Publications by authors named "Francisco Tibor Dénes"

39 Publications

Urinary extracellular matrix proteins as predictors of the severity of ureteropelvic junction obstruction in children.

J Pediatr Urol 2021 Mar 27. Epub 2021 Mar 27.

Pediatric Urology Unit, Division of Urology, Hospital das Clínicas, University of São Paulo Medical School, Brazil.

Introduction: Ureteropelvic junction obstruction (UPJO) particularly represents a challenge in regard to management, as not all hydronephrosis (HN) represent a kidney-damaging state. Urinary biomarkers have been proposed as noninvasive tools. Extracellular matrix (ECM) proteins are associated with tissue fibrosis in the setting of UPJO and is poorly explored.

Objective: To investigate whether urinary ECM proteins are useful to discriminate the severity of urinary obstruction on unilateral UPJO.

Study Design: Children with unilateral UPJO were prospective enrolled. Urinary (u) matrix metalloproteinases (MMP-1,-2,-9 and TIMP-1,-2) as well as clinical characteristics were measured in the following groups: 26 children with obstructive HN at initial diagnosis and after six months of dismembered pyeloplasty; 22 children with non-obstructive HN at diagnosis and after six months of observation; 26 children without any urinary tract condition, as the control group. Results were assessed statistically using for homogenous groups, a one-way analysis of variances (ANOVA) and for nonparametric groups, Mann-Whitney test or Kruskal-Wallis test was performed. ROC curves were performed.

Results: Baseline samples demonstrated a higher concentration of uMMP-1/Cr, uMMP-2/Cr, u-TIMP-1/Cr and u-TIMP-2/Cr in obstructive HN group; uMMP-9/Cr levels were higher in non-obstructive HN group and all studied biomarkers had lower concentrations for the control group. On follow-up, for the obstructive HN group, urinary concentration of uTIMP-1/Cr and uTIMP-2/Cr decreased, and uMMP-1/Cr, uMMP-2/Cr and uMMP-9/Cr increased when comparing preoperative to postoperative values. In the non-obstructive HN group, all proteins analyzed were stable after six months of observation. ROC curves analysis showed a promising diagnostic profile for the detection of obstructive HN for uTIMP-1/Cr (area under the curve -AUC-; of 0.692), uTIMP-2/Cr (AUC of 0.678) and for uMMP-2/Cr (AUC of 0.655).

Discussion: The severity of kidney obstruction could correlate with the urinary ECM proteins concentration in this study. This is concordant with prior studies demonstrating that a disruption of the balance of accumulation/degradation of the ECM proteins occur on obstructive uropathy. Limitations of our study include the older age of our patients and that these markers had no influence at all on the surgical decision.

Conclusion: We demonstrate that obstructive HN have significantly higher uMMP-2, uTIMP-1 and uTIMP-2 concentrations. Particularly, uTIMP-2 levels were correlated to severity of obstruction and therefore, it might be a useful urinary biomarker to correctly allocate children with HN between surgical management vs follow-up. After pyeloplasty, uTIMP-1 and uTIMP-2 presented a progressive decrease postoperatively, which is also highly desirable for urinary markers.
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http://dx.doi.org/10.1016/j.jpurol.2021.03.017DOI Listing
March 2021

Can extended upper pole ureterectomy prevent ureteral stump syndrome after proximal approach for duplex kidneys?

Int Braz J Urol 2021 Jul-Aug;47(4):821-826

Unidade de Urologia Pediátrica, Divisão de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo - FMUSP, SP, Brasil.

Introduction: Symptomatic duplex kidneys usually present with recurrent urinary tract infection due to ureteral obstruction (megaureter, ureterocele or ectopic ureter) and/or vesicoureteral reflux. Upper-pole nephrectomy is a widely accepted procedure to correct symptomatic duplex systems with poor functioning moieties, also known as upper or proximal approach. The distal ureteral stump syndrome (DUSS) can be a late complication of this approach. There is no consensus upon the length of ureteral dissection and the better approach to symptomatic disease in duplex systems, so we aim to identify if extended ureteral dissection can prevent DUSS in top-down approach.

Materials And Methods: Forty-four consecutive patients with symptomatic duplex system were retrospectively classified into two groups: those with limited ureteral excision after heminephrectomy (HN) (group-1) and those with extended ureterectomy after HN (group-2). Patients were followed-up for at least 36 months regarding outcomes of distal ureteral stump.

Results: Overall complication was 20%. A total of 8 patients required unplanned further surgery in Group-1 (30%) whereas only 1 patient required unplanned surgery in group 2 (6%) (p=0.07). Subgroup analysis showed that Group-1 presented more DUSS requiring surgery during follow-up than group-2 (p=0.04). Factors possibly affecting complications incidence (such as ureterocele or ectopic ureter) did not differ between groups (p=0.72 and p=0.78).

Conclusion: Upper pole nephrectomy should be performed with extended distal ureteral dissection to prevent ureteral stump complications.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2020.0686DOI Listing
April 2021

Hidden incision ureterocystoplasty: step-by-step description of a novel technique.

Cent European J Urol 2020 15;73(4):575. Epub 2020 Oct 15.

Hospital das Clínicas, University of São Paulo Medical School, Pediatric Urology Unit, Division of Urology, São Paulo, Brazil.

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http://dx.doi.org/10.5173/ceju.2020.0241.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848838PMC
October 2020

Laparoscopic hidden incision endoscopic surgery (hides) nephrectomy VS. Traditional laparoscopic nephrectomy: Non-inferior surgical outcomes and better cosmetic results.

J Pediatr Urol 2021 Jan 20. Epub 2021 Jan 20.

Pediatric Urology Unit, Division of Urology, Hospital Das Clínicas, University of São Paulo Medical School, Brazil.

Introduction: The benefits of laparoscopic total nephrectomy in pediatric patients are well established. Traditional Ports placement (TPP) still follows Clayman's classic description: except for the umbilical scar, the other laparoscopic scars are exposed in the abdomen. Advances in robotic surgery permitted the development of HidES (hidden incision endoscopic surgery) technique, to obtain a better final cosmetic aspect with the scars located intraumbilically and in the hypogastric region, in an area easily hidden by underwear. As robotic surgery is related to higher costs and lacks availability, a pure laparoscopic HidES technique was developed.

Objectives: 1.Evaluate safety and efficacy of pure laparoscopic HidES.2. Compare HidES with TPP nephrectomy series to assess non-inferiority and cosmetic outcomes.

Study Design: Twenty-one pediatric patients with symptomatic poor functioning kidneys (DMSA<10%) underwent HidES nephrectomy. Their intra and post-operative outcomes were recorded prospectively. HidES group was compared to an equivalent group of thirty-two patients who underwent TPP nephrectomy.

Results: There were no conversions to open surgery in the TPP or HidES groups. There was a significant difference in operative time between HidES (53.4min) and TPP (109.4 min), with p = 0.004 and the mean bleeding volume was 65.5 ml. There was no significant difference in bleeding between HidES (71 ml) and TPP (120 ml) (p = 0.06), no intraoperative complications and no complications above Clavien-Dindo II during the 6-week follow-up. Satisfaction reached 100% in HidES group, whereas in TPP satisfaction was 63% (p = 0.004).

Discussion: HidES benefit over TPP is to conceal visible scars above underwear, improving cosmetical outcome. A prospective HidES group was compared to a retrospective TPP database due to decreasing number of nephrectomies being performed, which is a limitation of our study. HidES surgeries were performed by pediatric urologists (associate staff) while TPP group surgeries were performed by PGY-5 urological residents assisted by the associate staff, which is a clear limitation and can explain shorter operative times for HidES. During HidES surgeries an improved visualization of the operative field by the inferior trocar positioning was noted, which helps the posterior dissection of renal pedicle. Previous published study comparing robotic TPP and HidES pyeloplasty showed equal results for both groups with cosmetic advantages. Objective satisfaction was assessed with statistically advantage in favor of HidES procedure, consonant with other evidence that supports the benefit of scar location in patient and parental satisfaction.

Conclusion: HidES nephrectomy proved to be safe, feasible and not inferior to the traditional nephrectomy in experienced hands, with better cosmesis.
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http://dx.doi.org/10.1016/j.jpurol.2021.01.018DOI Listing
January 2021

AUTHOR REPLY.

Urology 2020 Nov;145:295-296

Human Reproduction Unit, Division of Urology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Brazil.

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http://dx.doi.org/10.1016/j.urology.2020.04.128DOI Listing
November 2020

Management of functioning pediatric adrenal tumors.

J Pediatr Surg 2021 Apr 1;56(4):768-771. Epub 2020 Sep 1.

Pediatric Urology Unit, Division of Urology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, Brazil.

Aim: The aim of this study is to present our experience in the management of hormonally active adrenal tumors in children.

Material And Methods: We did a retrospective chart review of all children with hormonally active adrenal tumors evaluated at the endocrinology clinic and operated at our institution between 1983 and 2019.

Results: There were 75 patients included in the study, 58 with adrenocortical tumors (ACTs) and 17 with pheochromocytomas (PCCs). Within the group of patients with ACTs, there were 41 females and 17 males. The mean age was 58.3 (SD: 87.9; range: 9-211) months. The clinical manifestation of the tumor's hormonal activity was virilization in 37 cases, Cushing syndrome in 5, and mixed in 16. A positive family history was present in 11 patients (18.9%). The mean tumor size was 48.2 (SD: 22.4; range: 7-120) mm. The pathological diagnosis was adenoma in 42 cases, carcinoma in 15 cases, and macronodular hyperplasia in 1. Median follow-up was 192 (range: 50-290) months. Tumor recurrence occurred in 6 patients (10.3%), and there were three disease-related deaths (5%). Within the group of patients with PCCs, there were 11 males and 6 females. The mean age was 146.7 (SD: 71.2; range: 60-216) months. A positive family history was present in 7 patients (41.2%). The mean tumor size was 36.6 (SD: 16.7; range: 7-120) mm. The pheochromocytoma was classified as benign in 15 cases and as malignant in 2. During a median follow-up of 180 (range: 127-300) months, recurrence was observed in 6 cases (35.3%) and disease-related death in 1 case (5.9%).

Conclusions: Proper diagnosis and management at our referral center were associated with a high cure rate, even in cases of malignant tumors. Familial surveillance is highly recommended.

Level Of Evidence: Level IV.
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http://dx.doi.org/10.1016/j.jpedsurg.2020.08.020DOI Listing
April 2021

Prune perineum surgical correction - Treatment of a rare syndrome.

J Pediatr Urol 2020 10 19;16(5):723-724. Epub 2020 Aug 19.

Urology Unit, Hospital Das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.

Introduction: Prune Perineum Syndrome (PPS) is rare, with only three cases described in the literature. Treatment requires abdominal and pelvic surgeries. Our goal is to provide a video with steps of the surgical corrections of this syndrome.

Materials And Methods: We present a case of an 8 months-old boy with PPS. At our first evaluation, he had already been submitted to a colostomy with mucous fistula and a vesicostomy.

Results: By the time of this publication, he had been submitted to six surgical procedures. First, osteotomy, followed by colostomy, cystoscopic evaluation, cystoplasty, perineal and abdominal correction with a dual mesh, bilateral orchidopexy, treatment of the vesicocolonic fistula, sigmoidectomy and appendicectomy. He is 6 years old, walks with no assistance, has satisfactory abdominal tonus which allows him to void with Valsalva Maneuver. Clean intermittent catheterization is also performed. He had no UTI since his first surgery. Although submitted to several procedures, treatment is not yet concluded. A future urethral dilation together with a genitoplasty might improve his quality of life.

Conclusion: PPS is a very rare condition, with scarce literature concerning its treatment. Multiple procedures might be necessary to correct malformations and improve patient's quality of life.
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http://dx.doi.org/10.1016/j.jpurol.2020.08.013DOI Listing
October 2020

Gonadal Function and Reproductive System Anatomy in Postpubertal Prune-Belly Syndrome Patients.

Urology 2020 Nov 13;145:292-296. Epub 2020 Jun 13.

Human Reproduction Unit, Division of Urology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Objective: To gain insight into the causes of infertility in Prune Belly Syndrome (PBS) by evaluating reproductive system anatomy and gonadal function in a cohort of postpubertal PBS patients.

Methods: We contacted all PBS patients 14 years old or older treated and followed at our institution. Age at orchiopexy, type of orchiopexy (with or without ligation of gonadal vessels), testicular volumes and positions were evaluated. Pelvic magnetic resonance imaging (to assess prostate size, seminal vesicles, and vas) and hormonal profile were ordered. Sperm analysis and analysis of urine after masturbation were performed after informed consent.

Results: Fifteen patients were included in this study. Mean age was 19.2 years. Mean age at orchiopexy was 18 months. Fourteen patients (93.3%) had normal and orthotopic testes. Mean testicular volume was 6.9 cc. Eight patients collected semen, 5 of them (62.5%) had spermatozoa in the specimen and motile sperm was found in 4 (50%). Mean hormone levels were LH: 5.3 mg/dL, FSH: 6.9 mg/dL, testosterone 531 mg/dL. Magnetic resonance imaging revealed hypoplastic prostates in 66.6% and unilateral seminal vesicle absence in 66.6%. No vasal abnormality was noted.

Conclusion: Patients with PBS may have normal sexual hormonal levels. Motile spermatozoa were found in half of the patients. Our study highlights a high prevalence of prostate and seminal vesicle abnormalities that may represent an important cause for their infertility.
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http://dx.doi.org/10.1016/j.urology.2020.04.124DOI Listing
November 2020

High Prevalence of Alterations in DNA Mismatch Repair Genes of Lynch Syndrome in Pediatric Patients with Adrenocortical Tumors Carrying a Germline Mutation on .

Cancers (Basel) 2020 Mar 7;12(3). Epub 2020 Mar 7.

Laboratório de Hormônios e Genética Molecular LIM/42, Unidade de Suprarrenal, Serviço de Endocrinologia e Metabologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo 0540396, Brasil.

Adrenocortical cancer is a rare malignant neoplasm associated with a dismal prognosis. Identification of the molecular pathways involved in adrenal tumorigenesis is essential for a better understanding of the disease mechanism and improvement of its treatment. The aim of this study is to define the prevalence of alterations in DNA mismatch repair (MMR) genes in Lynch syndrome among pediatric patients with adrenocortical neoplasia from southern Brazil, where the prevalence of a specific germline mutation (p.Arg337His) is quite high. Thirty-six pediatric patients were retrospectively evaluated. Immunohistochemistry (IHC) for the MMR enzymes MLH1, MSH2, MSH6, and PMS2, as well as next-generation sequencing (NGS) were performed. For IHC, 36 pediatric tumors were tested. In all of them, the expression of all evaluated MMR proteins was well-preserved. For NGS, 35 patients with pediatric tumor were tested. Three patients (8.57%) with the p.Arg337His germline mutation presented pathogenic and likely pathogenic variants in the genes (two in and one in ). The prevalence of altered genes among pediatric patients was elevated (8.57%) and higher than in colorectal and endometrial cancer cohorts. Pediatric patients with adrenocortical tumors should, thus, be strongly considered as at genetic risk for Lynch syndrome.
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http://dx.doi.org/10.3390/cancers12030621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139318PMC
March 2020

Management of 46,XY Differences/Disorders of Sex Development (DSD) Throughout Life.

Endocr Rev 2019 12;40(6):1547-1572

Division of Endocrinology, Department of Internal Medicine, University of São Paulo Medical School, University of São Paulo, São Paulo, Brazil.

Differences/disorders of sex development (DSD) are a heterogeneous group of congenital conditions that result in discordance between an individual's sex chromosomes, gonads, and/or anatomic sex. Advances in the clinical care of patients and families affected by 46,XY DSD have been achieved since publication of the original Consensus meeting in 2006. The aims of this paper are to review what is known about morbidity and mortality, diagnostic tools and timing, sex of rearing, endocrine and surgical treatment, fertility and sexual function, and quality of life in people with 46,XY DSD. The role for interdisciplinary health care teams, importance of establishing a molecular diagnosis, and need for research collaborations using patient registries to better understand long-term outcomes of specific medical and surgical interventions are acknowledged and accepted. Topics that require further study include prevalence and incidence, understanding morbidity and mortality as these relate to specific etiologies underlying 46,XY DSD, appropriate and optimal options for genitoplasty, long-term quality of life, sexual function, involvement with intimate partners, and optimizing fertility potential.
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http://dx.doi.org/10.1210/er.2019-00049DOI Listing
December 2019

Single-stage Abdominoplasty Using Groin Flaps Without Osteotomies: Management of Exstrophy-epispadias Complex.

Urology 2018 Oct 19;120:266. Epub 2018 Jul 19.

Divisao de Urologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil.

Background And Objective: The optimal treatment for children born with exstrophy-epispadia complex is still a matter of debate. We demonstrate the Single-Stage Abdominoplasty using Groin Flap technique to close the abdominal wall of children with classic bladder exstrophy (CBE) without osteotomy neither radical soft tissue mobilization. Advantages over current techniques are less risk of penile tissue loss and avoidance of osteotomies.

Material And Methods: Abdominal wall repair consists in using the hypogastric skin, rectus, and obliquus externus abdominalis muscle fascial flaps. These groin flaps are rotated medially resulting in a very strong abdominal wall support. Groin flaps are made of rectus anterior fascia rotated medially, flipped over, and sutured with Prolene sutures to close the defect. By rotating the fascial flaps medially, complete reinforcement of the abdominal wall to the level of the pubic bone is achieved. This permits abdominal closure maintenance without tension.

Results: Groin flap was applied to 128 patients with CBE referenced from all over the country. Most of these patients returned to their home areas making difficult their follow up. However, we have 44 cases that have regular clinical visits. Mean follow-up was 10.3 ± 4.5 years (2 years 8 months-16 years). Successful closure was achieved in 43 patients (97.7%) as a single procedure; one patient had a complete wound dehiscence and needed another reconstruction (2.2%). Four patients (9.1%) presented abdominal hernias that needed surgical management. When continence is evaluated, we present similar literature rates (60%). CONCLUSION: Abdominal reconstruction using Groin flaps has advantages over the traditional approaches to CBE. It reduces the surgical steps and facilitates the closure of the abdominal wall without the need of osteotomies and consequent immobilization during the postoperative period. It is feasible at any age and can be also very useful as a salvage technique even after previous failed procedures. Finally, it minimizes the number of surgeries.
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http://dx.doi.org/10.1016/j.urology.2018.07.001DOI Listing
October 2018

Transperitoneal laparoscopic pyeloplasty in children: does upper urinary tract anomalies affect surgical outcomes?

Int Braz J Urol 2018 Mar-Apr;44(2):370-377

Unidade de Urologia Pediátrica, Faculdade de Medicina da Universidade de São Paulo - São Paulo, SP, Brasil.

Objective: To assess the feasibility and outcomes of laparoscopic pyeloplasty in children with complex ureteropelvic junction obstruction (UPJO) and compare to children with iso-lated UPJO without associated urinary tract abnormalities.

Material And Methods: Medical records of 82 consecutive children submitted to transperitoneal laparoscopic pyeloplasty in a 12-year period were reviewed. Eleven cases were con-sidered complex, consisting of atypical anatomy including horseshoe kidneys in 6 patients, pelvic kidneys in 3 patients, and a duplex collecting system in 2 patients. Patients were di-vided into 2 groups: normal anatomy (group 1) and complex cases (group 2). Demographics, perioperative data, outcomes and complications were recorded and analyzed.

Results: Mean age was 8.9 years (0.5-17.9) for group 1 and 5.9 years (0.5-17.2) for group 2, p=0.08. The median operative time was 200 minutes (180-230) for group 1 and 203 minutes (120-300) for group 2, p=0.15. Major complications (Clavien ≥3) were 4 (5.6%) in group 1 and 1 (6.3%) in group 2, p=0.52. No deaths or early postoperative complications such as: urinoma or urinary leakage or bleeding, occurred. The success rate for radiologic improvement and flank pain improvement was comparable between the two groups. Re-garding hydronephrosis, significant improvement was present in 62 patients (93.4%) of group 1 and 10 cases (90.9%) of group 2, p=0.99. The median hospital stay was 4 days (IQR 3-4) for group 1 and 4.8 days (IQR 3-6) for group 2, p=0.27.

Conclusions: Transperitoneal laparoscopic pyeloplasty is feasible and effective for the management of UPJO associated with renal or urinary tract anomalies.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2017.0224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050553PMC
May 2018

Editorial Comment.

J Urol 2017 09 20;198(3):700. Epub 2017 Jun 20.

Division of Urology, University of São Paulo Medical School, São Paulo, Brazil.

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http://dx.doi.org/10.1016/j.juro.2017.03.151DOI Listing
September 2017

Videolaparoscopic radical nephrectomy after chemotherapy in the treatment of Wilms' tumor: Long-term results of a pioneer group.

J Pediatr Urol 2017 Feb 19;13(1):50.e1-50.e5. Epub 2016 Oct 19.

Uropediatric Unit, Division of Urology, Hospital da Clínicas, University of São Paulo Medical School, São Paulo, Brazil. Electronic address:

Introduction: A high cure rate for Wilms' tumor has been achieved using a multidisciplinary approach. The natural step forward is to offer the benefits of a minimally invasive technique for surgery, which is an obligatory part of treatment. Nevertheless, some authors resist using videolaparoscopic radical nephrectomy (VRN) because of concerns about reducing the cure index.

Methods: The present study included children with unilateral Wilms' tumor treated from December 2003 to December 2015 with neoadjuvant chemotherapy followed by VRN. Patients were selected based on the size of their tumors compared with the contralateral kidney, and on their stature.

Results: VRN was performed in 24 patients of age range 10-93 months, with an average of 38.04 ± 23.37 months. The tumoral kidney's largest diameter after chemotherapy averaged 10% of a patient's height. There was no tumor rupture or spillage and no patient presented intra or immediate postoperative complications, except for prolonged ileum in two patients. One patient required intraoperative transfusion because of preoperative anemia. Another developed a late herniation in the umbilical port that required surgical correction. After an average of 6.65 years of follow-up, two patients presented relapse: one with a stage IV disease had relapse in the lung and another with a stage III, involving the liver, had local relapse because of an unwanted delay in the adjuvant treatment.

Conclusion: VRN can be considered a feasible alternative to open surgery in selected cases of children with Wilms' tumor. The present experience shows that besides the benefits of minimally invasive procedures and better cosmetic results, there is no evidence of increased tumor rupture or spillage, peritoneal or port site metastasis, and the long-term oncological results are the same as open procedures.
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http://dx.doi.org/10.1016/j.jpurol.2016.09.004DOI Listing
February 2017

Urethral duplication type influences on the complications rate and number of surgical procedures.

Int Braz J Urol 2017 Nov-Dec;43(6):1144-1151

Unidade de Urologia Pediátrica, Divisão de Urologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Brasil.

Introduction: Urethral duplication is rare. Characterized by the presence of two urethral channels. This anomaly presents a great variety of clinical findings that depend on the type of duplication that often is associated with other anomalies.

Material And Methods: We report thirteen boys with urethral duplication managed in our institution between 1988-2015. Clinical findings, associated anomalies, treatment of urethral duplication and our results are described. Patients were classified according to Effmann classification.

Results: Mean patient's age was 38.3±34.7 months (3-136 months). Mean follow-up was 7.7±3.4 years (3y8m-14y2m). Type II A2 was the most common pattern (8/13 patients, 61.5%), followed by type IA (3/13 patients, 23%) and IIA1 (2/13 patients, 15.3%). The most frequent clinical manifestations were urinary tract infections (UTI) observed in 11/13 patients (84.6%) and anal urinary leakage, found in 7/13 patients (53.8%). Associated anomalies were found in 9/13 patients (69.2%). Required surgeries were 3.53±2.84 procedures per patient. Considering groups: Type IIA2 4.25±3.28, type IIA1 4±1.41 and type IA 1.33±0.57 needed procedures per patient. Complications rate were 0% for type IA, 50% for type IIA1 and 75% for type IIA2.

Conclusions: Patients with incomplete duplication (type I A or I B) can totally be asymptomatic, with no need of surgical correction. Type IIA2 is the most complex form of duplication to correct and multiple procedures might be required because of the very hypoplastic orthotopic dorsal urethral tissue. Surgical treatment should be individualized and parents should be advised on complications and need of multiple surgeries according to urethral duplication type.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2016.0269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734079PMC
March 2018

Surgical Treatment after Failed Primary Correction of Urogenital Sinus in Female Patients with Virilizing Congenital Adrenal Hyperplasia: Are Good Results Possible?

Front Pediatr 2016 27;4:118. Epub 2016 Oct 27.

Division of Urology, Hospital das Clínicas, School of Medicine, University of São Paulo , São Paulo , Brazil.

Purpose: Genital reconstruction in female patients with virilizing congenital adrenal hyperplasia (CAH) is very challenging. Our aim was to evaluate the techniques employed to treat complications after failure of primary urogenital sinus (UGS) surgery, as well as the result of these reoperations.

Patients And Methods: Twenty girls with virilizing CAH who were previously submitted to genitoplasty in our service and elsewhere had recurrent UGS stenosis and vaginal introitus stenosis that required surgical treatment. The main symptoms were recurrent urinary tract infection (UTI) in nine, dyspareunia in six, and hematocolpos in three (two associated with sepsis). The anatomical findings were the persistence of UGS with stenosis in 17 patients and vaginal introitus stenosis in 3. The mean age at procedure was 15.2 years, averaging 13.1 years after the first surgery. The surgical techniques employed were isolated perineal flap in 17 patients and perineal flap with partial mobilization of UGS in 3. The mean follow-up after the procedure was 4.8 years (varying from 1 to 17 years).

Results: Vaginal dilations were performed after surgery in 15 patients. Good functional and anatomical results were obtained in 15 patients, with vaginal introitus amenable to dilators of 3.0 cm in diameter. Five patients with high vaginal insertion had recurrent vaginal stenosis and required a surgical revision. No patients presented menstrual obstruction or UTI after surgery. Eight of the 15 adult patients are sexually active.

Conclusion: The reoperation to treat failed primary UGS treatment using Y-V flap and partial mobilization techniques associated with vaginal dilations, promoted good anatomical, and functional results with low morbidity in 75% of the patients.
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http://dx.doi.org/10.3389/fped.2016.00118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081340PMC
October 2016

Reoperative Laparoscopic Ureteropelvic Junction Obstruction Repair in Children: Safety and Efficacy of the Technique.

J Urol 2017 03 24;197(3 Pt 1):798-804. Epub 2016 Oct 24.

Division of Urology, University of São Paulo School of Medicine, São Paulo, Brazil.

Purpose: Failure after pyeloplasty for ureteropelvic junction obstruction in children may occur in up to 10% of cases. Therapeutic options include Double-J® stent placement, endoscopic treatment and reoperation. Laparoscopic and robotic reoperative modalities seem safe and efficacious, although pediatric series are limited in the literature. We report the largest known series of reoperative laparoscopic ureteropelvic junction obstruction repair in children and compare this approach to primary laparoscopic pyeloplasty.

Materials And Methods: We reviewed all children undergoing laparoscopic pyeloplasty at a single institution from 2004 to 2015. Reoperative laparoscopic ureteropelvic junction obstruction repair was compared to primary pyeloplasty. Groups were analyzed regarding demographics, operative time, complications, length of hospital stay and success, defined by improvement of symptoms, ultrasound and renogram.

Results: We identified 11 cases of reoperation (8 redo pyeloplasties and 3 ureterocalycostomies) and 71 primary pyeloplasties. Groups were not different in age, gender or weight. Median followup was 37 months. Median time between primary pyeloplasty and reoperation was 34 months. Median operative time was 205 minutes for the reoperative group and 200 for primary pyeloplasty (p = 0.98). Length of stay was longer in the reoperative group (p = 0.049), although no major complications were recorded in this group. All reoperative cases and 96% of primary pyeloplasty cases remained asymptomatic following surgery (p = 0.99). Postoperative improvement was similar for both groups on ultrasound (90% for reoperation vs 92% for primary pyeloplasty, p = 0.99) and renogram (80% vs 88%, p = 0.6).

Conclusions: Laparoscopy seems to be safe and effective for management of failed pyeloplasty in children. Based on our data, reoperation is as safe and effective as primary pyeloplasty.
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http://dx.doi.org/10.1016/j.juro.2016.10.062DOI Listing
March 2017

Laparoscopic Pyeloplasty in children with Horseshoe Kidney.

Int Braz J Urol 2017 Mar-Apr;43(2):375

Divisão de Urologia do Departamento de Cirurgia, Universidade de São Paulo, SP, Brasil.

Introduction: Horseshoe kidney occurs in 1 per 400-800 live births and are more frequently observed in males (M:F 2:1). Ureteropelvic junction obstruction (UPJO) is commonly associated with horseshoe kidneys. The variable blood supply, presence of the isthmus and high insertion of the ureter contribute to this problem.

Case Report: An asymptomatic 6 year-old boy presented with antenatal hydronephrosis. Ultrasonography and CT scan demonstrated left UPJO associated with a horseshoe kidney. DMSA showed 33% of function on the left side. DTPA showed a flat curve and lack of washout. A left dismembered laparoscopic pyeloplasty was performed after identification of crossing vessels and abnormal implantation of the ureter. After one year, the child is asymptomatic. DTPA demonstrated a good washout curve.

Results: Our cohort consisted of six patients, five males and one female, with a mean age of 6 years (range 6m-17 years) and a mean follow-up of 3 years. Ureteropelvic junction obstruction was more common on the left side. Symptoms appeared only in 34% of the cases. Mean operative time was 198 minutes (range 120-270 minutes). Crossing vessels were common (observed in 50% patients). High implantation of ureter was seen in 67% patients and intrinsic obstruction in 83%. Surgical difficulties were found in two cases. Hospital stay was 4.3 days (3 to 6 days), with only one patient having a mild complication (pyelonephritis). All cases had clinical and radiologic improvement.

Conclusion: Laparoscopic pyeloplasty is safe and feasible in children with UPJO in horseshoe kidneys, with good results and minimal morbidity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433381PMC
http://dx.doi.org/10.1590/S1677-5538.IBJU.2016.0042DOI Listing
August 2017

MMP9 overexpression is associated with good surgical outcome in children with UPJO: Preliminary results.

BMC Urol 2016 Jul 23;16(1):44. Epub 2016 Jul 23.

Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.

Background: Ureteropelvic junction obstruction (UPJO) diagnosed prenatally occurs in 1:150 - 1:1200 pregnancies. Although many studies investigating the molecular changes of this obstructed segment have been performed, the underlying mechanisms are still unclear. The role of extracellular matrix (ECM) components remains controversial, and the investigations in the field of ECM changes, might help the better understanding of the pathogenesis of this common condition. The aim of the present study was to investigate for the first time in the literature whether MMP9 and its specific inhibitors, TIMP1 and RECK, are expressed in a reproducible, specific pattern in UPJ.

Methods: UPJO specimens were obtained from 16 children at the time of dismembered pyeloplasty due to intrinsic UPJ stenosis. Expression levels of the three genes (MMP9, TIMP1 and RECK) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Then correlated the expression levels of the genes according to grade study population that was divided in 2 categories according to Society of Fetal Urology classification, grade 3 (moderate) and 4 (severe). For DTPA we subdivided the childrens in 2 groups, obstructive (T 1/2 more than 20 min) and partial obstructive (T 1/2 between 10 and 20 min) and success in a surgery was defined as decrease in T 1/2 to less than 20 min, absence of symptoms, improving renal function and decreasing dilatation on successive exams.

Results: MMP9 was underexpressed and TIMP1 and RECK were overexpressed in children with obstructive DTPA but the differences were not statistically significant. Overexpression of MMP9 was higher among patients with severe grade of UPJ compared to those with moderate grade. Surprisingly expression levels of MMP-9 was three times higher in children who were successfully treated by surgery (n = 10) (p = 0.072), so those who were followed for at least 1 year after surgery and remained with improvement in renal function and decreasing dilation on intravenous urogram and TIMP-1 was underexpressed in 100 % of this cases (p = 0.00).

Conclusions: We showed an increase in expression of MMP9 and a decrease in expression of TIMP1 in children who improving renal function and decreasing dilation after surgery. We believe that the higher expression of MMP9 in these cases can reflect an increase in degradation and remodeling process that could be used as a marker for surgical outcome.
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http://dx.doi.org/10.1186/s12894-016-0162-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958283PMC
July 2016

Testicular Torsion-Can We Improve the Management of Acute Scrotum?

J Urol 2016 06 17;195(6):1650-1. Epub 2016 Mar 17.

Urology Service, Cardon Children's Medical Center, Mesa, Arizona.

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http://dx.doi.org/10.1016/j.juro.2016.03.066DOI Listing
June 2016

Malignant paraganglioma in children treated with embolization prior to surgical excision.

World J Surg Oncol 2016 Feb 2;14(1):26. Epub 2016 Feb 2.

Division of Urology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.

Background: Paragangliomas (PGL) are rare tumors derived from neural crest cells, whose origins may vary along the chain of the sympathetic nervous system. Such tumors are often characterized by secretion of catecholamines, but sometimes they are biochemically inactive, which makes diagnosis often challenging. Malignant paraganglioma is defined by the presence of this tumor at sites where chromaffin cells are usually not found or by local invasion of the primary tumor. Recurrence, either regional or metastatic, usually occurs within 5 years of the initial complete resection but long-term recurrence is also described. Malignancy is often linked to a SDHB mutation. Preoperative embolization has been applied in the surgical management of PGLs with the objective to decrease intra-operative blood loss and surgery length without complications.

Case Presentation: We report two cases of patients with abdominal or pelvic malignant PGLs who have been treated surgically at our center after preoperative embolization. Surgery was a very challenging procedure with multiple surgical teams involved and embolization did not prevent major blood loss and intraoperative complications. Patients required adjuvant treatment with either chemotherapy or radiotherapy.

Conclusions: Many studies in the adult population have established recommendations for the diagnosis and therapeutic management of PGL, but few studies concern the pediatric population. Because malignant PGL is more important in the pediatric population, screening and early diagnosis of PGL is advisable in children with genetic predisposing. Surgical resection is the mainstay of treatment, but a multimodal approach is often required due to the complexity of cases.  The role of preoperative embolization is not established and in our experience it has provided little benefit and major complications.
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http://dx.doi.org/10.1186/s12957-016-0778-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736257PMC
February 2016

Response to commentary to "27 years of experience with the comprehensive surgical management of prune belly syndrome".

J Pediatr Urol 2015 Oct 4;11(5):279. Epub 2015 Aug 4.

Uropediatric Unit, Division of Urology, University of São Paulo Medical School, Brazil.

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http://dx.doi.org/10.1016/j.jpurol.2015.06.012DOI Listing
October 2015

Serum and Urinary Values of CA 19-9 and TGFß1 in a Rat Model of Partial or Complete Ureteral Obstruction.

Eur J Pediatr Surg 2015 Dec 5;25(6):513-9. Epub 2015 Jan 5.

Division of Nephrology, University of São Paulo, São Paulo, Brazil.

Introduction: Abnormal levels of serum and urinary markers occur in the presence of renal damage associated to obstructive uropathy. Urinary and serum transforming growth factor beta 1 (TGFß1) and carbohydrate antigen (CA 19-9) have not yet been evaluated in an experimental model of obstructive uropathy.

Material And Methods: Rats were divided into seven groups: reference, sham operation, unilateral nephrectomy, complete unilateral ureteral obstruction, partial unilateral ureteral obstruction, partial bilateral ureteral obstruction, and unilateral nephrectomy with contralateral partial ureteral obstruction. Kidney and ureter morphometry, TGFß1 and CA 19-9 serum and urinary concentrations and CA 19-9 renal tissue expression were analyzed. Correlation of these markers to complete, partial obstruction, or unobstructed groups was performed.

Results: Pathological findings correlated positively with the degree of ureteral obstruction, but negatively with urinary CA 19-9 levels. Marked underexpression of CA 19-9 was observed in kidneys with complete ureteral obstruction. No statistically significant differences were found for urinary and serum TGFß1 and also for serum CA 19-9.

Conclusion: Urinary CA 19-9 correlated negatively with ureteral obstruction grade. Immunohistochemistry depicted CA 19-9 expression on epithelial tubular cells cytoplasm, suggesting renal origin. Serum and urinary TGFß1 did not show alterations in response to severity and length of urinary obstruction, which might be associated with less intense renal remodeling.
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http://dx.doi.org/10.1055/s-0034-1395263DOI Listing
December 2015

Wilms tumor: a retrospective study of 32 patients using videolaparoscopic and open approaches.

Urology 2014 Jul 22;84(1):191-5. Epub 2014 May 22.

Department of Urology, University of São Paulo Medical School, São Paulo, Brazil.

Objective: To compare videolaparoscopic nephrectomy and the open technique as treatments for Wilms tumor, specifically the surgical results, immediate and long-term complications, and patient survival.

Methods: A review of charts of children with unilateral Wilms tumor was performed. There were 2 surgical groups: (1) only open surgery and (2) videolaparoscopy. Complications, transfusion, ruptures, margins, conversions, lymph nodes, and relapse were analyzed.

Results: Seventeen children underwent laparoscopic nephrectomy and 15 underwent open nephrectomy. Mean surgical time was 164.71±26.07 minutes for the laparoscopic group, and there were no conversions or ruptures. The mean specimen weight was 145.01±105.85 g for the laparoscopic group and 257.40±162.70 g for the open surgery group. There was 1 preoperative rupture in the open surgery group. Transfusions were not required in either group. The surgical margins were positive in 1 of 17 cases (5.9%) in the laparoscopic group and in 3 of 15 cases (20%) in the open surgery group. One of the 17 (5.9%) laparoscopy-treated patients and 2 of the 15 open surgery-treated patients (13.3%) presented with local tumor relapse. The 5-year event-free survival rate was 93.3% (95% confidence interval, 0.61-0.99) for the laparoscopic group and 79.6% (95% confidence interval, 0.37-0.95] for the open surgery group (P=.446).

Conclusion: Both techniques showed similar immediate and long-term results.
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http://dx.doi.org/10.1016/j.urology.2014.02.026DOI Listing
July 2014

Long-term followup of a large cohort of patients with ovotesticular disorder of sex development.

J Urol 2014 May 26;191(5 Suppl):1532-6. Epub 2014 Mar 26.

Division of Endocrinology, Hospital das Clínicas, School of Medicine, University of São Paulo, São Paulo, Brazil.

Purpose: We present the followup of a large cohort of patients with ovotesticular disorder of sex development treated at a single tertiary center.

Materials And Methods: We reviewed the records of 20 patients with ovotesticular disorder of sex development. We retrospectively evaluated clinical and surgical characteristics. A prospective study was also performed, including evaluation of surgical results, gonadal function, sexual activity and voiding symptoms of these patients during adulthood.

Results: All patients had ambiguous genitalia, including 18 with a 46,XX karyotype and 2 with a 46,XX/46,XY karyotype. Gender assignment at birth was male in 13 patients and female in 7. Three females were later reassigned to the male gender. Bilateral gonadectomy was performed in 10 patients. Testicular tissue was preserved in 8 males and ovarian tissue was preserved in 2 females. Average followup was 25 years (range 4 to 46). Puberty started spontaneously in 14 patients between ages 11 and 14 years. Seven patients showed spontaneous puberty after conservative gonadal surgery and 4 required hormonal replacement during adulthood. The most frequent complications in males were urethral fistula in 6 and late urethral stenosis in 3. Two patients with urethral stenosis had symptoms 10 years postoperatively. One female presented with temporary dyspareunia. In adulthood 8 males and 2 females reported sexual activity. All male patients reported orgasm and 2 reported ejaculation.

Conclusions: Male gender assignment was more prevalent. Long-term followup revealed adequate pubertal development and sexual activity. Complications involving the urethra developed frequently in male patients.
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http://dx.doi.org/10.1016/j.juro.2013.10.037DOI Listing
May 2014

Monti's principle in the treatment of congenital uterovesical fistula.

Urology 2014 May 26;83(5):1170-2. Epub 2014 Feb 26.

Pediatric Urology Unit, Division of Urology, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil.

Congenital uterovesical fistula is rare and generally associated with genital tract abnormalities derived from mullerian ducts or urogenital sinus. Management is usually challenging, and it involves vaginal reconstruction. A 15-year-old female patient presented with a 2-year history of cyclical hematuria. Investigation revealed a bicornuate uterus and complete vaginal agenesis associated with congenital uterovesical fistula. The fistula was repaired, and a neovagina was created using Monti's technique. Postoperative recovery was uneventful with normal voiding and initiation of regular menstruation through the neovagina. We discuss the options of vaginal reconstruction and stress the advantages of the technique used in this case.
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http://dx.doi.org/10.1016/j.urology.2013.12.040DOI Listing
May 2014

Pediatric genitourinary oncology.

Front Pediatr 2013 Dec 16;1:48. Epub 2013 Dec 16.

Uropediatric Unit, Division of Urology, Hospital das Clínicas, University of São Paulo , São Paulo , Brazil.

Tumors of the kidney, bladder, prostate, testis, and adrenal represent a large part of the adult urologic practice, but are relatively infrequent in children. The natural history and management of these tumors in the pediatric age is different from that of the adults. As result of the successful work of several clinical trial groups in recent decades, there has been a significant improvement in their cure rates. The aim of this article is to review their most significant clinical aspects, as well as to present an update in their management.
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http://dx.doi.org/10.3389/fped.2013.00048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864259PMC
December 2013

Modified abdominoplasty for patients with the Prune Belly syndrome.

Urology 2014 Feb 12;83(2):451-4. Epub 2013 Nov 12.

Division of Urology, University of São Paulo Medical School, São Paulo, Brazil.

Objective: To present the results of a new technique for abdominoplasty in patients with the Prune Belly syndrome (PBS).

Methods: Since 1985, 46 children with PBS underwent surgical treatment that included urinary tract reconstruction (UTR), orchidopexy, and abdominoplasty. In 41 patients, we performed the abdominoplasty as follows: (1) fusiform longitudinal resection of the mid-abdominal skin and subcutaneous tissue, with preservation of the musculo-aponeurotic fascia (MAF) and umbilicus, (2) ellipsoid unilateral longitudinal incision of the MAF in the most weakened side of the abdomen, producing 2 flaps, with the umbilicus being kept intact in the widest flap, (3) after UTR and bilateral orchiopexy, suture fixation of the widest MAF layer to the inner side of the contralateral abdominal wall, creating an inner MAF layer, (4) lateral suture fixation of the other flap over the inner layer, creating an outer MAF layer with a buttonhole exposing the umbilicus, that is sutured to the outer layer, and (5) approximation of the skin edges with incorporation of the umbilicus in the suture.

Results: Skin coaptation was excellent in all patients, and no trimming was necessary in incision extremities. There was no dehiscence or skin necrosis and all patients presented immediate improvement of the abdominal tonus and appearance. Further improvement with growth was observed in all except 4 patients, 2 requiring secondary abdominoplasties.

Conclusion: We conclude that this technique is applicable in all forms of weakened abdomen typical of PBS, even in asymmetrical cases, requiring only 1 MAF incision, with good cosmetic and functional results.
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http://dx.doi.org/10.1016/j.urology.2013.09.031DOI Listing
February 2014

Laparoscopic ureterocalicostomy for complicated upper urinary tract obstruction: mid-term follow-up.

Int Urol Nephrol 2014 May 12;46(5):865-9. Epub 2013 Nov 12.

Division of Urology, University of Sao Paulo Medical School, São Paulo, Brazil,

Purpose: To report on the largest series of laparoscopic ureterocalicostomies done for complicated upper urinary obstruction.

Methods: We retrospectively reviewed the data from 6 transperitoneal laparoscopic ureterocalicostomies performed in our institution from January 2008 to January 2012. Symptomatic complicated upper urinary obstruction was the main reason for all the procedures. The recorded data included age, gender, clinical presentation, duration of symptoms, laterality, mean operative time, hospital stay, complications and clinical and functional outcomes.

Results: The median patient age was 20.1 (2-44) years, and all patients were females. Patients underwent laparoscopic ureterocalicostomy due to previous failed procedures (3 patients), anatomic abnormalities (2 patients) and a severe upper ureteral stenosis (1 patient). The median operative time was 215 (180-270) min. There were no major complications. There were no conversions to open surgery. In a median follow-up of 30 (8-56) months, all patients presented with clinical and radiological improvement with no signs of obstruction. In all cases, the postoperative renal scintigraphy revealed a T1/2 lower than 10 min.

Conclusion: Laparoscopic ureterocalicostomy is feasible and associated with high success rate in well-selected cases with complicated upper urinary obstructions.
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http://dx.doi.org/10.1007/s11255-013-0591-zDOI Listing
May 2014

Atorvastatin prevents the downregulation of aquaporin-2 receptor after bilateral ureteral obstruction and protects renal function in a rat model.

Urology 2012 Aug 13;80(2):485.e15-20. Epub 2012 Apr 13.

Division of Urology, Department of Surgery, University of São Paulo School of Medicine, São Paulo, Brazil.

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.
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http://dx.doi.org/10.1016/j.urology.2012.02.021DOI Listing
August 2012