Intrarenal modulation of NF-κB activity attenuates cardiac injury in a swine model of CKD: a renal-cardio axis.

Patients with chronic kidney disease (CKD) have a high cardiovascular mortality. CKD and heart failure (HF) coexist in up to 50% of patients, and both associate with inflammation. We aimed to define the cardiac phenotype of a novel swine model of CKD and test the hypothesis that inflammation of renal origin propels the development of precursors of HF in CKD.

A dose-escalating toxicology study of the candidate biologic ELP-VEGF.

Vascular Endothelial Growth Factor (VEGF), a key mediator of angiogenesis and vascular repair, is reduced in chronic ischemic renal diseases, leading to microvascular rarefaction and deterioration of renal function. We developed a chimeric fusion of human VEGF-A with the carrier protein Elastin-like Polypeptide (ELP-VEGF) to induce therapeutic angiogenesis via targeted renal VEGF therapy. We previously showed that ELP-VEGF improves renal vascular density, renal fibrosis, and renal function in swine models of chronic renal diseases.

Recovery of Renal Function following Kidney-Specific VEGF Therapy in Experimental Renovascular Disease.

Background: Chronic renovascular disease (RVD) can lead to a progressive loss of renal function, and current treatments are inefficient. We designed a fusion of vascular endothelial growth factor (VEGF) conjugated to an elastin-like polypeptide (ELP) carrier protein with an N-terminal kidney-targeting peptide (KTP). We tested the hypothesis that KTP-ELP-VEGF therapy will effectively recover renal function with an improved targeting profile.

Molecular targeting of renal inflammation using drug delivery technology to inhibit NF-κB improves renal recovery in chronic kidney disease.

Inflammation is a major determinant for the progression of chronic kidney disease (CKD). NF-κB is a master transcription factor upregulated in CKD that promotes inflammation and regulates apoptosis and vascular remodeling. We aimed to modulate this pathway for CKD therapy in a swine model of CKD using a peptide inhibitor of the NF-κB p50 subunit (p50i) fused to a protein carrier [elastin-like polypeptide (ELP)] and equipped with a cell-penetrating peptide (SynB1).

Macrophage polarization in chronic kidney disease: a balancing act between renal recovery and decline?

Macrophages are heterogenous cells of the innate immune system that can fluidly modulate their phenotype to respond to their local microenvironment. They are found throughout the renal compartments, where they contribute to homeostasis and function. However, renal injury activates molecular pathways that initially stimulate differentiation of macrophages into a proinflammatory M1 phenotype.

Targeted VEGF (Vascular Endothelial Growth Factor) Therapy Induces Long-Term Renal Recovery in Chronic Kidney Disease via Macrophage Polarization.

Chronic kidney disease (CKD) universally associates with renal microvascular rarefaction and inflammation, but whether a link exists between these 2 processes is unclear. We designed a therapeutic construct of VEGF (vascular endothelial growth factor) fused to an ELP (elastin-like polypeptide) carrier and show that it improves renal function in experimental renovascular disease. We test the hypothesis that ELP-VEGF therapy will improve CKD, and that recovery will be driven by decreasing microvascular rarefaction partly via modulation of macrophage phenotype and inflammation.

Biopolymer-delivered vascular endothelial growth factor improves renal outcomes following revascularization.

Renal angioplasty and stenting (PTRAs) resolves renal artery stenosis, but inconsistently improves renal function, possibly due to persistent parenchymal damage. We developed a bioengineered fusion of a drug delivery vector (elastin-like polypeptide, ELP) with vascular endothelial growth factor (VEGF), and showed its therapeutic efficacy. We tested the hypothesis that combined ELP-VEGF therapy with PTRAs improves renal recovery more efficiently than PTRAs alone, by protecting the stenotic renal parenchyma.

A translational model of chronic kidney disease in swine.

Animal models of chronic kidney disease (CKD) are critical for understanding its pathophysiology and for therapeutic development. The cardiovascular and renal anatomy and physiology of the pig are virtually identical to humans. This study aimed to develop a novel translational model of CKD that mimics the pathological features of CKD in humans.

A Retroperitoneal Serous Cystadenoma of Müllerian Origin Masquerading as a Massive Renal Cyst.

A 78-year-old woman presented to the urology clinic with a large, symptomatic left-sided abdominal cyst that was believed to be renal in etiology for many years and that had been percutaneously drained 3 times previously with persistent regrowth. The patient underwent laparoscopic resection of this mass, which proved to be a completely distinct retroperitoneal cystic structure and was not renal in nature. Pathologic analysis ultimately revealed a rare occurrence: a benign retroperitoneal Müllerian serous cystadenoma.

Vascular Endothelial Growth Factor and Podocyte Protection in Chronic Hypoxia: Effects of Endothelin-A Receptor Antagonism.

Background: Podocytes are major components of the filtration barrier and a renal source of vascular endothelial growth factor (VEGF). Chronic renovascular disease (RVD) progressively degrades the renal function, accompanied by podocyte damage and a progressive reduction in VEGF. We showed that the endothelin (ET) pathway contributes to this pathological process and ET-A (but not ET-B) receptor antagonism protects the kidney in RVD.

Seminal vesicle abscess following prostate biopsy requiring transgluteal percutaneous drainage.

Transrectal ultrasound guided biopsy (TRUSB) of the prostate directly contaminates the prostate with rectal flora. Patients commonly receive fluoroquinolone (FQ) antibiotics to prevent infection. Infectious complications following TRUSB are increasing.

Unclamped hand-assisted laparoscopic partial nephrectomy for predominantly endophytic renal tumors.

Purpose: To describe our initial experience with unclamped laparoscopic hand-assisted partial nephrectomy for predominantly endophytic renal masses in the setting of relative contraindication to warm ischemia.

Materials And Methods: Unclamped laparoscopic hand-assisted partial nephrectomy was performed on eight consecutive patients from June 2009 to March 2010. All patients had predominantly endophytic renal masses with a preferential enhancing rim noted on the pre-operative computed tomography.

Surgical complications after robot-assisted laparoscopic radical prostatectomy: the initial 1000 cases stratified by the clavien classification system.

Background And Purpose: Complications after robot-assisted prostatectomy are widely reported and varied. Our goal was to determine the incidence of surgical complications resulting from robot-assisted laparoscopic radical prostatectomy (RALP) during the initial phase of a new robotics program that was developed by two surgeons without laparoscopic or robotic fellowship training. A secondary goal was to see if experience changed the incidence of complications with this technology.

Rectal injury during robot-assisted radical prostatectomy: incidence and management.

Purpose: Rectal injury during robot-assisted radical prostatectomy is a rare but significant complication. Since the Clavien grading classification of complications does not include intraoperative injury without further sequelae, rectal injury may be underreported in the literature. We present what is to our knowledge the largest retrospective review to date of rectal injury and subsequent management.

Management of post-prostatectomy erectile dysfunction.

The management of post-prostatectomy erectile function has been debated since the nerve sparing radical prostatectomy was first introduced. A number of penile rehabilitation protocols have been proposed with varying degrees of success and patient satisfaction. My management of post-prostatectomy erectile dysfunction has evolved based on an honest and critical appraisal of the literature and my own experience and research.

Effect on sexual function of a vacuum erection device post-prostatectomy.

Introduction: Treatment of erectile dysfunction (ED) subsequent to bilateral nerve sparing robotic prostatectomy (BNSRP) with tadalafil plus a vacuum erection device (VED) may improve return of sexual function.

Materials And Methods: Men with prostate cancer who had BNSRP were randomized to receive tadalafil, 20 mg three times weekly, or tadalafil plus a VED, 10 minutes unbanded per day for at least 5 days weekly. Treatments started 1 month after surgery; clinic visits were at 1, 3, 6, 9 and 12 months.

Posterior rhabdosphincter reconstruction during robotic assisted radical prostatectomy: results from a phase II randomized clinical trial.

Purpose: Posterior rhabdosphincter reconstruction following radical prostatectomy was designed to improve early urinary continence. We executed a randomized clinical trial to test this conjecture in men undergoing robotic radical prostatectomy.

Materials And Methods: We conducted a phase II randomized clinical trial intended to detect a 25% difference in 3-month continence outcomes defined by a patient response of 0 or 1 to question 5 of the Expanded Prostate Cancer Index Composite questionnaire urinary domain, comparing standard running vesicourethral anastomosis (controls) to posterior rhabdosphincter reconstruction followed by standard running vesicourethral anastomosis (posterior rhabdosphincter reconstruction treated).

Changes in penile length after robot-assisted laparoscopic radical prostatectomy.

Background And Purpose: Radical prostatectomy is commonly performed for the treatment of patients with prostate cancer. Several studies have demonstrated a reduction in penile size after open radical retropubic prostatectomy. The objective of this study is to describe changes in penile length after after robot-assisted laparoscopic radical prostatectomy (RALRP).

Oncologic outcome of robot-assisted laparoscopic prostatectomy in the high-risk setting.

Background And Purpose: Previous studies have demonstrated the feasibility of open radical prostatectomy in the high-risk setting. Management of high-risk disease with robot-assisted laparoscopic radical prostatectomy (RALP) is controversial. We examined biochemical recurrence in a selected cohort of high-risk patients who were undergoing RALP.

Vascular pseudoaneurysms in urology: clinical characteristics and management.

Background And Purpose: Vascular pseudoaneurysm is a well-documented complication that results after injury to an arterial wall. We review the urologic literature for all reported postprocedural and post-traumatic cases of pseudoaneurysm.

Methods: A comprehensive review of the peer-reviewed literature was performed for reported cases of vascular pseudoaneurysm, with emphasis on clinical presentation and treatment options.

Recovery of erectile function after nerve sparing radical prostatectomy and penile rehabilitation with nightly intraurethral alprostadil versus sildenafil citrate.

Purpose: To our knowledge we report the first large, randomized, prospective penile rehabilitation clinical trial to compare the effectiveness of nightly intraurethral alprostadil vs sildenafil citrate after nerve sparing prostatectomy.

Materials And Methods: We performed a prospective, randomized, open label, multicenter American study in men with normal erectile function who underwent bilateral nerve sparing radical prostatectomy. The International Index of Erectile Function erectile function domain was the primary end point.

"Learning curve" may not be enough: assessing the oncological experience curve for robotic radical prostatectomy.

The use of robot-assisted laparoscopic radical prostatectomy (RALP) is widespread in the community. A definitive RALP "learning curve" has not been defined and existing learning curves do not account for urologists without prior advanced laparoscopic skills. Therefore, an easily evaluable metric, the "oncological experience curve," would be clinically useful to all urologists performing RALP.