Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout.

INTRODUCTION: The efficacy of pegloticase, a polyethylene glycol (PEG)-conjugated mammalian recombinant uricase, approved for chronic refractory gout, can be limited by the development of antibodies (Ab). Analyses from 2 replicate, 6-month, randomized controlled trials were performed to characterize Ab responses to pegloticase. METHODS: Anti-pegloticase, anti-PEG, and anti-uricase Ab were determined by validated enzyme-linked immunosorbent assays. Ab titers were analyzed for possible relationships with serum pegloticase concentrations, serum uric acid (sUA) lowering, and risk of infusion reactions (IRs). RESULTS: Sixty-nine (41%) of 169 patients receiving pegloticase developed high titer anti-pegloticase Ab (> 1:2430) and 40% (67/169) developed anti-PEG Ab; 1 patient receiving placebo developed high titer anti-pegloticase Ab. Only 14% (24/169) of patients developed anti-uricase Ab, usually at low titer. In responders, patients showing sustained UA lowering, mean anti-pegloticase titers at week 25 (1:837 ± 1687 with biweekly and 1:2025 ± 4506 with monthly dosing) were markedly lower than in nonresponders (1:34,528 ± 42,228 and 1:89,658 ± 297,797, respectively). Nonresponder status was associated with reduced serum pegloticase concentrations. Baseline anti-pegloticase Ab, evident in 15% (31/212) of patients, did not predict subsequent loss of urate-lowering response. Loss of sUA response preceded IRs in 44 of 56 (79%) pegloticase-treated patients. CONCLUSIONS: Loss of responsiveness to pegloticase is associated with the development of high titer anti-pegloticase Ab that increase clearance of pegloticase and are associated with a loss of the sUA lowering effect and increased IR risk. Pre-infusion sUA can be used as a surrogate for the presence of deleterious anti-pegloticase Ab. TRIAL REGISTRATION: NCT00325195. Registered 10 May 2006, NCT01356498. Registered 27 October 2008.

Effect of pegloticase on renal function in patients with chronic kidney disease: a post hoc subgroup analysis of 2 randomized, placebo-controlled, phase 3 clinical trials.

BACKGROUND: Pegloticase is approved in the US for treatment of refractory chronic gout. Since chronic kidney disease (CKD) is common in these patients, we conducted a post-hoc analysis of 2 replicate phase 3 trials and the subsequent open-label extension study to determine the effects of pegloticase on renal function in patients with CKD stages 3 and 4, as well as the effects of renal dysfunction on pegloticase efficacy and safety. FINDINGS: Patients with renal insufficiency were randomized to pegloticase 8 mg every 2 weeks (n = 42), pegloticase 8 mg every 4 weeks (n = 41), or placebo (n = 20) for 6 months as defined by the study protocols. Renal function was assessed by estimated glomerular filtration rate (eGFR). All patients completing the randomized trials could participate in an open-label extension study for a further 2.5 years. Uric acid response, the primary end point in the trials, was plasma uric acid <6.0 mg/dl for 80% of months 3 and 6.Mean eGFR in both pegloticase dosing cohorts remained constant over the randomized treatment phase and long-term open-label extension study. The number of patients achieving uric acid response was similar across CKD stages (32% stage 1, 23% stage 2, 35% stage 3, and 39% stage 4, respectively, P = 0.3). There was no difference in the pegloticase safety profile based on CKD stage. CONCLUSIONS: Pegloticase treatment does not impact eGFR in CKD patients and response to pegloticase is independent of CKD stage. TRIAL REGISTRATION: Clinical trial identifier: NCT00325195.

A randomized, double-blind, placebo-controlled study to assess the effect of recombinant human erythropoietin on functional outcomes in anemic, critically ill, trauma subjects: the Long Term Trauma Outcomes Study.

BACKGROUND: Achieving a higher hemoglobin (Hb) level might allow the anemic, critically ill, trauma patient to have an improved outcome during rehabilitation therapy. METHODS: Patients with major blunt trauma orthopedic injuries were administered epoetin alfa or placebo weekly both in hospital and for up to 12 weeks after discharge or until the Hb level was >12.0 g/dL, whichever occurred first. The 36-question Short Form Health Assessment questionnaire (SF-36) was used to evaluate physical function (PF) outcomes at baseline, at hospital discharge, and at several time points posthospital discharge. RESULTS: One hundred ninety-two patients were enrolled (epoetin alfa [n = 97], placebo [n = 95]). Hb increased from baseline to hospital discharge in both groups (epoetin alfa: 1.2 g/dL vs placebo: 0.9 g/dL), and transfusion requirements were similar between groups. Both groups showed improvements in SF-36 PF; there were no significant differences in the average of all posthospital discharge scores (epoetin alfa: 27.3 vs placebo 30.9; P = 0.38). Thromboembolic events were similar between groups. CONCLUSIONS: No differences were observed in physical function outcomes or safety in anemic, critically ill, trauma patients treated with epoetin alfa compared with placebo.

A randomized controlled study comparing once-weekly to every-2-week and every-4-week dosing of epoetin alfa in CKD patients with anemia.

BACKGROUND AND OBJECTIVES: Extended-interval dosing of epoetin alfa (EPO) is commonly used to treat anemia in patients with chronic kidney disease (CKD). This study aimed to demonstrate that EPO dosed every 2 weeks (Q2W) and every 4 weeks (Q4W) was noninferior to once-weekly (QW) dosing. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 430 anemic subjects with stage 3 to 4 CKD receiving a stable QW dose of EPO were randomized 1:1:2 to QW, Q2W, and Q4W dosing for 36 weeks. Hemoglobin (Hb) was measured weekly, and the dose of EPO was adjusted to maintain an Hb level of 11.0 to 11.9 g/dl. The primary endpoint was change in Hb from baseline to the average of the last 12 weeks of treatment. RESULTS: Both the Q2W and Q4W dosing groups were noninferior to the QW group. The estimated difference of the mean change in Hb between Q2W and QW was -0.03 g/dl; and between Q4W and QW was -0.09 g/dl. From weeks 13 to 37, the mean percentage of weeks per subject with Hb 10.0 to 11.9 g/dl, inclusive, was 81% for QW, 81% for Q2W, and 75% for Q4W. Death occurred, respectively, in 4%, 3%, and 4%; thromboembolic vascular events occurred in 3%, 5%, and 3%; and serious adverse events occurred in 22%, 26%, and 26% of subjects. CONCLUSIONS: Q2W and Q4W EPO dosing maintained Hb levels in subjects with stage 3 to 4 CKD. Deaths, thromboembolic vascular events, and serious adverse events were comparable across the dosing groups.

A randomized controlled study of weekly and biweekly dosing of epoetin alfa in CKD Patients with anemia.

BACKGROUND AND OBJECTIVES: In clinical practice, physicians often use once-weekly (QW) and biweekly (Q2W) dosing of epoetin alfa to treat anemia in patients with chronic kidney disease (CKD). Although the literature supports this practice, previous studies were limited by short treatment duration, lack of randomization, or absence of the approved three times per week (TIW) dosing arm. This randomized trial evaluated extended dosing regimens of epoetin alfa, comparing QW and Q2W to TIW dosing in anemic CKD subjects. The primary objective was to show that treatment with epoetin alfa at QW and Q2W intervals was not inferior to TIW dosing. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: 375 subjects with stage 3 to 4 CKD were randomized equally to the three groups and treated for 44 wk; to explore the impact of changing from TIW to QW administration on hemoglobin (Hb) control and adverse events, subjects on TIW switched to QW after 22 wk. The Hb was measured weekly, and the dose of epoetin alfa was adjusted to achieve and maintain an Hb level of 11.0 to 11.9 g/dl. RESULTS: Both the QW and Q2W regimens met the primary efficacy endpoint. More subjects in the TIW group than in the QW and Q2W groups exceeded the Hb ceiling. Adverse events were similar across treatment groups and consistent with the morbidities of CKD patients. CONCLUSIONS: Administration of epoetin alfa at QW and Q2W intervals are potential alternatives to TIW dosing for the treatment of anemia in stage 3 to 4 CKD subjects.

A randomized study of extended dosing regimens for initiation of epoetin alfa treatment for anemia of chronic kidney disease.

BACKGROUND AND OBJECTIVES: Although epoetin alfa is commonly initiated weekly (QW) in anemic chronic kidney disease (CKD) patients, recent evidence indicates that it can be initiated every 2 wk (Q2W) and used in maintenance therapy every 4 wk (Q4W). This study examined the feasibility of initiating epoetin alfa Q4W in anemic CKD patients not receiving dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This open-label study randomized subjects (1:2:2:2) to treatment with epoetin alfa 10,000 IU QW, 20,000 IU Q2W, 20,000 IU Q4W, or 40,000 IU Q4W for 16 wk. Subjects were > or =18 yr, had hemoglobin <11 g/dl, a glomerular filtration rate of 15 to 90 ml/min per 1.73 m(2), and had not received erythropoietic therapy within 8 wk. The primary analysis was a noninferiority comparison of the 40,000 IU Q4W to the 20,000 IU Q2W group in the per-protocol population with respect to hemoglobin change from baseline to the end of study. RESULTS: Of 262 subjects randomized, 229 comprised the per-protocol population. Mean hemoglobin change from baseline for the 40,000 IU Q4W group (1.24 g/dl) was not inferior to the 20,000 IU Q2W group (1.11 g/dl) with the lower limit of 95% CI, -0.21 g/dl. In the QW, 20,000 IU Q2W, 20,000 IU Q4W, and 40,000 IU Q4W groups, 90%, 87%, 75%, and 86% of subjects, respectively, achieved a hemoglobin increase > or =1 g/dl. Serious adverse events were similar across all groups. CONCLUSIONS: Epoetin alfa can be initiated Q4W in anemic CKD subjects.

Pharmacokinetic and pharmacodynamic profiles of extended dosing of epoetin alfa in anemic patients who have chronic kidney disease and are not on dialysis.

BACKGROUND AND OBJECTIVES: Emerging evidence suggests that epoetin alfa can be administered at extended intervals of up to 4 wk. This open-label, randomized study was performed to characterize the pharmacokinetic and pharmacodynamic profiles of four dosing regimens of epoetin alfa administered subcutaneously in anemic patients who had chronic kidney disease and were not on dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Thirty-eight patients, enrolled from nine centers in the United States, were > or =18 yr of age and had hemoglobin <11.0 g/dl and GFR 12 to 60 ml/min per 1.73 m(2). Patients received one of four epoetin alfa dosing regimens: 50 IU/kg three times per week, 10,000 IU once weekly, or 20,000 IU every 2 wk for 36 d or 40,000 IU every 4 wk for 64 d. Each regimen provided a similar dosage of epoetin alfa over 4 wk. Dosage adjustments were not permitted. RESULTS: Drug exposure to epoetin alfa over 4 wk, based on area under the curve, was somewhat higher with the extended interval regimens compared with the three-times-weekly regimen. Mean change in hemoglobin during the study period was similar for all regimens. No patients were transfused. Three patients experienced five serious adverse events, none of which was considered treatment related. CONCLUSIONS: Extended dosing interval regimens of epoetin alfa yielded modest pharmacokinetic differences but a similar pharmacodynamic response, suggesting that less frequent, higher dosages of epoetin alfa may be as effective as the current three-times-weekly regimen in anemic patients who have chronic kidney disease and are not on dialysis.

Epoetin alfa once every 2 weeks is effective for initiation of treatment of anemia of chronic kidney disease.

There are limited data suggesting that initiation of epoetin alfa at extended dosing intervals of every 2, 3, or 4 wk may be efficacious for treating anemia in patients who have chronic kidney disease and are not on dialysis (CKD-NOD). This open-label, multicenter, single-arm study investigated the efficacy of administration of 20,000 IU of epoetin alfa once every 2 wk as initiation therapy in these patients. Adults with CKD-NOD were eligible when they had hemoglobin (Hb) <11 g/dl, GFR of 10 to 60 ml/min per 1.73 m2, and stable serum creatinine for the past 6 mo. Patients received 20,000 IU of epoetin alfa subcutaneously every 2 wk for up to 27 wk, with dosage adjustments permitted after 4 wk of treatment. The primary efficacy end point was the proportion of patients with Hb response, defined as achievement of the target Hb range of 11 to 12 g/dl for at least two consecutive visits. Sixty-seven patients were enrolled; >88% (59 of 67) of patients achieved an Hb response. Mean Hb increased to the targeted range by week 6 and remained in the range through week 28. Hb increases of 1 and 2 g/dl were observed in 91 and 78% of patients, respectively. Epoetin Alfa was well tolerated; most adverse events were mild or moderate in nature and typical of the CKD patient population. In this study, results demonstrated that epoetin alfa can be initiated safely and effectively at an extended dosing interval of 20,000 IU every 2 wk in patients with CKD-NOD.

Correction of anemia with epoetin alfa in chronic kidney disease.

BACKGROUND: Anemia, a common complication of chronic kidney disease, usually develops as a consequence of erythropoietin deficiency. Recombinant human erythropoietin (epoetin alfa) is indicated for the correction of anemia associated with this condition. However, the optimal level of hemoglobin correction is not defined. METHODS: In this open-label trial, we studied 1432 patients with chronic kidney disease, 715 of whom were randomly assigned to receive a dose of epoetin alfa targeted to achieve a hemoglobin level of 13.5 g per deciliter and 717 of whom were assigned to receive a dose targeted to achieve a level of 11.3 g per deciliter. The median study duration was 16 months. The primary end point was a composite of death, myocardial infarction, hospitalization for congestive heart failure (without renal replacement therapy), and stroke. RESULTS: A total of 222 composite events occurred: 125 events in the high-hemoglobin group, as compared with 97 events in the low-hemoglobin group (hazard ratio, 1.34; 95% confidence interval, 1.03 to 1.74; P=0.03). There were 65 deaths (29.3%), 101 hospitalizations for congestive heart failure (45.5%), 25 myocardial infarctions (11.3%), and 23 strokes (10.4%). Seven patients (3.2%) were hospitalized for congestive heart failure and myocardial infarction combined, and one patient (0.5%) died after having a stroke. Improvements in the quality of life were similar in the two groups. More patients in the high-hemoglobin group had at least one serious adverse event. CONCLUSIONS: The use of a target hemoglobin level of 13.5 g per deciliter (as compared with 11.3 g per deciliter) was associated with increased risk and no incremental improvement in the quality of life. (ClinicalTrials.gov number, NCT00211120 [ClinicalTrials.gov].).

Effects of intraperitoneal hyaluronan on peritoneal fluid and solute transport in peritoneal dialysis patients.

BACKGROUND: Hyaluronan (HA) is a glycosaminoglycan found in connective tissues and tissue spaces, including the peritoneal cavity. In vivo studies in a rat model of peritoneal dialysis (PD) have shown that addition of HA to PD solution during an intraperitoneal dwell can alter peritoneal fluid transport and protect the peritoneal membrane from the effects of inflammation and repeated infusions of dialysis solution. The current study sought to evaluate the safety of intraperitoneal HA and its effect on peritoneal fluid and solute transport when administered during a dialysis dwell in humans. METHODS: 13 PD patients were enrolled in a prospective, randomized crossover study involving three dialysis treatments using the following PD solutions: (1) a commercially available PD solution (Dianeal PD-4, 1.36% glucose; Baxter Healthcare Corporation, Alliston, Ontario, Canada); (2) Dianeal PD-4 containing 0.1 g/L HA, and (3) Dianeal PD-4 containing 0.5 g/L HA. Each 6-hour dialysis exchange was separated from the other exchanges by a 2-week washout period. Radioiodinated human serum albumin (RISA) was administered with the dialysis solution to evaluate intraperitoneal volume, net ultrafiltration (UF), and fluid reabsorption. Peritoneal clearances, dialysate/plasma ratios (D/P), and mass transfer area coefficients (MTACs) were determined for sodium, urea, creatinine, albumin, and glucose. Safety was evaluated by monitoring adverse events and changes in serum chemistries. Ten patients completed all three dialysis exchanges and two additional patients completed at least one treatment exchange. RESULTS: There were no reported adverse events related to HA administration and no significant changes in serum chemistries. There were no significant differences in net UF or peritoneal volume profiles among the three treatments. Mean net UF calculated using residual volumes, estimated by RISA dilution, tended to be slightly higher during treatment with solution containing 0.1 g/L HA and 0.5 g/L HA [74 +/- 86 (SE) and 41 +/- 99 mL, respectively] compared to control treatment (-58 +/- 129 mL). Although not statistically significant, there was a trend toward decreased fluid reabsorption during treatment with HA. Solute clearances, D/P ratios, and MTACs were similar for the three treatments. Serum levels of HA were also unaffected by the two treatment solutions. CONCLUSIONS: These data support the acute safety of HA when administered intraperitoneally with the dialysis solution to PD patients. Due to the small sample size and variability in net UF and fluid reabsorption, statistically significant differences were not demonstrated for these parameters. However, a trend toward decreased fluid reabsorption was observed, suggesting that HA may act by a mechanism similar to that observed in animal studies. Further studies are necessary to evaluate whether the beneficial effects of HA observed in animal studies can be shown in humans.

Metabolic acidosis in maintenance dialysis patients: clinical considerations.

Metabolic acidosis in maintenance dialysis patients: Clinical considerations. Metabolic acidosis is a common consequence of advanced chronic renal failure (CRF) and maintenance dialysis (MD) therapies are not infrequently unable to completely correct the base deficit. In MD patients, severe metabolic acidosis is associated with an increased relative risk for death. The chronic metabolic acidosis of the severity commonly encountered in patients with advanced CRF has two well-recognized major systemic consequences. First, metabolic acidosis induces net negative nitrogen and total body protein balance, which improves upon bicarbonate supplementation. The data suggest that metabolic acidosis is both catabolic and antianabolic. Emerging data also indicate that metabolic acidosis may be one of the triggers for chronic inflammation, which may in turn promote protein catabolism among MD patients. In contrast to these findings, metabolic acidosis may be associated with a decrease in hyperleptinemia associated with CRF. Several studies have shown that correction of metabolic acidosis among MD patients is associated with modest improvements in the nutritional status. Second, metabolic acidosis has several effects on bone, causing physicochemical dissolution of bone and cell-mediated bone resorption (inhibition of osteoblast and stimulation of osteoclast function). Metabolic acidosis is probably also associated with worsening of secondary hyperparathyroidism. Data on the effect of correction of metabolic acidosis on renal osteodystrophy, however, are limited. Preliminary evidence suggest that metabolic acidosis may play a role in beta2-microglobulin accumulation, as well as the hypertriglyceridemia seen in renal failure. Given the body of evidence pointing to the several systemic consequences of metabolic acidosis, a more aggressive approach to the correction of metabolic acidosis is proposed.

A randomized controlled trial to evaluate the efficacy and safety of icodextrin in peritoneal dialysis.

BACKGROUND: This article presents the results of two randomized, double-blind, controlled studies conducted to compare the efficacy and long-term safety of icodextrin and 2.5% dextrose for the once-daily long dwell in continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). METHODS: Both studies were active-control comparisons of 7.5% icodextrin and 2.5% dextrose for the once-daily long dwell. The efficacy study was a 4-week evaluation of net ultrafiltration and peritoneal clearances of creatinine and urea nitrogen in 175 CAPD patients. The 52-week study in CAPD and APD patients examined the long-term safety of icodextrin and longer term effects, such as body weight and quality of life. RESULTS: Mean net ultrafiltration (587.2 versus 346.2 mL, P < 0.001) and clearances of urea nitrogen (4.5 versus 4.1 mL/min, P < 0.001) and creatinine (4.0 versus 3.5 mL/min, P < 0.001) were increased significantly with icodextrin. Patients receiving icodextrin had no increase in weight after 52 weeks, in contrast to a weight gain of almost 2 kg in the dextrose group (P < 0.05). There were significantly fewer patients reporting edema in the icodextrin group compared with the dextrose group (6.3% versus 17.9%, P < 0.01). There were no statistically significant differences between groups for the incidence and severity of adverse events. There were small decreases in sodium and chloride and increases in alkaline phosphatase with icodextrin. CONCLUSION: Icodextrin provides patients with greater fluid removal and small solute clearance, no weight gain over 52 weeks, and a decreased risk of edema.

Pharmacokinetics of icodextrin in peritoneal dialysis patients.

UNLABELLED: Pharmacokinetics of icodextrin in peritoneal dialysis patients. BACKGROUND: Icodextrin is a glucose polymer osmotic agent used to provide sustained ultrafiltration during long peritoneal dialysis (PD) dwells. A number of studies have evaluated the steady-state blood concentrations of icodextrin during repeated use; however, to date the pharmacokinetics of icodextrin have not been well studied. The current study was conducted to determine the absorption, plasma kinetics and elimination of icodextrin and metabolites following a single icodextrin exchange. METHODS: Thirteen PD patients were administered 2.0 L of solution containing 7.5% icodextrin for a 12-hour dwell. Icodextrin (total of all glucose polymers) and specific polymers with degrees of polymerization ranging from two to seven (DP2 to DP7) were measured in blood, urine and dialysate during the dwell and after draining the solution from the peritoneal cavity. RESULTS: A median of 40.1% (60.24 g) of the total administered dose (150 g) was absorbed during the 12-hour dwell. Plasma levels of icodextrin and metabolites rose during the dwell and declined after drain, closely corresponding to the one-compartment pharmacokinetic model assuming zero-order absorption and first-order elimination. Peak plasma concentrations (median C peak = 2.23 g/L) were observed at the end of the dwell (median Tmax = 12.7 h) and were significantly correlated with patients' body weight (R2 = 0.805, P < 0.001). Plasma levels of icodextrin and metabolites returned to baseline within 3 to 7 days. Icodextrin had a plasma half-life of 14.73 hours and a median clearance of 1.09 L/h. Urinary excretion of icodextrin and metabolites was directly related to residual renal function (R2 = 0.679 vs. creatinine clearance, P < 0.01). In the nine patients with residual renal function, the average daily urinary excretion of icodextrin was 473 +/- 77 mg per mL of endogenous renal creatinine clearance. Icodextrin metabolites DP2 to DP4 were found in the dialysate of subsequent dextrose exchanges, contributing to their elimination from blood. Changes in intraperitoneal concentrations of icodextrin metabolites during the dwell revealed a dual pattern, with a progressive rise in the dialysate concentration of smaller polymers (DP2 to DP4) and a progressive decline in the dialysate concentrations of the larger polymers (DP5 to DP7), suggesting some intraperitoneal metabolism of the glucose polymers. This increase in dialysate metabolite levels, however, did not contribute significantly to dialysate osmolality. In addition, some diffusion of maltose (DP2) from blood to dialysate may have occurred. There were no changes in serum insulin or glucose levels during icodextrin administration, indicating that icodextrin does not result in hyperglycemia or hyperinsulinemia as occurs during dextrose-based dialysis. Serum sodium and chloride declined in parallel with the rise in plasma levels of icodextrin, supporting the hypothesis that these electrolyte changes are the result of the increased plasma osmolality due to the presence of icodextrin metabolites. CONCLUSIONS: The pharmacokinetics of icodextrin in blood following intraperitoneal administration conforms to a simple, single-compartment model that can be approximated by zero-order absorption and first-order elimination. A small amount of intraperitoneal metabolism of icodextrin occurs but does not contribute significantly to dialysate osmolality. The metabolism of absorbed icodextrin and the resultant rise in plasma levels of small glucose polymers (DP2 to DP4) do not result in hyperglycemia or hyperinsulinemia, but may result in a small decrease in serum sodium and chloride.

Early quality of life benefits of icodextrin in peritoneal dialysis.

UNLABELLED: Early quality of life benefits of icodextrin in peritoneal dialysis. BACKGROUND: The impact of new therapies on patient quality of life (QOL) is emerging as an important indicator of the value of these therapies. In patients on dialysis, previous QOL evaluations have focused mainly on comparative approaches between modalities, or on longitudinal trends within a modality, but few have evaluated technical innovations or introduction of new therapies. The aim of the present study was to assess the early effects of a new dialysis solution (icodextrin) on the QOL of peritoneal dialysis patients. The QOL is compared with that of patients on dextrose, and the impact of demographic, and clinical characteristics on patients' QOL is examined. METHODS: The kidney disease quality of life questionnaire (KDQOL) was administered to patients who participated in a phase III double-blind, parallel group, active-controlled trial to evaluate the efficacy and safety of a peritoneal dialysis (PD) solution containing icodextrin in comparison with dextrose PD solution. A total of 93 patients (58 icodextrin, and 35 dextrose) completed the questionnaire at both baseline and after 13 weeks. In addition to patients QOL, patients' demographic and clinical characteristics were recorded at both baseline and 13 weeks. RESULTS: Mean change scores from baseline to 13 weeks of icodextrin patients were substantially higher (> or =5) than dextrose, particularly with respect to general health perception, physical functioning, role-physical, and many KDQOL symptom items such as lack of strength, washed out or drained, lack of appetite, faintness or dizziness, dry skin, cramps after an exchange or treatment, cramps during an exchange or treatment, and muscle spasms or twitching. At 13 weeks, icodextrin patients had significantly improved symptoms, and rated their health in general higher than those patients in the dextrose group. Upon multivariate analysis, icodextrin contributed significantly to the improvement of patients' mental health, general health, and symptoms such as muscle spasms or twitching, cramps during an exchange or treatment, cramps after an exchange or treatment, itchy skin, and faintness or dizziness. CONCLUSIONS: Peritoneal dialysis patients treated with icodextrin experienced substantial quality of life improvement at 13 weeks after the start of treatment when compared to dextrose patients. Further research is necessary to determine patients' quality of life over time in a longitudinal study setting.

Nutrition in elderly dialysis patients.

The end-stage renal disease (ESRD) population is aging, and currently approximately 50% of patients treated with maintenance dialysis are more than 65 years old. With advancing age comes challenges to maintaining the nutritional status of these patients. As patients get older, purchasing and preparing food may become more difficult. In addition, appetite may decrease, the occurrence of intercurrent illnesses may become more frequent, and nutrient requirements change. Mobility may decline, as well as cognitive function, and the combination of several of these factors may result in malnutrition. Since malnutrition has been demonstrated to impact survival in dialysis patients of all ages, appropriate attention to nutritional status and its management is essential for the elderly dialysis patient. This article reviews the issues associated with the maintenance of good nutrition in the elderly dialysis patient and describes the potential causes of malnutrition in these patients. It also reviews the nutrient requirements for older dialysis patients (which differ somewhat from those of younger patients), as well as the assessment of their nutritional status. Finally, recommendations for management of nutrition in the elderly dialysis patient are discussed.