The Benefit of a Glucose-Sparing PD Therapy on Glycemic Control Measured by Serum Fructosamine in Diabetic Patients in a Randomized, Controlled Trial (IMPENDIA).

BACKGROUND/AIMS: Poor glycemic control can lead to increased morbidity and mortality in peritoneal dialysis (PD) patients. Serum fructosamine may be a more reliable marker of glycemic control than HbA1c in dialysis patients. METHODS: We evaluated the effects of a glucose-sparing PD regimen on serum fructosamine. In the multicenter, controlled IMPENDIA trial, eligible diabetic PD patients were randomized (1:1) to a 24-hour combination of a glucose sparing regimen (n = 89) or a glucose-based therapy (n = 91). Serum fructosamine and HbA1c were measured at baseline, 3 months and 6 months; fructosamine measurements were corrected for serum albumin (AlbF). RESULTS: Serum fructosamine decreased from 297 to 253 µmol/l in the glucose-sparing group (95% confidence interval [CI] for the difference, -26 to -68, p < 0.001), and increased from 311 to 314 µmol/l in the glucose-only group (95% CI for the difference, -23 to +19, p = 0.87). The mean difference in change of fructosamine levels between groups at 6 months was 64 µmol/l (95% CI 29-99, p < 0.001). HbA1c decreased versus baseline in both groups (treatment difference 0.3%, p = 0.07). The correlation between AlbF and baseline fasting serum glucose was stronger than that seen between HbA1c and baseline fasting serum glucose (r = 0.47, p < 0.0001 and r = 0.31, p < 0.0001, respectively). CONCLUSION: A glucose-sparing regimen (P-E-N) improved glycemic control as measured by serum fructosamine. Further studies are needed to establish fructosamine targets that will reduce the morbidity risk related to hyperglycemia in PD patients.

Influence of low-glucose peritoneal dialysis on serum lipids and apolipoproteins in the IMPENDIA/EDEN trials.

BACKGROUND: Glucose, the conventional osmotic agent in peritoneal dialysis (PD) solutions, may contribute to atherogenic dyslipoproteinemia and increased cardiovascular risk. OBJECTIVE: To determine whether a low-glucose PD regimen may improve the serum lipid and lipoprotein profile in patients with diabetes. METHODS: A prospective, open-label, parallel group, multinational, randomized, controlled trial with a 6-month follow-up, comprising 251 patients with diabetes receiving PD. Patients were randomized to a low-glucose PD regimen (dextrose-based PD solution plus icodextrin, a starch polymer, and amino acids) or a conventional PD regimen (dextrose PD solutions). Serum lipid and apolipoprotein profiles were determined at baseline and 3 and 6 months. RESULTS: Serum triglycerides, very low-density-lipoprotein cholesterol, and apolipoprotein B (apoB) decreased significantly in the intervention group at both 3 and 6 months compared with baseline (serum triglycerides: median change at 3 months -0.5 mmol/L, P < .001, at 6 months -0.3 mmol/L, P < .001; very low-density-lipoprotein cholesterol: -0.3 mg/dL, P < .001; -0.3 mg/dL, P < .001; and apoB: -8.5 mg/dL, P < .001; -3.6 mg/dL, P = .043, respectively) and also compared with the control group. In contrast, apoB levels increased significantly in the control group at 3 and 6 months compared with baseline (5.3 mg/dL, P = .041; 5.2 mg/dL, P = .007, respectively). Percentage of patients on lipid-lowering medications at baseline and intensity of therapy was equivalent in each group. The apoB decrease was not affected by lipid-lowering medications in the intervention group. CONCLUSION: A low glucose-PD regimen significantly improved the atherogenic lipoprotein phenotype compared with PD patients treated with a conventional glucose regimen.

Randomized, controlled trial of glucose-sparing peritoneal dialysis in diabetic patients.

Glucose-containing peritoneal dialysis solutions may exacerbate metabolic abnormalities and increase cardiovascular risk in diabetic patients. Here, we examined whether a low-glucose regimen improves metabolic control in diabetic patients undergoing peritoneal dialysis. Eligible patients were randomly assigned in a 1:1 manner to the control group (dextrose solutions only) or to the low-glucose intervention group (IMPENDIA trial: combination of dextrose-based solution, icodextrin and amino acids; EDEN trial: a different dextrose-based solution, icodextrin and amino acids) and followed for 6 months. Combining both studies, 251 patients were allocated to control (n=127) or intervention (n=124) across 11 countries. The primary endpoint was change in glycated hemoglobin from baseline. Mean glycated hemoglobin at baseline was similar in both groups. In the intention-to-treat population, the mean glycated hemoglobin profile improved in the intervention group but remained unchanged in the control group (0.5% difference between groups; 95% confidence interval, 0.1% to 0.8%; P=0.006). Serum triglyceride, very-low-density lipoprotein, and apolipoprotein B levels also improved in the intervention group. Deaths and serious adverse events, including several related to extracellular fluid volume expansion, increased in the intervention group, however. These data suggest that a low-glucose dialysis regimen improves metabolic indices in diabetic patients receiving peritoneal dialysis but may be associated with an increased risk of extracellular fluid volume expansion. Thus, use of glucose-sparing regimens in peritoneal dialysis patients should be accompanied by close monitoring of fluid volume status.

Health-related quality of life in CKD Patients: correlates and evolution over time.

BACKGROUND AND OBJECTIVES: Very few large-scale studies have investigated the determinants of health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients not on dialysis or the evolution of HRQOL over time. DESIGN AND SETTING: A prospective evaluation was undertaken of HRQOL in a cohort of 1186 CKD patients cared for in nephrology clinics in North America. Baseline and follow-up HRQOL were evaluated using the validated Kidney Disease Quality Of Life instrument. RESULTS: Baseline measures of HRQOL were reduced in CKD patients in proportion to the severity grade of CKD. Physical functioning score declined progressively with more advanced stages of CKD and so did the score for role-physical. Female gender and the presence of diabetes and a history of cardiovascular co-morbidities were also associated with reduced HRQOL (physical composite score: male: 41.0 +/- 10.2; female: 37.7 +/- 10.8; P < 0.0001; diabetic: 37.3 +/- 10.6; nondiabetic: 41.6 +/- 10.2; P < 0.0001; history of congestive heart failure, yes: 35.4 +/- 9.7; no: 40.3 +/- 10.6; P < 0.0001; history of myocardial infarction, yes: 36.1 +/- 10.0; no: 40.2 +/- 10.6; P < 0.0001). Anemia and beta blocker usage were also associated with lower HRQOL scores. HRQOL measures declined over time in this population. The main correlates of change over time were age, albumin level and co-existent co-morbidities. CONCLUSIONS: These observations highlight the profound impact CKD has on HRQOL and suggest potential areas that can be targeted for therapeutic intervention.

A prospective evaluation of renal replacement therapy modality eligibility.

BACKGROUND: Patient eligibility for renal replacement therapy (RRT) modalities is frequently debated, but little prospective data are available from large patient cohorts. METHODS: We prospectively evaluated medical and psychosocial eligibility for the three RRT modalities in patients with chronic kidney disease (CKD) stages III-V who were enrolled in an ongoing prospective cohort study conducted at seven North American nephrology practices. RESULTS: Ninety-eight percent of patients were considered medically eligible for haemodialysis (HD), 87% of patients were assessed as medically eligible for peritoneal dialysis (PD) and 54% of patients were judged medically eligible for transplant. Age was the leading cause of non-eligibility for both PD and transplant. Anatomical concerns (adhesions, hernias) were the second most frequent concern for PD eligibility followed by weight. Weight was also a concern for transplant eligibility. The proportion of patients medically eligible for RRT did not vary by CKD stage. There was, however, significant inter-centre variation in the proportion of patients medically eligible for PD and transplant. Ninety-five percent of patients were considered psychosocially eligible for HD, 83% of patients were assessed as psychosocially eligible for PD and 71% of patients were judged psychosocially eligible for transplant. The percentage of patients who were assessed as having neither medical nor psychosocial contraindications for RRT was 95% for HD, 78% for PD and 53% for transplant. CONCLUSIONS: Most CKD patients are considered by their medical care providers to be suitable for PD. Enhanced patient education, promotion of home dialysis for suitable patients and empowerment of patient choice are expected to augment growth of home dialysis modalities.

Impact of age on peritonitis risk in peritoneal dialysis patients: an era effect.

BACKGROUND AND OBJECTIVES: Despite reductions in the frequency of peritoneal dialysis (PD)-related infectious complications over time, peritonitis and catheter infection remain important causes of morbidity and mortality. Given the increasing number of elderly patients reaching end-stage renal disease, making informed decisions about PD utilization is contingent on an understanding of the infectious complications of PD in this population. We therefore studied the impact of age on infection rates, organisms and outcomes. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: On the basis of data collected from 1996 to 2005 in the multicenter Baxter Peritonitis Organism Exit sites Tunnel infections database, the study population included 4247 incident Canadian PD patients: 1265 patients aged > or =70 yr and 2982 patients aged <70 yr. We defined two eras of PD initiation: 1996 to 2000 and 2001 to 2005. RESULTS: In a negative binomial model, older age was independently associated with a higher peritonitis rate (rate ratio [RR] 1.06 per decade increase; 95% CI 1.01 to 1.10; P = 0.008). However, this association was present only among those who initiated PD at an earlier time (RR 1.13 per decade increase; 95% CI 1.07 to 1.20; P < 0.001 in 1996 to 2000 versus 1.01 per decade increase; 95% CI 0.95 to 1.06; P = 0.81 in 2001 to 2005). Catheter-related infections were less frequent with increasing age regardless of era (RR 0.93 per decade increase; 95% CI 0.89 to 0.97). CONCLUSIONS: The higher peritonitis rate observed in elderly patients may represent an era effect, as age was not associated with peritonitis among patients initiating PD between 2001 and 2005. In addition, catheter infection was less frequent with increasing age.

Improving cycler prescriptions in peritoneal dialysis through informatic profiling.

Cycler-based dialysis is the most common form of peritoneal dialysis in the United States of America, accounting for more than two thirds of patients on the modality. The advent of modern cyclers has enhanced the accessibility of therapy-delivery data. Cyclers have transformed peritoneal dialysis from an unobserved home therapy into an observable home therapy on many levels. We will discuss 3 of these levels herein. The ability to profile prescription behavior at a population level with attention to fill volume, number of cycles used per night, and total time on the cycler will be analyzed. Insights into the dynamics of flow during cycler therapy and the concept of transition point will then be explored. Finally, we will review the impact on patient care of making the delivery of the dialysis prescription easily observable to the medical team. It is our contention that these 3 levels of profiling offer practical lessons to enhance delivery of care for patients on cycler-based peritoneal dialysis.

Intramyocardial transplantation of autologous CD34+ stem cells for intractable angina: a phase I/IIa double-blind, randomized controlled trial.

BACKGROUND: A growing population of patients with coronary artery disease experiences angina that is not amenable to revascularization and is refractory to medical therapy. Preclinical studies have indicated that human CD34+ stem cells induce neovascularization in ischemic myocardium, which enhances perfusion and function. METHODS AND RESULTS: Twenty-four patients (19 men and 5 women aged 48 to 84 years) with Canadian Cardiovascular Society class 3 or 4 angina who were undergoing optimal medical treatment and who were not candidates for mechanical revascularization were enrolled in a double-blind, randomized (3:1), placebo-controlled dose-escalating study. Patients received granulocyte colony-stimulating factor 5 microg x kg(-1) x d(-1) for 5 days with leukapheresis on the fifth day. Selection of CD34+ cells was performed with a Food and Drug Administration-approved device. Electromechanical mapping was performed to identify ischemic but viable regions of myocardium for injection of cells (versus saline). The total dose of cells was distributed in 10 intramyocardial, transendocardial injections. Patients were required to have an implantable cardioverter-defibrillator or to temporarily wear a LifeVest wearable defibrillator. No incidence was observed of myocardial infarction induced by mobilization or intramyocardial injection. The intramyocardial injection of cells or saline did not result in cardiac enzyme elevation, perforation, or pericardial effusion. No incidence of ventricular tachycardia or ventricular fibrillation occurred during the administration of granulocyte colony-stimulating factor or intramyocardial injections. One patient with a history of sudden cardiac death/ventricular tachycardia/ventricular fibrillation had catheter-induced ventricular tachycardia during mapping that required cardioversion. Serious adverse events were evenly distributed. Efficacy parameters including angina frequency, nitroglycerine usage, exercise time, and Canadian Cardiovascular Society class showed trends that favored CD34+ cell-treated patients versus control subjects given placebo. CONCLUSIONS: A randomized trial of intramyocardial injection of autologous CD34+ cells in patients with intractable angina was completed that provides evidence for feasibility, safety, and bioactivity. A larger phase IIb study is currently under way to further evaluate this therapy.

Collection of two units of leukoreduced RBCs from a single donation with a portable multiple-component collection system.

BACKGROUND: A portable automated component collection system that produces double (2) units of leukoreduced RBCs (DRBCs) from a single donation was evaluated. This study analyzed quality of the collected and final products, the efficacy of automated leukoreduction, and donor safety. STUDY DESIGN AND METHODS: The system was used to collect 120 DRBCs. WBCs were removed from 90 products with machine-controlled filtration. DRBCs were collected in ACD-A and stored in AS-1 for 42 days at 1 to 6 degrees C. Pre- and postprocedure donor vital signs and hematologic parameters were measured. Procedure time, product characteristics, and adverse events were also recorded. In vitro studies were performed on all products on Day 0 and at end of storage. In vivo recoveries of 28 leukoreduced and 9 nonleukoreduced products were measured on Day 42. RESULTS: Day 0 mean percentage of hemolysis for leukoreduced and nonleukoreduced units was 0.05 percent. DRBCs had residual WBC counts of less than 1 x 106 cells per unit and mean RBC recovery after filtration of 91.9 +/- 2.7 percent. Mean 24-hour recovery after infusion for leukoreduced units at end of storage was 80.9 +/- 6.9 percent and nonleukoreduced units was 77.6 +/- 5.8 percent (p> 0.05). No clinically significant changes in donor vital signs or serious adverse events were observed. CONCLUSIONS: The quality of leukoreduced RBCs collected with this portable automated component collection system met or exceeded FDA requirements. This automated system is safe and effective for collection and processing of 2 units of RBCs suitable for transfusion.