email blast reiterated the AUA Best Practice Statement on antibiotic prophylaxis. Two weeks later, an online anonymous secure survey was sent. Unique results ...
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THE JOURNAL OF UROLOGY姞
accumulation of extracellular matrix proteins in the kidneys contributes to the renal fibrosis. Since there is a strong association between hyperoxaluria and tubulointerstitial scarring, we investigated whether oxalate-induced TGF- 1 can stimulate the production of fibronectin (FN) via NADPH oxidase mediated ROS production in renal epithelial cells. METHODS: Confluent monolayers of LLC-PK1 cells pretreated with inhibitors of NADPH oxidase (DPI or apocynin) or neutralizing antibody to TGF- 1 were exposed to 0.75 mM oxalate for different time periods. Recombinant TGF- 1 was used as a positive control. ROS generation and LDH release were determined. Expression of TGF- 1 mRNA was analyzed by RT-PCR. Fibronectin and TGF- 1 levels were measured in culture supernatants by ELISA. TGF- 1 and FN protein expression were determined by western blot analysis. NADPH oxidase activity was determined by SOD-inhibitable cytochrome c reduction assay. RESULTS: Oxalate time dependently stimulated FN expression and secretion in LLC-PK1 cells. TGF- 1 mRNA and protein expression were augmented by oxalate exposure. Oxalate significantly increased NADPH oxidase activity in LLC-PK1 cells. Treatment with TGF 1 neutralizing antibody significantly inhibited oxalate -induced NADPH oxidase activity, ROS production and LDH release. The stimulatory effect of oxalate on FN secretion was inhibited by neutralizing antibodies against TGF- 1. Recombinant TGF- 1 dose dependently increased ROS generation, LDH release and FN expression and secretion in LLC-PK1 cells. In addition, pretreatment with NADPH oxidase inhibitors significantly decreased oxalate or recombinant TGF- 1 induced ROS generation, FN expression and secretion. CONCLUSIONS: Our findings demonstrate that TGF- 1-dependent activation of NADPH oxidase mediated ROS play an important role in oxalate-induced FN accumulation and development of renal interstitial fibrosis, and suggest that ROS signaling pathways may represent a novel therapeutic target to prevent the progression of tubulointerstitial fibrosis in patients with kidney stones. Source of Funding: NIH RO1 DK 56249
2153 METABOLIC ABNORMALITIES OF UROLITHIASIS PATIENTS WITH 25-HYDROXY VITAMIN- D DEFICIENCY Mohamed Elkoushy*, Ramsey Sabbagh, Bernard Unikowsky, Sero Andonian, Montreal, Canada INTRODUCTION AND OBJECTIVES: Vitamin D deficiency and replacement has risen in popularity in recent years. However, there is no data characterizing the metabolic abnormalities in vitamin D deficient patients presenting with urolithiasis. The aim of this work was to determine urinary and serum abnormalities in patients presenting with urolithiasis and found to have 25-hydroxy vitamin D deficiency. METHODS: A retrospective review of our prospectively collected data was performed to identify patients with 25, hydroxy vitamin D (VD) deficiency from August, 2009 to Jan, 2010. Patients with VD ⬍ 74 nmol/L were included and their demographic, medical and surgical data were recorded. Metabolic stone workup including 24-hours urine collection, serum calcium, PTH, TSH, and uric acid were performed. RESULTS: Sixty-nine patients were included in the study of whom 37 (53.6%) were males with a mean age of 50.4⫾15.8 years (range: 14 – 87) and a mean BMI of 27.4⫾ 6.6. Fifty-one percent had past history of urolithiasis and 54.1% had family history of stone disease. Secondary hyperparathyroidism was detected in 25.3% of these patients. Normalized ionized calcium was low in 36.2% of patients. Hyperuricemia was found in 11% of patients. Ninety-three percent of the 24-hours urine collections had at least one abnormality. The most prevalent patterns of urinary abnormalities in decreasing frequency were suboptimal urine volume (⬍2 L/day) in 45%, hypocitaturia in 24%, hypercalciuria in 20%, hyperuricosuria in 16%, cystinuria in 5%, and hyper-oxaluria in 3% of patients. Interestingly, 33% of patients had hypocalciuria.
Vol. 185, No. 4S, Supplement, Wednesday, May 18, 2011
CONCLUSIONS: Patients with 25- hydroxy VD deficiency have high incidence of abnormalities on metabolic stone workup. The relationship between vitamin D deficiency and these findings needs to be further evaluated. Source of Funding: None
2154 ANTIBIOTIC PRESCRIPTION AND POOR COMPLIANCE WITH AUA BEST PRACTICE STATEMENT Brian Eisner, Michael Kurtz*, Boston, MA; Stuart Wolf, Jr, Ann Arbor, MI INTRODUCTION AND OBJECTIVES: In 2008 the AUA published a best practice statement regarding antibiotic prophylaxis for all urologic procedures. In 2009, we performed an online survey through the Society of Endourology which demonstrated that compliance with these guidelines was quite poor, with approximately 69% of respondents prescribing antibiotics in excess of best-practice recommendations. The current study was undertaken to examine the current state of compliance with these guidelines. METHODS: A blast email restating practice guidelines was sent via the Endourological Society list serve (n ⫽ estimated at 1500). This email blast reiterated the AUA Best Practice Statement on antibiotic prophylaxis. Two weeks later, an online anonymous secure survey was sent. Unique results were tabulated and reviewed. RESULTS: In one year after in the initial survey, a minority of respondents reported prescription patterns compliant with guidelines, but the number has increased from 30.4% (2009) to 40% (present). When queried about factors that influenced decisions about postoperative antibiotics, 56.6% of respondents cited AUA Best Practice Statement published in 2008, 5.2% cited our initial abstract presented at AUA 2009 annual meeting, and 13% cited the email blast sent two weeks prior to the current survey.There were no significant differences between the respondents reporting compliant behavior with respect to the type of stenting used; no stent in 31.9 vs 26.3%, externalized catheter in 8.4 vs 10.3%, stent with a tether in 25.9 vs 27.6%, or cystoscopic removal in 41.2 vs. 48.3%. Doses prescribed in excess of AUA recommendations in the last 12 months by the survey respondents alone exceeded 3,628 doses of penicillin / cephalosporin, 2,670 doses of quinolone, 1,177 doses of trimethoprim, and 180 doses of nitrofurnatoin. CONCLUSIONS: Compliance with AUA Best Practice guildines for antibiotic prophylaxis after surgery is poor (40%). AUA published guidelines appear to have the greatest influence on this, but meeting abstracts and email blasts may also be useful for disseminating this type of information as well. There is great need, however, for improving methods of dissemination and enhancing compliance with clinical practice guidelines. Source of Funding: None
2155 ASSESSING THE USE OF HEMOSTATIC SEALANTS IN TUBELESS PERCUTANEOUS NEPHROSTOMY: THE EFFECTS ON RENAL HISTOLOGY IN AN EXPERIMENTAL PORCINE STUDY Christos Rigopoulos, Panagiotis Kallidonis*, Iason Kyriazis, Odysseas Andrikopoulos, Constantinos Constantinidis, Patras, Greece; Jens-Uwe Stolzenburg, Leipzig, Germany; Evangelos Liatsikos, Patras, Greece INTRODUCTION AND OBJECTIVES: Despite the relative common use of hemostatic sealants in tubeless percutaneous nephrolithotomy (PCNL) in the clinical practice, various experimental settings have questioned the safety of this application. These studies are mainly focusing on the potential of such materials to occlude urinary drainage. In this study, we question again the safety of various types of hemo-
