Søren Kissow Lildal

How should patients with cystine stone disease be evaluated and treated in the twenty-first century?

Cystinuria continues to be one of the most challenging stone diseases. During the latest decades our knowledge of the molecular basis of cystinuria has expanded. Today 160 different mutations in the SLC3A1 gene and 116 in the SLC7A9 gene are listed. The full implications of type A, B or AB status are not yet fully understood but may have implications for prognosis, management and treatment. Despite better understanding of the molecular basis of cystinuria the principles of recurrence prevention have remained essentially the same through decades. No curative treatment of cystinuria exists, and patients will have a life long risk of stone formation, repeated surgery, impaired renal function and quality of life. Therapy to reduce stone formation is directed towards lowering urine cystine concentration and increasing cystine solubility. Different molecules that could play a role in promoting nucleation and have a modulating effect on cystine solubility may represent new targets for cystinuria research. Investigation of newer thiol-containing drugs with fewer adverse effects is also warranted. Determining cystine capacity may be an effective tool to monitor the individual patient’s response. Compliance in cystinuric patients concerning both dietary and pharmacological intervention is poor. Frequent clinical follow-up visits in dedicated centres seem to improve compliance. Cystinuric patients should be managed in dedicated centres offering the complete range of minimal invasive treatment modalities, enabling a personalized treatment approach in order to reduce risk and morbidity of multiple procedures.

Pathophysiological aspects of ureterorenoscopic management of upper urinary tract calculi.

Purpose of review Indications for ureterorenoscopy are expanding without hard scientific evidence to support its efficacy. Therefore, it is extremely important to focus on potential harmful effects of the procedure itself. This review explores how physiology of the upper urinary tract reacts to ureterorenoscopy, potentially translating into harmful effects, and how such pathophysiological processes may be minimized. Recent findings Complications to ureterorenoscopy and postoperative pain seem to be related to intrarenal pressure and/or access. Mean intrarenal pressures in the range of 60–100 mmHg during ureterorenoscopy without access sheaths have been measured, thus by far exceeding the threshold for intrarenal backflow, potentially resulting in septic complications. Intrarenal pressure may be reduced by use of ureteral access sheaths, which, however, may cause ureteral damage due to the limited size of the ureter and strain-induced ureteral contractions (peristalsis). Different receptor types modulate this peristaltic activity. &bgr;-receptor agonists have been investigated in animal and human trials for the purpose of relaxing the ureter. In randomized, placebo-controlled trials in pigs and humans, usage of the &bgr;-receptor agonist isoproterenol in the irrigation fluid has shown a potential for reducing both intrarenal pressure and ureteral tone during ureterorenoscopy. Summary Upper urinary tract physiology has unique features that may be pushed into pathophysiological processes by the unique elements of ureterorenoscopy: access and irrigation. Pharmacological ureteral relaxation during ureterorenoscopy deserves further attention with regard to reducing complications and postoperative pain.

Ureteral Access Sheath Influence on the Ureteral Wall Evaluated by Cyclooxygenase-2 and Tumor Necrosis Factor-α in a Porcine Model.

Abstract Objective: To examine the effect of ureteral access sheath (UAS) on the expression of the pro-inflammatory mediators cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) in the ureteral wall. Material and Methods: In 22 pigs an UAS was inserted and removed after 2 minutes on one side and 2 hours on the contralateral side. Postoperatively ureters were excised in vivo, and tissue samples from the distal (2 minutes/2 hours) and proximal ureter (2 minutes/2 hours) were snap-frozen before quantitative polymerase chain reaction analysis of COX-2 and TNF-α. Five unmanipulated ureteral units from other pigs served as the control group. Results: Compared to controls COX-2 mRNA was significantly upregulated in all UAS treated ureteral groups. Similarly, TNF-α mRNA was upregulated in all groups except the 2-minute proximal ureteral group. Both COX-2 and TNF-α expression were significantly higher in the distal than in the proximal ureter in the UAS treated ureters. After UAS insertion for 2 minutes, expression levels in the distal ureter were increased 6.5- and 8-fold for COX-2 and TNF-α, respectively; and after 2 hours of UAS placement COX-2 and TNF-α mRNA expression levels were increased 9- and 9.5-fold, respectively. Conclusion: The pro-inflammatory mediators COX-2 and TNF-α were significantly upregulated in the ureteral wall by the influence of UAS. These findings may have implications for postoperative pain, drainage, and complications.

Pharmacological Relaxation of the Ureter When Using Ureteral Access Sheaths during Ureterorenoscopy: A Randomized Feasibility Study in a Porcine Model

Objective. High intraluminal pressure during ureterorenoscopy (URS) increases risk of infectious and haemorrhagic complications. Intrarenal pressure may be reduced by the use of ureteral access sheaths (UASs), which on the other hand may cause ureteral damage. We have previously shown that the β-agonist isoproterenol (ISO), when administered topically in the irrigation fluid, is able to inhibit ureteral muscle tone and lower intrarenal pressure during URS. The aim of this study was to examine the effect of ISO on the success rate of UAS insertion in a porcine model. Materials and Methods. 22 pigs in which a UAS could not initially be placed were randomized to endoluminal irrigation with either ISO (0.1 μg/mL) or saline before a new insertion trial. Subsequently, it was registered whether the UAS could be passed without resistance. During extraction of the sheath, any ureteral lesions were characterized ureteroscopically using the PULS classification system. Surgeons were blinded to randomization. Results. In the ISO group, the observed effect of irrigation was 63% successful UAS insertions, compared to 27% in the saline group. No serious lesions (<PULS grade 2) were observed in the ISO group. Conclusions. Endoluminal irrigation with ISO may facilitate UAS insertion and potentially decrease UAS related ureteral lesions.

Evaluation of ureteral lesions in ureterorenoscopy: impact of access sheath use

Abstract Objective: The aim of this study was to evaluate the incidence of ureteral lesions in retrograde intrarenal surgery (RIRS) with and without the use of a 10/12 Fr ureteral access sheath (UAS). A further objective was to search for preoperative factors that could influence the risk of ureteral damage. Materials and methods: Data were collected from a clinical database on 180 consecutive adult patients undergoing RIRS for kidney stones with or without a 10/12 Fr UAS. The primary outcome measure was ureteral lesions endoscopically identified at the end of surgery using the Post-Ureteroscopic Lesion Scale (PULS) classification system. Results: The use of 10/12 Fr UASs resulted in less severe lesions than reported previously with larger diameter UASs. There was a higher risk of superficial lesions in the UAS group, with a calculated crude odds ratio (OR) of 1.84 [95% confidence interval (CI) 1.00–3.37]. When adjusting for age and gender, the OR was 1.68 (95% CI 0.90–3.13; p = 0.10) and thus was not significant. The only factor that remained significant was age (OR =1.02/year, 95% CI 1.00–1.04). Conclusion: There was a trend towards a higher risk of ureteral lesions in RIRS with a 10/12 Fr UAS compared with an endoscope alone, but when adjusting for age and gender the incidence of ureteral lesions was comparable between RIRS with and without the use of a 10/12 Fr UAS.

The challenges of cystinuria in the twenty-first century: a mini review

The challenges of cystinuria in the twenty-first century – a mini review Louise F. Øbro1, Katja V. Pedersen2, Søren K. Lildal1, Susanne S. Osther1, Helene U. Jung1, Kim H. Andreassen1 and Palle J. S. Osther1 1Department of Urology, Urological Research Center, Lillebaelt Hospital, University of Southern Denmark, Fredericia, Denmark 2Department of Clinical Genetics, Lillebaelt Hospital, University of Southern Denmark, Vejle, Denmark