Kaplan, Bruce

Immunosuppressants are critical after transplantation and prescribed as immune‐modulators for autoimmune disorders and glomerulonephritides. Immunosuppressants include large (e.g., thymoglobulin, alemtuzumab, and rituximab) and small molecules (e.g., corticosteroids, calcineurin inhibitors, antimetabolites, and mammalian target of rapamycin (mTOR) inhibitors). The majority of the small molecules worsen traditional cardiovascular risks. This review describes cardiovascular risks of small molecule immunosuppressants: corticosteroids, calcineurin inhibitors (tacrolimus and cyclosporine), and mTOR inhibitors (rapamycin), by categorizing these risks into two categories: ischemic heart disease and nonischemic cardiac effects.

Tobacco use adversely affects transplant outcomes such as graft survival, patient survival, and other conditions that alter transplant patient longevity. Especially concerning is tobacco's relationship to cardiovascular disease, the number 1 cause of death in kidney transplant recipients. Many authors conclude that tobacco interventions ought to be provided to patients and sometimes lament that there are no tobacco dependence interventions designed for kidney transplant recipients. European Best Practice Guidelines for Renal Transplantation also support tobacco dependence interventions. The purpose of this article is to describe one institution's experience in implementing the clinical practice guideline for treating tobacco use and dependence within a kidney and pancreas transplant program.

Calcineurin inhibitors (CNIs), including tacrolimus and cyclosporine, are immune‐modulating agents used in autoimmune disorders, glomerulonephritides, and after transplantation. CNIs are implicated as diabetogenic drugs but the mechanism is not clearly elucidated. Calcineurin is a cytosolic‐phosphatase critical for T‐lymphocyte activation. Calcineurin is widely distributed in different tissues responsible for glucose‐regulation including pancreas, liver, skeletal muscle, adipocytes, brain, and gut. We describe the pharmacologic effects of CNIs in different tissues and impact on glucose regulation.

Background and objectives Delayed graft function is a form of AKI resulting from ischemia-reperfusion injury. Our aim was to study the effect of delayed graft function on the progression of interstitial fibrosis after deceased donor kidney transplantation. Design, setting, participants, & measurements Our study is a retrospective study of all patients transplanted at our center between July of 2003 and September of 2014 using a kidney from a deceased donor. The primary outcome was the progression of interstitial fibrosis on serial protocol biopsies done during the first year post-transplant. We analyzed the distribution of the change in the Banff interstitial fibrosis (ci) score between the delayed graft function and nondelayed graft function groups for all of the paired biopsies done at time 0 and 12 months post-transplant ( Δ fibrosis). We also performed a linear mixed model analyzing the difference in the slopes for the progression of mean Banff ci score for all of the biopsies done at time 0 and 1, 4, and 12 months post-transplant. Results There were 343 (36.7%) in the delayed graft function group and 591 in the control group. The biopsy rates for the delayed graft function and nondelayed graft function groups at time 0 were 65.3% ( n =224) and 67.0% ( n =396), respectively, and at 12 months, they were 64.4% ( n =221) and 68.4% ( n =404), respectively. Paired biopsies were available for 155 in the delayed graft function group and 283 in the control group. In a risk-adjusted model, Banff ci score >0 on the time 0 biopsy had a higher odds of delayed graft function (odds ratio, 1.70; 95% confidence interval, 1.03 to 2.82). The distribution of the Δ fibrosis between 0 and 12 months was similar in delayed graft function and control groups ( P =0.91). The slopes representing the progression of fibrosis were also similar between the groups ( P =0.66). Conclusions Donor-derived fibrosis may increase the odds of delayed graft function; however, delayed graft function does not seem to increase the progression of fibrosis during the first year after transplantation.