Rethinking procurement biopsy in donors with normal renal function: A barrier to kidney utilization without survival benefit

Table 1 Demographic data for deceased donor kidneys recovered for transplantation with normal renal function, n (%)/median (interquartile rage)

Characteristics	Not biopsied (n = 84589)	Biopsied (n = 73776)	P value1
Kidney			< 0.001
Dual/en bloc	2266 (2.7)	1014 (1.4)
Left	41450 (49.0)	36067 (48.9)
Right	40873 (48.3)	36695 (49.7)
Age, years	30 (21-40)	53 (43-60)	< 0.001
Male	55255 (65.3)	43675 (59.2)	< 0.001
Blood type			< 0.001
A	30963 (36.6)	28175 (38.2)
AB	2901 (3.4)	2680 (3.6)
B	9576 (11.2)	8326 (11.3)
O	41144 (48.6)	34591 (46.9)
Height, cm	173 (163-180)	170 (163-178)	< 0.001
Weight, kg	75.7 (63.5-89.9)	82.0 (69.0-98.6)	< 0.001
History of hypertension	10295 (12.2)	38077 (51.6)	< 0.001
Diabetes mellitus	1709 (2.0)	13900 (18.8)	< 0.001
DCD	18677 (22.1)	33835 (45.9)	< 0.001
COD: CVA/stroke	11818 (14.0)	26300 (35.7)	< 0.001
Creatinine terminal	0.8 (0.6-1.0)	0.8 (0.6-1.0)	0.16
eGFR terminal, mL/minute/1.73 m2	115.7 (93.8-130.6)	100 (80.0-111.9)	< 0.001
KDRI	1.00 (0.88-1.17)	1.44 (1.21-1.71)	< 0.001
KDPI, %	20 (9-38)	62 (42-79)	< 0.001
Disposition			< 0.001
Transplanted	80876 (95.6)	52952 (71.8)
Discarded	3713 (4.4)	20824 (28.2)

¹Categorical variables were compared using χ² or Fisher’s exact test, as appropriate. Continuous variables were compared using the Wilcoxon rank-sum test.

DCD: Donor after circulatory death; COD: Cause of death; CVA: Cerebrovascular accident; eGFR: Epidermal growth factor receptor; KDRI: Kidney Donor Risk Index; KDPI: Kidney Donor Profile Index.

Table 2 Nonuse reasons for deceased donor kidneys with normal kidney function recovered for transplant, n (%)

	Not biopsied (n = 84589)	Biopsied (n = 73776)	P value1
Nonuse	3713 (4.4)	20824 (28.2)	< 0.001
Nonuse reason
Anatomy	870 (1.0)	1086 (1.5)	< 0.001
Biopsy	0 (0)	4371 (5.9)	< 0.001
Function	187 (0.2)	603 (0.8)	< 0.001
Medical social history	64 (0.1)	344 (0.5)	< 0.001
Infection	240 (0.3)	384 (0.5)	< 0.001
Too long preservation	74 (0.1)	263 (0.4)	< 0.001
Other	984 (1.2)	2340 (3.2)	< 0.001
No recipient found	1294 (1.5)	11433 (15.5)	< 0.001

¹Compared using χ² or Fisher’s exact test, as appropriate.

Table 3 Pathology of kidney biopsied and pathology reason for discard, n (%)

Pathology results of biopsy		Non used for biopsy reason
Total biopsies	n = 73776	4371 (5.9)
Combination of lesions
0%-5% GS/absent-mild vascular/absent-mild IFTA	60251 (81.7)	2346 (53.7)
0%-5% GS/moderate-severe IFTA	1979 (2.7)	357 (8.2)
0%-5% GS/moderate-severe vascular	3049 (4.1)	436 (10.0)
0%-5% GS /moderate-severe vascular/moderate-severe IFTA	1320 (1.8)	451 (10.3)
≥ 6% GS/absent-mild vascular/absent-mild IFTA	5771 (7.8)	507 (11.6)
≥ 6% GS /moderate-severe IFTA	360 (0.5)	77 (1.8)
≥ 6% GS /moderate-severe vascular	728 (1.0)	114 (2.6)
≥ 6% GS/moderate-severe vascular/moderate-severe IFTA	318 (0.4)	83 (1.9)

GS: Glomerulosclerosis; IFTA: Interstitial fibrosis/tubular atrophy.

Table 4 Comparison of donor and recipient characteristics between biopsied and non-biopsied kidneys, n (%)/median (interquartile rage)

Characteristics	Not biopsied (n = 66057)	Biopsied (n = 51450)	P value1
Donor
Kidney			< 0.001
Dual/en bloc	1846 (2.8)	632 (1.2)
Left	29520 (44.7)	25037 (48.7)
Right	34691 (52.5)	25781 (50.1)
Age, years	31 (21-41)	51 (41-58)	< 0.001
Male	42927 (65.0)	31246 (60.7)	< 0.001
Blood type			< 0.001
A	24178 (36.6)	19457 (37.8)
AB	2437 (3.7)	1701 (3.3)
B	7437 (11.3)	5899 (11.5)
O	32005 (48.5)	24393 (47.4)
Height, cm	172 (163-179)	170 (164-178)	< 0.001
Weight, kg	76.5 (63.5-90.6)	83.0 (70-99.2)	< 0.001
History of hypertension	8080 (12.2)	23896 (46.5)	< 0.001
Diabetes mellitus	1277 (1.9)	7922 (15.4)	< 0.001
DCD	16099 (24.4)	22600 (43.9)	< 0.001
COD: CVA/stroke	9303 (14.1)	16890 (32.8)	< 0.001
eGFR terminal	115.6 (93.9-130.6)	102.3 (82.2-114.0)	< 0.001
KDRI	1.01 (0.89-1.17)	1.37 (1.16-1.59)	< 0.001
Recipient
Age, years	47 (35-59)	59 (50-66)	< 0.001
Male	37986 (57.5)	31525 (61.3)	< 0.001
Height, cm	168 (160-178)	170 (163-178)	< 0.001
Weight, kg	78.0 (64.0-93.3)	81.6 (69.0-95.3)	< 0.001
Diagnosis			< 0.001
Autoimmune/systemic	3122 (4.7)	1503 (2.9)
Cystic/genetic	5311 (8.0)	3903 (7.6)
Diabetes mellitus	13250 (20.1%	18007 (35.0)
Glomerular	10890 (16.5)	5992 (11.7)
Other	9943 (15.1)	5227 (10.2)
Retransplant	9595 (14.5)	5185 (10.1)
Vascular/hypertensive	13946 (21.1)	11633 (22.6)
cPRA	2.3 (0-72.3)	0 (0-48)	< 0.001
Peripheral vascular disease	6003 (9.1)	7108 (13.8)	< 0.001
Dialysis groups			< 0.001
Preemptive	6881 (10.4)	5059 (9.8)
≤ 1 year	5579 (8.5)	3690 (7.2)
> 1 year ≤ 3 years	15586 (23.6)	11935 (23.2)
> 3 years ≤ 5 years	14268 (21.6)	12275 (23.9)
> 5 years	23743 (35.9)	18492 (35.9)
Wait list, days	479 (121-1240)	535 (128-1305)	< 0.001
EPTS, %	33 (13-68)	62 (35-83)	< 0.001
Transplant
Year of transplant			< 0.001
2014-2019	29559 (44.7)	21139 (41.1)
2020-2024	36498 (55.3)	30311 (58.9)
HLA mismatches			< 0.001
0	3394 (5.1)	2542 (4.9)
1-2	4734 (7.2)	2937 (5.7)
3-4	28145 (42.6)	21267 (41.3)
5-6	29784 (45.1)	24704 (48.0)
Machine perfusion	19375 (29.3)	32399 (63.0)	< 0.001
Cold ischemia time, hours	16.5 (11.5-21.6)	19.5 (15.0-24.0)	< 0.001
Distance donor to transplant hospital, miles	88 (13-203)	97 (16-212)	< 0.001
Shared organ			< 0.001
Local	39177 (59.3)	28868 (56.1)
Regional	11703 (17.7)	10630 (20.7)
National	15177 (23.0)	11952 (23.2)

¹Categorical variables were compared using χ² or Fisher’s exact test, as appropriate. Continuous variables were compared using the Wilcoxon rank-sum test.

DCD: Donor after circulatory death; COD: Cause of death; CVA: Cerebrovascular accident; eGFR: Epidermal growth factor receptor; KDRI: Kidney Donor Risk Index; cPRA: Calculated panel reactive antibody; EPTS: Estimated post-transplant survival; HLA: Human leukocyte antigen.

Table 5 Multivariable Cox proportional hazard model clustered by transplant center for death-censored graft survival in the propensity-matched cohort

Variables	HR	95%CI	P value
Biopsy performed	1.12	1.05-1.19	< 0.001
Donor
Kidney
Left	Reference
Right	0.99	0.94-1.06	0.94
Age, years	1.014	1.01-1.02	< 0.001
Male	1.02	0.94-1.09	0.66
Blood type
A	0.94	0.88-0.99	0.046
B	0.98	0.89-1.07	0.62
O	Reference
Height, cm	0.989	0.986-0.992	< 0.001
Weight, kg	0.998	0.986-1.001	0.07
eGFR terminal	0.997	0.996-0.998	< 0.001
History of hypertension	1.14	1.07-1.22	< 0.001
Diabetes mellitus	1.60	1.43-1.79	< 0.001
DCD	1.26	1.17-1.35	< 0.001
COD: CVA/stroke	1.12	1.04-1.20	< 0.001
Recipient
Age, years	0.975	0.972-0.977	< 0.001
Male	0.92	0.86-0.99	0.049
Height, cm	1.003	0.99-1.01	0.17
Weight, kg	1.005	1.003-1.007	< 0.001
Diagnosis
Autoimmune/systemic	Reference
Cystic/genetic	0.66	0.54-0.80	< 0.001
Diabetes mellitus	0.99	0.85-1.17	0.97
Glomerular	0.96	0.81-1.13	0.63
Other	0.97	0.81-1.15	0.69
Retransplant	0.90	0.76-1.07	0.22
Vascular/hypertensive	1.02	0.87-1.20	0.81
cPRA	1.002	1.001-1.003	< 0.001
Peripheral vascular disease	1.10	0.99-1.22	0.06
Dialysis groups
Preemptive	0.77	0.66-0.88	< 0.001
≤ 1 year	0.92	0.80-1.05	0.22
> 1 year ≤ 3 years	Reference
>3 years ≤ 5 years	1.06	0.97-1.17	0.19
> 5 years	1.10	1.01-1.20	0.03
Wait list, days	1.002	1.001-1.04	0.005
Transplant
Year groups
2014-2019	Reference
2020-2024	1.03	0.96-1.11	0.40
HLA mismatches
0	Reference
1-2	1.48	1.23-1.79	< 0.001
3-4	1.51	1.28-1.77	< 0.001
5-6	1.76	1.49-2.07	< 0.001
Cold ischemia time, hours	1.009	1.005-1.014	< 0.001
Machine perfusion	0.97	0.91-1.05	0.48
Distance between donor and recipients’ hospital by 100 miles	0.99	0.98-1.01	0.12
Shared organ
Local	Reference
Regional	1.06	0.97-1.17	0.20
National	1.20	1.07-1.35	< 0.001

Hazard ratios are from a Cox proportional hazard model clustered by transplant center adjusted for all donor, recipients and transplant covariables listed. The primary variable of interest was biopsy performed (yes vs no). eGFR: Epidermal growth factor receptor; DCD: Donor after circulatory death; COD: Cause of death; CVA: Cerebrovascular accident; cPRA: Calculated panel reactive antibody; HLA: Human leukocyte antigen; HR: Hazard ratio; CI: Confidence interval.

Table 6 Weighted mixed-effect on transplant center linear regression of cold ischemia time in the propensity-matched cohort

Variables	Effect-hours (95%CI)	Effect-minutes (95%CI)	P value
Biopsy performed	+0.70 (0.58-0.81)	+42 (35-49)	< 0.001
Distance between donor and recipients’ hospital miles	+0.0035 (0.0034-0.0037)	Approximately 21 minutes per 100 miles	< 0.001
Sharing
Local	Reference
Regional	+2.9 (1.8-3.1)	+174 (108-186)	< 0.001
National	+4.2 (4.0-4.4)	+252 (240-264)	< 0.001

Estimates represent the effect of biopsy and other covariables on cold ischemia time, expressed in both hours and minutes. All donor covariables from Table 5 were included in the model for controls; only biopsy performed, distance, and organ sharing are shown here. CI: Confidence interval.

Table 7 Observed outcomes by biopsy status in the propensity-matched cohort, n (%)/median (interquartile rage)

Outcome	Not biopsied (n = 26047)	Biopsied (n = 26047)	P value1
Delayed graft function	7177 (27.6)	7957 (30.6)	< 0.001
Serum creatinine mg/dL 6 months	1.3 (1.1-1.7)	1.4 (1.1-1.7)	< 0.001
Serum creatinine mg/dL 12 months	1.3 (1.1-1.6)	1.4 (1.1-1.7)	< 0.001

¹χ² tests for categorical variables and Wilcoxon rank-sum tests for continuous variables.

Table 8 Weighted mixed- effect logistic regression for development of delayed graft function in the propensity-matched cohort

Characteristics	Odds ratio	95%CI	P value
Biopsy performed	1.16	1.11-1.21	< 0.001
Cold ischemia time, hour	1.025	1.02-1.03	< 0.001
Distance (per 1000 miles)	1.08	1.01-1.22	0.03
Share
Local	Ref
Regional	1.03	0.97-1.09	0.42
National	1.14	1.06-1.22	< 0.001

Odds ratios are from a weighted mixed logistic regression adjusted for all donor, recipient, and transplant covariates listed in the Cox model (Table 5). Only biopsy performed, cold ischemia time, distance, and sharing status are shown here.