Supplementary Material for: Clinical outcomes of patients undergoing hemodialysis with cool versus standard dialysate: A systematic review and meta-analysis.

Rationale & Objective: Clinical practice guidelines recommend lower (35.0°C–35.5°C) instead of standard dialysate temperature (36.5°C–37.0°C) to mitigate the risk of intradialytic hypotension. However, many studies have been available since the recommendations were published. Hence, the current study aims to provide an updated meta-analysis of clinical outcomes with cold versus standard dialysate. Study Design: Systematic review and meta-analysis of eligible articles indexed in PubMed, Cochrane, Web of Science, and Scopus. Participants: Hemodialysis patients Exposure: Cooled versus standard dialysate. Outcome: Intradialytic hypotension, mean arterial pressure, thermal-related discomfort, and body temperature. Analytical Approach: The random effects model was used for all outcomes due to high heterogeneity (I2: interdialytic hypotension=60%, mean arterial pressure=72%, symptoms of discomfort =41%, and decrease in body temperature=87%). The "leave-one-out" approach was used for sensitivity analysis, and the Cochrane risk-of-bias tool was used to evaluate study quality. Results: Pooled data from 31 studies indicate that cooled dialysis may be associated with a lower risk of intradialytic hypotension [RR 0.67 (95%CI 0.48–0.93), p=0.02] and higher mean arterial pressure [MD 7.18 (95%CI 3.79–10.58), p<0.01] compared to standard temperature dialysis. However, cooled dialysis was associated with a higher risk of discomfort [RR 1.55 (95% CI 1.25–1.93], p<0.01] and a decrease in body temperature [MD -0.29 (95%CI -0.52–-0.05), p=0.02]. Only five studies had a low risk of bias. Limitations: Most included studies were from over a decade ago, had a small participant size, and did not report other critical long-term outcomes such as mortality, cardiovascular events, treatment discontinuation, or hospitalization rate. Registration: Registered with ID CRD42024589307 at PROSPERO Conclusions: Using cooled dialysate might be a simple approach to reduce interdialytic hypotension risk and increase mean arterial pressure, albeit at the cost of patient discomfort. The limitations associated with the quality of included studies underscore the need for high–quality, multicenter studies with large/diverse study populations.