Impact of pretransplant donor-specific antibodies and human leukocyte antigen mismatches on graft and patient outcomes: A cohort from Saudi Arabia

doi:10.5500/wjt.122485

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World Journal of Transplantation

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2220-3230

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Retrospective Study

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Transplant. Sep 18, 2026; 16(3): 122485
Published online Sep 18, 2026. doi: 10.5500/wjt.122485

Table 1 Baseline characteristics, median (interquartile range)

Variable	Category	n (%)
Recipient gender	Male	155 (59.6)
	Female	105 (40.4)
Donor gender	Male	178 (68.5)
	Female	82 (31.5)
Donor type	Living	238 (91.5)
	Deceased	22 (8.5)
DSA presence	Present	151 (58.1)
	Absent	109 (41.9)
Induction therapy	ATG-based	214 (82.3)
	Basiliximab-based	43 (16.5)
	Mixed	3 (1.2)
Plasma exchange	Yes	8 (3.1)
Sensitizing events	None	243 (93.5)
	Re-transplantation	4 (1.5)
	Pregnancy	10 (3.8)
	Blood Transfusion	3 (1.2)
Maintenance therapy	FK + MMF + Pred	256 (98.5)
	CSA + MMF + Pred	4 (1.5)
Re-transplantation	No	255 (98.5)
	Yes	4 (1.5)
IVIG use	No	165 (63.7)
	Yes	94 (36.3)
Acute rejection	Yes	10 (3.8)
	No	250 (96.2)
Graft loss	Yes	12 (4.6)
	No	248 (95.4)
Delayed graft function	Yes	12 (4.6)
	No	248 (95.4)
Mortality	Yes	8 (3.1)
	No	252 (96.9)
CMV infection	Yes	5 (1.9)
	No	255 (98.1)
BKV infection	Yes	5 (2.1)
	No	234 (97.9)
Variable
Recipient age, years	43.0 [31.0-59.2]
Donor age, years	34.0 [28.0-42.0]
ATG dose, mg/kg	4.0 [4.0-5.0]
Length of stay, days	9.0 [8.0-12.0]
Creatinine - 4 months, µmol/L	92.0 [73.5-113.5]
Creatinine - 1 year, µmol/L	89.0 [73.0-111.0]
Creatinine - 2 years, µmol/L	90.5 [71.2-107.8]
eGFR - 4 months, mL/minute/1.73 m²	80.0 [64.0-94.0]
eGFR - 1 year, mL/minute/1.73 m²	83.0 [66.0-98.0]
eGFR - 2 years, mL/minute/1.73 m²	85.0 [71.5-97.0]

DSA: Donor-specific antibody; ATG: Antithymocyte globulin; FK: Tacrolimus; MMF: Mycophenolate mofetil; Pred: Prednisolone; CSA: Cyclosporine; IVIG: Intravenous immunoglobulin; CMV: Cytomegalovirus; BKV: BK virus; eGFR: Estimated glomerular filtration rate.

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Table 2 Univariate comparison between donor-specific antibody-positive and donor-specific antibody-negative kidney transplant recipients, n (%)/median (interquartile range)

Group and variable	DSA-negative	DSA-positive	Univariate
Recipient
Age	38.0 [29.0-58.0]	47.0 [35.0-61.0]	0.0121
Gender			0.8942
Male	66 (60.6)	89 (58.9)
Female	43 (39.4)	62 (41.1)
Donor
Age	33.0 [28.0-42.0]	34.0 [28.0-41.0]	0.7858
Gender			0.7613
Male	73 (67.0)	105 (69.5)
Female	36 (33.0)	46 (30.5)
Type			0.3038
Living donor	97 (89.0)	141 (93.4)
Deceased donor	12 (11.0)	10 (6.6)
DSA & HLA matching
HLA mismatches	5.0 [2.0-7.0]	7.0 [5.0-9.0]	0.0000
DSA strength			-
< 1000 MFI	-	71 (47.0)
≥ 1000 MFI	-	80 (53.0)
DSA type	-		-
Class I only	-	30 (19.9)
Class II only	-	52 (34.4)
Both	-	69 (45.7)
Number of DSAs		3.0 [1.0-6.0]	-
Cumulative MFI		2145.0 [895.5-4235.0]	-
Treatment & sensitization
ATG dose	4.0 [4.0-5.0]	5.0 [4.0-5.0]	0.1388
Sensitizing events			1.0000
Yes	7 (6.4)	10 (6.6)
No	102 (93.6)	141(93.4)
Induction therapy			0.0000
ATG-based	69 (63.3)	145 (96.0)
Basiliximab-based	37 (33.9)	6 (4.0)
Mixed	3 (2.8)	0 (0.0)
Maintenance therapy			1.0000
FK MMF Pred	107(98.2)	149 (98.7)
CSA MMF Pred	2 (1.8)	2 (1.3)
Diabetes pre-transplant			0.1624
Yes	40 (36.7)	69 (45.7)
No	69 (63.3)	82 (54.3)
Use of IVIG			0.0000
Yes	0 (0)	94 (57.6)
No	96 (100)	69 (42.3)
Previous transplant			0.1429
Yes	0 (0.0)	4 (2.6)
No	108 (100.0)	147 (97.4)
Graft function & outcomes
Acute rejection			0.5274
Yes	3 (2.8)	7 (4.6)
No	106 (97.2)	144 (95.4)
Graft loss			0.0796
Yes	2 (1.8)	10 (6.6)
No	10 (98.2)	141 (93.4)
Delayed graft function			1.0000
Yes	5 (4.6)	7 (4.6)
No	104 (95.4)	144 (95.4)
Death (mortality)			0.1442
Yes	1 (0.9)	7 (4.6)
No	108 (99.1)	144 (95.4)
CMV infection			1.0000
Yes	2 (1.8)	3 (2.0)
No	107 (98.2)	148 (98.0)
BKV infection			0.4066
Yes	1 (1.0)	4 (2.9)
No	98 (99.0)	136 (97.1)
Length of stay (days)	9.0 [8.0-12.0]	9.0 [7.0-12.0]	0.9488
Creatinine - 4 months	91.0 [74.0-110.0]	93.5 [73.2-114.0]	0.8153
Creatinine - 1 year	93.0 [73.5-111.5]	89.0 [73.0-109.0]	0.7218
Creatinine - 2 years	94.0 [72.0-103.0]	88.0 [71.0-110.0]	0.7605
eGFR - 4 months	83.0 [65.0-95.0]	77.5 [64.0-92.5]	0.2258
eGFR - 1 year	83.0 [67.0-97.0]	82.5 [65.0-99.0]	0.8518
eGFR - 2 years	83.0 [72.5-95.8]	86.0 [71.0-97.0]	0.9898

Statistical comparisons were conducted using the Mann-Whitney U test for continuous variables and χ² or Fisher’s exact test for categorical variables, depending on expected cell counts. A P value < 0.05 was considered statistically significant. Analyses were performed using listwise deletion to account for missing data. DSA: Donor-specific antibody; MFI: Mean fluorescence intensity; HLA: Human leukocyte antigen; ATG: Antithymocyte globulin; FK: Tacrolimus; MMF: Mycophenolate mofetil; Pred: Prednisolone; CSA: Cyclosporine; IVIG: Intravenous immunoglobulin; CMV: Cytomegalovirus; BKV: BK virus; eGFR: Estimated glomerular filtration rate.

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Table 3 Multivariable logistic regression for factors associated with donor-specific antibody positivity

Predictor	OR	95%CI	P value	Significance
Recipient age	1.02	1.01-1.04	0.009	Significant
HLA mismatches	1.31	1.18-1.44	0.0000	Significant
eGFR < 60 at 4 months	1.70	0.82-3.54	0.156	Not significant
Any sensitizing event	0.68	0.26-1.82	0.448	Not significant

eGFR: Estimated glomerular filtration rate; HLA: Human leukocyte antigen; OR: Odds ratio.

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Table 4 Univariate analysis of factors associated with acute rejection after kidney transplantation, n (%)/median (interquartile range)

Group and variable	AR-negative	AR-positive	Univariate
Recipient
Age	43.5 [31.2-60.0]	40.0 [30.8-45.2]	0.2584
Recipient gender			0.3243
Male	147 (58.8)	8 (80.0)
Female	103 (41.2)	2 (20.0)
Donor
Donor age	33.5 [28.0-42.0]	34.5 [31.2-36.8]	0.8586
Donor gender			0.7296
Male	172 (68.8)	6 (60.0)
Female	78 (31.2)	4 (40.0)
Donor type			0.5936
Living donor	229 (91.6)	9 (90.0)
Deceased donor	21 (8.4)	1 (10.0)
DSA & HLA matching
HLA mismatches	6.0 [5.0-8.0]	9.0 [7.2-9.0]	0.0048
DSA presence			0.5274
Yes	144 (57.6)	7 (70.0)
No	106 (42.4)	3 (30.0)
DSA strength			1.0000
< 1000 MFI	68 (47.2)	3 (42.9)
≥ 1000 MFI	76 (52.8)	4 (57.1)
DSA type			0.3598
Class I only	29 (20.1)	1 (14.3)
Class II only	51 (35.4)	1 (14.3)
Both	64 (44.4)	5 (71.4)
Number of DSAs	3.0 [2.0-6.0]	1.0 [1.0-2.0]	0.0698
Cumulative MFI	2205.0 [901.2-4195.0]	2010.0 [1191.5-5216.5]	0.9330
Treatment & sensitization
ATG dose	4.0 [4.0-5.0]	4.0 [4.0-6.0]	0.4704
Sensitizing events			0.0378
Yes	15 (6.1)	2 (18.2)
No	234 (93.9)	9 (81.8)
Induction therapy			0.6758
ATG-based	206 (82.4)	8 (80.0)
Basiliximab-based	41 (16.4)	2 (20.0)
Mixed	3 (1.2)	0 (0.0)
Maintenance therapy			1.0000
FK MMF ST	246 (98.4)	10 (100.0)
CSA MMF ST	4 (1.6)	0 (0.0)
Use of IVIG			0.1764
Yes	88 (35.3)	6 (60.0)
No	161 (64.7)	4 (40.0)
Previous transplant			1.0000
Yes	4 (1.6)	0 (0.0)
No	245 (98.4)	10 (100.0)
Pre-transplant diabetes			0.7463
Yes	104 (41.6)	5 (50.0)
No	146 (58.4)	5 (50.0)
Graft function & outcomes
Graft loss			0.0076
Yes	9 (3.6)	3 (30.0)
No	241 (96.4)	7 (70.0)
DGF			0.0716
Yes	10 (4.0)	2 (20.0)
No	240 (96.0)	8 (80.0)
Mortality			0.2725
Yes	7 (2.8)	1 (10.0)
No	243 (97.2)	9 (90.0)
CMV infection			1.0000
Yes	5 (2.0)	0 (0.0)
No	245 (98.0)	10 (100.0)
BKV infection			1.0000
Yes	5 (2.2)	0 (0.0)
No	225 (97.8)	9 (100.0)
Length of stay (days)	9.0 [8.0-12.0]	8.0 [7.0-9.0]	0.1376
Creatinine - 4 months	92.0 [73.0-112.0]	136.5 [106.5-148.0]	0.0217
Creatinine - 1 year	89.0 [73.0-109.0]	122.0 [95.0-126.0]	0.0649
Creatinine - 2 year	89.5 [71.8-104.5]	118.0 [79.2-129.8]	0.2531
eGFR - 4 months	80.0 [64.5-95.0]	57.5 [51.5-87.2]	0.1032
eGFR - 1 year	83.0 [66.8-98.0]	69.0 [62.0-93.0]	0.3210
eGFR - 2 years	85.0 [72.0-97.0]	75.5 [68.8-84.5]	0.4011
Class I antibody profile
Anti-A presence			0.6287
Yes	33 (13.2)	2 (20.0)
No	217 (86.8)	8 (80.0)
Anti-B presence			1.0000
Yes	25 (10.0)	1 (10.0)
No	225 (90.0)	9 (90.0)
Anti-C presence			0.2936
Yes	76 (30.4)	5 (50.0)
No	174 (69.6)	5 (50.0)
Class II antibody profile
Anti-DR presence			0.3975
Yes	80 (32.0)	5 (50.0)
No	170 (68.0)	5 (50.0)
Anti-DP presence			1.0000
Yes	52 (20.8)	2 (20.0)
No	198 (79.2)	8 (80.0)
Anti-DQ presence			0.7317
Yes	67 (26.8)	3 (30.0)
No	183 (73.2)	7 (70.0)

The Mann-Whitney U test was used for continuous variables, and the χ² or Fisher’s exact test was applied for categorical variables, depending on cell sizes. Statistical significance was defined as P < 0.05. AR: Acute rejection; ATG: Antithymocyte globulin; BKV: BK virus; CMV: Cytomegalovirus; CSA: Cyclosporine; DGF: Delayed graft function; DSA: Donor-specific antibody; eGFR: Estimated glomerular filtration rate; FK: Tacrolimus; HLA: Human leukocyte antigen; IQR: Interquartile range; IVIG: Intravenous immunoglobulin; MFI: Mean fluorescence intensity; MMF: Mycophenolate mofetil; OR: Odds ratio; Pred: Prednisolone; ST: Steroid; TCMR: T cell-mediated rejection.

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Table 5 Multivariable logistic regression for acute rejection

Predictor	OR	95%CI	P value	Significance
HLA mismatches	1.44	1.03-2.01	0.0333	Significant
eGFR < 60 at 4 months	7.75	1.69-35.63	0.0085	Significant
Sensitizing events	4.18	0.68-25.64	0.1227	Borderline
ATG dose (mg/kg)	1.36	0.59-3.12	0.4721	Not significant
DSA presence	1.09	0.18-6.48	0.9252	Not significant

The model included five clinically relevant variables: Human leukocyte antigen mismatches (continuous), glomerular filtration rate < 60 at 4 months, sensitizing events prior to transplantation, antithymocyte globulin dose, and donor-specific antibody (DSA) presence. ATG: Antithymocyte globulin; DSA: Donor-specific antibody; eGFR: Estimated glomerular filtration rate; HLA: Human leukocyte antigen; OR: Odds ratio.

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Table 6 Kidney transplant rejection summary

ID.	Tx type	Tx date	Rejection type(s)	Rejection date(s)	Time post-Tx	Banff grade	C4d status	SV40	Primary disease	DSA	HLA mismatch	Class I antibodies	Class II antibodies
29	LRRT	April 26, 2021	Acute AMR	May 12, 2021	2 weeks	-	Inconclusive	Negative	Unknown	Positive	7	AntiC (1091.0)	AntiDR (615)
41	LRRT	June 13, 2021	Acute TCMR/Acute AMR	July 5, 2021/July 19, 2021	3 weeks/1 month	Type IIB	Negative	Negative	Unknown	Positive	11	AntiA (879.0) \| AntiC (985.0)	AntiDR (905+561) \| AntiDQ (567.0)
47	ERRT	September 20, 2021	Mixed acute TCMR/CAAMR	April 27, 2023/April 8, 2024	1.5 years	Type IB	Positive	Negative	Unknown	Positive	9	AntiC (1290.0)	AntiDQ (720.0)
118	LRRT	September 29, 2022	Acute TCMR	September 18, 2024	2 years	Type IB	Negative	Negative	Unknown	Negative	9	-	-
113	LURT	November 5, 2022	Acute TCMR	November 29, 2022	3 weeks	Type IIB	Negative	Negative	Unknown	Positive	8	AntiB (647.0) \| AntiC (3027.0)	AntiDR (1022+699+902) \| AntiDP (1227)
161	LRRT	June 12, 2023	Acute TCMR	August 13, 2023	2 months	Borderline	Negative	Negative	Unknown	Positive	9	AntiC (677.0)	-
171	LRRT	July 15, 2023	Acute TCMR	January 25, 2024	6 months	Type IA	Negative	Negative	Unknown	Negative	11	-	-
225	DDRT	May 11, 2024	Acute AMR	June 5, 2024	1 month	-	Focally positive	Not done	FSGS	Positive	9	AntiA (4641.0)	AntiDR (707) \| AntiDP (559.0) \| AntiDQ (629.0)
44	LRRT	June 28, 2021	Acute TCMR	January 28, 2025	3.5 years	-	Negative	Negative	Lupus Nephritis	Negative	6	-	-
104	LRRT	October 6, 2022	Mixed Acute TCMR/AMR	May 27, 2025	2.5 years	Type IB, ptc 2-3	Negative	Negative	FSGS/SCD	Positive	7	-	AntiDR (616)

AMR: Antibody-mediated rejection; ATG: Antithymocyte globulin; CAAMR: Chronic active antibody-mediated rejection; DSA: Donor-specific antibody; DDRT: Deceased donor renal transplant; eGFR: Estimated glomerular filtration rate; ERRT: Emotionally related renal transplant; FSGS: Focal segmental glomerulosclerosis; HLA: Human leukocyte antigen; IQR: Interquartile range; IVIG: Intravenous immunoglobulin; LRRT: Living related renal transplant; LURT: Living unrelated renal transplant; MFI: Mean fluorescence intensity; MMF: Mycophenolate mofetil; OR: Odds ratio; Pred: Prednisolone; SCD: Sickle cell disease; SV40: Simian virus 40; TCMR: T-cell-mediated rejection.

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Table 7 Clinical and immunological profiles by rejection group

Group	n	Median HLA mismatches	Median LOS	DSA class profile	Median DSA count	Median DSA MFI	Sensitizing events (%)	Graft loss (%)
DSA+ AMR	2	8.0	8.5 days	Both	3.5	4121.0	50.0	0.0
DSA+ mixed	3	9.0	8.0 days	Both, Class II	1.0	2010.0	33.3	100.0
DSA+ TCMR	2	8.5	8.5 days	Both, Class I	1.0	4100.5	50.0	0.0
DSA- TCMR	3	9.0	9.0 days	-	-	-	0.0	0.0

AMR: Antibody-mediated rejection; DSA: Donor-specific antibody; HLA: Human leukocyte antigen; LOS: Length of stay; MFI: Mean fluorescence intensity; TCMR: T cell-mediated rejection.

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Table 8 Multivariable Cox regression identifying predictors of the composite outcome

Predictor	HR	95%CI	P value	Significance
HLA mismatches ≥ 7	1.95	1.42-2.66	< 0.005	Significant
DSA present	1.23	0.84-1.80	0.29	Not significant
eGFR < 60 at 4 months	2.71	1.52-4.84	< 0.005	Significant
ATG dose (mg/kg)	1.24	0.93-1.64	0.14	Borderline
Sensitizing events	2.91	1.22-6.90	0.02	Significant
Gender male (vs female)	1.33	0.92-1.92	0.13	Borderline

Cox proportional hazards model was used to evaluate independent risk factors for a composite outcome comprising acute rejection, graft loss, or patient mortality in a cohort of 260 kidney transplant recipients. Six clinically relevant variables were selected a priori: HLA mismatches (≥ 7), donor-specific antibody presence, estimated glomerular filtration rate at 4 months (glomerular filtration rate < 60), ATG dose, sensitizing events, and recipient gender. ATG: Antithymocyte globulin; DSA: Donor-specific antibody; eGFR: Estimated glomerular filtration rate; HR: Hazard ratio; HLA: Human leukocyte antigen.

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Citation: Al-Qurashi SH, Khalil MAM, Mahmood HHK, Altom AA, Alqurashi YF, Alsaedi ZA, Cruz AJD, Alsharif MM, Bawayan RM, Housawi AA, Sadagah NM. Impact of pretransplant donor-specific antibodies and human leukocyte antigen mismatches on graft and patient outcomes: A cohort from Saudi Arabia. World J Transplant 2026; 16(3): 122485
URL: https://www.wjgnet.com/2220-3230/full/v16/i3/122485.htm
DOI: https://dx.doi.org/10.5500/wjt.122485

Al-Qurashi SH, Khalil MAM, Mahmood HHK, Altom AA, Alqurashi YF, Alsaedi ZA, Cruz AJD, Alsharif MM, Bawayan RM, Housawi AA, Sadagah NM. Impact of pretransplant donor-specific antibodies and human leukocyte antigen mismatches on graft and patient outcomes: A cohort from Saudi Arabia. World J Transplant 2026; 16(3): 122485 [DOI: 10.5500/wjt.122485]

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