Identification of successful CRRT discontinuation
There were no differences regarding different clinical and laboratory variables, including mean arterial blood pressure, PCT, and lactate, between the successful and unsuccessful CRRT discontinuation groups (Table 2). However, the TIMP-2*IGFBP7 levels at enrollment and at CRRT discontinuation were significantly lower in patients in which CRRT discontinuation was successful, whereas urine output was significantly increased in this patient group compared to patients in which CRRT discontinuation failed (Table 2). The CRRT treatment duration was significantly longer in patients who had a TIMP-2*IGFBP7 concentration > 2 (ng/ml)2/1000 at enrollment (9.93 ± 1.59 days versus 5.43 ± 0.66 days, P = 0.013).
Table 2
Comparison between successful CRRT discontinuation patients and unsuccessful CRRT discontinuation patients
Parameter | Successful discontinuation | Unsuccessful discontinuation | P |
MAP start CRRT (mmHg) | 78.19 ± 15.14 | 71.32 ± 14.42 | 0.130 |
Scr start CRRT (mg/dl) | 2.38 (1.46, 4.09) | 2.20 (1.33, 3.80) | 0.821 |
Urine output start CRRT (ml) | 525.00 (41.25, 1277.50) | 140.00 (27.50, 1147.50) | 0.590 |
Hb start CRRT (g/dl) | 109.00 (91.50, 118.00) | 101.00 (87.00, 117.00) | 0.300 |
Bilirubin start CRRT (mg/dl) | 0.80 (0.60, 1.90) | 0.90 (0.60, 3.10) | 0.428 |
PCT start CRRT (g/l) | 2.86 (0.62, 54.45) | 4.76 (0.75, 42.63) | 0.898 |
Lactate start CRRT (mmol/l) | 2.70 (1.70, 5.50) | 3.65 (1.40, 12.05) | 0.713 |
NC enrollment | 1.68 ± 2.15 | 4.02 ± 3.24 | 0.002 |
NC discontinue CRRT | 0.16 (0.06, 0.47) | 1.41 (0.27, 4.74) | 0.001 |
Urine output discontinue CRRT (mL) | 1500.00 (450.00, 3210.00) | 300.00 (92.50, 600.00) | 0.000 |
Hb discontinue CRRT (g/dl) | 96.00 (90.50, 104.50) | 92.50 (81.00, 108.75) | 0.321 |
Bilirubin discontinue CRRT (mg/dl) | 1.70 (0.55, 2.88) | 2.00 (0.70, 3.25) | 0.396 |
PCT discontinue CRRT (g/l) | 2.69 (0.88, 18.68) | 4.28 (1.32, 8.08) | 0.678 |
Lactate discontinue CRRT (mmol/l) | 1.30 (1.10, 1.70) | 1.90 (0.83, 6.83) | 0.187 |
CRRT treatment time (days) | 5.00 (3.00, 11.00) | 4.00 (2.25, 13.00) | 0.973 |
MAP: mean arterial pressure; SCr: serum creatinine, mg/dL to µmol/L, × 88.4; Hb: hemoglobin; PCT: procalcitonin; NC: NephroCheck; CRRT: continuous renal replacement. |
The successful CRRT discontinuation was higher in patients with a negative TIMP-2*IGFBP7 at enrollment (82.4%) compared to TIMP-2*IGFBP7-positive patients (52.9%; P = 0.057) (Table 3). However, the successful discontinuation (p = 0.001) and renal recovery rate (p = 0.009) was significantly higher in TIMP-2*IGFBP7-negative patients at CRRT discontinuation compared to TIMP-2*IGFBP7-positive patients at this time point (Table 3). Patients with a TIMP-2*IGFBP7 level < 2 (ng/ml)2/1000 at enrollment had a significantly higher successful CRRT discontinuation rate compared to patients with TIMP-2*IGFBP7 levels > 2(ng/ml)2/1000 at enrollment (72.5% versus 42.9%; p = 0.027) (Table 3). The CRRT treatment time was significant longer in patients with a TIMP-2*IGFBP7 concentration > 2(ng/ml)2/1000 at enrollment (9.93 ± 1.59 days VS. 5.43 ± 0.66 days, P = 0.013).
Table 3
TIMP-2*IGFBP7 predicted successful CRRT discontinuation and renal recovery
Variable | NC (+) enrollment | NC (-) enrollment | P | NC > 2 enrollment | NC < 2 enrollment | P | NC (+) stop CRRT | NC (-) stop CRRT | P |
Successful discontinuation | 52.9% | 82.4% | 0.057 | 42.9% | 72.5% | 0.027 | 61.1% | 88.5% | 0.001 |
Renal recovery | 41.2% | 58.8% | 0.418 | 21.4% | 62.5% | 0.003 | 44.4% | 69.2% | 0.009 |
NC: NephroCheck; NC (+): NephroCheck concentration > 0.3(ng/ml)2/1000; CRRT: continuous renal replacement. |
In univariate regression analysis, we found a significant association between successful discontinuation of CRRT and TIMP-2*IGFBP7-negative at CRRT stop, and TIMP-2*IGFBP7 concentration < 2 (ng/ml)2/1000 at enrollment.
When biomarker levels were measured at CRRT discontinuation, the risk of unsuccessful CRRT discontinuation was nearly 5 times higher in TIMP-2*IGFBP7-positive patients compared to TIMP-2*IGFBP7-negative patients (OR 4.879, 95% CI 1.055–22.565, P = 0.043), whereas the unsuccessful CRRT discontinuation was 3.5 times higher in patients with a TIMP-2*IGFBP7 concentration > 2 (ng/ml)2/1000 compared to patients with a TIMP-2*IGFBP7 concentration < 2 (ng/ml)2/1000 patients (OR 3.515, 95% CI 1.267–9.755, P = 0.016) when measured at enrollment.
When we substituted TIMP-2*IGFBP7-negative at CRRT stop and TIMP-2*IGFBP7 concentration < 2 (ng/ml)2/1000 at enrollment into the multivariate Cox regression formula, we found a significant association between successful discontinuation of CRRT and TIMP-2*IGFBP7-negative at CRRT stop (RR 0.436, 95% CI 0.202–0.939, P = 0.034).
There was no multiple collinearity in our model by calculating the variance inflation factor (VIF) cut-off below 10.
Among the 29 patients, who had an urine output less than 400 ml at the moment when CRRT was stopped, successful CRRT discontinuation rate increased form 0% in biomarker-positive at CRRT discontinuation to 88.9% in biomarker-negative patients (P = 0.000).
The AUC of the ROC curves for the TIMP-2*IGFBP7 concentrations at enrollment and discontinuation of CRRT for successful discontinuation of CRRT were 0.828 (95% CI 0.670–0.986; p = 0.003) and 0.814 (95% CI 0.658–0.969; p = 0.005) (Fig. 2), with an optimal cut-off of 1.73 (ng/ml)2/1000 and 0.90 (ng/ml)2/1000, sensitivity 0.89 and 0.56, specificity 0.68 and 0.97, positive predictive value of 80.0% and 89.2%, and negative predictive value of 60.6% and 85.7%. The AUC of the ROC curve of the final model, including TIMP-2*IGFBP7 concentrations at enrollment and discontinuation of CRRT, was 0.882 (95% CI 0.720–0.998, p = 0.001).
Identification of renal recovery
Patients in the renal recovery group had significantly lower TIMP-2*IGFBP7 levels at enrollment and at CRRT discontinuation as well as a significantly increased urine output compared to the patients in the non-recovery groups (Table 4). There were no differences regarding the other parameters between the recovery and non-recovery group (Table 4).
Table 4
Comparison between renal recovery patients and non-renal recovery patients
Parameter | Renal recovery | Non-renal recovery | P |
Number, % | 34, 46.6% | 39, 53.4% | |
Age (years) | 60.88 ± 19.82 | 63.10 ± 15.74 | 0.596 |
Sex (male, %) | 15, 44.1% | 16, 41% | 0.816 |
BMI (kg/m2) | 28.50 ± 9.63 | 26.18 ± 6.70 | 0.338 |
Hypertension | 22, 64.7% | 20, 51.3% | 0.343 |
Diabetes | 21, 61.8% | 21, 53.8% | 0.636 |
CKD | 19, 55.9% | 20, 51.3% | 1.000 |
MAP (mmHg) | 81.09 ± 25.04 | 79.13 ± 22.41 | 0.780 |
eGFR (ml/min/1.73 m2) | 75.71 ± 31.13 | 71.30 ± 36.10 | 0.604 |
SCr (mg/dl) | 0.92 (0.73, 1.31) | 0.98 (0.67, 1.64) | 0.802 |
MAP start CRRT (mmHg) | 75.00 ± 14.56 | 75.67 ± 15.84 | 0.883 |
Scr start CRRT (mg/dl) | 1.90 (1.23, 3.92) | 2.51 (1.57, 3.96) | 0.238 |
Urine output start CRRT (ml) | 625.00 (95.00, 1700.00) | 270.00 (20.00, 845.00) | 0.228 |
Hb start CRRT (g/dl) | 107.00 (91.00, 120.25) | 101.50 (91.50, 117.25) | 0.426 |
Bilirubin start CRRT (mg/dl) | 1.00 (0.60, 2.05) | 0.80 (0.60, 2.35) | 0.724 |
PCT start CRRT (g/l) | 4.50 (0.89, 103.80) | 3.29 (0.57, 46.34) | 0.514 |
Lactate start CRRT (mmol/l) | 2.35 (1.45, 4.18) | 4.40 (1.50, 13.20) | 0.082 |
NC enrollment | 1.51 ± 0.37 | 3.54 ± 0.51 | 0.002 |
NC discontinue CRRT | 0.15 (0.06, 0.47) | 0.36 (0.18, 1.73) | 0.019 |
Urine output discontinue CRRT (mL) | 1816.76 ± 264.33 | 940.00 ± 180.80 | 0.008 |
Hb discontinue CRRT (g/dl) | 98.50 (90.50, 111.25) | 95.00 (88.00, 103.00) | 0.135 |
Bilirubin discontinue CRRT (mg/dl) | 0.90 (0.50, 2.40) | 2.20 (0.75, 3.23) | 0.141 |
PCT discontinue CRRT (g/l) | 6.18 (1.11, 40.53) | 1.58 (0.65, 7.26) | 0.064 |
Lactate discontinue CRRT (mmol/l) | 1.35 (1.03, 1.60) | 1.40 (1.00, 4.00) | 0.265 |
CRRT treatment time (days) | 5.00 (2.75, 8.25) | 4.00 (3.00, 13.00) | 0.367 |
BMI: body mass index; CKD: chronic kidney disease; MAP: mean arterial pressure; eGFR: estimated glomerular filtration rate; SCr: serum creatinine, mg/dL to µmol/L, × 88.4; Hb: hemoglobin; PCT: procalcitonin; NC: NephroCheck; CRRT: continuous renal replacement. |
TIMP-2*IGFBP7-positive patients at enrollment had the same renal recovery rate as compared to TIMP-2*IGFBP7-negative patients (TIMP-2*IGFBP7-positive: 41.2% versus TIMP-2*IGFBP7-negative: 58.8%; p = 0.418). Renal recovery rate significantly increased form 21.4% in patients with a TIMP-2*IGFBP7 concentration > 2(ng/ml)2/1000 at enrollment to 62.5% in patients with a TIMP-2*IGFBP7 concentration < 2(ng/ml)2/1000 (P = 0.003), and from 44.4% in biomarker-positive patients at CRRT discontinuation to 69.2% in biomarker-negative patients (P = 0.009) (Table 3).
TIMP-2*IGFBP7 values were significantly higher in non-renal recovery patients compared to patients with renal recovery at enrollment and at the discontinuation of CRRT (Table 4).
The risk of non-renal recovery was 6 times higher when TIMP-2*IGFBP7 concentrations were > 2 (ng/ml)2/1000 at enrollment compared to TIMP-2*IGFBP7 concentrations < 2 (ng/ml)2/1000 patients (OR 6.111, 95% CI 2.021–18.481, P = 0.001). By calculating the VIF cut-off below 10, there was no multiple collinearity between TIMP-2*IGFBP7 concentration at enrollment and at discontinuation of CRRT.
Kaplan-Meier curves revealed that TIMP-2*IGFBP7 concentration < 2 (ng/ml)2/1000 at enrollment and TIMP-2*IGFBP7 turning negative were positively related to high renal recovery rate (Fig. 3).