Hypophosphatemia is a known issue during continuous renal replacement therapies (CRRT) reported in up to 80% of cases when standard CRRT solutions are used (Santiago MJ - 2009 [1]). RRT-related phosphate depletion should be avoided in critically ill patients and the adoption of phosphate-containing CRRT solutions could be helpful to reduce the incidence of hypophosphatemia and/or to minimize the need for parenteral phosphorus supplementation (Broman M - 2011 [2] (full text), Chua HR - 2012 [3], Morabito S - 2013 [4] (full text)).
The aim was to evaluate the effects on serum phosphate and phosphorus supplementation needs of a regional citrate anticoagulation (RCA) protocol for CRRT combining the use of citrate with a phosphate-containing CRRT solution.
In heart surgery patients undergoing CRRT for acute kidney injury, we adopted RCA in CVVH or CVVHDF modality combining an 18 mmol/l citrate solution with a phosphate-containing replacement fluid acting as dialysate and/or replacement fluid (Figure 1).
RCA-CRRT was performed using the Prismaflex system (Gambro, Sweden) and PAES hemofilters (HF 1000, 1.15 m2; Gambro). The citrate solution rate was initially set to obtain an estimated circuit citrate concentration of 2.5-3 mmol/l, calculated in plasma water, with a target circuit Ca2+ (c-Ca2+) ≤0.5 mmol/l. Phosphate-containing replacement solution flow rate was adjusted to obtain a prescribed dialysis dose, corrected for pre-dilution, of at least 25 ml/kg/h. Calcium chloride (10%) was infused in a separate central venous line to maintain a target systemic Ca2+ (s-Ca2+) of 1.1-1.25 mmol/l.
Hypophosphatemia was defined as mild (<0.81 mmol/l), moderate (<0.61 mmol/l) and severe (<0.32 mmol/l).
Potassium, phosphate and magnesium losses with CRRT were replaced, when needed, respectively with potassium chloride, d-fructose-1,6-diphosphate (FDP; Esafosfina® 5 g/50 ml) and magnesium sulphate. In particular, FDP administration was scheduled in case of phosphate levels <0.9 mmol/l.
Nutritional support was provided mainly via parenteral route associated, if tolerated, with enteral route; energy and protein intake targets were 25 Kcal/Kg/day and 1.5 g/Kg/day with a phosphorus intake of about 20–30 mmol/day.
Over a two-years period (Sept 2011-Sept 2013) 48 patients were treated with RCA-CVVH or RCA-CVVHDF for at least 72 hours. RCA-CRRT initial parameters are showed in Figure 2 while patient’s characteristics at the start of the treatment are reported in Table I.
Gender
15 F, 33 M
Age, years
69 (60-74)
Oliguric AKI
37/48 (77.1%)
Mechanical ventilation
42/48 (87.5%)
Artificial nutrition
48/48 (100%)
APACHE II score
32 (26-34)
SOFA score
13 (11-15)
SOFA cardiovascular score
3 (1-3)
Serum creatinine, mg/dl
2.1 (1.6-2.9)
Blood urea nitrogen, mg/dl
34.5 (28.5-55.2)
Sodium, mmol/l
140 (138-143)
Potassium, mmol/l
4.3 (4.1-4.6)
Total Calcium, mmol/l
2.1 (1.9-2.2)
Phosphorus, mmol/l
1.4 (1.16-1.8)
Magnesium, mmol/l
0.74 (0.7-0.95)
pH, units
7.40 (7.36-7.43)
Bicarbonate, mmol/l
22 (21-23)
Base Excess
-2 (-3 to -0.5)
pCO2, mmHg
37 (34-40)
Lactate, mmol/l
1.5 (1.2-2.4)
Albumin, g/dl
2.5 (2.2-2.8)
Two-hundred and nineteen RCA circuits were used with a mean filter life of 57.1±41.7 hours (median 47, IQR 24-83, total running time 12.502 hours). RCA targets (c-Ca2+, s-Ca2+) were easily maintained without episodes of clinical relevant hypo- or hypercalcemia (Table II). RCA-CRRT provided an adequate control of acid-base status without the need for additional interventions on RCA-CRRT parameters (Table II). Serum phosphate was steadily maintained in a narrow range throughout RCA-CRRT days (Table II, Figure 3).
7.43 (7.40-7.47)
Blood HCO3–, mmol/l
25.3 (23.8-26.6)
0.9 (-0.7 to 2.4)
Serum phosphate, mmol/l
1.2 (0.97-1.45)
Systemic Ca2+, mmol/l
1.16 (1.12-1.21)
Total serum calcium, mmol/l
2.3 (2.18-2.41)
Calcium ratio
1.97 (1.87-2.07)
Circuit Ca2+, mmol/l
0.42 (0.36-0.48)
Serum Na+, mmol/l
134 (133-136)
Serum K+, mmol/l
4.2 (4-4.4)
Serum Mg2+, mmol/l
0.79 (0.73-0.84)
CaCl2 infusion, mmol/h
2.2 (1.9-2.6)
KCl infusion, mmol/h
2 (0-4)
Magnesium sulphate infusion, g/24h
3 (3-3)
Phosphate supplementation need, n (%)
20.8% (10/48)
Supplementation (g/day)
1.05±2.04
At some times during CRRT, only 10 out of 48 patients (20.8%) received a low amount of phosphate supplementation (FDP; Esafosfina® 1.05±2.04 g/day) for mild (n=7) to moderate (n=3) hypophosphatemia. Considering all patients, only 33 out of 513 serum phosphorus determinations met the criteria for mild (n=24) to moderate (n=9) hypophosphatemia.
[1] Santiago MJ, López-Herce J, Urbano J et al. Hypophosphatemia and phosphate supplementation during continuous renal replacement therapy in children. Kidney international 2009 Feb;75(3):312-6
[2] Broman M, Carlsson O, Friberg H et al. Phosphate-containing dialysis solution prevents hypophosphatemia during continuous renal replacement therapy. Acta anaesthesiologica Scandinavica 2011 Jan;55(1):39-45 (full text)
[3] Chua HR, Baldwin I, Ho L et al. Biochemical effects of phosphate-containing replacement fluid for continuous venovenous hemofiltration. Blood purification 2012;34(3-4):306-12
[4] Morabito S, Pistolesi V, Tritapepe L et al. Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid-base status and phosphate supplementation needs. BMC nephrology 2013 Oct 25;14:232 (full text)
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