As part of triple-drug immunosuppression, everolimus (1.5 or 3 mg/day) was as efficacious as MMF, although the side-effect profile featured increased adverse events. Nephrotoxicity/calcineurin-inhibitor-related adverse events will require judicious lowering of CsA exposure with monitoring of everolimus troughs.

Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

Single nucleus ATAC-seq (snATAC-seq) creates new opportunities to dissect cell type-specific mechanisms of complex diseases. As pancreatic islets are central to type 2 diabetes (T2D), we profiled 15.3k islet cells using combinatorial barcoding snATAC-seq and identified 12 clusters, including multiple alpha, beta and delta cell states. We cataloged 228,873 accessible chromatin sites and identified transcription factors underlying lineage- and state-specific regulation. We observed state-specific enrichment of fasting glucose and T2D GWAS for beta cells as well as enrichment for other endocrine cell types. At T2D signals localized to islet accessible chromatin, we prioritized variants with predicted regulatory function and co-accessibility with target genes. A causal T2D variant rs231361 at the KCNQ1 locus had predicted effects on a beta cell enhancer co-accessible with INS , and genome editing in embryonic stem cell-derived beta cells affected INS levels. Together our findings demonstrate the power of single cell epigenomics for interpreting complex disease genetics.

Tacrolimus in combination with an initial dose of MMF 2 g/day is a very effective and safe regimen in cadaveric kidney transplant recipients.

En bloc transplantation optimizes the outcome of transplantation with very young kidneys. We recommend induction therapy and cyclosporine immunosuppression with cyclosporine levels similar to adult target levels to minimize rejection episodes and, thus, improve outcome. These kidneys should be distributed nationally, because better HLA matching is associated with improved short-term graft survival. Our high ureteral leak rate indicates that alternatives to unstented ureteroneocystostomy should be considered.