Preliminary studies of boceprevir and telaprevir based antiviral therapy in liver transplant (LT) recipients with hepatitis C have demonstrated dramatic increases in tacrolimus, cyclosporine, and the mTOR inhibitor exposure. In addition to empiric dose reductions, daily monitoring of immunosuppressant blood levels is required when initiating as well as discontinuing the protease inhibitors to maximize patient safety. Although improved suppression of HCV replication is anticipated, 20 to 40% of treated subjects have required early treatment discontinuation due to various adverse events including anemia (100%), infection (30%), nephrotoxicity (20%) and rejection (5 to 10%). Simeprevir and faldepravir are 2nd generation protease inhibitors which may have improved efficacy and tolerability profiles but potential drug interactions with other OATP1B1 substrates and unconjugated hyperbilirubinemia are expected. In contrast, sofosbuvir and daclatasvir based therapies are not expected to lead to clinically significant drug-drug interactions in LT recipients but confirmatory studies are needed. Liver transplant recipients may also be at increased risk of developing drug induced liver injury (DILI). Establishing a diagnosis of DILI in the transplant setting is very difficult with the variable latency, laboratory features and histopathological manifestations of hepatotoxicity associated with a given drug, the need to exclude competing causes of allograft injury, and the lack of an objective and verifiable confirmatory test. Nonetheless, a heightened awareness of the possibility of DILI is warranted in light of the large number of medications used in LT recipients and the potential adverse impact that DILI may have on patient outcomes.

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Background.New-onset stage 4–5 chronic kidney disease (CKD) after liver transplantation (LT) is associated with high morbidity, mortality, and economic burden. In 2010, we instituted an early renal sparing immunosuppression (RSI) protocol for LT recipients with severe renal dysfunction (pre-LT dialysis/estimated glomerular filtration rate (eGFR)<30mL/min/1.73 m2 or post-LT acute kidney injury) consisting of 2 doses of basiliximab for induction and delaying tacrolimus to post-LT day 4–7. We examined the effect of early RSI on post-LT renal outcomes.Methods.Data on all adults who had LT between January 1, 2010, and December 12, 2014 were collected. We calculated the renal risk index (RRI) score for each LT recipient (https://rri.med.umich.edu). Primary outcome was new-onset post-LT stage 4–5 CKD.Results.Of 214 LT recipients, 121 (57%) received early RSI and 93 (43%) received standard immunosuppression. Cumulative incidence of new-onset stage 4–5 CKD was higher in early RSI compared with standard immunosuppression (P = 0.03). Female sex and RRI score were the significant risk factors for development of post-LT stage CKD in the entire study cohort as well as the LT recipients with RRI ≥ sixth decile (high-risk group).Conclusions.Delaying tacrolimus initiation combined with basiliximab induction did not have a durable effect on long-term renal outcomes in high-risk LT recipients. Further studies are needed to identify the effective strategies to preserve renal function by targeting patients at high risk for CKD progression.

Objective This systematic review describes the efficacy, safety, and drug interactions of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose transport protein 2 (SGLT2) inhibitors in kidney transplant recipients (KTRs). Data Sources Articles were identified by English-language MEDLINE search, published prior to May 2020, using the terms kidney transplant, OR PTDM, OR NODAT, AND metformin, OR DPP4, OR GLP1, OR SGLT2. Study Selection and Data Extraction All selected studies were included if the study population was composed of adult KTRs who were diagnosed with either impaired glucose tolerance, diabetes mellitus (DM), new-onset diabetes after transplant (NODAT), or posttransplantation diabetes mellitus (PTDM). Data Synthesis In KTRs, there is evidence for safety with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors. However, urinary tract infections and a slight initial decrease in renal function may limit use of SGLT2 inhibitors. As compared with the nontransplant type 2 DM population, SGLT2 inhibitors are not as efficacious in KTRs. Relevance to Patient Care and Clinical Practice This review provides an overview of the current literature on newer antidiabetic agents, addressing efficacy, safety, and drug interactions to help guide clinical decision-making for their use in KTRs. Conclusion Newer antidiabetic agents have been recommended by the American Diabetes Association for potential cardiovascular, renal, and hypoglycemic benefits. Particular agents, such as DPP-4 inhibitors and GLP-1 RAs may play a role in correcting PTDM-related defects. Clinicians need to take into account both patient-specific and drug-specific characteristics when initiating these agents in KTRs.

The prevention and treatment of osteoporosis is an increasingly important topic in the solid organ transplant (SOT) population. Compared to the general population, these patients are at an elevated risk of developing osteoporosis due to progressive disease, lifelong immunosuppressant therapy, and malnutrition. As patients live longer after transplant, chronic disease management is increasingly more important. Supplementation with calcium and vitamin D is often necessary in the SOT population due to a high incidence of vitamin D deficiency. Bisphosphonate therapy is most commonly used for prevention and treatment of osteoporosis, but therapy can be limited by renal dysfunction which is common in transplant recipients. Alternative agents such as teriparatide and calcitonin have not been shown to provide a significant impact on the rate of fractures in this population. Additionally, denosumab may be a promising treatment option due to its novel mechanism of action, and is currently being studied in renal transplant patients. Timely initiation of supplementation and treatment, and minimizing glucocorticoid exposure prior to and after transplantation will aid in the prevention and proper management of osteoporosis in these patients.