Kathie Wong

Incidental renal stones in potential live kidney donors: prevalence, assessment and donation, including role of ex vivo ureteroscopy

Previously, donors with asymptomatic stones found incidentally on CT were not considered ideal donor candidates because of the presumed risk of morbidity to both the donor and recipient. Increasingly, studies show that these risks are low. This study aims to evaluate the long‐term safety of using ex vivo ureteroscopy to remove the stones from the donor kidney on the bench before donation. Outcomes so far suggest that this technique can safely render a kidney stone‐free before transplantation. This has led to 20 more transplants in our institution than would otherwise be possible.

Outpatient laser ablation of non‐muscle‐invasive bladder cancer: is it safe, tolerable and cost‐effective?

To evaluate the safety, tolerability and effectiveness of outpatient (office‐based) laser ablation (OLA), with local anaesthetic, for non‐muscle‐invasive bladder cancer (NMIBC) in an elderly population with and without photodynamic diagnosis (PDD). To compare the cost‐effectiveness of OLA of NMIBC with that of inpatient cystodiathermy (IC).

Cystinuria-a urologist's perspective.

Cystinuria is a genetic disease that leads to frequent formation of stones. In patients with recurrent stone formation, particularly patients <30 years old or those who have siblings with stone disease, urologists should maintain a high index of suspicion of the diagnosis of cystinuria. Patients with cystinuria require frequent follow-up and a multidisciplinary approach to diagnosis, prevention and management. Patients have reported success in preventing stone episodes by maintaining dietary changes using a tailored review from a specialist dietician. For patients who do not respond to conservative lifestyle measures, medical therapy to alkalinize urine and thiol-binding drugs can help. A pre-emptive approach to the surgical management of cystine stones is recommended by treating smaller stones with minimally invasive techniques before they enlarge to a size that makes management difficult. However, a multimodal approach can be required for larger complex stones. Current cystinuria research is focused on methods of monitoring disease activity, novel drug therapies and genotype–phenotype studies. The future of research is collaboration at a national and international level, facilitated by groups such as the Rare Kidney Stone Consortium and the UK Registry of Rare Kidney Diseases.

The Genetic Diversity of Cystinuria in a UK Population of Patients

To examine the genetic mutations in the first UK cohort of patients with cystinuria with preliminary genotype/phenotype correlation.

Is percutaneous nephrolithotomy in solitary kidneys safe

OBJECTIVE To review our experience from a high volume stone center with a focus on efficacy, safety, and renal function. METHODS Stones requiring percutaneous nephrolithotomy (PCNL) in patients with solitary kidneys can pose significant anxiety to the urologist. Limited data are available in published reports in this setting. A comprehensive retrospective review of medical records was performed on patients who underwent PCNL and had a solitary kidney or a single functioning renal unit. Data were collected on patient demographics, stone burden, outcomes, complications, and renal function. RESULTS Of 378 PCNLs performed between January 2003 and September 2011, 22 were performed in 17 patients with a single functioning kidney. Three procedures were performed in a transplanted kidney. In those with solitary calculus, the longest mean length and stone surface area were 37 mm and 825 mm(2), respectively. Stone-free rate was 59%. Auxiliary procedures were required in 6 cases, resulting in a stone-free rate of 77%. Median inpatient stay was 4 days. Serum creatinine values improved from 144 to 126 umol/L before and after the procedure and mean estimated glomerular filtration rate improved similarly from 51 to 59 mls/minute, respectively. Blood transfusion was required in 1 patient, sepsis developed in 3, and 2 patients required a stent for obstruction. CONCLUSION PCNL in solitary kidneys is safe with an acceptable complication rate if performed in a high volume center. Outcomes are good, although auxiliary procedures may be necessary. Renal function remains stable or improves after procedure.

Management of stones in renal transplant.

Purpose of review Increasingly, screening of both deceased and living donor organs has led to the early detection of kidney stones prior to donation. A number of transplant recipients will still present with donor-gifted and de-novo stones. A range of treatment modalities is available in the management of renal transplant stones. Recent findings Stones can be pretreated in the (living) donor prior to transplantation, managed at the time of transplantation or treated in the recipient post-transplant. The options include conservative management, extracorporeal shockwave lithotripsy, percutaneous nephrolithotomy, ureteroscopy or open surgery depending on the size and location of the stone(s). Various techniques to deal with a transplant kidney are described. Ex-vivo ureteroscopy or pyeloscopy can safely render a kidney-stone free prior to transplantation and in living donors this means without subjecting the living donor to an additional stone removing procedure. Summary The cause of renal transplant lithiasis is multifactorial. More research is needed to understand the factors associated with de-novo stone formation. Early detection of donor-gifted stones can allow stones to be removed at the time of transplantation. Close follow up of both living donors and transplant recipients is necessary to ensure long-term safety is maintained.

The forgotten ureteric stent: what next?

The forgotten ureteric stent is a ‘never event’, because it is entirely preventable and conveys the potential for serious harm. Forgotten stents tend to encrust and encrusted stents are difficult to remove, frequently entailing significant complications [1]. Singh et al. [2], from a retrospective series of 19 forgotten ureteric stents, even reported one death as a direct consequence. Clearly, strategies for the prevention of this harm are essential.

Can the Presence of Crystalluria Predict Stone Formation in Patients with Cystinuria

OBJECTIVES To determine the feasibility of crystalluria as a biomarker for stone disease in patients with cystinuria. PATIENTS AND METHODS All patients attending a multidisciplinary cystinuria clinic provided early morning urine (EMU) and clinic urine (CU) samples for crystal measurement over a 2-year period (August 1, 2010, to July 31, 2012). Association between presence of crystals, presence of stone(s), and new stone growth (NSG) was determined using the chi-square test. Crystal numbers in EMU and CU were compared in patients with stones/NSG and no stones/stable disease using the Mann-Whitney U test. RESULTS There was a statistically significant difference between the presence of crystalluria and presence of stones for CU (chi-square test = 5.86, df = 1, p = 0.02) but not EMU (chi-square test = 1.92, df = 1, p = 0.17) and between the presence of crystalluria and NSG for CU (chi-square test = 8.10, df = 1, p = 0.004) but not EMU (chi-square test = 1.32, df = 1, p = 0.25). Patients with stones and NSG have higher levels of crystalluria in CU than patients with no stones or stable disease (stones, median = 41, interquartile range [IQR] = 600 vs median = 0, IQR = 21, p = 0.01; NSG, median = 49, IQR = 525 vs median = 0, IQR = 40, p = 0.01). CONCLUSION The presence of crystalluria in CU samples is associated with the presence of stones. Crystalluria is comparable to ultrasound and may serve as a useful adjunct to predict whether a patient with cystinuria has stones, which could guide the frequency of clinic review and imaging.

The Role of Protein Modelling in Predicting the Disease Severity of Cystinuria

Mutations in one of two genes (SLC3A1 and SLC7A9) are responsible for the majority of cystinuria phenotypes. A defective renal tubular protein transporter causes high levels of urinary cystine and the dibasic amino acids lysine, arginine, and ornithine. Cystine is relatively insoluble in urine and forms stones. We have found 57 different mutations in our UK cohort [1]. Most are missense mutations and it is unclear what effect they have on protein function and how this translates to phenotype. The aim of this study was to use protein modelling to investigate how missense mutations may affect protein function. Limited experimental data are available because experimental techniques are time-consuming and results would lag significantly behind the rate at which new

Associating mutations causing cystinuria with disease severity with the aim of providing precision medicine

BackgroundCystinuria is an inherited disease that results in the formation of cystine stones in the kidney, which can have serious health complications. Two genes (SLC7A9 and SLC3A1) that form an amino acid transporter are known to be responsible for the disease. Variants that cause the disease disrupt amino acid transport across the cell membrane, leading to the build-up of relatively insoluble cystine, resulting in formation of stones. Assessing the effects of each mutation is critical in order to provide tailored treatment options for patients. We used various computational methods to assess the effects of cystinuria associated mutations, utilising information on protein function, evolutionary conservation and natural population variation of the two genes. We also analysed the ability of some methods to predict the phenotypes of individuals with cystinuria, based on their genotypes, and compared this to clinical data.ResultsUsing a literature search, we collated a set of 94 SLC3A1 and 58 SLC7A9 point mutations known to be associated with cystinuria. There are differences in sequence location, evolutionary conservation, allele frequency, and predicted effect on protein function between these mutations and other genetic variants of the same genes that occur in a large population. Structural analysis considered how these mutations might lead to cystinuria. For SLC7A9, many mutations swap hydrophobic amino acids for charged amino acids or vice versa, while others affect known functional sites. For SLC3A1, functional information is currently insufficient to make confident predictions but mutations often result in the loss of hydrogen bonds and largely appear to affect protein stability. Finally, we showed that computational predictions of mutation severity were significantly correlated with the disease phenotypes of patients from a clinical study, despite different methods disagreeing for some of their predictions.ConclusionsThe results of this study are promising and highlight the areas of research which must now be pursued to better understand how mutations in SLC3A1 and SLC7A9 cause cystinuria. The application of our approach to a larger data set is essential, but we have shown that computational methods could play an important role in designing more effective personalised treatment options for patients with cystinuria.