This Month in Investigative Urology

Article Outline

• Atorvastatin may Inhibit Renal Stone Formation
• Microrobot Assisted Laparoscopic Surgery
• Predicting Irreparable Renal Ischemic Injury Using Real-Time Markers
• Disrupting the Interaction Between HOX and PBX Causes Renal Cancer Cell Death
• Effects of Dietary Soy on the Female Urethra
• Copyright

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Atorvastatin may Inhibit Renal Stone Formation 

The interactions between crystals and renal tubular cells are important factors in urolithiasis formation. Moreover, some reports have suggested the involvement of renal tubular cell injury in crystal-cell interaction processes. Atorvastatin, which is a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A, is prescribed to decrease high cholesterol levels, and it has anti-inflammation and antioxidization activities. Tsujihata et al (page 2212) from Suita, Japan investigated whether atorvastatin can prevent renal tubular cell injury by oxalate and inhibit renal crystal retention. The ethylene glycol rat model of hyperoxaluria and the effect of atorvastatin treatment were analyzed in 4 experimental groups. Urinary N-acetyl glucosaminidase and 8-hydroxy-2′-deoxyguanosine levels were decreased significantly by atorvastatin treatment in the stone forming rat model. Atorvastatin treatment increased the superoxide dismutase level and inhibited the degree of apoptosis of renal tubular cells. A decrease in renal crystal retention was recognized in the evaluation of excised kidneys following atorvastatin treatment. Atorvastatin was found to have inhibitory effects on renal tubular cell injury and oxidative stress caused by oxalate and crystals. Atorvastatin inhibited renal crystal retention and, thus, may be helpful in the prevention and treatment of renal crystal formation.

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Microrobot Assisted Laparoscopic Surgery 

Robotic technologies have had a significant impact on surgery. Joseph et al (page 2202) from Rochester, New York report what is to their knowledge the first use of microrobots to perform laparoscopic urological surgery in a canine model. Nonsurvival laparoscopic radical prostatectomy and radical nephrectomy were performed using microrobotic camera assistance. Following the administration of general anesthesia miniature camera robots were inserted in the insufflated abdomen via a 15 mm laparoscopic port. These microrobots were mobile, controlled remotely to desired locations and provided views of the abdominal cavity, assisting the laparoscopic procedures. Additional ports and laparoscopic instruments were placed in the abdomen using the views supplied by these microrobots. The microrobots provided additional views from several angles, aiding in the performance of the procedures. With added functionality these new robots have the potential to further evolve the robotic armamentarium for surgeons.

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Predicting Irreparable Renal Ischemic Injury Using Real-Time Markers 

Partial nephrectomy, renal transplantation and certain vascular surgery procedures involve the temporary interruption of renal blood flow. Prolonged warm ischemia may have adverse effects on renal function. Recent clinical series report varying opinions supporting a maximal renal tolerance of less than 30 minutes or significantly longer safe warm ischemia times. A renal unit specific marker of ischemic injury is desirable. Microdialysis is a technique that involves placing a small probe in the organ of interest to collect samples that can be analyzed for interstitial molecules. Weld et al (page 2218) from Lackland Air Force Base, Texas determined the maximal renal tolerance of warm ischemia using renal cortical interstitial metabolic changes to identify a potential real-time marker of irreparable renal function. The changes in renal interstitial fluid metabolite concentrations were measured in a single kidney porcine model before, during and after ischemia to evaluate them as markers for the unique recoverability of individual renal units. The real-time markers were correlated with reparable and irreparable ischemic injuries (up to 180 minutes) as determined by functional and histological data.

Interstitial glucose and pyruvate concentrations decreased while lactate concentrations increased to stable levels during ischemia. Glutamate spiked at 30 minutes of ischemia and subsequently tapered while glycerol increased throughout the warm ischemia time. At post-ischemia day 28 renal function returned to pre-ischemia baseline levels in the group with 120 minutes of ischemia but did not recover to baseline in the 150 and 180-minute ischemic groups. The functional data correlated with histological findings. Exposure of porcine kidneys to ischemic insults resulting in renal cortical interstitial glycerol concentrations higher than 167 μmol/l was associated with irreparable functional damage in this model. Interstitial glycerol is a real-time, renal unit specific, minimally invasive marker of renal function deterioration.

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Disrupting the Interaction Between HOX and PBX Causes Renal Cancer Cell Death 

The HOX genes are a family of homeodomain containing transcription factors that determine embryonic tissue identity, and also have regulatory and oncogenic roles in adult cells. Shears et al (page 2196) from Surrey, United Kingdom quantified the expression of HOX genes in normal kidney tissue, primary tumors and derived cell lines, and examined their role in renal cancer cell survival. Quantitative polymerase chain reaction was used to evaluate HOX gene expression in cells and tissues. HOX gene function was disrupted using a peptide that blocks the interaction between HOX proteins and their PBX cofactor, and apoptosis was assessed. Primary renal tumors and derived cell lines showed abnormal HOX gene expression. Blocking HOX activity by targeting the interaction between HOX and its cofactor PBX caused apoptotic and necrotic cell death in renal cancer cell lines while sparing normal adult kidney cells. This suggests that the HOX/PBX dimer is a potential therapeutic target in renal cancer.

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Effects of Dietary Soy on the Female Urethra 

Agonistic effects of estrogen on the female urethra include an increase in contractile function, blood flow and mucosal hyperplasia. Whether such effects can be achieved by soy based phytoestrogen diets is unclear. Gratzke et al (page 2247) from Winston-Salem, North Carolina studied the effects of chronic phytoestrogen treatment on the structural and functional properties of the urethra in ovariectomized monkeys. Following ovariectomy 18 monkeys were fed a diet containing soy or casein based protein for 32 months. At necropsy the urethra and bladder were removed, and the urethra was separated into 3 segments of equal length (proximal, middle and distal). Each urethral segment and 1 bladder segment was tested in vitro. Chronic phytoestrogen treatment results in increased responsiveness of the proximal urethra to pharmacological and electrical stimulation, which is associated with an increase in urothelial thickness and mucosal area. This study indicates that dietary soy may have estrogen agonist effects on the urethra and bladder in estrogen deficient females.