Recipient functional status impacts on short and long-term intestinal transplant outcomes in United States adults

Table 1 Karnofsky Performance Status rating and categories for patient functionality

Functional level	Score range (%)	Patient capabilities and care requirements
High function	80-100	100%: Fully active, no symptoms of disease
		90%: Minor symptoms, fully active
		80%: Some symptoms, normal activity with effort
Moderate function	50-70	70%: Manages self-care, limited activity
		60%: Occasionally needs help but manages most personal needs
		50%: Requires regular assistance and medical care
Low function	0-40	40%: Disabled, requires special assistance
		30%: Severely disabled, frequent hospital care
		20%: Very ill, active medical intervention needed
		10%: Terminally ill, rapid disease progression
		0%: Deceased

Table 2 Comparison of patient outcomes by functional status categories, n (%)/mean ± SD

	Functional status at transplant
	Requires no assistance (n = 251)	Requires some assistance (n = 648)	Near death or severely disabled (n = 355)	Total (n = 1254)	P value
Gender					0.0341
Female	130 (51.8)	368 (56.8)	172 (48.5)	670 (53.4)
Male	121 (48.2)	280 (43.2)	183 (51.5)	584 (46.6)
Age (Year)					0.222
n	251	648	355	1254
Mean (SD)	40.9 (14.18)	42.7 (13.04)	42.1 (12.79)	42.1 (13.21)
Median	41.0	44.0	42.0	43.0
Range	18.0-73.0	18.0-72.0	18.0-70.0	18.0-73.0
Race					0.791
Hispanic	22 (8.8)	49 (7.6)	31 (8.7)	102 (8.1)
Non-Hispanic Asian	3 (1.2)	11 (1.7)	5 (1.4)	19 (1.5)
Non-Hispanic Black	29 (11.6)	71 (11.0)	43 (12.1)	143 (11.4)
Non-Hispanic White	194 (77.3)	515 (79.5)	275 (77.5)	984 (78.5)
Other/Multiracial	3 (1.2)	2 (0.3)	1 (0.3)	6 (0.5)
Patients on life support					0.00402
No	242 (96.4)	602 (92.9)	317 (89.3)	1161 (92.6)
Yes	9 (3.6)	46 (7.1)	38 (10.7)	93 (7.4)
Sex match					0.161
No	125 (49.8)	288 (44.4)	177 (49.9)	590 (47.0)
Yes	126 (50.2)	360 (55.6)	178 (50.1)	664 (53.0)
Recipient total bilirubin at transplantation (mg/dL)					0.00062
n	249	644	354	1247
Mean (SD)	2.2 (5.36)	2.3 (4.57)	4.6 (8.44)	2.9 (6.15)
Median	0.8	0.8	1.1	0.9
Range	0.1-50.0	0.1-43.0	0.1-48.2	0.1-50.0
Serum creatinine at time of transplantation (mg/dL)					0.361
n	251	645	353	1249
Mean (SD)	1.0 (0.72)	1.1 (0.96)	1.2 (1.04)	1.1 (0.94)
Median	0.9	0.9	0.9	0.9
Range	0.3-7.6	0.3-10.1	0.1-9.0	0.1-10.1
Total ischemic time (sec)					0.0102
n	222	619	347	1188
Mean (SD)	6.9 (1.88)	7.5 (2.32)	7.5 (2.28)	7.4 (2.24)
Median	7.0	7.3	7.4	7.2
Range	1.0-11.8	0.4-31.5	0.9-31.7	0.4-31.7
Recipient's primary diagnosis					0.010411
Short gut syndrome	154 (19.8)	409 (52.5)	216 (27.7)	779 (62.1)
Functional bowel problem	27 (28.1)	51 (53.1)	18 (18.8)	96 (7.7)
Retransplant	4 (6.2)	39 (60.9)	21 (32.8)	64 (5.1)
Others	66 (21.0)	149 (47.3)	100 (31.7)	315 (25.1)
Donor age (years)					0.362
n	251	648	355	1254
Mean (SD)	22.4 (10.79)	21.1 (10.54)	21.3 (11.47)	21.4 (10.86)
Median	20.0	19.0	20.0	19.0
Range	4.0-56.0	2.0-52.0	1.0-59.0	1.0-59.0
Race match					0.431
No	119 (47.4)	278 (42.9)	152 (42.8)	549 (43.8)
Yes	132 (52.6)	370 (57.1)	203 (57.2)	705 (56.2)
Weight mismatch					0.00691
NA	4 (1.6)	7 (1.1)	0 (0.0)	11 (0.9)
No mismatch	170 (67.7)	397 (61.3)	201 (56.6)	768 (61.2)
Weight mismatch	77 (30.7)	244 (37.7)	154 (43.4)	475 (37.9)
History of diabetes					0.0821
Diabetes	21 (8.4)	68 (10.5)	49 (13.9)	138 (11.0)
Not diabetes	230 (91.6)	580 (89.5)	303 (86.1)	1113 (89.0)
Liver function					< 0.00011
Liver dysfunction	62 (24.9)	148 (23.0)	126 (35.6)	336 (26.9)
No dysfunction	187 (75.1)	496 (77.0)	228 (64.4)	911 (73.1)
Renal function					0.0381
No dysfunction	244 (97.2)	617 (95.7)	328 (92.9)	1189 (95.2)
Renal dysfunction	7 (2.8)	28 (4.3)	25 (7.1)	60 (4.8)
HLA mismatch					0.201
High HLA mismatch	208 (87.0)	522 (82.6)	293 (85.7)	1023 (84.3)
Low HLA mismatch	31 (13.0)	110 (17.4)	49 (14.3)	190 (15.7)
Recipient's weight (kg)					0.0572
n	247	641	355	1243
Mean (SD)	68.0 (17.35)	66.8 (17.16)	69.2 (17.83)	67.7 (17.41)
Median	65.8	64.0	66.8	65.1
Range	34.0-130.0	36.3-140.1	27.4-122.0	27.4-140.1
Calculated body mass index of recipients (kg/m2)					0.282
n	246	635	355	1236
Mean (SD)	23.9 (5.25)	23.4 (4.83)	23.9 (5.28)	23.7 (5.05)
Median	23.2	22.8	23.0	23.0
Range	15.0-40.6	15.1-41.9	15.1-44.2	15.0-44.2

¹Chi-Square P-value.

²Kruskal-Wallis P-value.

HLA: Human leukocyte antigen.

Table 3 Hazard ratios for functional status in transplant outcomes

Variable	Timepoints	Unadjusted HR			Adjusted HR1
Functional status		HR	95%CI	P value	HR	95%CI	P value
None (Ref.)	1 year	1.00			1.00
Moderate		1.03	0.84-1.28	0.77	1.10	0.90–1.37	0.36
Severe		1.24	0.99–1.57	0.066	1.56	1.23–1.98	0.00029
None (Ref.)	5 years	1.00			1.00
Moderate		1.03	0.83–1.27	0.78	1.09	0.89–1.36	0.38
Severe		1.27	1.00–1.61	0.042	1.58	1.24–2.00	0.00019

¹Adjusted hazard ratio is adjusted for recipient creatinine levels, era, weight mismatch between donor and recipient and age of donor.

HR: Hazard ratio.

Table 4 Hazard ratios for functional status in transplant outcomes for era 2005-2014

Variables	Timepoints	Unadjusted HR			Adjusted HR1
Functional status		HR	95%CI	P value	HR	95%CI	P value
None (Ref.)	1 year	1.00			1.00
Moderate		1.11	0.86-1.44	0.4247	1.09	0.84–1.41	0.52
Severe		1.63	1.20–2.23	0.002	1.64	1.19–2.24	0.002
None (Ref.)	5 years	1.00			1.00
Moderate		1.10	0.85–1.42	0.487	1.08	0.83–1.39	0.57
Severe		1.69	1.24–2.30	< 0.0001	1.70	1.24–2.32	< 0.0001

¹Adjusted hazard ratio is adjusted for recipient creatinine levels, race matching, weight mismatch between donor and recipient and age of donor.

HR: Hazard ratio.

Table 5 Hazard ratios for functional status in transplant outcomes for era 2014-2022

Variables	Timepoints	Unadjusted HR			Adjusted HR1
Functional status		HR	95%CI	P value	HR	95%CI	P value
None (Ref.)	1 year	1.00			1.00
Moderate		1.12	0.77–1.64	0.56	1.14	0.78–1.68	0.49
Severe		1.48	1.00–2.18	0.049	1.53	1.03–2.26	0.034
None (Ref.)	5 years	1.00			1.00
Moderate		1.11	0.76–1.62	0.59	1.13	0.77–1.66	0.54
Severe		1.48	1.00–2.19	0.046	1.53	1.04–2.26	0.035

¹Adjusted hazard ratio is adjusted for recipient creatinine levels, race matching, weight mismatch between donor and recipient and age of donor.

HR: Hazard ratio.

Table 6 Prognostic factors for survival in patients with decreased Karnofsky Performance Status undergoing intestinal transplantation

Variable	HR	95%CI	P value
Age	1.02	1.00-1.03	0.001
Race
Hispanic	1.21	0.66-2.23	0.53
Non-Hispanic Asian	1.20	0.287-4.98	0.81
Non-Hispanic Black	1.98	1.27-3.08	0.003
Other/Multiracial	2.77	0.38-20.46	0.32
Non-Hispanic White (Ref.)	1.00
Female gender	0.85	0.62-1.17	0.32
Donor age	1.02	1.01-1.04	0.008
Weight matched	0.78	0.55-1.09	0.008
ICU stay	2.13	1.36-3.38	0.001
Total bilirubin	1.02	1.01-1.03	0.04
Total ischemic time	1.05	0.99-1.10	0.09

ICU: Intensive care unit; HR: Hazard ratio.

Table 7 Post transplant survival probabilities of intestinal transplant recipients by changes in Karnofsky Performance Status after transplant, 95%CI

Time since transplant
Changes in KPS	6 months	1 year	2 years	3 years	5 years
Low KPS at transplant
Improvement by ≥ 50% (%)	100 (100-100)	97 (92-100)	60 (46-79)	51 (37-71)	31 (19-51)
Improvement by 10%–40% (%)	98 (96-100)	80 (71-90)	57 (46-70)	38 (28-52)	17 (9.9-29)
No improvement (%)	39 (26-60)	21 (11-41)	12 (4.8-30)	12 (4.8-30)	6.1 (1.6-23)
Intermediate KPS at transplant
Improvement by ≥ 30% (%)	98 (95-100)	95 (89-100)	75 (64-87)	61 (49-75)	48 (37-63)
Improvement by 10%–20% (%)	98 (95-100)	87 (80-94)	71 (63-81)	60 (51-70)	46 (37-57)
No improvement (%)	81 (74-89)	62 (53-72)	36 (28-47)	31 (24-42)	21 (14-30)
High KPS at transplant
Decrease by at least 10% (%)	81 (68-96)	48 (34-70)	26 (14-47)	16 (7.2-36)	13 (5.2-32)
Improvement by ≥ 0% (%)	100 (100-100)	96 (92-100)	76 (66-88)	65 (54-79)	47 (36-62)

KPS: Karnofsky Performance Status.

Table 8 Post transplant median survival times of intestinal transplant recipients by changes in Karnofsky Performance Status after transplant, 95%CI

Characteristic	Median survival
Low KPS at transplant
Improvement by = 50%	1146 (641-1971)
Improvement by 10%–40%	828 (651-1128)
No improvement	177 (136-243)
Intermediate KPS at transplant
Improvement by = 30%	1783 (945-2369)
Improvement by 10%–20%	1712 (1226-2132)
No improvement	533 (415-641)
High KPS at transplant
Decrease by at least 10%	304 (251-641)
Improvement by = 0%	1703 (1331-2556)

KPS: Karnofsky Performance Status.

Table 9 E-values for the hazard ratios of functional status in transplant outcomes at one year and five years

Functional Status	Timepoints	Adjusted HR1	E-value (point estimate)2	E-value (lower 95%CI)
Moderate	1 year	1.10	1.43	1
Severe		1.56	2.49	1.76
Moderate	5 years	1.09	1.40	1
Severe		1.58	2.54	1.79

¹Adjusted hazard ratio is adjusted for recipient creatinine levels, era, weight mismatch between donor and recipient and age of donor.

²The E-values indicate the minimum strength of association that an unmeasured confounder would need to have with both functional status and transplant outcomes, above and beyond the measured confounders, to fully explain away the observed associations.

HR: Hazard ratio.