Development of a nomogram for the prediction of acute kidney injury after liver transplantation: a model based on clinical parameters and postoperative cystatin C level

Figures & data

Figure 1. Flow diagram of patient enrolment. Abbreviations: LT: liver transplantation; AKI: acute kidney injury.

Table 1. Characteristics of study population.

Characteristics	Total (n = 120)	AKI (n = 58)	No-AKI (n = 62)	p-Value
Demographic data
Age (years)	53 (10)	53 (11)	52 (10)	0.581
Sex, male (N, %)	96 (80%)	45 (77.6%)	51 (82.3%)	0.523
BMI (kg/m^2)	24.48 (3.57)	24.64 (3.76)	24.33 (3.42)	0.644
Primary liver disease
Liver cancer (N, %)	64 (53.3%)	28 (48.3%)	36 (58.1%)	0.283
Liver failure (N, %)	40 (33.3%)	24 (41.4%)	16 (25.8%)	0.071
Liver complications
Encephalopathy (N, %)	25 (20.8%)	17 (29.3%)	8 (12.9%)	0.027*
Ascites (N, %)	65 (55.1%)	29 (50.9%)	36 (59%)	0.374
Baseline medical status
Coronary heart diseases (N, %)	4 (3.3%)	2 (3.2%)	2 (3.2%)	0.985
Hypertension (N, %)	20 (16.7%)	12 (20.7%)	8 (12.9%)	0.253
Diabetes mellitus (N, %)	22 (18.3%)	10 (17.2%)	12 (19.4%)	0.817
Biliary tract disease (N, %)	2 (1.7%)	1 (1.7%)	1 (1.6%)	0.977
Hepatorenal syndrome (N, %)	2 (1.7%)	2 (3.4%)	0 (0%)	0.141
Preoperative infections (N, %)	28 (23.3%)	16 (27.6%)	12 (19.4%)	0.287
Child–Pugh classification
I	30 (25.4%)	14 (24.1%)	16 (26.7%)	0.003*
II	38 (32.2%)	11 (19%)	27 (45%)
III	50 (42.4%)	33 (56.9%)	17 (28.3%)
MELD score	10 (6,19)	11 (7,23)	9 (6,14)	0.097
Preoperative laboratory data
Serum creatinine (μmol/L)	64 (24)	65 (32)	62 (13)	0.434
ALT (U/L)	32 (23, 64)	32 (22, 68)	32 (23, 57)	0.684
AST (U/L)	51 (31, 94)	52 (31, 120)	49 (31, 77)	0.297
TB (μmol/L)	47 (20, 212)	71 (28, 271)	36 (20, 105)	0.023*
Na^+ (mmol/L)	138 (134, 141)	139 (134, 141)	138 (134, 140)	0.548
Intraoperative details
Cold ischaemia time (h)	5 (4, 5.5)	5 (4.2, 5.3)	5 (4,5. 85)	0.46
Anhepatic phase (min)	66 (14)	69 (13)	63 (13)	0.015*
Surgical approach, classic (N, %)	80 (74.1%)	39 (69.6%)	41 (78.8%)	0.275
Operative time (h)	7.55 (1.2)	8.02 (1.20)	7.14 (0.99)	<0.001*
Intraoperative bleeding (mL)	1200 (850, 1800)	1500 (1000, 2500)	1000 (700, 1600)	0.002*
Blood product transfusions (mL)	1600 (800, 000)	1600 (800, 2400)	1200 (800, 2000)	0.02*
Intraoperative fluid balance (mL)	4400 (3450, 5400)	4840 (1863.24)	3695 (1871)	0.002*
Intraoperative hypotension (N, %)	54 (45.4%)	33 (57.9%)	21 (33.9%)	0.009*
Intraoperative hypotension time (min)	0 (0,15)	10 (0,20)	0 (0,9)	0.005*
Intraoperative urine output (mL)	1195 (938, 1500)	1175 (840, 1450)	1280 (1000, 1530)	0.048*
Postoperative laboratory data
Lactic acid after surgery (mmol/L)	2.86 (2,4.09)	3.57 (2.27, 4.62)	2.53 (1.91, 3.36)	0.007*
ALT after surgery (U/L)	480 (303, 719)	558 (324, 893.5)	460 (264, 590)	0.054
ALT 7 days after surgery (U/L)	88 (56, 188)	110 (68, 260)	73 (53, 117)	0.028*
Highest ALT after surgery (U/L)	514 (346, 819)	675 (357, 958)	484 (266, 741)	0.020*
AST after surgery (U/L)	954 (564, 1538)	1219 (572, 2023)	905 (565, 1387)	0.045*
AST 7 days after surgery (U/L)	36 (22, 67)	50 (28, 95)	30 (19, 43)	0.002*
Highest AST after surgery (U/L)	1049 (656, 1674)	1400 (781,2613)	951 (584, 1495)	0.003*
TB after surgery (μmol/L)	68 (43, 136)	80 (49, 150)	58 (33, 96)	0.008*
TB 7 days after surgery (μmol/L)	46 (26, 96)	59 (38, 106)	34 (21, 66)	0.005*
Highest TB after surgery (μmol/L)	86 (48, 161)	117(60, 208)	58 (40, 126)	0.001*
Postoperative parameter
EAD (N, %)	25 (20.8%)	19 (32.8%)	6 (9.7%)	0.002*
ARDS (N, %)	32 (33.7%)	26 (51%)	6 (13.6%)	<0.001*
Duration of mechanical ventilation (h)	24 (13, 48)	39 (18, 73)	23 (12, 36)	0.001*
Re-intubation (N, %)	18 (15.0%)	12 (20.7%)	6 (9.7%)	0.142
Shock (N, %)	19 (16.1%)	15 (26.3%)	4 (6.6%)	0.001*
Infection (N, %)	77 (65.8%)	45 (78.9%)	32 (53.3%)	0.002*
RRT (N, %)	8 (6.7%)	8 (13.8%)	0 (0%)	0.002*
Duration of ICU stay (days)	4 (3,5)	4 (3,5)	3 (2,4)	<0.001*
Died in hospital (N, %)	10(8.3%)	7(12.1%)	3(4.8%)	0.195

Normally distributed continuous variables were displayed as mean ± SD; non-normally distributed continuous variables were displayed as median and IQR. Abbreviations: BMI: body mass index; MELD: Model for End-Stage Liver Disease; ALT: alanine aminotransferase; AST: aspartate aminotransferase; TB: serum total bilirubin; EAD: early allograft dysfunction; ARDS: acute respiratory distress syndrome; RRT: renal replacement therapy; ICU: intensive care unit.

*p-Value <0.05.

Figure 2. Novel biomarkers for AKI after LT. (A) serum cystatin C concentration, (B) serum NGAL concentration, (C) serum endostatin concentration and (D) serum MIF concentration. Abbreviations: AKI: acute kidney injury; NGAL: neutrophil gelatinase-associated lipocalin; MIF: macrophage migration inhibition factor; PRE: preoperative; POS: postoperative. ns: not statistically significant, ***p-value < 0.001.

Figure 3. The forest plot of univariable logistic regression analysis for the predictors of AKI after LT. Abbreviations: OR: odds ratio; 95% CI (OR): 95% confidence interval of OR; TB: serum total bilirubin; ALT: alanine aminotransferase; AST: aspartate aminotransferase; EAD: early allograft dysfunction; ARDS: acute respiratory distress syndrome. *p-Value < 0.05.

Figure 4. The ROC curves of two models and postoperative cystatin C level. (a) The model showing the area under the ROC curve (AUC) was 0.815 [95% CI: 0.737–0.894]. (b) Postoperative cystatin C level, AUC was 0.721 (95% CI: 0.629–0.813). (c) The model only with clinical factors, AUC was 0.770 (95% CI: 0.682–0.858). Abbreviations: TPR: true positive rate; FPR: false positive rate.

Table 2. Multivariate logistic regression model for the prediction of post-LT AKI.

Variables	OR (95% CI)	p-Value
Operative time (h)	1.728 (1.121–2.663)	0.013
Intraoperative hypotension (N, %)	3.235 (1.316–7.952)	0.011
Postoperative cystatin C (μg/L)	1.002 (1.001–1.004)	0.005
Shock (N, %)	4.002 (0.893–17.945)	0.070

Abbreviations: OR: odds ratio; CI: confidence interval.

Figure 5. Development of a nomogram for the prediction of post-LT AKI.

Figure 6. Decision curve analysis (A) and calibration curves (B) of the nomogram for the prediction of post-LT AKI.

Figure 7. Correlation between postoperative cystatin C level, intraoperative parameters and postoperative laboratory results. The values are presented as Spearman’s r of 120 runners for operative cystatin C. Colormap with range between 1 and −1 and blue for the largest value and red for the smallest value. Abbreviations: ALT: alanine aminotransferase; AST: aspartate aminotransferase; TB: serum total bilirubin.

Data availability statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.