mass index.

Results: Of 2871 total SNPs in these genes, 13 SNPs in (a4 subunit of hydrogen- adenosine triphosphatase), (sodium/hydrogen exchanger, isoform 3), and (Rhesus C glycoprotein), and 12 SNPs from insulin-like growth factor binding protein 7 () had a meta-analysis value <0.01 in the joint analysis plus a consistent direction of effect and at a least suggestive association ( < 0.1) in both cohorts. The maximal effect size (in pH units) for each additional minor allele of the identified SNPs was -0.13 for , -0.08 for , 0.06 for , and -0.06 for ; SNP rs34447434 in had the lowest meta-analysis value ( = 7.1 × 10). After adjusting for net alkali absorption, urine pH remained suggestively associated with multiple SNPs in , 1 SNP in , and a new SNP in (phosphate-dependent glutaminase).

Discussion: Overall, these findings suggest that variants in common genes involved in ammonia metabolism may substantively contribute to basal urine pH regulation. These variations might influence the likelihood of developing disease conditions associated with altered urine pH, such as uric acid or calcium phosphate kidney stones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ekir.2017.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733879PMC
November 2017

Oxalobacter formigenes colonization normalizes oxalate excretion in a gastric bypass model of hyperoxaluria.

Surg Obes Relat Dis 2017 Jul 23;13(7):1152-1157. Epub 2017 Mar 23.

Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida.

Background: Hyperoxaluria and oxalate kidney stones frequently develop after Roux-en-Y gastric bypass (RYGB). Oxalobacter formigenes can degrade ingested oxalate.

Objectives: Examine the effect of O. formigenes wild rat strain (OXWR) colonization on urinary oxalate excretion and intestinal oxalate transport in a hyperoxaluric RYGB model.

Setting: Basic Science Laboratory, United States.

Methods: At 21 weeks of age, 28 obese male Sprague-Dawley rats survived Sham (n = 10) or RYGB (n = 18) surgery and were maintained on a 1.5% potassium oxalate, 40% fat diet. At 12 weeks postoperatively, half the animals in each group were gavaged with OXWR. At 16 weeks, percent dietary fat content was lowered to 10%. Urine and stool were collected weekly to determine oxalate and colonization status, respectively. At week 20, [14 C]-oxalate fluxes and electrical parameters were measured in vitro across isolated distal colon and jejunal (Roux limb) tissue mounted in Ussing Chambers.

Results: RYGB animals lost 22% total weight while Shams gained 5%. On a moderate oxalate diet, urinary oxalate excretion was 4-fold higher in RYGB than Sham controls. OXWR colonization, obtained in all gavaged animals, reduced urinary oxalate excretion 74% in RYGB and 39% in Sham and was further augmented by lowering the percentage of dietary fat. Finally, OXWR colonization significantly enhanced basal net colonic oxalate secretion in both groups.

Conclusions: In our model, OXWR lowered urinary oxalate by luminal oxalate degradation in concert with promotion of enteric oxalate elimination. Trials of O. formigenes colonization and low-fat diet are warranted in calcium oxalate stone formers with gastric bypass and resistant hyperoxaluria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soard.2017.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535072PMC
July 2017

Evaluating Region of Interest Measurement Strategies to Characterize Upper Urinary Tract Stones on Computerized Tomography.

J Urol 2017 03 27;197(3 Pt 1):715-722. Epub 2016 Oct 27.

Department of Urology, University of Florida College of Medicine (VMN), Gainesville, Florida. Electronic address:

Purpose: Computerized tomography imaging is regularly used to assess stone HU values as a surrogate for stone composition and fragility. Techniques for measuring HU values are unstandardized, leading to high variability. We investigated several region of interest measurement strategies to quantify this variability.

Materials And Methods: Patients from an institutional database who underwent preoperative computerized tomography, surgical stone extraction and stone composition analysis were identified. HU measurements were made of each patient stone using transverse/coronal slices in the abdominal/bone windows with 4 region of interest techniques, including 1) the maximum diameter region of interest, 2) the maximum diameter region of interest at all stone inclusive slices, 3) 2 equal-sized, nonoverlapping circular regions of interest and 4) 3 to 5 smaller nonoverlapping regions of interest randomly placed on the stone. Stones that were 80% or greater pure by composition were separately analyzed.

Results: A total of 172 patients were included in study. Mean ± SD stone size was 19.3 ± 15.6 mm. On subtype analysis 51 stones were calcium oxalate monohydrate, 9 were calcium oxalate dihydrate, 7 were calcium phosphate hydroxyapatite/brushite and 16 were uric acid. Mean HU values in the abdominal window for all stones identified by region of interest techniques 1 to 4 were 457 ± 253, 351 ± 210, 581 ± 363 and 587 ± 329, respectively. The distribution of means significantly differed across region of interest techniques, planes and windows when considering all stones together (p <0.0001), stones with greater than 80% calcium oxalate dihydrate (p = 0.0113) and greater than 80% calcium oxalate monohydrate (p <0.0001), and uric acid stones (p <0.0001).

Conclusions: HU values obtained to assess stone density vary depending on window, plane and region of interest technique. We recommend that clinicians select a single region of interest measurement technique and use it consistently to minimize interinstitutional variability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.juro.2016.10.066DOI Listing
March 2017

Alpha blockers for treatment of ureteric stones: systematic review and meta-analysis.

BMJ 2016 Dec 1;355:i6112. Epub 2016 Dec 1.

Minneapolis Veterans Administration Health Care System and Department of Urology, University of Minnesota, Mayo Memorial Building, 420 Delaware St SE, MMC 394, Minneapolis, MN 55455, USA.

Objective:  To investigate the efficacy and safety of alpha blockers in the treatment of patients with ureteric stones.

Design:  Systematic review and meta-analysis.

Data Sources:  Cochrane Central Register of Controlled Trials, Web of Science, Embase, LILACS, and Medline databases and scientific meeting abstracts to July 2016.

Review Methods:  Randomized controlled trials of alpha blockers compared with placebo or control for treatment of ureteric stones were eligible. : Two team members independently extracted data from each included study. The primary outcome was the proportion of patients who passed their stone. Secondary outcomes were the time to passage; the number of pain episodes; and the proportions of patients who underwent surgery, required admission to hospital, and experienced an adverse event. Pooled risk ratios and 95% confidence intervals were calculated for the primary outcome with profile likelihood random effects models. Cochrane Collaboration's tool for assessing risk of bias and the GRADE approach were used to evaluate the quality of evidence and summarize conclusions.

Results:  55 randomized controlled trials were included. There was moderate quality evidence that alpha blockers facilitate passage of ureteric stones (risk ratio 1.49, 95% confidence interval 1.39 to 1.61). Based on a priori subgroup analysis, there seemed to be no benefit to treatment with alpha blocker among patients with smaller ureteric stones (1.19, 1.00 to 1.48). Patients with larger stones treated with an alpha blocker, however, had a 57% higher risk of stone passage compared with controls (1.57, 1.17 to 2.27). The effect of alpha blockers was independent of stone location (1.48 (1.05 to 2.10) for upper or middle stones; 1.49 (1.38 to 1.63) for lower stones). Compared with controls, patients who received alpha blockers had significantly shorter times to stone passage (mean difference -3.79 days, -4.45 to -3.14; moderate quality evidence), fewer episodes of pain (-0.74 episodes, -1.28 to -0.21; low quality evidence), lower risks of surgical intervention (risk ratio 0.44, 0.37 to 0.52; moderate quality evidence), and lower risks of admission to hospital (0.37, 0.22 to 0.64; moderate quality evidence). The risk of a serious adverse event was similar between treatment and control groups (1.49, 0.24 to 9.35; low quality evidence).

Conclusions:  Alpha blockers seem efficacious in the treatment of patients with ureteric stones who are amenable to conservative management. The greatest benefit might be among those with larger stones. These results support current guideline recommendations advocating a role for alpha blockers in patients with ureteric stones.

Systematic Review Registration:  PROSPERO registration No CRD42015024169.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131734PMC
http://dx.doi.org/10.1136/bmj.i6112DOI Listing
December 2016

Kidney stones.

Nat Rev Dis Primers 2016 02 25;2:16008. Epub 2016 Feb 25.

Division of Urology, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Kidney stones are mineral deposits in the renal calyces and pelvis that are found free or attached to the renal papillae. They contain crystalline and organic components and are formed when the urine becomes supersaturated with respect to a mineral. Calcium oxalate is the main constituent of most stones, many of which form on a foundation of calcium phosphate called Randall's plaques, which are present on the renal papillary surface. Stone formation is highly prevalent, with rates of up to 14.8% and increasing, and a recurrence rate of up to 50% within the first 5 years of the initial stone episode. Obesity, diabetes, hypertension and metabolic syndrome are considered risk factors for stone formation, which, in turn, can lead to hypertension, chronic kidney disease and end-stage renal disease. Management of symptomatic kidney stones has evolved from open surgical lithotomy to minimally invasive endourological treatments leading to a reduction in patient morbidity, improved stone-free rates and better quality of life. Prevention of recurrence requires behavioural and nutritional interventions, as well as pharmacological treatments that are specific for the type of stone. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more-effective drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nrdp.2016.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685519PMC
February 2016

Oxalate-degrading microorganisms or oxalate-degrading enzymes: which is the future therapy for enzymatic dissolution of calcium-oxalate uroliths in recurrent stone disease?

Urolithiasis 2016 Feb 8;44(1):45-50. Epub 2015 Dec 8.

Department of Infectious Diseases and Pathology, University of Florida College of Veterinary Medicine, P.O Box 100125, VAB, Bldg 1017, Gainesville, FL, 32610, USA.

Renal urolithiasis is a pathological condition common to a multitude of genetic, physiological and nutritional disorders, ranging from general hyperoxaluria to obesity. The concept of quickly dissolving renal uroliths via chemolysis, especially calcium-oxalate kidney stones, has long been a clinical goal, but yet to be achieved. Over the past 25 years, there has been a serious effort to examine the prospects of using plant and microbial oxalate-degrading enzymes known to catabolize oxalic acid and oxalate salts. While evidence is emerging that bacterial probiotics can reduce recurrent calcium-oxalate kidney stone disease by lowering systemic hyperoxaluria, the possible use of free oxalate-degrading enzyme therapy remains a challenge with several hurdles to overcome before reaching clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00240-015-0845-6DOI Listing
February 2016

Calcium Oxalate Stone Fragment and Crystal Phagocytosis by Human Macrophages.

J Urol 2016 04 26;195(4 Pt 1):1143-51. Epub 2015 Nov 26.

Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, Florida. Electronic address:

Purpose: In murine and human hyperoxaluric conditions macrophages can be seen surrounding renal calcium oxalate crystal deposits. We hypothesized that macrophages have a role in degrading and destroying these deposits. We investigated the inflammatory response and phagocytic mechanisms when macrophages were exposed to human kidney stones and inorganic crystals.

Materials And Methods: Human monocytes were differentiated into resting, fully differentiated macrophages by treatment with recombinant human macrophage colony-stimulating factor (M-CSF) or GM-CSF (granulocyte M-CSF) for 6 days. After confirming phenotype by flow cytometry the macrophages were exposed for 20 hours to fragments of sterile human calcium oxalate stones or calcium oxalate crystals. Crystal uptake was determined, and supernatant cytokine and chemokine profiles were analyzed using antibody arrays. Quantitative reverse transcriptase-polymerase chain reaction was done to validate mRNA profile expression.

Results: Under direct vision fluorescence microscopy activated human macrophages were noted to surround stone fragments and synthesized crystals, and destroy them in a step-by-step process that involved clathrin mediated endocytosis and phagocytosis. An inflammatory cascade was released by macrophages, including the chemokines chemokine ligand (CCL)2, CCL3, interleukin (IL)-1 receptor antagonist (IL-1ra), complement component C5/C5a and IL-8. Response patterns to stone and crystal material depended on macrophage phenotype and activation status.

Conclusions: In our in vitro study macrophages differentiated with M-CSF showed greater ability to phagocytize crystal deposits than those treated with GM-CSF. Following clathrin mediated endocytosis macrophages released a number of cytokines that are crucial for the inflammatory immune response. This suggests that tissue macrophages have an important role in preventing kidney stone disease by removing and digesting interstitial renal crystal deposits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.juro.2015.11.048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882284PMC
April 2016

The mechanistic basis of hyperoxaluria following gastric bypass in obese rats.

Urolithiasis 2016 Jun 19;44(3):221-30. Epub 2015 Nov 19.

Department of Urology, College of Medicine, University of Florida, Gainesville, FL, 32610, USA.

Roux-en-Y gastric bypass (RYGB) surgery is a popular and extremely effective procedure for sustained weight loss in the morbidly obese. However, hyperoxaluria and oxalate kidney stones frequently develop after RYGB and steatorrhea has been speculated to play a role. We examined the effects of RYGB and the role of dietary fat in an obese rat model by measuring fecal fat content and transmural oxalate fluxes across the distal colon compared to sham-operated controls (SHAM). Direct measurements of fecal fat content confirmed that RYGB on a 10 % fat diet excreted 40-fold more fecal fat than SHAM and, on a 40 % fat diet, RYGB excreted sevenfold more fecal fat than SHAM fed similarly. Results from the transport studies revealed a clear effect of high dietary fat (40 %) on colonic oxalate permeability and tissue conductance (G T) with comparable oxalate fluxes in RYGB and in SHAM. Administering a diet containing 10 % fat to both groups distinguished differences between RYGB and SHAM, revealing a 40 % increase in G T in RYGB and a reversal in the direction of net oxalate flux from absorption in SHAM to secretion in RYGB. These changes in colonic oxalate permeability were associated with a fourfold increase in urinary oxalate excretion in RYGB compared to SHAM. Therefore, oxalate solubility and permeability in the RYGB model are promoted by steatorrhea and result in enhanced passive oxalate absorption and hyperoxaluria. To our knowledge, these are the first measurements of intestinal oxalate transport in rats with RYGB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00240-015-0836-7DOI Listing
June 2016

Changing Default Fluoroscopy Equipment Settings Decreases Entrance Skin Dose in Patients.

J Urol 2016 Apr 23;195(4 Pt 1):992-7. Epub 2015 Oct 23.

Department of Urology, University of Florida, Gainesville, Florida.

Purpose: Proper fluoroscopic education and protocols may reduce the patient radiation dose but few prospective studies in urology have been performed. Using optically stimulated luminescent dosimeters we tested whether fluoroscopy time and/or entrance skin dose would decrease after educational and radiation reduction protocols.

Materials And Methods: At default manufacturer settings fluoroscopy time and entrance skin dose were prospectively measured using optically stimulated luminescent dosimeters in patients undergoing ureteroscopy, retrograde pyelogram/stent or percutaneous nephrolithotomy with access for stone disease. A validated radiation safety competency test was administered to urology faculty and residents before and after web based, hands-on fluoroscopy training. Default fluoroscopy settings were changed from continuous to intermittent pulse rate and from standard to half-dose output. Fluoroscopy time and entrance skin dose were then measured again.

Results: The cohorts of 44 pre-protocol and 50 post-protocol patients with stones were similarly matched. The change in mean fluoroscopy time and entrance skin dose from pre-protocol to post-protocol was -0.6 minutes and -11.6 mGy (33%) for percutaneous nephrolithotomy (p = 0.62 and <0.001), 0.5 minutes and -0.1 mGy (34%) for ureteroscopy (p = 0.42 and 0.31), and 0.1 minute and -0.1 mGy (29%) for retrograde pyelogram/stent (p = 0.85 and 0.49, respectively). Urologist post-training test scores increased 30% from pretraining scores (p = 0.1).

Conclusions: Radiation safety training protocols improved clinical knowledge but did not significantly alter fluoroscopy time. Changing equipment default settings to intermittent pulse rate (12 frames per second) and half-dose lowered the entrance skin dose by 30% across all endourology patients but most significantly during percutaneous nephrolithotomy. To limit patient radiation exposure fluoroscopy default settings should be decreased before all endourology procedures and image equipment manufacturers should consider lowering standard default renal settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.juro.2015.10.088DOI Listing
April 2016

Comment On: Prospective evaluation of urinary metabolic indices in severely obese adolescents after weight loss surgery.

Surg Obes Relat Dis 2016 Feb 8;12(2):367-8. Epub 2015 Apr 8.

Department of Urology, University of Florida, Gainesville, Florida; North Florida/South Georgia Veterans Affairs Medical Center, Gainesville, Florida.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.soard.2015.04.001DOI Listing
February 2016

Editorial comment.

Urology 2015 May 12;85(5):1013. Epub 2015 Mar 12.

Department of Urology, University of Florida, Gainesville, FL.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2014.11.059DOI Listing
May 2015

Kidney stone risk following Roux-en-Y gastric bypass surgery.

Transl Androl Urol 2014 Sep;3(3):242-249

Department of Urology, University of Florida, Gainesville, FL, USA ; Department of Urology, University of South Florida, Tampa, FL, USA.

Since the first report in 2005, Roux-en-Y gastric bypass (RYGB) surgery has been linked to a variety of metabolic changes that alter kidney stone risk. The studies with the highest level of evidence, performed in non-stone forming patients before and after RYGB, cite a number of kidney stone risk factors, including a 25% increase in urinary oxalate, a 30% decrease in urinary citrate, and reduction in urine volume by half a liter. In addition to these, recent clinical and experimental studies have contributed to our understanding of the pathophysiology of stone disease in this unique population. This review summarizes the current RYGB urinary chemistry profiles and epidemiological studies, outlines known and theoretical mechanisms of hyperoxaluria and hypocitrituria, and provides some standard recommendations for reducing stone risk in RYGB stone formers as well as some novel ones, including correction of metabolic acidosis and use of probiotics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3978/j.issn.2223-4683.2014.06.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249680PMC
September 2014

Calcium nephrolithiasis and bone demineralization: pathophysiology, diagnosis, and medical management.

Curr Opin Urol 2014 Nov;24(6):633-8

aUrology Department, Hospital La Inmaculada, Huercal-Overa, Almeria, Spain bDepartment of Urology, University of Florida, Gainesville, Florida, USA cUrology Department, San Cecilio University Hospital, Granada, Spain.

Purpose Of Review: To establish the relationship between calcium nephrolithiasis, bone densitometry scoring, and bone mineral density (BMD) loss according to bone turnover markers (BTMs) and urinary metabolites.

Recent Findings: Patients with recurrent calcium nephrolithiasis and idiopathic fasting hypercalciuria (urinary calcium/creatinine ratio >0.11) are more likely to have BMD loss that may lead to osteopenia or osteoporosis. In these patients, BTMs may be used as a surrogate for both bone health and stone recurrence. Suspect higher lithogenic states when calcium stone formers have serum beta-crosslaps (resorptive marker) greater than 0.311 ng/ml, serum osteocalcin (formative marker) greater than 13.2 ng/ml, and beta-crosslaps/osteocalcin ratio greater than 0.024.

Summary: Patients with recurrent calcium nephrolithiasis and fasting hypercalciuria have a higher incidence of osteopenia and osteoporosis, measured by the dual-energy X-ray absorptiometry. These patients present not only with hypercalciuria and increased BTMs (mainly resorptive), but also up to 30% have hypocitraturia and increased urinary calcium/citrate ratio (>0.25). On the basis of these results, a diagnostic algorithm was created, classifying hypercalciurics according to their fasting calcium/creatinine and calcium/citrate ratio. Medical therapy for these patients is aimed at improving the dietary habits (normocalcemic, low salt, low animal protein diet), prescribing combinations of potassium citrate, thiazides, and bisphosphonates, and correcting bone and urinary abnormalities that may lower future skeletal and kidney stone risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOU.0000000000000111DOI Listing
November 2014

Unified theory on the pathogenesis of Randall's plaques and plugs.

Urolithiasis 2015 Jan 14;43 Suppl 1:109-23. Epub 2014 Aug 14.

Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL, 32610, USA,

Kidney stones develop attached to sub-epithelial plaques of calcium phosphate (CaP) crystals (termed Randall's plaque) and/or form as a result of occlusion of the openings of the Ducts of Bellini by stone-forming crystals (Randall's plugs). These plaques and plugs eventually extrude into the urinary space, acting as a nidus for crystal overgrowth and stone formation. To better understand these regulatory mechanisms and the pathophysiology of idiopathic calcium stone disease, this review provides in-depth descriptions of the morphology and potential origins of these plaques and plugs, summarizes existing animal models of renal papillary interstitial deposits, and describes factors that are believed to regulate plaque formation and calcium overgrowth. Based on evidence provided within this review and from the vascular calcification literature, we propose a "unified" theory of plaque formation-one similar to pathological biomineralization observed elsewhere in the body. Abnormal urinary conditions (hypercalciuria, hyperoxaluria, and hypocitraturia), renal stress or trauma, and perhaps even the normal aging process lead to transformation of renal epithelial cells into an osteoblastic phenotype. With this de-differentiation comes an increased production of bone-specific proteins (i.e., osteopontin), a reduction in crystallization inhibitors (such as fetuin and matrix Gla protein), and creation of matrix vesicles, which support nucleation of CaP crystals. These small deposits promote aggregation and calcification of surrounding collagen. Mineralization continues by calcification of membranous cellular degradation products and other fibers until the plaque reaches the papillary epithelium. Through the activity of matrix metalloproteinases or perhaps by brute physical force produced by the large sub-epithelial crystalline mass, the surface is breached and further stone growth occurs by organic matrix-associated nucleation of CaOx or by the transformation of the outer layer of CaP crystals into CaOx crystals. Should this theory hold true, developing an understanding of the cellular mechanisms involved in progression of a small, basic interstitial plaque to that of an expanding, penetrating plaque could assist in the development of new therapies for stone prevention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00240-014-0705-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373525PMC
January 2015