Continuous ambulatory peritoneal dialysis: pharmacokinetics and clinical outcome of paclitaxel and carboplatin treatment.

PURPOSE: Administration of chemotherapy in patients with renal failure, treated with hemodialysis or continuous ambulatory peritoneal dialysis (CAPD) is still a challenge and literature data is scarce. Here we present a case study of a patient on CAPD, treated with weekly and three-weekly paclitaxel/carboplatin for recurrent ovarian cancer. EXPERIMENTAL: During the first, second and ninth cycle of treatment, blood, urine and CAPD samples were collected for pharmacokinetic analysis of paclitaxel and total and unbound carboplatin-derived platinum. RESULTS: Treatment was well tolerated by the patient. No excessive toxicity was observed and at the end of treatment she was in a complete remission. The plasma pharmacokinetics of paclitaxel were unaltered compared to historical data, with neglectable urinary and CAPD clearance. In contrast, the pharmacokinetics of carboplatin were altered, with doubled half-lives compared to patients with normal renal function. Of the administered carboplatin dose, up to 20% was cleared via the dialysate, while only up to 8% was cleared via the urine. CONCLUSION: Paclitaxel and carboplatin can be safely administered to patients with chronic renal failure on CAPD. For paclitaxel the generally applied dose can be administered, and although for carboplatin dose-adjustment is required due to the diminished renal function, the dose can be calculated using Calvert's formula.

Posttransplant encapsulating peritoneal sclerosis: a worrying new trend?

Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication in patients on peritoneal dialysis (PD). We describe a cluster of 13 EPS cases occurring in 2 university hospitals in The Netherlands. Most of these cases were diagnosed after recent kidney transplantation, when the patients developed severe symptoms of bowel obstruction. This accumulation raised the question as to whether other than known risk factors, such as duration of PD treatment, could be involved in the development or course of EPS after transplantation. According to various publications, EPS has been diagnosed often after withdrawal from PD, suggesting that cessation in itself may be a risk factor. In addition, transplantation-related management should be considered to play a role, including the use of the profibrotic calcineurin inhibitors and the trend to reduce the load of corticosteroids in treatment regimes. To identify risk factors, further multicenter studies are required, paying special attention to alterations in immunosuppressive treatment regimens as well as PD prescriptions, including PD fluid characteristics. Transfer from PD to hemodialysis should be under serious consideration in patients eligible for kidney transplantation as soon as there are indications of ultrafiltration failure.

Persistent (not intermittent) nasal carriage of Staphylococcus aureus is the determinant of CPD-related infections.

BACKGROUND: We investigated the impact of staphylococcal carriage among patients on continuous peritoneal dialysis (CPD) in a university hospital. METHODS: Patients were screened for Staphylococcus aureus carriage and categorized as persistent, intermittent, or non-S. aureus nasal carriers. Patients were subsequently recultured every 12 weeks for S. aureus and coagulase negative staphylococcal (CoNS) carriage, and followed-up for CPD-related infections and antibiotic resistance. RESULTS: Fifty-two patients were included: 20 peristent, 10 intermittent, and 22 non-S. aureus carriers. Only persistent S. aureus carriage was significantly associated with an increased risk for all CPD-related infections [incidence rate ratio (IRR) 3.52 (95% CI: 2.56-4.85)], exit site infections [IRR 5.59 (95% CI: 3.50-8.92)], and peritonitis [IRR 2.19 (95% CI: 1.39-3.45)], as well as increased antibiotic use [IRR 3.43 (95% CI: 2.50-4.72)], including vancomycin [IRR 2.15 (95%: 2.13-2.16)]. No vancomycin-resistant S. aureus strains were detected. However, eight (2%) out of 407 CoNS strains isolated were vancomycin intermediately susceptible. In all five patients (four persistent and one intermittent carriers) concerned, this was significantly related to a higher antibiotic (including vancomycin) usage [IRR 2.65 (95% CI: 1.82-3.84)]. CONCLUSION: Persistent-but not intermittent-S. aureus nasal carriage is the major determinant of CPD-related infections, and is associated with a significantly higher consumption of antibiotics, including vancomycin. The highly diverse population of CoNS appears to be the prime reservoir of staphylococcal vancomycin resistance. Accurate determination of the S. aureus nasal carriage state of CPD patients is essential to better target intervention strategies to prevent CPD-related infections.

Culture-negative peritonitis associated with the use of icodextrin-containing dialysate in twelve patients treated with peritoneal dialysis.

BACKGROUND: In the first half of the year 2001, an unusually large number of culture-negative peritonitis episodes occurred in Center A. One patient noticed that his culture-negative antibiotic-resistant peritonitis promptly cleared after inadvertently stopping the use of icodextrin-containing dialysate, but recurred immediately after using icodextrin again. This observation led to the recognition of eight contemporaneous cases of icodextrin-induced culture-negative peritonitis in Center A, and identification of three additional cases in Center B. DESIGN: Case studies in 12 patients. SETTING: Peritoneal dialysis unit of a university hospital and an affiliated unit (Center A), and a second university hospital (Center B). PATIENTS: 12 patients on peritoneal dialysis presenting with culture-negative peritonitis. RESULTS: At presentation, abdominal pain was absent or mild and dialysate leukocyte counts were moderately elevated (approximately 100-1,500 cells/mm3). Differentiation of the dialysate leukocytes showed a low fraction of neutrophils (approximately 35%). In eight cases, the evidence that the peritonitis was caused by icodextrin was very strong (the clinical picture and laboratory results mentioned above, unresponsiveness to antibiotic therapy, cure after withdrawal of icodextrin, relapse after rechallenge); in 3 patients, the evidence was strong (as in the cases mentioned above, but no rechallenge was performed). Stopping icodextrin promptly relieved the symptoms and normalized the dialysate leukocyte counts. After rechallenge, a relapse invariably occurred, usually within a few days. In one case, the evidence was circumstantial. CONCLUSION: Our findings are compatible with icodextrin-induced peritonitis. This entity is characterized by mild abdominal pain at presentation, a moderate dialysate leukocytosis with a low fraction of neutrophils in the differential count, and resistance to antibiotic treatment. Speculations about the pathogenesis of this type of peritonitis include chemical peritonitis due to a contaminating substance or hypersensitivity to icodextrin.