Richard W. Carson

Reduced inter- and intrasubject variability in cyclosporine pharmacokinetics in renal transplant recipients treated with a microemulsion formulation in conjunction with fasting, low-fat meals, or high-fat meals

This cross-over study compared the pharmacokinetic parameters obtained from cyclosporine (CsA) concentration-time profiles after administration of the corn oil-based soft gel cap (CsA-GC) with those with the microemulsion (CsA-ME) gel cap. Neither the fasting state nor the coadministration of a low- or high-fat breakfast affected the pharmacokinetics of CsA presented in either formulation. Comparisons of the three sets of pharmacokinetic parameters--namely, after fasting or after low-fat or after high-fat diets--demonstrated the CsA-ME formulation to display greater intraindividual reproducibility of the C0 and C12 trough levels (TLs), Cmax, tmax, and area under the concentration-time curve (AUC) than the CsA-GC formulation. Although the degree of interindividual variation in AUC, Cmax and tmax after CsA-ME administration was slightly, but significantly, less than after CsA-GC administration, there was no difference between the two formulations in terms of the customarily monitored C0 or C12 TL values. CsA-ME showed higher correlation coefficients of drug exposure (AUC) with C12 than CsA-GC (0.910 versus 0.712). However, CsA-ME administration resulted in only modest improvement over CsA-GC administration in the relationships between drug dose and C0, C12, or AUC--namely, 0.645 versus 0.496, 0.611 versus 0.517, and 0.700 versus 0.501, respectively. Correlation analysis between individual timed samples and AUC determinations revealed that CsA-ME requires significantly less frequent blood monitoring for prediction of total drug exposure than does CsA-GC. Although the clinical utility of this reproducible pharmacokinetic behavior remains to be demonstrated in the de novo transplant setting, the markedly reduced intraindividual variation produced by administration of CsA-ME will likely improve the accuracy of pretransplant prediction of, and reduce the frequency of subsequent adjustments in, CsA doses.

Renal allograft and patient outcome after transplantation pancreas-kidney versus kidney-alone transplants in type 1 diabetic patients versus kidney-alone transplants in nondiabetic patients

Despite recent advances and improved outcome, pancreas transplantation remains controversial. The purpose of this review was to study renal allograft outcome after simultaneous pancreas-kidney transplants (SPK, n = 61), kidney-alone transplants in type I diabetic patients (KA-D, n = 63), and kidney-alone transplants in nondiabetic patients (KA-ND, n = 80). Patients were matched for donor age, donor gender, donor race, interval from donor admission to procurement, DR mismatch, and recipient gender. The mean renal allograft cold ischemic time and recipient age were lower in the SPK group. Patient survival was highest in the KA-ND group (99% and 86% at 1 and 5 years, respectively), intermediate in the SPK group (90% and 78% at 1 and 5 years, respectively), and lowest in the KA-D group (89% and 66% at 1 and 5 years, respectively) (P = 0.004). similarly, renal allograft survival was higher in the KA-ND (89% and 63% at 1 and 5 years, respectively) and SPK (82% and 69% at 1 and 5 years, respectively) groups compared with the KA-D group (76% and 49% at 1 and 5 years, respectively) (P = 0.07). This difference disappeared when renal graft survival was censored for death, which probably reflects the selection bias. Actuarial pancreas graft survival was 76% and 62% at 1 and 5 years, respectively. Acute rejection (AR) was more frequent in the SPK group than in the KA-D and KA-ND groups (41% v 16% v 29%; P = 0.007). Delayed graft function (DGF), on the other hand, occurred more frequently in the KA-D group than in the KA-ND and SPK groups (66% v 55% v 38%; P = 0.08). Death as a result of a cardiovascular event occurred more frequently in the KA-D group. Cardiovascular death and renal graft failure occurred earlier in the SPK group. Cox regression analysis revealed a 1.6 and 1.8 times higher risk of renal graft failure in the SPK group when the donor was > or = 40 years old or female and a five times higher risk of graft failure in the KA-ND group in the presence of AR. Graft survival in patients with AR/DGF was lower than that in patients with no AR/no DGF in both the KA-D (71% and 63% v 100% and 100% at 1 and 5 years, respectively; P = 0.03) and KA-ND (90% and 56% v 100% and 100% at 1 and 5 years, respectively; P = 0.001) groups. Acute rejection did not affect graft survival in the SPK group. In the absence of AR, DGF had no effect on graft survival in any of the groups. Although the selection bias in favor of pancreas transplantation does not allow for definitive conclusions, our results show that outcome after SPK transplantation is acceptable and factors that influence the outcome after this procedure may be different from the ones affecting KA-D recipients.

Pasteurella multocida Peritonitis in an HIV-Positive Patient on Continuous Cycling Peritoneal Dialysis

Pasteurella multocida has been reported only once previously as a cause of peritonitis in a patient undergoing chronic peritoneal dialysis. The present report describes findings associated with a case of P. multocida peritonitis in a human immunodeficiency virus (HIV)-positive patient in which renal replacement therapy consisted of continuous cycling peritoneal dialysis. To our knowledge this is the first report of this unique infection in an HIV-positive end-stage renal disease patient. In addition, the recent literature on this unusual organism is reviewed in detail. These findings emphasize the potential for increased susceptibility to zoonoses in immunocompromised patients, particularly with indwelling intraperitoneal catheters which may serve as a portal of entry for unusual organisms.

Familial Adult Glomerulocystic Kidney Disease

During an evaluation for nephrotic syndrome, a 20-year-old woman was found by ultrasonographic examination to have large kidneys with multiple renal cysts suggestive of polycystic kidney disease. A subsequent renal biopsy revealed membranous glomerulopathy due to systemic lupus erythematosus, as well as the unexpected finding of glomerulocystic kidney disease (GCKD), an uncommon disorder previously reported to occur primarily in infants and children. No evidence of renal dysplasia was present and no cysts were found in any abdominal or pelvic organs. Other than one bifid renal pelvis, no significant congenital anomalies or structural chromosomal abnormalities were present. Ultrasonographic evaluation of the patients family revealed similar-appearing cortical cysts in several members, all of whom had no clinical evidence of renal dysfunction. The pattern of involvement was compatible with autosomal dominant inheritance. Follow-up ultrasonograms of the patient and affected family members 1 year after the initial study showed enlargement of the cysts with development of additional cysts in two individuals and no change in the other family members. Although renal failure was present and progressed in our patient, renal function remained normal in all affected family members 1 year after detection of the renal cysts. This patient and her family provide additional insight into the inheritance and natural history of GCKD and demonstrate that this condition should be considered in the evaluation of multicystic renal disease in adults. In contrast to several previously reported cases, it appears that GCKD may be associated with normal renal function for many years.

Color M-mode flow propagation velocity versus conventional Doppler indices in the assessment of diastolic left ventricular function in patients on chronic hemodialysis.

Background and Objective: Color M‐mode flow propagation velocity (Vp) has been reported as a preload‐independent measure of diastolic function. To study the effects of loading conditions on diastolic function assessment in patients on chronic hemodialysis, we measured Vp and conventional Doppler indices pre‐ and posthemodialysis. Methods: Twenty hemodialysis patients with normal systolic function underwent measurement of Vp, early filling velocity (E), its deceleration time (DT), atrial contraction velocity (A), isovolumic relaxation time (IVRT), and pulmonary atrial flow reversal velocity (PFR) pre‐ and posthemodialysis. Twelve healthy controls underwent these same measurements. Results: Hemodialysis patients had significantly slower Vp at baseline than normal controls, while E/A, DT, IVRT, and pulmonary flow reversal were not significantly different. E, IVRT, and PFR were affected by hemodialysis, while color M‐mode flow propagation velocities, A, and DT were not. Conclusions: Color M‐mode flow propagation velocity seems to be a preload‐independent measure of diastolic function in chronic hemodialysis patients in whom isolated diastolic dysfunction appears prevalent.

A Cost-Effectiveness Analysis of Epoetin Usage for Patients with AIDS

SummaryEpoetin (recombinant human erythropoietin) therapy for patients with AIDS may reduce the need for blood transfusion; however, it is expensive. We conducted a cost-effectiveness analysis of the use of epoetin for AIDS patients from a healthcare system perspective. We constructed a decision analysis model using probability. Outcome and cost data from the literature and hospital sources.The incremental cost-effectiveness ratio was measured in dollars per unit of blood saved. In AIDS patients undergoing transfusion with serum epoetin concentrations ⩽500 U/L treatment with epoetin cost

Erythropoietin for the Treatment of Porphyria Cutanea Tarda in a Patient on Long-Term Hemodialysis

US1007 per unit of blood saved compared with treatment without epoetin. One-way sensitivity analysis revealed that the incremental cost-effectiveness ratio was sensitive 10 the efficacy and unit price of epoetin, but less sensitive to the current price cap determined by the distributor.