Faculty Bibliography

Tamm-Horsfall protein (THP) is the most abundant protein in urine, yet its function remains incompletely understood. It has been hypothesized that THP contributes to the maintenance of urinary homeostasis. We report a case of a 71-year-old male with a history of renal cell carcinoma treated with partial nephrectomy in 2017. He represented 8 years later with an enlarging, enhancing renal mass concerning for recurrence. A radical nephrectomy was performed and revealed a benign specimen with a positive PAS stain, consistent with THP. To our knowledge this is the first report of THP deposition in the renal parenchyma after partial nephrectomy.

OBJECTIVE:To measure lithogenic changes during pregnancy in patients on a standardized diet without a prior history of nephrolithiasis. METHODS:IRB approval was obtained. The metabolic needs of pregnant participants were determined, and standardized diet administered with Boost shakes and unlimited water. 24-hour urine collections were obtained during the third trimester, post-partum, and post-lactation. Subjects remained on the controlled diet for 24-hour prior to and during the collection. Standard statistical analysis was performed. RESULTS:Of 18 patients, 6 had a de novo stone event during pregnancy. Of these, 83% were composed of calcium phosphate. Stone events with calcium phosphate presented later than calcium oxalate. Stone-formers had an intra-partum body mass index greater than non-stone formers (33.1 vs 26.7, P <.05). All participants had hypercalciuria, but stone-formers were found to have a nearly 2X greater urine calcium compared to non-stone formers on their controlled diet (392.1 vs 205.9, P <.05). Post-partum, we observed a decrease in urine calcium, citrate, pH, and supersaturation of calcium oxalate and phosphate (P <.05). CONCLUSION/CONCLUSIONS:This is the first study to identify lithogenic changes during pregnancy in de novo stone formers on a standardized diet. We show that stone-formers have primarily calcium phosphate stones. They also have an elevated body mass index and are significantly more hypercalciuric without other demonstratable lithogenic differences compared to non-stone formers. Post-partum, we demonstrate reduction in intra-partum lithogenicity that may mitigate stone risk. These data suggest an underlying mechanism exists in stone formers that increases urine calcium above what would be expected in gestational hypercalciuria.

INTRODUCTION/BACKGROUND:Free radical-mediated oxidative renal tubular injury secondary to hyperoxaluria is a proposed mechanism in the formation of calcium oxalate stones. Vitamin E, an important physiologic antioxidant, has been shown in rat models to prevent calcium oxalate crystal deposition. Our objective was to determine if low dietary vitamin E intake was associated with a higher incidence of stones. MATERIALS AND METHODS/METHODS:We analyzed data from the 2017 to 2020 National Health and Nutrition Examination Survey, a nationally representative sample (n = 7,707). A multivariable logistic regression model was used to assess the association between elevated dietary vitamin E intake (≥ 15 mg/day) and nephrolithiasis controlling for key demographic variables: water and nutrient intake (sodium, calcium, vitamin C), and diabetes mellitus. RESULTS:The incidence of nephrolithiasis was 1.66% (1.38% - 1.95%). In patients consuming &lt; 15 mg/day vitamin E, the incidence was 1.8% compared to 0.8% in patients with vitamin E intake ≥ 15 mg/day (p = 0.024). In adjusted models, participants with low vitamin E intake had a significantly higher odds of reporting stone passage (aOR = 2.83, 95% CI (1.07 - 7.5)). CONCLUSION/CONCLUSIONS:We found that low vitamin E intake is associated with a > 2.5× greater odds of stone passage. These data are consistent with animal models suggesting that vitamin E may play an important protective role in the pathogenesis of calcium oxalate stone formation. This is the first study assessing the relationship between vitamin E intake and nephrolithiasis in humans. Future investigation of vitamin E supplementation in stone formers may help further determine if vitamin E is useful in the management of calcium oxalate stones.

OBJECTIVE:To review pharmacology, efficacy, safety, and considerations for use, of second-generation androgen receptor (AR) antagonists in treatment of nonmetastatic castrate-resistant prostate cancer (M0CRPC). DATA SOURCES:Conducted search in PubMed and Google scholar (January, 1, 2002-December 31, 2022), using relevant terms. STUDY SELECTION AND DATA EXTRACTION:Relevant English-language studies, conducted in humans evaluating second-generation AR antagonists for M0CRPC, and additional articles and package inserts were considered. DATA SYNTHESIS:Apalutamide, darolutamide, and enzalutamide are effective in delaying the time to development of metastatic prostate cancer in men with M0CRPC with a rapid prostate-specific antigen (PSA) doubling time (<10 months). No head-to-head, randomized, clinical trials have been conducted. The most common adverse effects include fatigue and hypertension, and quality of life is maintained in most patients. Cost is similar among the agents (~$15,000/month). Drug-drug interactions vary among these agents and should be considered, when selecting therapy as well as likely adherence. Darolutamide is administered twice daily with the others once daily. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE:Second-generation AR antagonists are effective in reducing time to development of metastatic disease and prolonging overall survival in patients with M0CRPC and a PSA doubling time of <10 months. Recent imaging advances may alter how we evaluate outcomes. CONCLUSIONS:Second-generation AR antagonists improve disease control and overall survival. Generally, they are well tolerated and QOL is maintained. Selection of the best agent is based on the adverse effect profile, potential for drug- and disease-interactions, administration, cost, and patient preference.

OBJECTIVE:To determine if accurate documentation of bladder cancer risk was associated with a clinician surveillance recommendation that is concordant with AUA guidelines among patients with nonmuscle invasive bladder cancer (NMIBC). METHODS:We prospectively collected data from cystoscopy encounter notes from four Department of Veterans Affairs (VA) sites to ascertain whether they included accurate documentation of bladder cancer risk and a recommendation for a guideline-concordant surveillance interval. Accurate documentation was a clinician-recorded risk classification matching a gold standard assigned by the research team. Clinician recommendations were guideline-concordant if the clinician recorded a surveillance interval that was in line with the AUA guideline. RESULTS:Among 296 encounters, 75 were for low-, 98 for intermediate-, and 123 for high-risk NMIBC. 52% of encounters had accurate documentation of NMIBC risk. Accurate documentation of risk was less common among encounters for low-risk bladder cancer (36% vs 52% for intermediate- and 62% for high-risk, P < .05). Guideline-concordant surveillance recommendations were also less common in patients with low-risk bladder cancer (67% vs 89% for intermediate- and 94% for high-risk, P < .05). Accurate documentation was associated with a 29% and 15% increase in guideline-concordant surveillance recommendations for low- and intermediate-risk disease, respectively (P < .05). CONCLUSION:Accurate risk documentation was associated with more guideline-concordant surveillance recommendations among low- and intermediate-risk patients. Implementation strategies facilitating assessment and documentation of risk may be useful to reduce overuse of surveillance in this group and to prevent unnecessary cost, anxiety, and procedural harms.

INTRODUCTION:To evaluate patient preference for sperm disposition in case of death based on demographic factors and infertility etiology. MATERIALS AND METHODS:This retrospective cohort study was performed at a university hospital-affiliated fertility center. Charts of 550 men undergoing cryopreservation for assisted reproductive technologies (ART) between 2016-2019 were reviewed to create a descriptive dataset. Patients previously signed consent forms stating their preference for sperm transfer to their partner or disposal in the event of their subsequent death. Patients undergoing sperm cryopreservation for the purpose of ART were analyzed to assess associations between demographic characteristics and etiology of infertility and their choice to either transfer sperm to their partner or discard. RESULTS:A total of 84.9% (342/403) of patients included in final analyses elected to transfer their sperm to their partner in the event of their death. Factors associated with a significantly increased likelihood to transfer versus discard included a male-factor infertility diagnosis compared to female-factor infertility diagnosis (transfer rate 89.3% vs. 79.9%; p = .022) and commercial insurance coverage versus non-commercial/no insurance coverage (transfer rate 86.3% vs. 75.0%, p = .029). No significant differences relating to age, race/ethnicity, occupation classification, marital status or duration of marriage, or prior paternity were found. CONCLUSION:A majority of male patients seeking sperm cryopreservation for ART elected to transfer their sperm to their partner if future death should occur. There does not appear to be a clear factor that would impact this decision based on demographic characteristics.