Abstract
OBJECTIVE: Glucose-free dialysate may heighten the risk of hypoglycemia, which is associated with seizures, stroke, and increased mortality. Incorporating an appropriate amount of glucose into the dialysate potentially helps to reduce the incidence of hypoglycemia. However, the efficacy and safety of glucose-containing dialysates during hemodialysis (HD) remain contentious. METHODS: PubMed, Embase, Web of Science, Scopus, the Cochrane database, the China National Knowledge Infrastructure, and WanFang Database were searched from inception to 30 June 2025. All comparative studies involving glucose-containing and glucose-free dialysates for diabetic and nondiabetic end-stage kidney disease (ESKD) patients with HD were included. The risk of bias was assessed using the RoB 2.0 tool for randomized trials, ROBINS-I for nonrandomized interventional studies, and the Newcastle-Ottawa Scale (NOS) for observational studies. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were pooled. The quality of evidence was evaluated using the GRADE approach. RESULTS: Thirty-nine studies from 41 articles with 2043 HD patients were included in this study. Both randomized and nonrandomized studies demonstrated that low glucose-containing dialysate significantly reduced the proportion of participants with hypoglycemia compared to glucose-free dialysate (randomized studies: OR 0.18, 95% CI 0.09-0.33, high certainty; nonrandomized studies: OR 0.15, 95% CI 0.06-0.35). Similarly, the proportion of hypoglycemic events was also lower with low glucose-containing dialysate (randomized studies: OR 0.14, 95% CI 0.05-0.38, high certainty; nonrandomized studies: OR 0.14, 95% CI 0.07-0.31). High glucose-containing dialysate further reduced hypoglycemia incidence compared to both glucose-free (OR 0.03, 95% CI 0.00-0.19, high certainty) and low-glucose dialysates (OR 0.43, 95% CI 0.19-0.97, moderate certainty). Subgroup analyses of diabetic and nondiabetic patients and network meta-analysis (NMA) yielded consistent results. Although the overall statistical analysis did not reveal significant differences for both blood pressure parameters, patients receiving low glucose-containing dialysate may exhibit higher post-HD SBP (randomized studies: MD 0.71, 95% CI -0.22 to 1.64, low certainty) and DBP (randomized studies: MD 1.18, 95% CI 0.15 to 2.20, low certainty) compared to those using glucose-free dialysate. Additionally, low glucose-containing dialysate was associated with a lower incidence of intradialytic hypotension (IDH) than glucose-free dialysate. However, insufficient data were available for meta-analysis on the effects of glucose-containing dialysates on heart rate variability (HRV), fatigue severity, erythrocytes, and oxidative stress. CONCLUSION: Glucose-containing dialysates showed advantages in preventing hypoglycemia and maintaining stable blood pressure during HD. Further studies are warranted to investigate the influence on HRV, fatigue severity, and oxidative stress. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42024559339). Date of registration: 25 June 2025.