Pharmacokinetics of lamivudine in subjects receiving peritoneal dialysis in end-stage renal failure.

AIMS: To establish whether peritoneal dialysis (PD) requires dosing modification from the CL(CR)-corrected lamivudine dose in end-stage renal failure subjects. METHODS: This was an open-label cohort study. A total of 12 subjects undergoing PD, six continuous ambulatory peritoneal dialysis (CAPD) and six automated peritoneal dialysis (APD), for at least 3 months received lamivudine 10 mg (5 mg ml (-1) x 2 ml) daily for 8 consecutive days, followed by an intensive pharmacokinetic assessment. Urine and dialysate were collected from 0 to 24 h postdose on day 8 where possible. Pharmacokinetic parameters were calculated using noncompartmental techniques. RESULTS: The plasma pharmacokinetic results demonstrated that peritoneal dialysis clearance (CL(D)) of lamivudine was similar between APD and CAPD patients with median (range) of 0.19 l h(-1) (0.14-0.25) and 0.1 l h(-1) (0.09-0.25), respectively. CL(D) was approximately 1/15th to 1/30th of plasma clearance, demonstrating that peritoneal dialysis does not contribute significantly to overall lamivudine clearance in this patient population. The AUC(0,24 h) of lamivudine given 10 mg daily to APD and CAPD patients was 3430 ng ml(-1) h and 3469 ng ml(-1) h, respectively, similar to historical data obtained in patients with normal renal function administered at the normal dose of 100 mg daily (3781 ng ml(-1) h). There were no clinically significant changes in any safety assessments that were attributable to lamivudine. CONCLUSIONS: ESRD patients who receive CAPD or APD require no supplemental dosing. These patients should follow the standard dosing reduction for patients infected with HIV or HBV with renal dysfunction.

Quality of life in CAPD, transplant, and chronic renal failure patients with diabetes.

UNLABELLED: Although quality of life (QoL) is an important outcome measure, there are few studies of QoL in diabetic patients. We performed a cross-sectional study to assess QoL in such patients comparable for age, sex, and co-morbidity. PATIENTS: Group CAPD: DM (n = 19, 12 males), diabetic CAPD patients; group CAPD: no DM (n = 26, 15 males) CAPD patients without diabetes; group TXP (n = 20, 10 males), diabetic transplant patients; and group CKD: DM (n = 20, 11 males), diabetics with chronic kidney disease. Two valid QoL instruments were used: a generic one (SF-36) and one that is disease-specific (RQLP). RESULTS: As a whole, CAPD patients scored badly as far as concerned the physical domain, but with a good mental adaptation. Diabetic CAPD patients exhibited worse QoL for physical functioning, energy, vitality, leisure activity, and eating/drinking limitations. Diabetic transplant patients exhibited the best QoL. The RQLP instrument had better discriminative power for domains such as eating/drinking, treatment effects, and psychosocial aspects. Using analysis of co-variance and adjusting for age, sex, and co-morbidity, QoL differences disappeared. In conclusion, diabetic CAPD patients exhibited the worst QoL though with a satisfactory mental adaptation, a renal-specific instrument had better discriminative power, and the prevention of co-morbidity is likely to improve QoL in such patients.

Single-center experience of encapsulating peritoneal sclerosis in patients on peritoneal dialysis for end-stage renal failure.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD). It is characterized by a progressive, intra-abdominal, inflammatory process resulting in sheets of fibrous tissue that cover, bind, and constrict the viscera, thereby compromising the motility and function of the bowel. Although recent therapeutic approaches have been reported with variable success, the ability to detect reliably at an early stage patients at risk for EPS would be beneficial and allow treatment standardization. The aim of this study was to evaluate the clinical features of EPS and identify possible risk factors for its development in CAPD and APD patients. METHODS: This was a review of all cases of EPS in a single center over the last 5 years. RESULTS: There were 810 CAPD and APD patients, managed in our program over this period. We identified 27 cases of EPS, giving an overall of 3.3% in this population. The mean duration of CAPD before diagnosis of EPS was 72.6 +/- 39.7 months (range 16-172). Sixteen cases required surgical treatment and were classified as severe; others were treated conservatively (mild to moderate group). Ten patients received tamoxifen treatment with apparent benefit. The overall mortality rate was 29.6%. Eight patients from the severe group and the entire moderate group survived on hemodialysis or transplantation at 48.71 and 27.63 months follow-up, respectively. Peritonitis rates were not different between the 2 groups and peritoneal history was unremarkable compared to overall peritonitis rates in the unit. Data on small solute transport were not available in all patients in this retrospective analysis. CONCLUSION: EPS is a serious, life-threatening complication of CAPD. Most cases had PD duration of more than 4 years. Careful monitoring by CT scans of the peritoneal membrane in patients beyond 5 years, and early catheter removal in patients with peritoneal thickening should be considered for long-term CAPD patients. Treatment with tamoxifen may be of benefit in these patients.

Peritoneal catheters and exit-site practices toward optimum peritoneal access: a review of current developments.

OBJECTIVE: This review updates the 1998 International Society for Peritoneal Dialysis (ISPD) recommendations for peritoneal dialysis catheters and exit-site practices (Gokal R, et al. Peritoneal catheters and exit-site practices toward optimum peritonealaccess: 1998 update. Perit Dial Int 1998; 18:11-33.) DATA SOURCES: The Ovid and PubMed search engines were used to review the Medline databases of January 1980 through June 2003. Searches were restricted to human data; primary key word searches included dialysis, peritoneal dialysis, and continuous ambulatory peritoneal dialysis cross referenced with access, catheter, dialysis catheter, peritoneal dialysis catheter, and Tenckhoff catheter. Related searches were provided via the PubMed related articles link. STUDY SELECTION: Reports were selected if they provided identifiable information on catheter design, catheter placement technique, and survival or placement complications. Reports without such data were excluded from review. Each study was then categorized by its characteristics: single-center or multicenter; retrospective or prospective; controlled trial, with or without random patient assignment; or review article. MAIN RESULTS: There are few randomized controlled evaluations testing how catheter design and/or placement influence long-term survival and function, and these are typically conducted at a single center. The majority of reports represent retrospective single-center experiences, and these are supplemented by occasional multicenter data registries. CONCLUSIONS: There is substantial variability in catheter outcomes between centers, and this variability is more closely correlated with operator and center characteristics than with catheter design. Some catheter designs appear to impact long-term catheter success, and, in some cases, specific patient characteristics and dialysis formats combine with specific catheter designs to influence catheter survival. Most reporters prefer two-cuff designs and placement of the deep cuff at an intramuscular location. Intramuscular cuff placement results in fewer pericatheter leaks and hernias, but makes catheter removal more difficult. High-risk patients (those with previous pelvic surgery) benefit from visual inspection of the peritoneum during catheter placement, and in randomized controlled trials, catheters with pre-shaped arcuate subcutaneous segments ("swan neck" designs) reduce the risk of early drainage failure via "migration."

Sterile peritonitis in the peritoneal dialysis patient.

Peritonitis is a serious and common problem in the peritoneal dialysis (PD) population. Abdominal pain, fever, and cloudy PD fluid usually heralds the onset of infective peritonitis. However, in up to 20% of cases, no organism is identified. In these situations, diagnosis can be made only by excluding a microbiological cause and performing a cytological examination of the PD fluid to determine the cellular or noncellular constituents. This review examines the differential diagnosis of sterile peritonitis and uses cytological examination to facilitate the appropriate diagnosis.

A trial of subcutaneous administration of darbepoetin alfa once every other week for the treatment of anemia in peritoneal dialysis patients.

BACKGROUND: Darbepoetin alfa (Aranesp, Amgen) is an erythropoietic stimulating protein with a three fold longer terminal half life than recombinant human erythropoietin (rHuEPO). The purpose of this single center, single arm study was to determine whether darbepoetin alfa is as effective as rHuEPO for the treatment of renal anemia in patients on peritoneal dialysis when administered at a reduced dosing frequency of once every other week irrespective of the initial rHuEPO dose frequency. METHODS: A total of 17 patients on peritoneal dialysis receiving stable rHuEPO therapy were changed to darbepoetin alfa every other week, using the recommended 200:1 conversion factor . The doses of darbepoetin alfa were titrated to maintain hemoglobin within -1.0 to +1.5 g/dL of the patients' baseline value and also within a range of 10.0 to 13.0 g/dL for up to 24 weeks (20 weeks dose titration period followed by 4 week evaluation period). The primary end point was change in hemoglobin levels between baseline and evaluation period. RESULTS: Mean change in hemoglobin levels from baseline to evaluation period was 0.03 g/dL (95% CI -0.62 to +0.69). This was not a statistically significant or clinically relevant difference, despite the reduced frequency of darbepoetin alfa administration. There were no serious or major adverse effects observed with darbepoetin alfa during the study. CONCLUSION: These results show that darbepoetin alfa maintains hemoglobin concentrations effectively and safely in patients on peritoneal dialysis, but with a reduced dose frequency as compared to rHuEPO.

Adequacy targets in peritoneal dialysis.

Adequate solute and fluid removal are the cornerstones of dialysis treatment. In peritoneal dialysis, what constitutes adequate removal, has been hitherto controversial, based as it was on DOQI guidelines. There are now 2 randomised controlled trials that address solute removal--both indicate that the minimal Kt/V needs to be 1.7. This needs to be adjusted in individual cases based on clinical and other parameters. Fluid removal and blood pressure control are also important adequacy parameters. Sub-clinical fluid overload is a common feature and relates to left ventricular hypertrophy. This also needs addressing but estimating fluid status is difficult.

Decrease in infections with the introduction of mupirocin cream at the peritoneal dialysis catheter exit site.

UNLABELLED: Staphylococcus aureus associated peritonitis and catheter exit site infections (ESI) are an important cause of hospitalization and catheter loss in the patients undergoing chronic peritoneal dialysis (PD). We aimed to determine the potential effectiveness of the application of mupirocin cream at the catheter exit site in preventing exit site infection and peritonitis. METHODS: This prospective historically controlled study was done in a total of 86 patients who entered our PD program from April 1999 to January 2001. They were instructed to apply Mupirocin cream 2% to the exit site daily or on alternate days. The patients were not screened to determine whether they were staphylococcus aureus carriers. One hundred and thirteen patients on PD prior to April 1999 acted as historical controls. Both groups were followed prospectively for a period of 22 months. RESULTS: In the study group application of mupirocin lead to a significant reduction in the incidence rate of both exit site infections overall (0.43 vs. 0.09; p<0.0001) and ESI due staphylococcus aureus (0.14 vs. 0.02; p=0.004) amounting to a relative reduction of 79% and 85% respectively. Although the overall incidence of peritonitis did not change (0.28 vs. 0.26; p=0.7) there was a significant reduction in peritonitis caused by staphylococcus aureus (0.07 vs. 0; p=0.01) Although only one catheter required removal in the mupirocin group as against 5 in the control group, this was not statistically significant. CONCLUSIONS: Mupirocin application at the exit site significantly lowers the incidence of ESI and peritonitis caused by staphylococcus aureus without any significant side effects.

Pure red cell aplasia secondary to epoetin alpha responding to Darbepoetin alpha in a patient on peritoneal dialysis.

Recombinant Human Erythropoietin (EPO) is extensively used for anemia in renal failure patients. It is normally safe and effective, improving symptoms of anemia. We report here a case of renal anemia in a patient undergoing peritoneal dialysis (PD) for end stage renal failure from renovascular disease. He initially responded well to Epoetin alpha (Eprex) but subsequently developed EPO antibodies and pure red cell aplasia (PRCA), becoming blood transfusion dependent. Subsequently, he responded to Darbepoetin alpha (Aranesp), without any complications in the presence of persisting EPO antibodies. This positive response, which restored hemoglobin values to normal, occurred despite general belief that any form of EPO will cross-react to EPO antibodies. This is the first case report where PRCA with EPO antibodies responded well to another EPO preparation without intervention from immunosuppression therapy.