[Focusing on peritoneal dialysis adequacy]. / Adéquation en dialyse péritonéale : mise au point.

The optimal method to assess the adequacy of peritoneal dialysis therapies is controversial. Today, the adequacy must not be considered as a number or a concept assessed only by two parameters (total KT/V urea and total solute clearance) but defined by many more items. In the absence of data, based on theoretical considerations, the reanalysis of the CANUSA study showed that renal kidney function, rather than peritoneal clearance, was associated with improved survival. Residual renal function is considered as a major predictor factor of cardiovascular mortality. Results of this reanalysis were supported by the adequacy data in ADEMEX, EAPOS and ANZDATA studies. Therefore, clinical assessment plays a major role in PD adequacy. The management of fluid balance, the regular monitoring of malnutrition, the control of mineral metabolism and particularly the glucose load, considered as the "corner-stone" of the system, are the main points to be considered in the adequacy of PD patients. The essential goal is to minimize glucose load by glucose-sparing strategies in order to reduce the neoangiogenesis of the peritoneal membrane.

The contribution of combined crystalloid and colloid osmosis to fluid and sodium management in peritoneal dialysis.

The achievement of euvolemia is essential to the successful management of peritoneal dialysis patients. However, the concern that hypertonic glucose exchanges may have a role in long-term changes to the peritoneal membrane has lead to an alternative strategy to enhance ultrafiltration (UF) over the long dwell by combining crystalloid and colloid osmosis. This review summarizes the experience of mixing glucose or amino acids with polyglucose (icodextrin), with particular focus given to data from studies using glucose/icodextrin in combinations of 1.36%/7.5% and 2.61%/6.8%. Both combinations demonstrate a significant increment of UF volume and sodium removal compared with the component osmotic agents used individually over long dwells, with the 2.61%/6.8% mixture having an effect over dwells extending to 15 h. Hypothetically, the mechanism of the enhanced UF is the attenuation by the colloid osmotic force of the backflow of water through small pores from dialysate to the peritoneal capillary circulation once the crystalloid osmotic force has dissipated. This experience provides promising data that deserves further examination in longer term clinical studies.

Anti-viral drugs in continuous ambulatory peritoneal dialysis (CAPD).

The prevalence of HIV-positive subjects in dialysis (hemodialysis and peritoneal dialysis) population varies from 0.13 to 0.36% in italian and french studies, respectively. Most drugs used in HIV therapy are primarily excreted by the kidney. In patients with renal insufficiency, careful dosage adjustment is mandatory to optimize drug exposure and reduce the risk for adverse events. We review the impact of peritoneal dialysis on the pharmacokinetics of antiviral drugs, and discuss on the dosage recommendations needed to achieve efficacy and avoid toxicity in patients with end-stage renal disease undergoing continuous ambulatory peritoneal dialysis (CAPD).

Neurotoxicity of valacyclovir in peritoneal dialysis: a pharmacokinetic study.

Valacyclovir is an effective oral agent for the treatment of herpes virus infection, however, the pharmacokinetics of the drug are altered in renal failure. It is increasingly recognized that dose adjustment of oral valacyclovir in renal failure is necessary to avoid neurotoxicity. We studied this drug in a continuous ambulatory peritoneal dialysis (CAPD) and immunocompromised patient. She developed neurotoxicity with an adjustment dosage of valacyclovir for a cutaneous zoster infection. The elimination half-time (15 h) was similar to that reported for end-stage renal disease patients, while the steady-state volume of distribution (85 l) and the area under the curve concentration (127 mg/l.h) were greater. The mean CAPD dialysance was only 5.27 ml/min with less than 1% of an administered dose being recovered in the 24-hour dialysate. 48 h after interrupting treatment, she recovered normal neurological status and 500 mg of valacyclovir every 2 days was effective and well tolerated.

Antioxidant status of elderly chronic renal patients treated by continuous ambulatory peritoneal dialysis.

BACKGROUND: An oxidative stress has been reported in patients with chronic renal failure (CRF) treated by haemodialysis. To our knowledge, only scant information is available concerning CRF patients treated by continuous ambulatory peritoneal dialysis (CAPD) with regard to their redox and nutritional status. METHODS: The oxidative stress and the biological nutritional status were evaluated in 20 elderly CRF patients treated by CAPD, compared with a control group of 30 elderly non-CRF patients. Plasma peroxidation products were assayed as thiobarbituric acid-reactive substances (TBARS), and two enzymatic antioxidant systems were determined: erythrocyte superoxide dismutase (SOD), glutathione peroxidase activity in plasma (P-GSH-Px) and in erythrocytes (E-GSH-Px). Selenium, vitamin E, beta-carotene and vitamin A were evaluated as plasma non-enzymatic antioxidants. Nutritional status and iron status were assessed by determining serum albumin, prealbumin, iron, ferritin and transferrin concentrations. RESULTS: Plasma TBARS concentration was high in both groups (CAPD: 1.37 +/- 0.06 mumol/l versus non-CRF: 1.41 +/- 0.06 mumol/l; P = NS), compared with usual values (0.60 to 1.20 mumol/l), on account of the patients' ages. SOD and E-GSH-Px activities were normal in both groups. A significant lowering in P-GSH-Px activity was observed only in CAPD patients (211 +/- 14 U/l, usual values: 480 to 650 U/l). Plasma selenium concentration, decreased in both groups, was significantly lower in CAPD than in non-CRF patients (P < 0.01). Plasma vitamin E, beta-carotene and vitamin A concentrations were significantly enhanced only in CAPD patients (P < 0.0001, P < 0.005 and P < 0.0001, respectively. Biological nutritional markers were similar in both groups and within usual values. CONCLUSIONS: This study demonstrated the existence of an oxidative stress in CAPD-treated elderly CRF patients, evidenced by a decrease in plasma selenium levels and in P-GSH-Px activity. However, plasma TBARS were not higher in CAPD patients than in age-matched non-CRF control subjects, probably on account on the patients' ages.

How to reach optimal creatinine clearances in automated peritoneal dialysis.

This paper summarizes the basis of prescription for automated peritoneal dialysis (APD) established during a French national conference on APD. Clinical results and literature data show that peritoneal clearances are closely determined by peritoneal permeability and hourly dialysate flow rate, independently of dwell time or number of cycles. With APD, peritoneal creatinine clearance increases according to the hourly dialysate flow rate to a maximum (plateau), then decreases because of the multiplication of the drain-fill times. The hourly dialysate flow giving the maximum peritoneal creatinine clearance is defined as the "maximal effective dialysate flow" (MEDF). MEDF is higher for high peritoneal permeabilities: MEDF is 1.8 and 4.2 L/hr with nocturnal tidal peritoneal dialysis (TPD) for a 4-hr creatinine dialysate-to-plasma ratio (D/P) of 0.50 and 0.80, respectively. With nightly intermittent peritoneal dialysis (NIPD), MEDF is 1.6 and 2.3 L/hr for a D/P of 0.50 and 0.78, respectively. Under these conditions, tidal modalities can only be considered as a way to increase the MEDF. Using the MEDF concept for an identical APD session duration, the maximal weekly normalized peritoneal creatinine clearance can vary by 340% when 4-hr D/P varies from 0.41 to 0.78. APD is not recommended when 4-hr creatinine D/P is lower than 0.50. However, the limits of this technique may be reached at higher peritoneal permeabilities in anurics because of the duration of sessions and/or the additional exchanges required by these patients.

213 elderly uremic patients over 75 years of age treated with long-term peritoneal dialysis: a French multicenter study.

UNLABELLED: We report our experience in 213 elderly patients over 75 years treated by peritoneal dialysis (PD) as first and exclusive dialysis therapy. The mean age at start of PD was 79.4 +/- 3.6 years, and the cumulative time on PD was 4551 months (mean time: 21.4 +/- 19.8 months). Twenty-six patients lived in institutions and 187 lived at home. Thirty patients had an effective autonomy with the ability to carry on normal activities. One hundred and two patients were cared for by a private nurse at home, and 46 patients were cared for in a family environment. Most cases were treated by three exchanges per day (152 cases) and used a nondisconnect system (175 cases) on account of absence of autonomy. The rate of peritonitis per patient-month was one episode per 16.8 patient-months. Patient survival (Kaplan-Meier curves) was 74%, 59%, 45%, and 19% at one, two, three, and five years, respectively. The causes of death were various with a higher frequency of cardiovascular causes (48.3% of the 116 deaths). Thirty-three patients died in less than six months including 18 patients in less than three months. IN CONCLUSION: elderly uremic patients can be treated with long-term PD with relatively good results. Mortality is high but essentially due to age and poor general status-the dedication of private home nursing is very important in treating elderly PD patients. This fact often is a necessary condition in maintaining these elderly patients at home.

[Treatment by continuous ambulatory peritoneal dialysis for chronic renal insufficiency in the diabetic]. / Le traitement par dialyse péritonéale continue ambulatoire de l'insuffisance rénale chronique chez le diabétique.

The number of diabetics with end stage renal failure is growing. The best treatment at the lowest cost possible should be offered to all diabetics if therapeutics facilities are available. Such a policy requires that all dialysis methods and transplantation should be available and that transfer from one method to another should always be allowable. Results observed among diabetics are improving steadily, even in the older age group. However they are inferior to those observed in non diabetic people of the same age. In diabetic patients under fifty years of age, renal transplantation using a kidney from a cadaver or a related donor should be the first choice. In some cases kidney and pancreas transplantation is possible. However, for most patients dialysis methods are required as the only treatment or while waiting for a transplant. If home dialysis is considered, continuous ambulatory peritoneal dialysis offers the opportunity to treat many insulin or non insulin-dependent diabetics at home even those in the high risk population because of age and/or cardio-vascular instability with excellent control of blood glucose levels, hypertension, vision, residual renal function, despite the peritoneal infections. These results are obtained from data in the literature and the survey of patients treated at the Hospital de la Pitié.

Is overhydration in CAPD patients a contraindication to renal transplantation?

Over a 14 year period, 56 of 415 CAPD patients (34 male, 22 female), aged 42.7 +/- 11 years, underwent renal transplantation (TR). A cadaver kidney was used in 53 patients (kidney-pancreas in 2), and a human leucocyte antibody (HLA) identical related donor organ was used in 3. Underlying renal diseases were chronic glomerulonephritis in 30 patients, diabetic nephropathy in 10, interstitial nephropathy in 5, vascular in 4, polycystic kidney in 3, and undetermined in 4. Mean duration of CAPD prior to TR was 13 months (2-56 months). A three-week peritonitis episode-free interval was requested prior to TR. At year 1, actuarial patient and graft survival (96% and 86%, respectively), plasma creatinine, and number of rejection episodes were not different from those recorded in patients treated with hemodialysis (HD) prior to TR. At TR, pulmonary artery pressure (PAP) was elevated (average 21.1 +/- 7.4 mm Hg), > or = 25 mm Hg and > or = 30 mm Hg in 36% and 14.6% of CAPD patients, respectively. Post-TR, HD was performed in 4 patients; no peritoneal infection occurred. Postoperative sonography disclosed ascitis in 12.7% of CAPD patients. The PD catheter was removed two months post-TR. Hemodynamic findings at TR suggest a frequently underestimated overhydration in CAPD patients, which should be detected and treated in order to reduce acute cardiovascular complications at TR.

Daily subcutaneous administration of recombinant human erythropoietin (rhEPO) in peritoneal dialysis patients: a European dose-response study.

In a prospective randomized open multicenter study, 107 anemic (Hct < = 28%) peritoneal dialysis (PD) patients were treated with s.c. rhEPO daily. The mean observation period was 299 days (range 14-479 days). Patients were randomly assigned to 3 groups with different initial doses: 5 U/kg (G5), 10 U/kg (G10), 20 U/kg (G20). Initial doses were maintained for at least 8 weeks unless the target Hct (30-35%) was achieved earlier. The weekly increase of Hct was significantly (p < 0.05) dose-dependent: 0.19% in G5, 0.5% in G10 and 0.94% in G20. In case of insufficient response (< 0.5% per week), the dose was doubled every 4 weeks. Final doses on achieving the target Hct ranged from 5 to 40 U/kg (median 20 U/kg). The dose was then reduced to 50% and adjusted individually. The median maintenance dose was 9.9 U/kg/day. No tendency towards higher blood pressure or intensification of antihypertensive treatment was observed. When rhEPO is administered daily, 10 U/kg/day (70 U/kg weekly) is the recommended starting dose. The need for higher doses used in unsatisfactory response, should lead to further examination to rule out iron deficiency and other reasons for non-response. The median maintenance dose reported here is the lowest published in the literature for PD patients and seems to be linked to the daily injections.

Lipoprotein(a) in patients treated by continuous ambulatory peritoneal dialysis.

Lipoprotein(a) [Lp(a)] has been identified as an independent, inherited risk factor for atherosclerotic vascular disease. An elevation of Lp(a) plasma levels has been documented in several series of uremic patients submitted to maintenance dialysis treatment methods or after renal transplantation. We have measured the plasma levels of Lp(a) using an enzyme-linked immunosorbent enzyme method in 19 patients treated with continuous ambulatory peritoneal dialysis (CAPD). Mean (+/- SD) concentration of Lp(a) was significantly higher in the patients than in the 19 healthy controls (51 +/- 48 mg/dL v 16 +/- 15 mg/dL, P < 0.005). No significant differences in Lp(a) levels were found between diabetic patients (n = 5) and nondiabetic patients (n = 14) or between patients who had (n = 6) or had not (n = 13) suffered a previous major cardiovascular complication. No correlation was evident between Lp(a) levels and the patients' ages, period of time on CAPD treatment, or any other lipid-lipoprotein investigated parameter. The mechanisms accounting for the elevation of Lp(a) levels in CAPD patients as well as the specific value of increased Lp(a) concentration as a cardiovascular risk predictor in uremic patients remain thus far speculative. Additional experimental and clinical studies are warranted before the administration of drugs to attempt to lower Lp(a) levels in CAPD patients can be recommended.

Exit-site care and exit-site infection in continuous ambulatory peritoneal dialysis (CAPD): results of a randomized multicenter trial.

A total of 127 patients from 8 hospitals were randomized into 1 of 2 exit-site care regimes to evaluate their effect on rate of exit-site infection (ESI). Group 1 used povidone iodine and nonocclusive dressings changed 2 to 3 times weekly; Group 2 simply cleansed the exit site with nondisinfectant soap and water. Incidence, cause, duration, and treatment of ESI and peritonitis (P) were noted. Groups were analysed for age, sex, end-stage renal disease (ESRD), catheter, and systems. Total cumulative follow up time was 95.6 years. There was a significantly higher rate (p = 0.0183) of ESI in Group 2 (soap and water). The mean rate of ESI was 0.27 episodes/patient year for Group 1 versus 0.71 episodes/patient year for Group 2. Rates of P for the two groups were not significantly different (p greater than 0.50): 0.446 episodes/year for Group 1 versus 0.574 episodes/year for Group 2. S. aureus was responsible for 83% of ESI in Group 1 and 67% of ESI in Group 2. Protective dressing with a disinfectant is associated with significantly less ESI than minimum care. However, further research in exit-site care aimed specifically at reducing S. aureus infection is still required.