BK Virus in Kidney Transplant Recipients: The Influence of Immunosuppression

The incidence of BK virus infection in kidney transplant recipients has increased over recent decades, coincident with the use of more potent immunosuppression. More importantly, posttransplant BK virus replication has emerged as an important cause of graft damage and subsequent graft loss. Immunosuppression has been accepted as a major risk for BK virus replication. However, the specific contribution of individual immunosuppressive medications to this risk has not been well established. The purpose of this paper is to provide an overview of the recent literature on the influence of the various immunosuppressant drugs and drug combinations on posttransplant BK virus replication. Evidence supporting the various immunosuppression reduction strategies utilised in the management of BK virus will also be briefly discussed

Comparison of the influence of cyclosporine and tacrolimus on the pharmacokinetics of prednisolone in adult male kidney transplant recipients

Cyclosporine has been observed to precipitate cushingoid features in kidney transplant recipients already on prednisolone. Some pharmacokinetic studies have demonstrated increased prednisolone exposure in patients on cyclosporine therapy compared with azathioprine, whereas other studies have found no difference. The objective of this study was to determine whether cyclosporine impacts on prednisolone exposure as compared with tacrolimus

Renal Safety of a Tenofovir-Containing First Line Regimen: Experience from an Antiretroviral Cohort in Rural Lesotho

Current guidelines contraindicate TDF use when creatinine clearance (CrCl) falls below 50 ml/min. We report prevalence of abnormal renal function at baseline and factors associated with abnormal renal function from a community cohort in Lesotho

Rationale and design of the oral HEMe iron polypeptide Against Treatment with Oral Controlled Release Iron Tablets trial for the correction of anaemia in peritoneal dialysis patients (HEMATOCRIT trial)

Background: The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin (R) ES) administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA)-treated peritoneal dialysis (PD) patients than conventional oral iron supplementation (Ferrogradumet (R))

Pharmacogenetic influences on mycophenolate therapy

Mycophenolic acid (MPA) is a cornerstone immunosuppressant therapy in solid organ transplantation. MPA is metabolized by uridine diphosphate glucuronosyltransferase to inactive 7-O-MPA-glucuronide (MPAG). At least three minor metabolites are also formed, including a pharmacologically active acylglucuronide. MPA and MPAG are subject to enterohepatic recirculation. Biliary excretion of MPA/MPAG involves several transporters, including organic anion transporting polypeptides and multidrug resistant protein-2 (MRP-2). MPA metabolites are also excreted via the kidney, at least in part by MRP-2. MPA exerts its immunosuppressive effect through the inhibition of inosine-5-monophosphate dehydrogenase. Several SNPs have been identified in the genes encoding for uridine diphosphate glucuronosyltransferase, organic anion transporting polypeptides, MRP-2 and inosine-5-monophosphate dehydrogenase. This article provides an extensive overview of the known effects of these SNPs on the pharmacokinetics and pharmacodynamics of MPA

Residential Location and Kidney Transplant Outcomes in Indigenous Compared With Nonindigenous Australians

Background: Indigenous Australians experience significantly worse graft and patient outcomes after kidney transplantation compared with nonindigenous Australians. It is unclear whether rural versus urban residential location might contribute to this.Methods: All adult patients from the Australia and New Zealand Dialysis and Transplant Registry who received a kidney transplant in Australia between January 1, 2000, and December 31, 2012, were investigated. Patients\u27 residential location was classified as urban (major city + inner regional) or rural (outer regional - very remote) using the Australian Bureau of Statistics Remoteness Area Classification.Results: Of 7826 kidney transplant recipients, 271 (3%) were indigenous. Sixty-three percent of indigenous Australians lived in rural locations compared with 10% of nonindigenous Australians (P < 0.001). In adjusted analyses, the hazards ratio for graft loss for Indigenous compared with non-Indigenous race was 1.59 (95% confidence interval [95% CI], 1.01-2.50; P = 0.046). Residential location was not associated with graft survival. Both indigenous race and residential location influenced patient survival, with an adjusted hazards ratio for death of 1.94 (95% CI, 1.23-3.05; P = 0.004) comparing indigenous with nonindigenous and 1.26 (95% CI, 1.01-1.58; P = 0.043) comparing rural with urban recipients. Five-year graft and patient survivals were 70% (95% CI, 60%-78%) and 69% (95% CI, 61%-76%) in rural indigenous recipients compared with 91% (95% CI, 90%-92%) and 92% (95% CI, 91%-93%) in urban nonindigenous recipients.Conclusions: Indigenous kidney transplant recipients experience worse patient and graft survival compared with nonindigenous recipients, whereas rural residential location is associated with patient but not graft survival. Of all groups, indigenous recipients residing in rural locations experienced the lowest 5-year graft and patient survivals

Prevention of access-related infection in dialysis

Access-related infections (ARIs), such as exit-site infections, tunnel infections, bacteremia, fungemia and peritonitis, are the Achilles' heel of dialysis, and contribute significantly to morbidity, mortality and excess healthcare costs in hemodialysis and peritoneal dialysis patient populations. Despite international guidelines recommending the avoidance of catheters for hemodialysis access, hospital admissions for vascular ARIs have doubled in the last decade. Moreover, repeated use of antibiotics to treat ARIs has been associated with the selection of multiresistant organisms, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. ARIs result from direct inoculation of skin organisms during access cannulation/connection, migration of skin organisms along dialysis catheters into the bloodstream or peritoneal cavity, or contamination and colonization of catheter lumens with subsequent biofilm formation. This paper will review the epidemiology, pathogenesis and prevention of ARIs. It will focus specifically on randomized, controlled trial evidence in relation to the safety and efficacy of aseptic techniques, nasal eradication of S. aureus, oral antimicrobial prophylaxis, topical antimicrobial prophylaxis (including disinfectants, antibiotics and antibacterial honey), antimicrobial catheter lock solutions (including gentamicin, citrate and ethanol), antimicrobial-impregnated catheters, catheter design (straight vs coiled, single vs double cuff), peritoneal dialysis catheter connectology, catheter insertion technique, germicidal devices, vaccines and preinsertion antibiotic prophylaxis