Safety and predictors of complications of renal biopsy in the outpatient setting.

AIM: It has been recommended that patients should be admitted for 24 h of observation after percutaneous renal biopsy. This may be performed in the ambulatory outpatient setting, though its safety in this setting is an area of debate. We aim to demonstrate the safety of biopsy in the ambulatory outpatient setting. METHODS: We performed a retrospective cohort study of 475 biopsies performed in the ambulatory outpatient setting to examine safety and risk factors for complications. Transplant and native kidney biopsies performed at the Canberra Hospital, a tertiary referral university hospital, from 2006 until 2010 were included. Patients were observed for 6 h before discharge. Study outcomes were minor complications, defined as pain, hemorrhage or postural hypotension; or major complications, defined as complications requiring therapeutic intervention including blood product transfusion. RESULTS: The overall complication rate was 8.2%. There were 33 minor complications (6.9%) and 6 major complications (1.3%). All complications occurring outside the period of observation were safely managed. Significant predictors of any complication was hemoglobin (OR 1.03, 95% CI 1.01 - 1.06), kidney size (OR 0.93, 95% CI 0.89 - 0.98), and proceduralist. CONCLUSIONS: Percutaneous renal biopsy is safe in the ambulatory outpatient setting. Establishing ongoing quality assurance programs may be helpful in early identification of operator-dependent factors.

Prognostic efficacy of cardiac biomarkers for mortality in dialysis patients.

BACKGROUND: The high prevalence of cardiovascular mortality in the end-stage renal disease population is well established. The aim of this current study was to document the relative prognostic significance of established cardiac biomarkers troponin T (TnT), troponin I (TnI), B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-pro-BNP) in this population. METHODS: A prospective cohort study of dialysis patients undertaken in a single tertiary centre in Australia. Relevant clinical and biochemical information was collected at entry and all patients followed up prospectively without any loss to follow up. End-point of interest was all-cause mortality. Statistical analysis using Cox proportional hazards was used to study relationship between competing covariates and outcome. A total of 143 patients with a mean age of 59.67 +/- 15.49 years was followed up for a median duration of 30 months. Of these patients, 89.3% were white Australians of European ancestry. Twenty-seven per cent had an established diagnosis of diabetes mellitus. The mean concentrations (+/-SD) of TnT, TnI, BNP and N-terminal peptide pro-BNP (NT-pro-BNP) were 0.08 +/- 0.04 microg/L, 0.09 +/- 0.2 microg/L, 270 +/- 117 ng/L and 1434 +/- 591 ng/L respectively. RESULTS: Twenty-eight subjects died during the period of follow up. By univariate analysis, all cardiac markers (TnT, TnI, BNP, NT-pro-BNP and C-reactive protein) were significantly associated with an increase in mortality. On Cox proportionate hazards analysis, only albumin and NT-pro-BNP showed a significant association with mortality, with hazard ratios of 0.834, 95% confidence interval (CI) 0.779-0.893, P < 0.001, and 1.585, 95%CI 1.160-20165, P = 0.004 respectively. CONCLUSION: In patients with end-stage renal failure on dialysis NT-pro-BNP provides greater prognostic information compared with TnT and TnI.

Testing switchability of a new microemulsion formulation of cyclosporine.

We assessed the bioavailability of cyclosporine (CyA) in the test formulation (Cap Arpimune ME) relative to the reference formulation (Cap Sandimmune Neoral) to ascertain the switchability between the two formulations in patients. The study population included 30 patients on maintenance hemodialysis awaiting renal transplantation. The study adopted a randomized open-label, two-way, two-period, two-sequence crossover design. The dose administered was 8 mg/kg/d in two divided doses for 5 days in each study period with a washout period of 1 week between the two periods. A five-point blood sampling (at 0, 1, 2, 3, and 4 hours postdose) was done on the last day of each study period for CyA level monitoring. The study measures included C(max) (maximum blood concentration), AUC (area under the blood CyA concentration versus time curve, 0 to 4 hours) and actual time concentrations at individual sampling times. The differences in mean values for all parameters and the least significant differences were less than 20% of reference mean. Assessment of bioequivalence using log-transformed data showed that the point estimate (ratio test: reference) for C(max) was 0.9717 with a 90% confidence interval (CI) of 0.88 to 1.06 and that for AUC was 1.0053 with a 90% CI of 0.90 to 1.12. The bioequivalence obtained suggests that the test formulation can replace the reference formulation in patients who require CyA therapy.

Pre- and postrenal transplantation pharmacokinetics of cyclosporine microemulsion.

UNLABELLED: The availability of a microemulsion formulation (ME) of cyclosporin (CyA) displays improved bioavailability and reduced inter and intra-patient variability, resulting in improved long-term outcomes. Recent developments in therapeutic drug monitoring stress the need to optimize peak drug levels during the early posttransplant period to obtain long-term benefit. METHODS: We studied early CyA-ME pharmacokinetics, comparing pre- versus immediate posttransplant values, to assess predictability of pre-transplant profiles in 22 patients including 3 diabetics. An 8 mg/kg per day amount in two divided doses was administered, for 5 days pretransplant and 10-14 days posttransplant before performing the pharmacokinetic studies. Drugs interacting with CyA metabolism/absorption were withdrawn and patients with liver disease were excluded the CyA level monitoring used a 5-point blood sampling (at 0 hours, 1 hours, 2 hours, 3 hours, and 4 hours post-dose). The study compared actual concentrations at each individual time and the limited 0-4 hour AUC. RESULTS: The paired values at each point pre- and posttransplant were: C0 = 171 +/- 63 and 215 +/- 112, C1 = 723.86 +/- 345 and 1239.95 +/- 415, C2 = 972 +/- 185 and 1249.95 +/- 336, C3 = 822 +/- 242 and 942.7 +/- 286, and C4 = 601.54 +/- 190 and 670.5 +/- 208 ng/mL respectively. The C1 and C2 values were significantly higher posttransplant (P =.008 and 0.0045 respectively), suggesting a steeper absorption phase, a conclusion consistent with the higher 0-4 hour AUC posttransplant (P =.0089). However, linear regression analysis of pre- versus posttransplant values showed poor correlations. CONCLUSIONS: CyA absorption is significantly lower among patients on maintenance hemodialysis and showed no predictive correlation with posttransplant levels. The possible role of uremia in retarding absorption which may have clinical significance for primary graft dysfunction, needs further evaluation.