Objective

To raise awareness that patients with proximal ureteral stricture who elect for nephrectomy can consider donating the kidney. We present a series of patients undergoing therapeutic living donor nephrectomy (TLDN), a scenario in which a patient undergoing nephrectomy for an underlying medical problem donates the kidney to a person with end-stage renal disease. This practice is underutilized, and only a single TLDN with proximal ureteral stricture has been previously described. We aim to help define the indications, risks, and benefits for patients.

Methods

This is a retrospective case series of seven therapeutic donors with proximal ureteral pathology and stone disease. Patient characteristics, donor work up, operative details, and donor and recipient outcome were collected.

Results

All seven donors had proximal ureteral pathology, and six of the seven had nephrolithiasis or ureterolithiasis. After electing for nephrectomy, the mean time to TLDN was 57.9 days. No recipients experienced delayed graft function . Mean follow up was 40.1 months (range 8-131), and the most recent follow-up mean creatinine was 1.08 (mg/dL). Graft and recipient survival is 100%. No recipients developed recurrence of ureteral stricture or stones.

Conclusion

This is the first series demonstrating patients with proximal ureteral stricture, even with concomitant stone disease, may donate kidneys for transplantation. Recipient outcomes suggest this practice is safe, and appropriately selected patients that have already elected for nephrectomy should receive counseling about this opportunity. Importantly, patients who donate a kidney receive waiting list priority if they ever need a kidney transplant in the future.

Introduction

Hepatolithiasis (intrahepatic stones) is rare in adolescent patients and requires complex management strategies to prevent recurrent infections and progression to hepatic fibrosis. Surgical management is often required. In cases of unclear etiology, further work-up is indicated to provide insight into future management. In this report we describe an extensive stone analysis.

Presentation of case

A 20-year-old Caucasian female presented with known hepatolithiasis and multiple prior recurrent bouts of abdominal pain requiring hospitalization. Magnetic resonance cholangiopancreatography (MRCP) demonstrated an abnormal left-sided hepatic biliary ductal system dilatation. She was treated surgically with a formal left hepatectomy and preservation of the caudate lobe. The right ductal system had no stones or evidence of inflammation, and her bile and stones cultures were negative for organism growth. An extensive analysis demonstrated stone composition primarily of cholesterol.

Discussion

Adolescent presentations of hepatolithiasis are rare and considerations in the differential diagnosis include primary sclerosing cholangitis, bile acid transporter defects, and other known genetic diseases. This case is unique because only the left half of the intrahepatic ductal system had evidence of stone disease and the bile was sterile. A detailed stone analysis demonstrating cholesterol supersaturation provides additional context though the etiology remains unclear in this case and will require lifelong follow-up.

Conclusion

Early-onset hepatolithiasis is rare and requires expert management, and in some cases definitive surgical management with life-long follow-up. Extensive stone analysis and genetic testing can be performed to help identify disease etiology in unique cases.

The advent of large-scale in vitro differentiation of human stem cell-derived insulin-producing cells (SCIPC) has brought us closer to treating diabetes using stem cell technology. However, decades of experiences from islet transplantation show that ischemia-induced islet cell death after transplant severely limits the efficacy of the therapy. It is unclear to what extent human SCIPC are susceptible to ischemia. In this study, we show that more than half of SCIPC die shortly after transplantation. Nutrient deprivation and hypoxia acted synergistically to kill SCIPC in vitro. Amino acid supplementation rescued SCIPC from nutrient deprivation, likely by providing cellular energy. Generating SCIPC under physiological oxygen tension of 5% conferred hypoxia resistance without affecting their differentiation or function. A two-pronged strategy of physiological oxygen acclimatization during differentiation and amino acid supplementation during transplantation significantly improved SCIPC survival after transplant.