Glucose-sparing Peritoneal Dialysis Regimen Shows Positive HbA1c and Lipids Results

In a study of patients with diabetes and end stage renal disease (ESRD) on peritoneal dialysis (PD), use of a low-glucose PD fluid showed beneficial effects on metabolic measures such as blood glucose control, serum cholesterol, and triglycerides compared with conventional PD solutions with higher glucose content. Joanne Bargman, MD, professor of medicine at the University of Toronto and a staff nephrologist at the Toronto General Hospital in Toronto, Ontario, Canada, presented the combined results of the IMPENDIA (Improved Metabolic Control of Physioneal, Extraneal, Nutrineal versus Dialneal only in Diabetic CAPD and APD Patients) and EDEN (Evaluation of Dianeal, Extraneal, and Nutrineal versus Dianeal Only in Diabetic CAPD Patients) trials at the 49th European Renal Association–European Dialysis and Transplant Association Congress in Paris in May.

Diabetic nephropathy accounts for 25 percent to 50 percent of new cases of ESRD in developed countries. Patients on PD or hemodialysis have similar survival rates, but overall, survival is poor. Each form of dialysis has certain adverse effects associated with it. In the case of PD, continuous glucose loading from the conventional dialysis solution may contribute to the increased cardiovascular risk that is a major cause of death in ESRD patients.

Glucose absorption makes it difficult for patients with diabetes to achieve their target blood glucose levels. “The sugar that’s absorbed from the PD fluid is going to make their blood sugar go even higher,” Bargman explained, “and that’s going to affect their sugar control, how much insulin they have to use, and more downstream, will raise some types of cholesterol and fats in the blood. So every study that has looked at it has shown that patients on PD have worse levels of blood cholesterol and fats compared to hemodialysis,” she said.

Patients on PD typically use four fluid bag exchanges a day containing glucose. In the IMPENDIA and EDEN trials, two of the bags were substituted with osmotic solutions not containing glucose.

These international, open-label, prospective trials randomly assigned 251 diabetic patients on PD to a glucose-sparing (GS) regimen using a combination of Physioneal (glucose), Extraneal (icodextrin), and Nutrineal (amino acids) solutions or DIANEAL (glucose), Extraneal, and Nutrineal solutions (124 patients) versus a non–glucose sparing regimen control group (NGS; 127 patients) using DIANEAL only.

At baseline, study participants incluede men or women 18 years or older with ESRD and a diagnosis of type 1 or type 2 diabetes using glycemic control medication and who were using at least one exchange of 2.5 percent or 4.25 percent dextrose per day by continuous ambulatory PD or automated PD. They had hemoglobin A1c (HbA1c) measures greater than 6.0 percent and no higher than 12.0 percent, with blood hemoglobin between 8.0 mg/dL and 13.0 mg/dL.

At 3 and 6 months, the GS group showed a significant HbA1c drop from 7.7 percent to 7.2 percent, whereas the HbA1c of the NGS control group did not change (p = 0.006). Compared to the NGS group, the patients on the GS regimen had a significant drop in their fasting triglyceride (p = 0.002), very low-density lipoprotein cholesterol (p = 0.003), and apolipoprotein B levels (p = 0.03). Apolipoprotein is a component of low-density lipoprotein cholesterol. There was also a nonsignificant trend toward lower total cholesterol levels in the GS group.

Bargman concluded that the results of these randomized, controlled trials are strong evidence that the composition of the PD fluid influences metabolic end points. She said the modest changes in HbA1c, very low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were statistically significant and were probably clinically significant as well. However, she noted the study ran for only 6 months.

She suggested that further research explore ways to perform PD with regimens containing low or no glucose. The glucose is in the PD solutions as an osmotic agent, meaning that it helps to draw water and toxins out of the body into the fluid.

Important to note, there were 10 deaths and three withdrawals for adverse effects in the GS group compared to three deaths and three withdrawals for adverse effects in the NGS group. The GS group experienced more occurrences of volume overload and hypertensive encephalopathy.

Bargman said that all the deaths and serious adverse events happened at two participating clinical sites in Chile, and the investigators are trying to determine the reasons. Nonetheless, even if the reasons can be discerned, the results from these sites must be included in the overall analysis and cannot be ignored.

GS regimens will be more expensive than NGS ones, but Bargman noted that in either case, PD is less expensive than in-center hemodialysis.

Notes

[1] IMPENDIA: Improved Metabolic Control of Physioneal, Extraneal, Nutrineal versus Dialneal only in Diabetic CAPD and APD Patients

EDEN: Evaluation of Dianeal, Extraneal, and Nutrineal versus Dianeal Only in Diabetic CAPD Patients

Dr. Bargman is a consultant for Baxter, Amgen, and Otsuka. She is on the speakers’ bureau of DaVita, Amgen, Baxter, and Otsuka. The trial was sponsored by Baxter Healthcare Corporation.

49th European Renal Association - European Dialysis and Transplant Association Congress: No abstract (Late Breaker). Presented May 25, 2012.