Alexandre Danilovic

Sustained Decrease in Superoxide Dismutase Activity Underlies Constrictive Remodeling After Balloon Injury in Rabbits

Objective—The redox pathophysiology of vascular repair is incompletely understood. We assessed the role of vascular superoxide dismutase (SOD) activity in oxidative/nitrative stress and caliber loss postinjury (PI). Methods and Results—Rabbits submitted to iliac artery balloon overdistension were followed for 14 days PI. Significant decrease in vascular SOD activity occurred at 7 and 14 days PI (by 45% and 34%, respectively, versus control, 96±1 U/mg, P <0.05). Separation in concanavalin-A column showed that both extracellular SOD (ecSOD) and CuZn SOD activities were reduced, whereas Western analysis showed normal or augmented protein expression. Immunoreactivity to nitrotyrosine, neuronal NO synthase (NOS), and inducible NOS (iNOS) increased in media and neointima PI; iNOS mRNA also augmented. Administration of ecSOD from days 7 to 14 PI corrected the SOD activity decrease and minimized caliber loss by 59% (P =0.007) despite unaltered neointima. Nitrate levels markedly increased with ecSOD in injured artery homogenates (26±5 versus 4±0.3 &mgr;mol/L per mg, P =0.001). Such increase was 70% inhibited by specific iNOS antagonist 1400w. Nitrotyrosine and neuronal NOS expression decreased after ecSOD. Conclusions—Sustained low vascular SOD activity has a key role in constrictive remodeling after injury, promoting oxidative/nitrative stress and impairment of iNOS-derived NO bioavailability. SOD function may critically determine whether iNOS induction is beneficial or deleterious in vivo. (Arterioscler Thromb Vasc Biol. 2003;23:2197-2202.)

N-acetylcysteine protects against renal injury following bilateral ureteral obstruction.

Background. Obstructive nephropathy decreases renal blood flow (RBF) and glomerular filtration rate (GFR), causing tubular abnormalities, such as urinary concentrating defect, as well as increasing oxidative stress. This study aimed to evaluate the effects of N-acetylcysteine (NAC) on renal function, as well as on the protein expression of aquaporin 2 (AQP2) and endothelial nitric oxide synthase (eNOS), after the relief of bilateral ureteral obstruction (BUO). Methods. Adult male Wistar rats were divided into four groups: sham (sham operated); sham operated + 440 mg/kg body weight (BW) of NAC daily in drinking water, started 2 days before and maintained until 48 h after the surgery; BUO (24-h BUO only); BUO + NAC-pre (24-h BUO plus 440 mg/kg BW of NAC daily in drinking water started 2 days before BUO); and BUO + NAC-post (24-h BUO plus 440 mg/kg BW of NAC daily in drinking water started on the day of BUO relief). Experiments were conducted 48 h after BUO relief. Results. Serum levels of thiobarbituric reactive substances, which are markers of lipid peroxidation, were significantly lower in NAC-treated rats than in the BUO group rats. The administration of NAC provided significant protection against post-BUO GFR drops and reductions in RBF. Renal cortices and BUO rats presented decreased eNOS protein expression of eNOS in the renal cortex of BUO group rats, whereas it was partially recovered in BUO + NAC-pre group rats. Urine osmolality was significantly lower in BUO rats than in sham group rats or NAC-treated rats, the last also presenting less interstitial fibrosis. Post-BUO downregulation of AQP2 protein expression was averted in the BUO + NAC-pre group rats. Conclusions. This study demonstrates that NAC administration ameliorates the renal function impairment observed 48 h after the relief of 24-h BUO. Oxidative stress is important for the suppression of GFR, RBF, tissue AQP2 and eNOS in the polyuric phase after the release of BUO.

Protective Effect of N-acetylcysteine on Early Outcomes of Deceased Renal Transplantation

We investigated the effects of the antioxidant N-acetylcysteine (NAC) on early outcomes of deceased donor renal transplantation. Between April 2005 and June 2008, adult primary graft recipients of deceased renal donors were assigned to treatment (n = 38) or control (n = 36) groups and evaluated for 90 days and one year after renal transplantation. The treatment group received NAC orally (600 mg twice daily) from day 0 to 7 postoperatively. Renal function was determined by serum creatinine, MDRD and Cockcroft-Gault estimated GFR (eGFR), delayed graft function (DGF) and dialysis free Kaplan-Meier estimate curve. Serum levels of thiobarbituric acid reactive substances (TBARS), were employed as markers of oxidative stress. The NAC group displayed a lower mean serum creatinine during the first 90 days (P = .026) and at 1 year after transplantation (P = .005). Furthermore, the NAC group showed a higher mean eGFR throughout the first 90 days and at 1 year. DGF was lower among the NAC group (P = .017) and these recipients required fewer days of dialysis (P = .012). Oxidative stress was significantly attenuated with NAC (P < .001). Our results suggested that NAC enhanced early outcomes of deceased donor renal transplantation by attenuating oxidative stress.

Adjuvant Tamsulosin or Nifedipine After Extracorporeal Shock Wave Lithotripsy for Renal Stones: A Double Blind, Randomized, Placebo-controlled Trial

OBJECTIVE To evaluate the effects of the adjuvant use of tamsulosin or nifedipine after extracorporeal shock wave lithotripsy for nonlower pole kidney stones 5-20 mm in size. METHODS We conducted a randomized double-blind trial involving 136 patients with radiopaque kidney stones. The patients received daily treatment with 0.4 mg tamsulosin, 20 mg nifedipine retard, or placebo for ≤30 days after 1 session of extracorporeal shock wave lithotripsy. Success was defined as plain film radiography showing the patient was completely stone free or with asymptomatic stone fragments ≤4 mm in size at any time during the weekly follow-up. RESULTS The success rate was 60.5% (23 of 38) in the tamsulosin group, 48.6% (17 of 35) in the nifedipine group, and 36.8% (14 of 38) in the placebo group (P = .118). In the subgroup analysis, stones 10-20 mm had significantly greater success rates in the tamsulosin (13 of 21, 61.9%) and nifedipine (15 of 25, 60%) groups compared with the placebo group (6 of 23, 26.1%; P = .024), but not for stones 5-9 mm (P = .128). The number needed to treat was 2.9 for tamsulosin and 3 for nifedipine. Adverse events were more frequent in the nifedipine than in the placebo group (28.5% vs 2.6%, respectively, P = .009), but without a significant difference between the nifedipine and tamsulosin (28.5% vs 15.8%, P = .15) or the tamsulosin and placebo (P = .54) groups. No difference was found among the groups with regard to pain intensity, interval to clearance, or steinstrasse. CONCLUSION The stone-free rates after extracorporeal shock wave lithotripsy with adjuvant tamsulosin or nifedipine were significantly increased only for nonlower pole renal stones 10-20 mm in size compared with placebo. Nifedipine was associated with more adverse effects than placebo.

Surgical aspects of third and subsequent renal transplants performed by the extraperitoneal access

Background. We reviewed our experience with third, fourth, and fifth renal transplants performed by the extraperitoneal access. Methods. The charts of 21 third and subsequent transplants performed extraperitoneally were reviewed. Surgical aspects, the occurrence of rejection episodes, delayed graft function (DGF), graft and patient survival were evaluated and compared with 1560 first transplants in adults with nonmanipulated fossa performed in the same period. Results. Transfusion was necessary in 52% of the retransplants and in 5.7% of the first transplants (P<0.0001). Mean operative time was 327 min for retransplants and 212 min for first transplants (P<0.0001). Surgical complications occurred in 4 patients (19%): two arterial thrombosis and two ureteral obstructions. DGF occurred in 11 patients (52%) among retransplants and in 453 (29%) among first transplants (P=0.028). Acute rejection occurred in 7 (33.3%) retransplants and in 530 first transplant patients (33.9%). The mean serum creatinine among retransplant patients 30 days and one year after transplantation was 2.5 mg/dl and 1.8 mg/dl. One-year graft survival was 57.1% (75% for live and 46% for cadaver donors) for retransplants and 86% for first transplant patients (P<0.0001). Conclusion. Third and subsequent transplants performed extraperitoneally are more time-consuming and require more transfusions in the perioperative period. A higher but acceptable incidence of arterial thrombosis and urinary obstruction were observed. One-year graft survival was better with live donor grafts, but was still lower when compared with first transplants using the same surgical technique.

Percutaneous Nephrolithotomy in Obese Patients: Comparison Between the Prone and Total Supine Position

BACKGROUND Percutaneous nephrolithotomy (PCNL) can be performed in the prone or in the supine position. Comparisons between the two techniques in obese patients are rare in the current literature. METHODS The records of obese patients (body mass index >30) who underwent PCNL in the prone or complete supine positions were reviewed. All patients had a noncontrast CT before and after the procedure. Stones were graded according to the Guy stone score and complications according to the Clavien grading. The stone-free rates, operative time, surgical complications, and hospital stay were analyzed. RESULTS A total of 56 PCNL were performed in 42 patients. Twenty-four PCNL were performed in the prone and 32 in the total supine position. Stone-free rate on the first postoperative day was 50% in the prone and 46.9% in the supine position (P=1.0). Final stone-free rates were 83.3% and 78.1%, respectively (P=0.74). Mean operative time was 164.6 minutes in the prone and 120.3 minutes in the supine position (P=0.0017), and hospital stay was 4.38 and 2.68 days (P=0.014), respectively. The transfusion rate was 20.8% in the prone and zero in the supine position patients (P=0.01). Excluding Guy IV stones, transfusion rate was 8.3% in the prone position (P=0.1). Significant surgical complications rate was 12.5% in the prone and 3.1% in the supine position (P=0.302). CONCLUSION PCNL performed in the prone or in the complete supine position in obese patients presents similar outcomes. The supine decubitus position has the advantages of a significantly shorter operative time and hospital stay.

Modified Complete Supine Percutaneous Nephrolithotomy: Solving Some Problems

BACKGROUND AND PURPOSE Percutaneous nephrolithotomy (PCNL) is the gold standard treatment for patients with renal stones larger than 2 cm. In this article, we aim to describe our modified technique with the patient in a complete supine position for PCNL (csPCNL). PATIENTS AND METHODS A total of 117 patients (120 renal units) who underwent csPCNL for large stones from November 2008 to November 2011 were prospectively evaluated. One surgeon worked in two different institutions and performed all operations. All patients underwent CT preoperatively, and the stones were classified according to the Guy score. Patients were placed in the supine decubitus position with the posterior axillary line located just outside the border of the surgical table, and the flank was extended to increase the space between the last rib and the iliac crest. The csPCNL was performed without a rolled towel under the flank, and the patients remained in the same position during the entire procedure. Success was evaluated based on CT findings at the end of follow-up. RESULTS There was no failure of access. The median operative time was 100 (20-240) minutes. The immediate and final success rates were 72.5% and 90.4%, respectively. The complication rate was 16.8% (12.7% of Clavien I or II and 4.1% of Clavien III or IV). There were no colon injuries or deaths. The median hospital stay was 48 (24-840) hours. CONCLUSION Modified csPCNL is a safe and effective procedure with excellent outcomes and a low rate of major complications. It provides a good area for renal puncture and surgical instrumentation.

Percutaneous nephrolithotomy: Current concepts.

Percutaneous nephrolithotomy (PNL) is the procedure of choice for large renal stones. Since its introduction in 1976, many aspects of the operative technique and the endoscopic equipments have had constant evolution, increasing the success rates of the procedure. We performed a literature search using Entrez Pubmed from January 2000 to July 2007 concerning PNL and many aspects related to all steps of the procedure. We could verify that PNL in supine position has been proved as an acceptable option, but more worldwide experience is necessary. Urologists must be trained to gain their own renal tract access. Minipercutaneous PNL still needs equipments improvements for better results. Tubeless PNL is increasing in popularity and different tract sealants have been studied. Medical prevention is proved to be effective against stone recurrence and should be always used after PNL. Although the evolution of the technique in the last 20 years, urologists must continue to improve their skills and develop new technologies to offer to the patients more and more a safe and effective option to treat large renal stones.

Atorvastatin Prevents the Downregulation of Aquaporin-2 Receptor After Bilateral Ureteral Obstruction and Protects Renal Function in a Rat Model

OBJECTIVE To assess the effects of atorvastatin (ATORV) on renal function after bilateral ureteral obstruction (BUO), measuring inulin clearance and its effect on renal hemodynamic, filtration, and inflammatory response, as well as the expression of Aquaporin-2 (AQP2) in response to BUO and after the release of BUO. METHODS Adult Munich-Wistar male rats were subjected to BUO for 24 hours and monitored during the following 48 hours. Rats were divided into 5 groups: sham operated (n = 6); sham + ATORV (n = 6); BUO (n = 6); BUO + ATORV (10 mg/kg in drinking water started 2 days before BUO [n = 5]; and BUO + ATORV (10 mg/kg in drinking water started on the day of the release of BUO [n = 5]). We measured blood pressure (BP, mm Hg); inulin clearance (glomerular filtration rate [GFR]; mL/min/100 g); and renal blood flow (RBF, mL/min, by transient-time flowmeter). Inflammatory response was evaluated by histologic analysis of the interstitial area. AQP2 expression was evaluated by electrophoresis and immunoblotting. RESULTS Renal function was preserved by ATORV treatment, even if initiated on the day of obstruction release, as expressed by GFR, measured by inulin clearance. Relative interstitial area was decreased in both BUO + ATORV groups. Urine osmolality was improved in the ATORV-treated groups. AQP2 protein expression decreased in BUO animals and was reverted by ATORV treatment. CONCLUSION ATORV administration significantly prevented and restored impairment in GFR and renal vascular resistance. Furthermore, ATORV also improved urinary concentration by reversing the BUO-induced downregulation of AQP2. These findings have significant clinical implication in treating obstructive nephropathy.

Management of chronic unilateral hematuria by ureterorenoscopy.

BACKGROUND AND PURPOSE Chronic unilateral hematuria is characterized by intermittent or continuous gross hematuria that cannot be diagnosed using standard radiology and hematology methods. In the past, it was managed with partial or total nephrectomy. In the age of minimally invasive procedures, however, endoscopy has enabled more accurate diagnosis and management. We analyzed our experience with transurethral ureterorenoscopy using a flexible ureteroscope to determine the feasibility and success of endoscopic management of renal hematuria. PATIENTS AND METHODS We reviewed the records of 13 patients who presented with chronic unilateral hematuria, in whom radiologic and laboratory tests failed to reveal the source of bleeding. In the cases in which the lesion was identified, after complete inspection of the collecting systems, the bleeding site was treated ureteroscopically with a holmium: yttrium-aluminum-garnet (YAG) laser. RESULTS Follow-up ranged from 4 to 60 months (mean 26 mos). During the follow-up of the 13 patients, 11 remained symptom-free, with only one session of flexible ureterorenoscopy necessary. Relapse occurred in two patients after 4 months and 6 months, respectively; during a second session of flexible ureteroscopy, the bleeding site was successfully identified and cauterized with a holmium:YAG laser. No surgical complications occurred. CONCLUSIONS Conservative treatment of patients with chronic unilateral hematuria should always be considered. Laser ureteroscopic treatment is an excellent method and should be considered as the first option for the management of chronic unilateral hematuria.