Participants
The ethical committee of the First Peoples’ Hospital approved this study, and it was registered with the US National Institutes of Health Clinical Trials Register (NCT02536027). Patients or their next of kin signed informed consent forms of their own accord after being fully informed of all the relevant details of the study. All patients with septic acute kidney injury (SAKI) undergoing CVVH in the general ICU were consecutively enrolled in the study during the period from August 1, 2014, to December 31, 2015.
Inclusion and exclusion criteria
Adult (>18 years) patients with SAKI undergoing continuous renal replacement therapy (CRRT) were assessed for inclusion. The urine output and SCr parameters were used from the 2012 Kidney Disease Improving Global Outcomes criteria [14], which were based on the Risk, Injury, Failure, Loss, End-stage/Acute Kidney Injury Network definitions. These included an absolute increase in SCr of ≥26.4 μmol/L over 48 h, a percentage increase in SCr of ≥50 % from baseline over the previous 7 days, or urine output ≤0.5 mL/(kg · h) for a period of ≥6 h. Furthermore, based on the diagnostic criteria of the 2001 International Sepsis Definition Conference [15], sepsis was defined as a systemic, deleterious host response to infection resulting in a systemic inflammatory response syndrome characterized by two or more of the following (definitions in parentheses): hypothermia or fever (body temperature <36 °C or >38.5 °C), tachycardia (>90 beats/min), tachypnea (>20 breaths/min or PaCO2 < 32 mm Hg on mechanical ventilation), leukocytosis (>12,000/mm3), leukopenia (<4000/mm3), or increased immature band forms (>10 %).
The following patients were excluded: (1) those with end-stage renal disease; (2) those with a history of renal transplant; (3) those with cancer; (4) those with acquired immunodeficiency syndrome; and (5) who had undergone high-dose steroid treatment.
CRRT procedure
CVVH was performed with a Fresenius 4008S CRRT plus machine (Fresenius Medical Care, Homburg, Germany) after establishing venous access in the femoral or jugular vein with an 11- to 14-Fr double-lumen catheter. The hemodiafilter membrane used was Fresenius AV600S (Fresenius, Homburg, Germany). In principle, patients were hemofiltered at a blood flow rate of 180–220 mL/min in 2 L postdilution CVVH mode. An initial dose of heparin 400–1000 IU/h was given, with adjustment of the heparin infusion based on patient coagulation function. Anticoagulation also included a postfilter infusion of protamine, with a ratio of heparin 100 IU to protamine 1 mg.
Data collection
Baseline patient data (age, gender, etiological factors, and underlying diseases) were collected on patient admission to the ICU. The white blood cell (WBC) count, C-reactive protein (CRP), and procalcitonin (PCT) levels were obtained at CVVH initiation. Clinical data necessary to calculate sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scores were also collected.
Measurement of plasma NGAL
Prefilter, postfilter, and ultrafiltrate samples were obtained at the beginning of CRRT and again after 2, 4, 8, and 12 h (T0, T2h, T4h, T8h, and T12h, respectively). The NGAL level was measured using an enzyme-linked immunosorbent assay (Lipocalin2/NGAL Duoset, DY1757, R&D Systems, UK) with a measurable range of 20–3000 ng/mL.
Calculation
Based on the mass conservation principle, NGAL total mass removal rate (Mtr), mass adsorption rate (Mad), sieving coefficient (SC), and plasma clearance (PC) were calculated using the following formulas [12]:
$$ {Q}_{\mathrm{i}}={Q}_{\mathrm{b}}\times \kern0.5em \left(1\ \hbox{--}\ \mathrm{H}\mathrm{c}\mathrm{t}\right) $$
$$ {Q}_{\mathrm{o}}={Q}_{\mathrm{i}} $$
$$ {M}_{\mathrm{i}}={Q}_{\mathrm{i}}\times {C}_{\mathrm{i}} $$
$$ {M}_{\mathrm{o}}={Q}_{\mathrm{o}}\times {C}_{\mathrm{o}} $$
$$ {M}_{\mathrm{uf}}={Q}_{\mathrm{uf}}\times {C}_{\mathrm{uf}} $$
$$ {M}_{\mathrm{tr}}={M}_{\mathrm{i}}\hbox{--} {M}_{\mathrm{o}} $$
$$ {M}_{\mathrm{ad}}={M}_{\mathrm{tr}}\hbox{--} {M}_{\mathrm{uf}} $$
$$ \mathrm{P}\mathrm{C} = {M}_{\mathrm{tr}}/{C}_{\mathrm{i}} $$
$$ \mathrm{S}\mathrm{C} = 2 \times {C}_{\mathrm{uf}}/\left(C+{C}_{\mathrm{o}}\right) $$
Abbreviations:
Ci: Concentration in inlet plasma before addition of replacement fluid (ng/mL)
Co: Concentration in outlet plasma (ng/mL)
Cuf: Concentration in the ultrafiltrate (ng/mL)
Qb: Inlet blood flow rate (mL/min)
Qi: Inlet plasma flow rate (mL/min)
Qo: Outlet plasma flow rate (mL/min)
Quf: Ultrafiltration flow rate (mL/min)
Mi: Mass inlet rate (ng/min)
Mo: Mass outlet rate (ng/min)
Muf: Mass ultrafiltration rate (ng/min)
Mtr: Mass removal rate (ng/min)
Mad: Mass adsorption rate (ng/min)
RF: Replacement fluid flow rate (ng/min)
SC: Sieving coefficient
Statistical analysis
Continuous variable data with normal distributions were provided as mean ± standard deviation (SD). Non-normally distributed continuous variable data were presented as median (25th, 75th percentiles). The Kruskal–Wallis test was used to compare measured and calculated data. Qualitative variable data were expressed as frequencies (n) and percentages (%). Statistical analyses were conducted using IBM SPSS 19.0 (SPSS; Chicago, IL, USA), and a P value of <0.05 was considered statistically significant.
