Development and External Verification of a Nomogram for Patients with Persistent Acute Kidney Injury in the Intensive Care Unit

Figures & data

Table 1 Clinicopathological Characteristics of All Patients

Characteristics	Training Set (n=5237)			Internal Validation Set (n=2254)			External Validation Set (n=2648)
	Persistent AKI	Transient AKI	P value	Persistent AKI	Transient AKI	P value	Persistent AKI	Transient AKI	P value
N	1891	3346		812	1442		705	1943
Age, years	64.8±16.1	66.4±15.3	0.001	69.1±15.4	64.2±15.9	0.004	62.3±15.0	65.6±15.1	<0.001
Gender, male, n(%)	1166(61.7)	2024(60.5)	0.404	466(57.4)	852(59.1)	0.433	393(55.7)	1037(53.4)	0.279
Weight, kg	86.0±26.1	86.0±24.6	0.953	85.2±23.0	84.6±23.9	0.502	87.0±29.8	87.6±29.3	0.633
Ethnicity, n(%)			0.404			0.442			0.377
White	1171(61.9)	2130(63.7)		524(64.6)	955(66.2)		556(78.9)	1553(79.9)
Black	260(13.7)	453(13.5)		105(12.9)	196(13.6)		94(13.3)	223(11.5)
Other	460(24.3)	763(22.8)		182(22.4)	291(20.2)		55(7.8)	167(8.6)
AKI stage			<0.001			0.004			<0.001
Stage I	1363(72.1)	2670(79.8)		599(73.8)	1150(79.8)		472(67.0)	1627(83.7)
Stage II	257(13.6)	395(11.8)		115(14.2)	153(10.6)		82(11.6)	103(5.3)
Stage III	271(14.3)	281(8.4)		98(12.1)	139(9.6)		151(21.4)	213(11.0)
Comorbidities, n(%)
Hypertension	814 (43.0)	1615 (48.3)	<0.001	329 (59.5)	659 (45.7)	<0.001	387 (54.9)	1115 (57.4)	0.039
Diabetes	677 (35.8)	1232 (36.8)	0.137	316 (38.9)	479 (33.2)	<0.001	277 (39.3)	741 (38.1)	0.293
CAD	434 (23.0)	621 (18.6)	<0.001	163 (20.1)	282 (19.6)	0.554	58 (8.2)	191 (9.1)	0.012
Cerebrovascular disease	290 (15.3)	521 (15.6)	0.651	117 (14.4)	197 (13.7)	0.327	75 (10.6)	224 (11.5)	0.198
COPD	128 (6.8)	216 (6.5)	0.380	57 (7.0)	111 (7.7)	0.238	101 (14.3)	344 (17.7)	<0.001
CKD	689 (36.4)	982 (29.3)	<0.001	316 (38.9)	427 (29.6)	<0.001	224 (31.8)	427 (22.0)	<0.001
Cancer	283 (15.0)	533 (15.9)	0.064	118 (14.5)	211 (14.6)	0.897	84 (11.9)	280 (14.4)	0.001
Severity of illness, points
GCS score	14.1±2.3	14.3±1.8	0.001	14.0±2.1	14.6±1.9	0.034	12.6±3.5	13.1±3.0	0.002
SOFA score	4.5±2.5	4.0±2.2	<0.001	5.3±2.5	4.2±2.5	0.025	8.1±7.2	6.9±6.3	<0.001
OASIS score	38.3±9.6	38.3±9.5	0.736	37.9±9.7	38.3±9.6	0.348	30.3±11.8	29.5±10.7	0.144
APSIII score	69.7±28.0	68.3±27.2	0.088	66.5±26.0	68.8±28.5	0.053	71.2±27.7	63.4±26.1	<0.001
Vital signs
Heart rate, bpm	107.8±22.9	107.8±21.8	0.960	108.4±22.8	106.6±22.0	0.061	109.1±28.4	107.1±27.2	0.094
SBP, mmHg	148.2±24.2	148.6±24.4	0.574	150.3±25.8	147.8±24.8	0.026	129.0±34.4	127.5±33.2	0.300
DBP, mmHg	86.4±20.8	86.5±20.9	0.862	88.6±22.9	86.4±20.2	0.018	67.1±22.2	67.0±21.1	0.952
MAP, mmHg	107.1±30.8	106.7±30.0	0.640	108.3±30.1	107.0±30.6	0.330	86.1±26.7	85.3±26.4	0.503
Respiratory rate, bpm	28.9±6.7	29.0±6.9	0.696	29.1±6.6	28.8±6.8	0.264	26.0±9.7	25.8±9.1	0.576
Temperature, °C	36.1±0.9	36.2±0.8	0.072	36.1±1.0	36.2±0.8	0.101	37.6±1.3	37.5±1.3	0.175
SpO2, %	99.6±1.4	99.6±0.9	0.072	99.6±1.0	99.6±1.0	0.787	96.7±5.5	96.8±3.9	0.540
Laboratory results
WBC, × 10^9/L	16.6±5.7	16.5±5.5	0.800	16.6±6.5	16.4±4.6	0.595	18.1±6.1	18.3±5.4	0.697
Hemoglobin, g/dL	9.4±2.2	9.7±2.2	<0.001	9.2±2.2	9.8±2.2	0.028	9.4±2.2	9.8±2.3	<0.001
Platelets, × 10^9/L	212.5±80.6	224.7±84.8	0.001	218.8±89.4	220.2±89.2	0.798	228.6±88.2	243.8±91.1	0.008
RBC, × 10^12/L	3.1±0.8	3.2±0.8	<0.001	3.0±0.8	3.7±0.8	0.021	3.2±0.7	3.4±0.7	<0.001
Hematocrit, %	34.2±6.5	34.5±6.5	0.003	34.1±6.4	34.9±6.6	0.036	34.2±7.3	36.1±7.0	<0.001
Neutrophils, × 10^9/L	12.4±7.0	12.3±6.2	0.867	12.7±7.6	12.4±6.9	0.533	13.6±5.2	13.0±6.5	0.574
Lymphocytes, × 10^9/L	7.1±3.7	7.5±3.4	0.578	5.7±2.5	6.8±2.5	0.281	8.3±2.5	9.1±3.1	0.091
Monocytes, × 10^9/L	2.6±2.0	2.3±2.0	0.284	2.4±2.1	2.0±2.2	0.665	3.4±2.0	3.0±2.1	0.119
MCH, pg	29.8±2.7	29.7±2.6	0.202	29.7±2.8	30.0±2.7	0.170	29.6±2.5	29.4±2.8	0.261
MCHC, g/L	32.3±1.7	32.4±1.6	0.224	32.2±1.7	32.4±1.7	0.011	32.7±1.5	32.6±1.5	0.484
RDW, %	15.4±2.4	15.1±2.3	0.001	15.4±2.4	15.1±2.2	0.010	17.3±4.0	16.5±2.7	<0.001
AST, U/L	548.9±78.0	281.4±50.7	<0.001	450.5±57.3	335.3±71.6	0.100	104.2±45.9	93.1±38.8	0.071
ALT, U/L	311.2±62.1	184.4±56.4	<0.001	235.0±82.1	198.1±79.0	0.294	74.4±31.3	74.1±27.5	0.967
Albumin, g/dL	3.1±0.5	3.2±0.5	<0.001	3.1±0.5	3.2±0.5	<0.001	2.7±0.7	3.0±0.7	<0.001
Total bilirubin, mmol/L	3.5±1.3	2.5±1.5	<0.001	3.0±1.0	2.5±1.2	0.016	2.1±1.8	1.6±1.3	<0.001
Anion gap, mEq/L	18.6±6.1	18.0±5.3	<0.001	18.5±6.0	17.7±5.3	0.001	14.8±5.3	14.9±5.3	0.626
Bicarbonate, mEq/L	23.5±4.6	23.8±4.6	0.011	23.6±4.7	24.0±4.4	0.024	24.7±5.1	25.0±5.2	0.138
BUN, mg/dL	39.8±8.2	36.1±6.4	<0.001	40.0±8.0	36.9±7.6	0.010	48.0±7.2	43.5±6.0	0.001
Baseline creatinine, mg/dL	1.6±1.6	1.6±1.8	0.088	1.7±1.5	1.6±1.7	0.404	1.7±1.5	1.5±1.3	<0.001
Glucose, mg/dL	187.3±62.1	189.2±61.5	0.559	191.7±66.1	184.2±63.5	0.147	208.2±58.9	208.5±55.9	0.958
ALP, U/L	110.1±45.1	100.1±45.7	0.002	110.0±55.2	102.3±45.6	0.105	143.8±58.4	124.1±45.1	0.001
Lactate, mmol/L	3.9±1.0	3.3±1.5	<0.001	4.0±1.1	3.2±1.3	<0.001	3.7±1.8	3.4±1.5	0.005
Sodium, mmol/L	139.8±5.5	139.8±5.4	0.956	140.0±5.4	139.7±5.6	0.440	139.7±5.6	140.1±6.3	0.095
Potassium, mmol/L	4.9±1.0	4.8±0.9	0.009	4.8±0.9	4.8±0.9	0.158	4.7±0.9	4.7±0.9	0.995
Calcium, mg/dL	8.6±1.1	8.6±0.9	0.295	8.6±1.0	8.6±1.0	0.226	8.2±0.9	8.2±0.8	0.396
Chloride, mmol/L	105.9±7.3	106.0±7.0	0.485	105.6±6.9	105.6±7.2	0.996	106.2±7.3	106.9±7.7	0.029
INR	1.9±1.6	1.7±1.2	<0.001	1.8±1.3	1.7±1.1	0.077	1.8±1.1	1.9±1.4	0.367
Prothrombin time, s	20.7±5.3	18.6±4.7	<0.001	19.6±5.2	18.7±6.0	0.099	20.0±7.4	20.4±8.3	0.427
APTT, s	51.6±15.9	49.0±16.7	0.007	52.2±14.4	48.3±13.0	0.009	42.4±16.3	41.3±15.5	0.116
PH	7.4±0.1	7.4±0.1	0.461	7.4±0.1	7.4±0.1	0.222	7.3±0.1	7.3±0.1	0.982
PO2, mmHg	242.1±71.0	236.6±68.6	0.054	238.5±67.3	236.5±70.0	0.723	108.2±63.9	106.9±66.1	0.685
PCO2, mmHg	47.9±13.4	47.6±13.0	0.383	49.1±13.3	47.8±12.0	0.021	40.2±11.9	40.2±13.3	0.990
PaO2/FiO2 ratio	214.7±103.7	218.9±95.0	0.147	208.9±98.0	222.8±99.8	0.001	205.7±24.4	204.8±13.7	0.214
Base excess, mmol/L	−0.1±1.5	0.1±1.3	0.060	0.1±1.7	0.2±1.1	0.519	1.0±1.2	1.4±1.8	0.055
Interventions first day
RRT first day, n(%)	269 (14.2)	291 (8.7)	<0.001	126 (15.5)	129 (8.9)	<0.001	176 (25.0)	125 (6.4)	<0.001
MV first day, n(%)	1271 (67.2)	2156 (64.4)	0.042	538 (66.3)	900 (62.4)	<0.001	334 (47.4)	715 (36.8)	<0.001
Input first day, mL	10950(5470, 18,910)	10,427(5100, 17,419)	0.003	11,045(4646, 19,247)	9982(4698, 16,844)	0.001	2154(0, 9043)	1906(0, 9917)
Output first day, mL	1070(450, 1935)	1298(731, 2095)	<0.001	1078(470, 1899)	1356(737, 2221)	<0.001	1200(106, 3687)	1550(200, 4350)
Length of hospital, days	14.9(8.7, 23.7)	13.1(8.2, 22.2)	0.026	14.7(8.5, 23.3)	12.8(7.7, 21.1)	0.033	18.5(12.5, 27.4)	14.1(9.0, 21.4)	<0.001
Hospital mortality, n (%)	463 (24.5)	440 (12.8)	<0.001	181 (22.3)	202 (14.0)	<0.001	178 (25.2)	272 (14.0)	<0.001
Length of ICU, days	6.2(3.0, 12.1)	5.3(2.7, 10.8)	<0.001	5.9 (2.9, 12.0)	5.3 (2.9, 10.1)	0.045	9.8 (5.3, 14.8)	5.3 (2.8, 10.4)	<0.001
ICU mortality, n (%)	329 (17.4)	261 (7.8)	<0.001	128 (15.8)	117 (8.1)	<0.001	131 (18.6)	143 (15.2)	<0.001

Notes: For all continuous covariates except for input and output first day, length of hospital and length of ICU, the mean values and standard deviations are reported.

Abbreviations: AKI, acute kidney injury; CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; CKD, chronic kidney disease; GCS, Glasgow; SOFA, sequential organ failure assessment; OASIS, Oxford acute severity of illness score; APSIII, acute physiology score III; SBP, systolic pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; WBC, white blood cell; RBC, red blood cell; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; RDW, red cell distribution width; AST, aspartate aminotransferase; ALT, alanine aminotransferase; BUN, blood urea nitrogen; ALP, alkaline phosphatase; INR, international normalized ratio; APTT, activated partial thromboplastin time; PO2, partial pressure of oxygen; PCO2, partial pressure of carbon dioxide; MV, mechanical ventilation; RRT, renal replacement therapy; ICU, intensive care unit.

Figure 1 The flow chart of this study.

Figure 2 Survival analyses comparing between persistent and transient acute kidney injury patients in the training cohort (A), internal validation cohort (B) and external validation cohort (C).

Figure 3 Selection of significant indexes associated with persistent acute kidney injury patients. (A) LASSO Cox regression model. (B) Support vector machine model. (C) The overlapping features identified by the two models.

Figure 4 The predictive nomogram for persistent acute kidney injury.

Figure 5 Calibration and clinical utility of the predictive nomogram. The predictive nomogram exhibited a high correlation between the actual probability and predicted probability in the training cohort (A), internal validation cohort (B) and external validation cohort (C). Decision curves analysis for the predictive nomogram to predict the persistent acute kidney injury in the training cohort (D), internal validation cohort (E) and external validation cohort (F).