Post-transplant outcomes in recipients of living donor kidneys and intended recipients of living donor kidneys.

Background: Long-term kidney transplant survival at the population level is consistently favorable, but this survival varies widely at an individual level due to both recipient and donor factors. The distinct contribution of recipient and donor factors to individual post kidney transplant outcome remains unclear. Comparing outcomes in deceased donor (DD) recipients with potential but non-actualized living donors (DD1) to those recipients with actualized living donors (LD), and to DD recipients without potential living donors (DD0) may provide transplant candidates with more information about their own post-transplant prognosis.

Safety and efficacy of prophylaxis for Pneumocystis jirovecii pneumonia involving trimethoprim-sulfamethoxazole dose reduction in kidney transplantation.

Background: Trimethoprim-sulfamethoxazole (TMP-SMX) is the drug of choice for anti-Pneumocystis jirovecii pneumonia (PcP) prophylaxis in kidney transplant recipients (KTR). Post-transplant management balances preventing PcP with managing TMP-SMX-related adverse effects. TMP-SMX dose reduction addresses adverse effects but its implications to incident PcP are unclear.

The Impact of Total Gastrectomy on Pharmacokinetics in Kidney Transplant Immunosuppressive Drug Regimes: A Case Study.

Background: Ensuring reliable gastrointestinal drug absorption of orally administered immunosuppressive medications posttransplant is critical to ensuring graft survival.

Methods: A 66-year-old man of East Asian origin with a previous total gastrectomy was evaluated for living donor kidney transplantation. Pretransplant pharmacokinetic testing was performed to determine the most appropriate posttransplant medication strategy.

Reduction in new-onset diabetes mellitus after renal transplant with erythropoietin-stimulating agents: a retrospective cohort study.

Background: Studies have shown that erythropoietin-stimulating agents (ESAs) protect mice against the development of diabetes through direct effects on pancreatic ß cells. However, the effect of ESAs on the incidence of diabetes in humans has not been well studied. It is unknown whether exposure to ESAs is associated with a reduced incidence of new-onset diabetes after transplant (NODAT).

Commercial kidney transplantation is an important risk factor in long-term kidney allograft survival.

Transplant tourism, a form of transplant commercialization, has resulted in serious short-term adverse outcomes that explain reduced short-term kidney allograft survival. However, the nature of longer-term outcomes in commercial kidney transplant recipients is less clear. To study this further, we identified 69 Canadian commercial transplant recipients of 72 kidney allografts transplanted during 1998 to 2013 who reported to our transplant center for follow-up care.

The role of CYP3A5 polymorphism and dose adjustments following conversion of twice-daily to once-daily tacrolimus in renal transplant recipients.

Background: Tacrolimus is available as twice-daily Prograf® (Tac-BID) and the once-daily formulation, Advagraf® (Tac-OD). Although therapeutically equivalent, some transplant recipients require dose adjustments to achieve similar tacrolimus trough concentrations [Tac C0] after conversion between formulations. Tacrolimus is primarily metabolized by cytochrome P450 3A5 (CYP3A5).

Lithium-Induced Minimal Change Disease and Acute Kidney Injury.

Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI).

IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer.

IL-15 has pivotal roles in the control of CD8(+) memory T cells and has been investigated as a therapeutic option in cancer therapy. Although IL-15 and IL-2 share many functions together, including the stimulation of CD8 T cell proliferation and IFN-γ production, the different in vivo roles of IL-15 and IL-2 have been increasingly recognized. Here, we explored the different effects of IL-15 and IL-2 on tumor-infiltrating (TI) T cells from resected breast tumors.

A clinical and pathological variant of acute transplant glomerulopathy.

Acute transplant glomerulopathy transplant glomerulopathy (TG) is a common cause of late renal allograft loss. We describe a unique case of a renal transplant recipient who developed rapid-onset nephrotic-range proteinuria and acute kidney injury secondary to C4d negative acute TG. Two courses of intravenous Rituximab resulted in significant improvement in proteinuria and allograft function.

Metabolic syndrome definitions and components in predicting major adverse cardiovascular events after kidney transplantation.

Metabolic syndrome (MetS) associates with cardiovascular risk post-kidney transplantation, but its ambiguity impairs understanding of its diagnostic utility relative to components. We compared five MetS definitions and the predictive value of constituent components of significant definitions for major adverse cardiovascular events (MACE) in a cohort of 1182 kidney transplant recipients. MetS definitions were adjusted for noncomponent traditional Framingham risk factors and relevant transplant-related variables.

A randomized cross-over comparison of short-term exposure of once-daily extended release tacrolimus and twice-daily tacrolimus on renal function in healthy volunteers.

Calcineurin inhibitor nephrotoxicity remains an issue for transplant recipients. The pharmacokinetic profile (PK) of the once-daily tacrolimus extended release (Tac-ER) includes equivalent exposure [AUC(0-24 h) ] but lower Cmax versus twice-daily tacrolimus immediate release (Tac-IR). We hypothesized that the unique PK profiles would result in pharmacodynamic differences in renal function.

A prospective cohort conversion study of twice-daily to once-daily extended-release tacrolimus: role of ethnicity.

Background: Tacrolimus is a widely used calcineurin inhibitor in kidney transplantation. It is available as twice-daily Prograf® (Tac-BID) and once-daily Advagraf® (Tac-OD). Although therapeutically equivalent, some patients require dose adjustments to achieve similar trough concentrations [C0] after conversion.

A comparison of the extended-release and standard-release formulations of tacrolimus in de novo kidney transplant recipients: a 12-month outcome study.

BACKGROUND: Limited comparative data are available on the outcomes between extended-release and standard-release tacrolimus when used de novo in kidney transplant recipients (KTRs). METHODS: We identified KTRs transplanted at our institution during 2009-10 routinely prescribed extended-release tacrolimus and compared them with those transplanted during 2008-09 prescribed standard-release tacrolimus. Graft function (eGFR by MDRD-7 equation) at 12 months post-transplant (primary outcome); new-onset diabetes and other cardiovascular risk factors, BK viremia incidence, acute rejection, and graft survival to 12 months (secondary outcomes) were compared by intent-to-treat analysis.

A pilot study of reduced dose cyclosporine and corticosteroids to reduce new onset diabetes mellitus and acute rejection in kidney transplant recipients.

Background: New onset diabetes mellitus (NODM) and acute rejection (AR) are important causes of morbidity and risk factors for allograft failure after kidney transplantation.

Methods: In this multi-center, open label, single-arm pilot study, 49 adult (≥18 years of age), low immunologic risk, non-diabetic recipients of a first deceased or living donor kidney transplant received early steroid reduction to 5 mg/day combined with Thymoglobulin® (Genzyme Transplant, Cambridge, MA, USA) induction, low dose cyclosporine (2-hour post-dose (C2) target of 600 to 800 ng/ml) and mycophenolic acid (MPA) therapy.

Results: Six months after transplantation, two patients (4%) developed NODM and one patient (2%) developed AR.

A comparison of short-term exposure of once-daily extended release tacrolimus and twice-daily cyclosporine on renal function in healthy volunteers.

Background: Calcineurin inhibitor nephrotoxicity remains an issue for recipients of solid organ transplants. After cyclosporine A (CsA) microemulsion administration, effective renal plasma flow (ERPF) and glomerular filtration rate(GFR) are decreased coincident with the maximal concentration (Cmax) of CsA. The pharmacokinetic (PK) profile of the once-daily formulation of tacrolimus extended release (Tac ER) includes an equivalent AUCPK 0-24 hr and a lower Cmax versus twice-daily Tac immediate release.

South Asian ethnicity as a risk factor for major adverse cardiovascular events after renal transplantation.

Background And Objectives: South Asians (SAs) comprise 25% of all Canadian visible minorities. SAs constitute a group at high risk for cardiovascular disease in the general population, but the risk in SA kidney transplant recipients has never been studied.

Design, Setting, Participants, & Measurements: In a cohort study of 864 kidney recipients transplanted from 1998 to 2007 and followed to June 2009, we identified risk factors including ethnicity associated with major cardiac events (MACEs, a composite of nonfatal myocardial infarction, coronary intervention, and cardiac death) within and beyond 3 months after transplant.

Hypocomplementaemic immune complex tubulointerstitial nephritis.

We report a rare cause of rapidly progressive renal failure associated with low complement, positive ANA but negative anti DS-DNA. A renal biopsy demonstrated tubulointerstitial nephritis with positive immunoglobulin staining involving the interstitium and tubular basement membrane but glomerular sparing. A review of the literature and differential diagnosis are discussed.

Microalbuminuria post-renal transplantation: relation to cardiovascular risk factors and C-reactive protein.

Microalbuminuria predicts graft loss and all-cause mortality in renal transplant recipients. In the general population, it clusters with both traditional cardiovascular risk factors and elevated C-reactive protein (CRP). Our objective was to define the relationship between microalbuminuria and these risk factors in stable renal transplant recipients.

Association of uric acid with inflammation, progressive renal allograft dysfunction and post-transplant cardiovascular risk.

Hyperuricemia is common after kidney transplantation. Although its risk factors are well established, its relation to inflammation, progressive renal dysfunction, and cardiovascular events is unknown. In this study, 405 stable renal transplant recipients with > or = 3 uric acid (UA) and C-reactive protein measurements from January 2005 to April 2008 were identified to determine the relations between UA and C-reactive protein and between UA and the rate of decrease in the estimated glomerular filtration rate (eGFR; using the Modification of Diet in Renal Disease equation) and cardiovascular events.

Five-year study of tacrolimus as secondary intervention versus continuation of cyclosporine in renal transplant patients at risk for chronic renal allograft failure.

Background: Chronic allograft nephropathy is the most frequent cause of long-term kidney allograft loss. Studies are desperately needed to improve long-term survival. Tacrolimus has been associated with less rejection and better kidney function compared with cyclosporine in clinical trials.

Seasonal variation of serum lipid levels in stable renal transplant recipients.

Background/aims: Seasonal variation in lipid levels is well described in the general population, but has not been examined in renal transplant recipients (RTR). We sought to determine whether seasonal differences exist in RTR, a group at high risk for hyperlipidemia.

Methods: We reviewed our population of 920 adults, identifying primary allograft recipients with survival > or =1 year, stable function, and > or =1 pair of post-6 months 'winter' (December 21 to March 20) plus 'summer' (June 21 to September 22) fasting lipid measurements within the same year.

Mycophenolate mofetil and C-reactive protein in renal transplant recipients.

Background: C-reactive protein (CRP) is a strong predictor of cardiovascular disease, all-cause mortality, and renal allograft loss. Little is known about the effects of immunosuppressive and cardiovascular risk-modifying drugs on CRP in renal transplant recipients.

Methods: We retrospectively identified stable patients with > or =1 highly sensitive CRP measurements between January 1 and August 31, 2005.