ABSTRACT:The incidence of hepatitis B virus (HBV) infection in dialysis populations has declined over recent decades, largely because of improvements in infection control and widespread implementation of HBV vaccination. Regardless, outbreaks of infection continue to occur in dialysis units, and prevalence rates remain unacceptably high. For a variety of reasons, dialysis patients are at increased risk of acquiring HBV. They also demonstrate different disease manifestations compared with healthy individuals and are more likely to progress to chronic carriage. This paper will review the epidemiology, modes of transmission and diagnosis of HBV in this population. Prevention and treatment will be discussed, with a specific focus on strategies to improve vaccination response, new therapeutic options and selection of patients for therapy.

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Objectives: The aims of this study were to develop a population pharmacokinetic model of tacrolimus in adult kidney transplant recipients; to use this model to compare cytochrome P450 3A5 (CYP3A5) genotype based initial dosing of tacrolimus to standard per-kilogram based dosing; and to predict the best starting dose of tacrolimus based on patient genotype to achieve a trough concentration between 6 and10 µg/L by day 5 post-transplantation.Methods: Population analysis was performed using the software program NONMEM®. Tacrolimus

Prednisolone and prednisone are integral components of induction and maintenance immunosuppressive regimens in solid organ transplantation. The pharmacokinetics of these agents are extremely complex. Prednisolone is the active drug moiety while prednisone is both a pro-drug and inactive metabolite of prednisolone. Within the dosage range used in transplantation, prednisolone and prednisone exhibit concentration-dependent non-linear pharmacokinetics when parameters are measured with reference to total drug concentration. Dose dependency disappears when free (unbound) prednisolone is measured. Altered organ function, changing biochemistry and use of a number of concomitant medicines in transplantation appear to lead to pharmacokinetic differences in transplant recipients compared with other patient groups. Greater than threefold variability in dose-adjusted exposure to total prednisolone in transplant recipients is evident. Time post-transplant, hepatic and renal dysfunction, patient age, sex, bodyweight, serum albumin concentration, concomitant medication exposure, various disease states and genetic polymorphisms in metabolic enzymes and drug transporters have sometimes been associated with prednisolone pharmacokinetic variability. The clinical impact of corticosteroid therapy on the disposition of ciclosporin, tacrolimus and sirolimus and the impact of different immunosuppressant therapy combinations on prednisolone exposure needs to be further elucidated. Patient response patterns to prednisolone are consistent with delayed and indirect mechanisms of corticosteroid action involving modification of nuclear transcription and protein synthesis. Many adverse effects have been linked with prednisolone and prednisone therapy, but not all of these have been investigated thoroughly in transplant populations. Dyslipidaemia, growth restriction, diabetogenesis, hypertension and cataracts are well studied toxicities. Evidence is less clear for prednisolone-induced osteonecrosis, obesity and hypertriglyceridaemia. There have been some reports of a relationship between prednisolone pharmacokinetics and incidence of acute rejection, Cushing's syndrome and adverse cardiovascular and metabolic events. Dosing of prednisolone and prednisone in transplantation is typically empirical and varies significantly across transplant centres. Currently, authoritative guidelines are conflicting in their opinions regarding corticosteroid avoidance and early discontinuation in adult kidney transplantation. Overall, data suggest the promise of corticosteroid-free immunosuppression in paediatric patients. Further investigation of the pharmacokinetics and pharmacodynamics of prednisolone and prednisone in transplant recipients based on new chromatography assay techniques and free drug measurement, population pharmacokinetic/pharmacodynamic modelling approaches, genetic testing and larger studies in patients on modern day immunosuppressant protocols may lead to better individualization of corticosteroid therapy in the future.

Graft Loss and Mortality Outcomes from kidney transplantation remain suboptimal. 1-3 Effective immunosuppressive drugs, along with attention to cardiovascular disease 4 and prophylaxis against infection, 5 have significantly reduced rates of acute rejection (15.4%), graft loss (3.6%), and death (2.8%) in the first posttransplant year for standard risk recipients. 6 However, time to allograft failure remains substantially shorter than typical recipient life expectancy following transplantation, due largely to chronic antibody-mediated rejection. 7-10 Approximately 20% of kidney allograft

Background: Glomerular filtration rate (GFR) estimation equations have never been validated in the HIV population. This pilot study aimed to compare all currently available methods of kidney function assessment with nuclear GFR in HIV-infected adults. Methods: Patients underwent GFR measurement with ^99mTc-diethylenetriaminepentaacetic acid (Tc-99m Pentetate), and measured values were compared with results of creatinine-based estimation equations [abbreviated 4-variable Modification of Diet in Renal Disease (MDRD) formula and Cockcroft-Gault (CG) formulae], 24-hour urine creatinine clearance and estimated cystatin C GFR. Results: Twenty-seven HIV-infected adults were studied. Most were male and Caucasian, with a mean age of 52 years. Median CD4 was 290 cells/mm³, 70% of patients had HIV RNA <50 copies/ml and all were receiving highly active antiretroviral therapy (median 5 drugs). Median Tc-99m Pentetate-GFR was 91 ml/min/1.73 m². Despite greater bias and similar accuracy, the MDRD formula was more precise than the CG formula, regardless of whether CG estimations were corrected for ideal body weight or body surface area. Relative accuracy within 30% of nuclear GFR was greater for the MDRD formula than for all other methods. The performance of 24-hour urine creatinine clearance was similar to that of the MDRD formula for patients with GFR <90 ml/min/1.73 m², although it performed less well at higher GFR. The performance of cystatin C GFR was inferior to that of all the creatinine-based methods. Conclusions: While no method of kidney function estimation performed highly, both 24-hour urine creatinine clearance and the MDRD formula performed with a level of precision and accuracy sufficient for clinical decision making. Our findings support the preferential use of the MDRD formula in the treated HIV population and suggest that there are no HIV-specific factors that limit equation applicability. Larger validation studies are needed to confirm our findings and allow generalization to the HIV population at large.

Corynebacterium is an uncommon but significant cause of PD-associated peritonitis. Complete cure with antibiotics alone is possible in the majority of patients, and rates of adverse outcomes are comparable to those seen with peritonitis due to other organisms. Use of vancomycin rather than cephazolin as empiric therapy does not impact outcomes, and a 2-week course of antibiotic therapy appears sufficient. If catheter removal is required, outcomes are improved by removing the catheter within 1 week of peritonitis onset.