Preventing CRRT-induced hypophosphatemia by using a phosphate-containing CRRT solution in the setting of Regional Citrate Anticoagulation


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.

Table I – Clinical characteristics of the patients (N=48) at the start of CRRT [median (IQR) or %].


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%)


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).

Table II – Acid-Base status, electrolytes and supplementations during RCA-CRRT (CVVH/CVVHDF) [median(IQR)].

pH, units

7.43 (7.40-7.47)

Blood HCO3, mmol/l

25.3 (23.8-26.6)

Base Excess

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)


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.


  • The use of a phosphate-containing CRRT solution, accounting for about 50-60% of CRRT dose in the setting of RCA-CVVH or RCA-CVVHDF, allowed to prevent CRRT-induced phosphate depletion in most of the patients minimizing the need for phosphate supplementation.
  • Phosphorus levels were maintained in a progressively narrower near normal range throughout RCA-CVVH days.