Publications

Data from recent high-throughput studies analyzing local and advanced prostate cancer have revealed an incredible amount of biological diversity, which has led to the classification of distinct molecular tumor subtypes. While integrating prostate cancer genomics with clinical medicine is still at its infancy, new approaches to treat prostate cancer are well underway and being studied. With the recognition that DNA damage repair (DDR) mutations play an important role in the pathogenesis of this disease, clinicians can begin to utilize genomic information in complex treatment decisions for prostate cancer patients. In this Review, we discuss the role of DDR mutations in prostate cancer, including deficiencies in homologous repair and mismatch repair (MMR), and how this information is revolutionizing the treatment landscape. In addition, we highlight the potential resistance mechanisms that may result as we begin to target these pathways in isolation and discuss potential combinatorial approaches that may delay or overcome resistance.

BACKGROUND

Urinary neutrophil gelatinase-associated lipocalin (uNGAL)-associated acute kidney injury is common after liver transplantation (LT), but whether early acute kidney injury predicts chronic kidney disease (CKD) and mortality remains uncertain.

METHODS

Adults with LT from 2008 to 2010 in a previously published prospective cohort evaluating serial uNGAL pre- and post-LT were retrospectively assessed to evaluate uNGAL as a predictor of long-term outcomes post-LT. The primary outcomes were post-LT CKD, defined as Modification of Diet in Renal Disease estimated glomerular filtration rate less than 60 mL/min per 1.73 m for 3 continuous months, and death.

RESULTS

uNGAL at 24 hours postreperfusion was significantly higher among patients who developed CKD. Multivariable modeling for the development of CKD demonstrated that uNGAL at 24-hours postreperfusion, 24 hours post-LT renal function, initial calcineurin inhibitor, and age were independent predictors of the development of CKD at in this cohort with long-term follow-up post-LT. Further, this association was stronger in those with preserved pre-LT renal function, a population where renal outcomes are often difficult to predict.

CONCLUSIONS

We propose that perioperative uNGAL may identify patients at risk for CKD and allow for targeted early implementation of renal-sparing strategies.