A Novel Peritoneal Dialysis Fluid Based on Succinylated Gelatin and Citrate: A Preliminary Investigation of Efficacy, Safety, and Biocompatibility

<b>Introduction:</b> The metabolic complications and poor biocompatibility of conventional glucose-based (GLU) peritoneal dialysis fluid (PDF) have driven the need for improved alternatives. To address this, we developed and evaluated a novel PDF utilizing succinylated gelatin (GEL) as osmotic agent and citrate as buffer, designed to provide effective solute clearance while offering enhanced biocompatibility. <b>Methods:</b> Physicochemical parameters (pH and osmolality) of the novel GEL-PDF were measured. Its performance was assessed in rats with chronic kidney disease. A total of 20 rats were randomized into short-term experiments to evaluate 4 h creatinine clearance and ultrafiltration (UF). A 12-week long-term experiment (<i>n</i> = 35) compared the GEL-PDF against normal saline (NS), GLU, and icodextrin-based (ICO) PDFs, monitoring survival, biochemical parameters, peritoneal membrane histology, and kidney histology. <b>Results:</b> The GEL-PDF demonstrated a neutral pH (7.30) and lower osmolality (317 mOsm/L) compared to GLU-PDF. In the short-term experiment, GEL-PDF achieved effective creatinine clearance by 4 h and provided higher 4 h UF than NS and GLU, comparable to ICO. However, during prolonged dwells (6-16 h), its UF was inferior to ICO. In the long-term experiment, GEL-PDF preserved peritoneal membrane structure, showing the least thickness and collagen deposition. Furthermore, the GEL-PDF demonstrated superior preservation of serum albumin compared to the GLU-PDF. It also exhibited a more favorable lipid profile, as evidenced by significantly lower total cholesterol levels than the ICO group at 12 weeks (<i>p</i> = 0.035), with no adverse effects on electrolytes, liver function, or glucose metabolism. <b>Conclusions:</b> The novel GEL and citrate-based PDF provide effective short-dwell UF and solute removal while exhibiting superior biocompatibility, as evidenced by significant protection against peritoneal membrane injury and favorable metabolic profiles. Although its long-duration UF was lower than that of ICO, it substantially outperformed GLU-PDF. These properties position the GEL-PDF as a promising candidate for short- to medium-dwell exchanges, particularly for daytime use, where it could fill an important clinical gap by providing enhanced UF without the high GLU exposure associated with conventional PDF.