Mark D. White

Topiramate-induced nephrolithiasis

Topiramate is a recently developed antiepileptic medication that is becoming more widely prescribed because of its efficacy in treating refractory seizures. Urologists should be aware that this medication can cause metabolic acidosis in patients secondary to inhibition of carbonic anhydrase. In addition, a distal tubular acidification defect may result, thus impairing the normal compensatory drop in urine pH. These factors can lead to the development of calcium phosphate nephrolithiasis. We report the first two cases of topiramate-induced nephrolithiasis in the urologic literature.

Pediatric Urinary Stone Disease—Does Age Matter?

PURPOSE It has been proposed that younger children are less likely to pass renal calculi spontaneously, and that children younger than 10 years are more likely to have an identifiable metabolic abnormality and subsequently a higher risk of recurrence. We report our clinical outcomes in children with urinary calculi, specifically examining these factors. MATERIALS AND METHODS We performed a retrospective review of all pediatric patients diagnosed with renal or ureteral calculi at our institution between 2000 and 2007. Of 150 patients evaluated and treated during this period 80 (86 stones) had sufficient followup data to be included. Patients were divided into 2 groups according to age, namely 10 years or younger and older than 10 years. There were 39 patients in the younger group and 41 patients in the older group. Stone size and location, successful passage or intervention, recurrence and 24-hour urine metabolic study results were recorded. RESULTS Of the younger cohort stones were ureteral in 43% and renal in 57%. The opposite trend was seen in older patients, with 69% having ureteral and 31% having renal stones (p = 0.02). Mean stone size (greatest dimension) did not differ significantly between the older and younger groups (6.9 mm vs 5.5 mm, p = 0.17). Overall stone passage rate was 34% for younger and 29% for older patients (p = 0.65). No significant mean size differences in passed stones existed between the groups (3.2 mm vs 2.5 mm, p = 0.31). Overall younger vs older ureteral stone passage rate was 37% vs 41% (p = 0.58), and for renal stones it was 32% vs 0%. Stones recurred in 7 younger and 6 older patients. CONCLUSIONS Younger children were more likely to present with renal stones, while older children had more ureteral stones. Overall children 10 years old or younger are as likely to pass stones as older children. Renal stones are more likely to be successfully managed expectantly in younger children. Metabolic abnormalities and stone recurrences are observed at similar rates between younger and older children.

High Recurrence Rate at 5-Year Followup in Children after Upper Urinary Tract Stone Surgery

PURPOSE Pediatric urolithiasis has been treated with shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy with high success rates during short-term followup. We studied our success rate and modifiable risk factors in patients with at least 5 years of followup postoperatively. MATERIALS AND METHODS Retrospective chart review was performed for patients younger than 18 years who underwent upper tract stone surgery between 1999 and 2007, were stone-free afterward and had at least 5 years of followup. Recurrence rate, and anatomical and metabolic abnormalities were assessed. RESULTS Of 60 eligible children 30 (33 kidneys) had at least 5 years of followup. Average patient age at surgery was 10 years, 17 patients were female and 20 kidneys had anatomical abnormalities. Overall recurrence rate at 5 years was 55% (95% CI 38%-70%). Ureteral stones had a lower recurrence rate than renal stones (5 of 19 and 13 of 14, respectively, p <0.001). Patients with abnormal anatomy had a 65% (95% CI 43%-82%) chance of recurrence within 5 years vs 38% (95% CI 18%-65%) in those with normal anatomy (p = 0.17). Of the 18 recurrences 10 required a second operation, 7 demonstrated abnormal anatomy and 14 involved calcium based stones. A 24-hour urine test in 13 children revealed 10 with hypercalciuria and 11 with hypocitraturia, with 9 patients exhibiting both conditions. CONCLUSIONS We found a high recurrence rate in children with stones requiring surgical intervention, particularly those with abnormal anatomy. This finding should be confirmed in a larger multicenter study of recurrence rates. In the meantime our results suggest a need for aggressive diagnosis and treatment of metabolic abnormalities.

Urine risk factors in children with calcium kidney stones and their siblings.

Calcium nephrolithiasis in children is increasing in prevalence and tends to be recurrent. Although children have a lower incidence of nephrolithiasis than adults, its etiology in children is less well understood; hence treatments targeted for adults may not be optimal in children. To better understand metabolic abnormalities in stone forming children, we compared chemical measurements and the crystallization properties of 24-hour urine collections from 129 stone formers matched to 105 non-stone forming siblings and 183 normal, healthy children with no family history of stones; all aged 6 to 17 years. The principal risk factor for calcium stone formation was hypercalciuria. Stone formers have strikingly higher calcium excretion along with high supersaturation for calcium oxalate and calcium phosphate, and a reduced distance between the upper limit of metastability and supersaturation for calcium phosphate, indicating increased risk of calcium phosphate crystallization. Other differences in urine chemistry that exist between adult stone formers and normal individuals such as hyperoxaluria, hypocitraturia, abnormal urine pH and low urine volume were not found in these children. Hence, hypercalciuria and a reduction in the gap between calcium phosphate upper limit of metastability and supersaturation are crucial determinants of stone risk. This highlights the importance of managing hypercalciuria in children with calcium stones.

Bilateral large cell calcifying sertoli cell tumor of the testis in a 7-year-old boy

Large cell calcifying Sertoli cell tumor of the testis is a rare tumor with less than 25 cases reported in the world medical literature. Sex cord stromal tumors account for approximately 3 to 4% of all testicular tumors, with pure Sertoli cell tumors accounting for less than 1% of all testicular neoplasms.’ The tumor is predominantly associated with complex dysplastic syndromes and frequently has a multifocal presentation. We report on a young child initially diagnosed with a testicular mass at age 5 years who subsequently presented with contralateral testicular lesions that proved to be large cell calcifying Sertoli cell tumors. We discuss the case management strategies for this tumor. CASE HISTORY A 5-year-old white boy presented for urologic evaluation after detection of right hemiscrotal and testicular swelling. The child was otherwise healthy with no significant medical problems or antecedent trauma to the genitalia. On examination, no definite hernia defects were detected. The left testis and cord structures were normal; however, the right hemiscrotum was markedly enlarged. The testis and epididymis could not be distinguished by palpation. A firm mass that did not transmit light was also present. Subsequent ultrasound of the scrotum revealed enlargement of the right testis (2.5 x 1.4 x 2.2 cm.) with a diffusely heterogeneous appearance, but no significant hydrocele or epididymal enlargement. The contralateral testis was of normal echotexture and size. The patient subsequently underwent right inguinal exploration and radical orchiectomy. Pathologic

Splenda® Improves Tolerance of Oral Potassium Citrate Supplementation for Prevention of Stone Formation: Results of a Randomized Double-Blind Trial

BACKGROUND AND PURPOSE Oral citrate supplements have been shown to decrease kidney stone recurrence rates in both laboratory and clinical studies. The taste of the citrate supplements, however, is poor, and long-term compliance is low. Our objective was to determine if Splenda(®) added to potassium citrate (KCit) improves palatability without changing 24-hour urine parameters. PATIENTS AND METHODS 12 subjects were randomly assigned to receive either KCit alone for 3 days or KCit + Splenda in a double-blind trial. The 24-hour urine collections were performed before and after 3 days of therapy. After 1 week, the two groups switched treatments. After each treatment, a visual analog taste scale was completed to gauge the taste and palatability. The 24-hour urine parameters of kidney stone risk factors were compared between groups. The primary end points were to determine whether Splenda improved palatability of citrate supplementation and whether it altered 24-hour urine parameters. RESULTS Taste was judged to be 2.5 ± 0.9 points better in the Splenda + KCit compared with KCit alone (P=0.02). The 24-hour Cit, K, and pH were significantly higher in the KCit and KCit + Splenda groups compared with baseline, but not significantly different from each other. CONCLUSION Splenda significantly improves the palatability of KCit therapy and does not alter the beneficial effects of KCit on 24-hour urine Cit, K, or pH. The addition of Splenda altered the average taste score from one that might prohibit compliance to one that would not.

Tissue-marking scheme for a cost-effective extended prostate biopsy protocol

OBJECTIVES Extended biopsy schemes are now the standard of care for detection of prostate cancer. Submitting biopsy cores individually raises the cost of pathologic evaluation significantly while important prognostic information is lost when the samples are bundled into fewer containers. We devised a protocol for bundling biopsy cores to reduce the cost while maintaining our ability to identify important biopsy features. MATERIALS AND METHODS Four hundred fifty-two consecutive men underwent a prostate biopsy using our prospectively designed protocol. The lateral peripheral cores were marked with India ink and combined with cores from the corresponding sextant site into one container (maximum containers = 6). Prognostic information from each core was recorded. Cost analysis was based on the reimbursement rates for variable number of containers. RESULTS Tissue-labeling protocol did not increase the procedure time or introduce any tissue artifacts. Cancer was detected in 177 (39%) men with mean Gleason score of 7. A single core with cancer was noted in 28%, and cancer in < or =25% of the core was found in 41%. Thirteen of 64 (20%) men undergoing radical prostatectomy had extracapsular extension (ECE) and 10 (15%) had a positive surgical margin. The location of ECE on prostatectomy specimen correlated with a positive biopsy site in 9 (70%) patients. The cost of histopathologic evaluation is based on number of individually labeled specimen containers. By reducing the number of specimen containers from 12 to 6, the potential savings may be in hundreds of million per year. CONCLUSIONS This simple tissue-labeling protocol facilitates extended prostate biopsies in a cost-effective manner, while maintaining our ability to glean important prognostic information from each core.

Examining Pediatric Cases From the Clinical Research Office of the Endourological Society Ureteroscopy Global Study

OBJECTIVE To evaluate the characteristics and outcomes of ureteroscopy (URS) in children treated in several hospitals participating in the Clinical Research Office of the Endourological Society (CROES) Study, and to present the overall results of pediatric URS compared with adults. PATIENTS AND METHODS The CROES Study collected data on consecutive patients treated with URS for urolithiasis at each participating center over a 1-year period. The collected prospective global database includes data for 11,885 patients who received URS at 114 centers in 32 countries. Of these URS-treated patients, 192 were ≤18 years old. RESULTS Of the 114 centers participating in the study, 42% had conducted pediatric URS. Among the pediatric cases, 7 were infants, 53 were small children, 59 were school-aged children, and 73 were adolescents. A considerable number (37%) of the pediatric cases had previously undergone URS treatment. No differences in the surgical outcomes of the adults and children were reported. The URS-treated children had a greater number of positive preoperative urine cultures when compared with adult cases treated. A semirigid scope was used in the vast majority of pediatric cases (85%). According to the present data, within the group of URS-treated children, the younger the child, the more readmissions occurred. CONCLUSION URS is as efficient and safe in children as it is in adults. The data suggest that readmissions among URS-treated children are associated with age, with the likelihood of readmissions greater among younger age groups.

Phenytoin metabolite renal calculus: an index case.

INTRODUCTION Drugs and their metabolites are known factors in 1% to 2% of all kidney stones. Certain antiepileptic drugs are known to cause stone formation. Phenytoin is used as a first line antiepileptic therapy for many seizure disorders. We present what we believe to be the first report of a phenytoin metabolite urinary stone. METHODS A 79-year-old woman with a fever and seizure disorder was found to have a right pelvic kidney with hydronephrosis and multiple large calcifications. She had been taking the antiepileptic medication phenytoin for the past 10 years. Average total serum phenytoin level from the year prior was in the normal range. Free phenytoin levels were not routinely monitored, but the one value available was elevated at 5.1 ng/dL. The patient underwent a percutaneous nephrolitomy, ultimately expiring from medical complications after the procedure. Final stone analysis revealed a composition of 35% phenytoin metabolite (5-(para-hydroxyphenyl)-5-phenylhydantoin) and 65% proteinaceous material. An extensive review of literature including PubMed, MedLine, and various internet search engines was performed, searching for any prior reports of urinary calculi formed from phenytoin or its metabolite. RESULTS No previous reports of phenytoin or phenytoin metabolite urinary stones were found in the medical literature. Phenytoin has many known ill effects on the genitourinary system including acute interstitial nephritis, nephrotic syndrome, acute renal failure, and priapism. Now we can add urinary lithiasis to the list of its potential adverse effects. This article represents the first report of a phenytoin metabolite urinary stone. CONCLUSION A metabolite of the commonly used antiepileptic medication phenytoin can cause clinically relevant urolithiasis leading to significant morbidity and even mortality. Clinicians should have an increased level of suspicion for metabolite stone formation in symptomatic patients taking antiepileptic medications. Further studies on phenytoin metabolism and its potential for inducing urinary lithiasis should be performed.

Editorial Comment on END-0940-OR.R1

The current study shows the utility of opportunistic capture of bone mineral density (BMD) measurement utilizing noncontract CT scans in patients being monitored for stone recurrence. With the ubiquitous adoption of CT scanning worldwide, there are many clinical data points that can be measured on each study. Similar studies monitoring bone density loss have been described in male patients who smoke cigarettes (BMD obtained on screening chest CT) and a proof-of-concept study comparing female patients with osteoporosis (BMD measured on noncontrast CT imaging compared with the gold-standard dual-energy X-ray absorptiometry [DEXA] scan.). As expected, the authors documented increased BMD with thiazide diuretic therapy and citrate supplementation on longitudinal BMD measurements. Importantly, two-thirds of the study patients had increased bone density after treatment and 16% had increased bone density back to the normal range after only 1 year of medical therapy. Somewhat surprisingly, citrate therapy alone appeared to demonstrate quite significant increased bone density than either combination therapy or the use of thiazide diuretics alone. The caveats for the study are the need to correlate the CT density measurement in Hounsfield units with conventional DEXA scanning and to agree on the best anatomic site to follow serial measurements for longer time intervals. Osteopenia and osteoporosis remain important clinical conditions that often require additional pharmacologic therapy for decades. For stone-forming patients, the use of thiazides and citrate is the basis of our stone prevention interventions as documented in the current guidelines for medical treatment of stone disease. With increasing attention to limiting medical expenditures and possibly curtailing imaging studies, physicians should maximize clinical data obtained from all imaging modalities while monitoring patients over time. The authors should be commended for undertaking this study and should continue longitudinal monitoring to help validate this technique for wider clinical practice. Many studies often generate more questions than are answered by the original hypothesis. Ideally, larger population-based studies need to be done to correlate the BMD measurements and possibly modify our medical therapy and surveillance guidelines based on the longer term results.