Abstract Background and Aims Sustained-Low Efficiency Dialysis (SLED) is a hybrid Renal Replacement Therapy (RRT) increasingly used in critically ill patients with Acute Kidney Injury (AKI). Usually lasting 8-12 hours, this modality combines several advantages of both intermittent and continuous RRT (CRRT). Regional citrate anticoagulation (RCA) represents the most adequate anticoagulation strategy to avoid the extracorporeal circuit clotting. Hypophosphatemia (serum phosphorus, s-P, levels ≤ 2.5 mg/dl) is a common electrolyte disorder in critically ills, with an increased incidence in course of prolonged RRTs, especially when standard dialysis/replacement solutions and highly intensive modalities are employed. Given the potentially negative impact of hypophosphatemia on patients’ outcomes, strategies aimed at preventing its onset should be appropriately implemented. This pilot study is aimed at evaluation of safety and efficacy of a simplified RCA protocol for SLED, based on the combination of a low-concentrated citrate solution with a phosphate-containing solution. Methods a prospective observational study was conducted on critically ill patients with AKI requiring RRT or End Stage Renal Disease (ESRD) previously on RRT admitted to our renal Intensive Care Unit (ICU). SLED was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 haemofilters (ST 150, 1.5 m2, Baxter). 8-hours SLED sessions were prescribed, in the SLED-f variant, by using a 18 mmol/l pre-dilution trisodium citrate solution (Regiocit 18/0, Baxter) combined with a phosphate-containing solution acting as dialysate (Ca2+ 0, HPO42- 1, Mg2+ 0.75, HCO3- 22 mmol/l; Biphozyl, Baxter) and a standard RRT solution acting as post-dilution replacement fluid (Prismasol 4, Baxter). Calcium chloride (CaCl 10%) was infused in a separate central venous line to maintain the systemic Ca2+ (s-Ca2+) within a normal range. Each patient underwent three consecutive daily SLED sessions. The activated coagulation time (ACT), acid–base parameters, s-Ca2+ and potassium were measured at SLED start and every 2 h. Phosphorus and magnesium losses with RRT were replaced, when needed, with sodium glycerophosphate pentahydrate (GlycophosTM 20 mmol/20 ml, Fresenius Kabi Norge AS, Halden, Norvegia) and magnesium sulphate. Results a total of 60 SLED-f sessions were performed in 20 ICU patients. At ICU admission, the average APACHE II score was 21.8 and half of patients were mechanically ventilated. Many of them showed hemodynamic instability and AKI was oliguric in 90% of cases. No premature interruptions for irreversible filter clotting occurred and the prescribed dialysis dose was delivered in 95% of cases. No statistically significant differences were observed between systemic ACT at SLED start and during RRT sessions, and no major hemorrhagic events were observed. Regarding RCA, no clinically relevant episode of hypo or hypercalcemia was observed, and calcium infusion rate remained constant in course of treatments. Acid-base status was effectively maintained during the entire period of treatment and no episodes of clinically relevant metabolic acidosis or alkalosis were registered. The analysis of the main laboratory variables at SLED start, in course and after 24 h of treatment did not show statistically significant differences. Regardless of starting values, s-P and s-Mg were progressively corrected and maintained within the normality range, limiting the need for exogenous supplementations. Conclusions These preliminary data suggest that our simplified RCA protocol for SLED, combining a low-citrate solution with a phosphate-containing solution, is safe and efficacious allowing to optimizing acid-base balance and to preventing RRT-related hypophosphatemia.