Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation

doi:10.12998/wjcc.v7.i3.270

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World Journal of Clinical Cases

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Observational Study

World J Clin Cases. Feb 6, 2019; 7(3): 270-290
Published online Feb 6, 2019. doi: 10.12998/wjcc.v7.i3.270

Table 1 Donor, transplant, and recipient characteristics of the study population

Variables	Median (IQR) or n (%)
Patients	629
Recipient Male : Female	372:257
Caucasian ethnicity	279/629 (44.3)
Afro-Caribbean ethnicity	114/629 (18.1)
Recipient age (yr)	47 (36-55)
Recipient body mass index (kg/m²)	25.2 (22.2-27.5)
Pre-transplant diabetes	83/629 (13.2)
Pre-transplant cardiovascular disease	62/629 (9.9)
Recipient cytomegalovirus IgG positive	431/629 (68.5)
Glomerular disease	185/629 (29.4)
Polycystic kidney disease	71/629 (11.3)
Tubular-interstitial nephropathy	81/629 (12.9)
Diabetic nephropathy	49/629 (7.8)
Hypertension	55/629 (8.7)
Unknown renal disease	141/629 (22.4)
Other renal disease	47/629 (7.5)
Haemodialysis	295/629 (46.9)
Peritoneal dialysis	136/629 (21.6)
Peritoneal dialysis and haemodialysis	118/629 (18.8)
Pre-emptive transplant	80/629 (12.7)
Panel-reactive antibody > 50%	101/629 (16.1)
Primary transplant	550/629 (87.4)
Deceased donor	395/629 (62.8)
Donation after brain death donor	263/629 (41.8)
ABO-incompatible transplant	25/629 (4.0)
Donor age (yr)	48 (39-57)
Donor-recipient gender mismatch	340/629 (54.1)
Donor cytomegalovirus IgG positive	354/629 (56.3)
Cytomegalovirus D⁺R^- immunization	83/629 (13.2)
Cold ischemia time (hours)	12 (4-16)
Cold ischemia time >12 h	282/629 (44.8)
Cumulative HLA mismatch	3 (2-4)
HLA mismatch > 4	92/629 (14.6)
Induction treatment
Anti-IL2-receptor antagonist	431/629 (68.5)
Rabbit anti-thymocyte globulin	169/629 (26.9)
Rituximab	25/629 (4.0)
Alemtuzumab	3/629 (0.5)
Muromonab-CD3	1/629 (0.2)
Maintenance immunosuppression
CyA-MMF-steroid	422/629 (67.1)
CyA-AZA-steroid	3/629 (0.5)
Tacrolimus-MMF-steroid	109/629 (17.3)
Tacrolimus-AZA-steroid	79/629 (12.6)
Tacrolimus-MMF	12/629 (1.9)
Tacrolimus-AZA	2/629 (0.3)
AZA-MMF-steroid	1/629 (0.2)
AZA-steroid	1/629 (0.2)
CyA-based scheme	425/629 (67.6)
Tacrolimus-based scheme	202/629 (32.1)
CNI-free scheme	2/629 (0.3)
MMF-containing scheme	544/629 (86.5)
AZA-containing scheme	86/629 (13.7)
Steroid-free scheme	14/629 (2.2)
Cytomegalovirus prophylaxis	241/629 (38.3)

IQR: Interquartile range; IgG: Immunoglobulin class G; HLA: Human leukocyte antigen; CyA: Cyclosporine; MMF: Mycophenolate mofetil; AZA: Azathioprine; CNI: Calcineurin inhibitor.

Table 2 Characteristics of kidney recipients with or without BK-viremia

Variables	Median (IQR) or n (%)		P
Variables	No BKV group	BKV group	P
Patients	569	60	-
Recipient Male : Female	333 : 236	39 : 21	0.4076
Caucasian ethnicity	255/569 (44.8)	24/60 (40)	0.4977
Afro-Caribbean ethnicity	94/569 (16.5)	20/60 (33.3)	0.0024
Recipient age (years)	47 (36-55)	48.5 (37-53.25)	0.7263
Recipient age ≥ 60 yr	74/569 (13)	10/60 (16.7)	0.4255
Recipient BMI ≥ 30 kg/m²	79/569 (13.9)	8/60 (13.3)	1.0000
Pre-transplant diabetes	77/569 (13.5)	6/60 (10)	0.5499
Pre-transplant cardiovascular disease	55/569 (9.7)	7/60 (11.7)	0.5473
Recipient CMV IgG positive	391/569 (68.7)	40/60 (66.7)	0.7707
Primary renal disease
Glomerular disease	167/569 (29.4)	18/60 (30)
Polycystic kidney disease	62/569 (10.9)	9/60 (15)
Tubular-interstitial nephropathy	77/569 (13.5)	4/60 (6.7)
Diabetic nephropathy	45/569 (7.9)	4/60 (6.7)
Hypertension	47/569 (8.3)	8/60 (13.3)
Unknown renal disease	130/569 (22.8)	11/60 (18.3)
Other renal disease	41/569 (7.2)	6/60 (10)
Haemodialysis	266/569 (46.7)	28/60 (46.7)	1.0000
Peritoneal dialysis	123/569 (21.6)	13/60 (21.7)	1.0000
Pre-emptive transplant	72/569 (12.7)	8/60 (13.3)	0.8395
Panel-reactive antibody test > 50%	83/569 (14.6)	18/60 (30)	0.0047
Primary transplant	497/569 (87.3)	53/60 (88.3)	1.0000
Deceased donor	357/569 (62.7)	38/60 (63.3)	1.0000
Donation after brain death donor	235/569 (41.3)	27/60 (45)	0.5848
ABO-incompatible transplant	21/569 (3.7)	4/60 (6.7)	0.2856
Donor age (yr)	47 (38-57)	51.5 (40.75-60.25)	0.0483
Donor age ≥ 60 yr	115/569 (20.2)	17/60 (28.3)	0.1808
Donor-recipient gender mismatch	308/569 (54.1)	32/60 (53.3)	1.0000
Donor CMV IgG positive	323/569 (56.8)	31/60 (51.7)	0.4947
Cytomegalovirus D⁺R^- immunization	79/569 (13.9)	4/60 (6.7)	0.1582
Cold ischemia time (h)	12 (4-16)	12 (4-17.25)	0.9920
Cumulative HLA mismatch	3 (2-4)	3 (2-5)	0.0759
HLA mismatch > 4	76/569 (13.4)	16/60 (26.7)	0.0110
HLA-A mismatch	1 (1-2)	1 (1-2)	0.6079
HLA-B mismatch	1 (1-1)	1 (1-2)	0.1896
HLA-DR mismatch	1(0-1)	1 (0-1.25)	0.0482
Induction treatment
Anti-IL2-receptor antagonist	388/569 (68.2)	43/60 (71.7)
Rabbit anti-thymocyte globulin	156/569 (27.4)	13/60 (21.7)
Rituximab	21/569 (3.7)	4/60 (6.7)
Alemtuzumab	3/569 (0.5)	0/60 (0)
Muromonab-CD3	1/569 (0.2)	0/60 (0)
Maintenance immunosuppression
CyA-based scheme	385/569 (67.7)	40/60 (66.7)
Tacrolimus-based scheme	182/569 (32.0)	20/60 (33.3)
MMF-containing scheme	490/569 (86.1)	54/60 (90)
AZA-containing scheme	80/569 (14.1)	6/60 (10)
CNI-free scheme	2/569 (0.4)	0/60 (0)
Steroid-free scheme	13/569 (2.3)	1/60 (1.7)
Cytomegalovirus prophylaxis	224/569 (39.4)	17/60 (28.3)	0.1239
DGF	152/569 (26.7)	15/60 (25)	0.8783
BPR within 30 d of transplantation	54/569 (9.5)	13/60 (21.7)	0.0073

BKV: BK-virus; IQR: Interquartile range; BMI: Body mass index; CMV: Cytomegalovirus; IgG: Immunoglobulin class G; HLA: Human leukocyte antigen; CyA: Cyclosporine; MMF: Mycophenolate mofetil; AZA: Azathioprine; CNI: Calcineurin inhibitor; DGF: Delayed graft function; BPR: Biopsy-proven rejection.

Table 3 Characteristics of kidney recipients with BK-viremia and negative (No polyomavirus-associated nephropathy group) or positive allograft histology (Polyomavirus-associated nephropathy group)

Variables	Median (IQR) or n (%)		P
Variables	No PVAN group	PVAN group	P
Patients	20	40
Recipient Male : Female	13 : 7	26 : 14	1.0000
Caucasian ethnicity	9/20 (45)	15/40 (37.5)	0.5896
Afro-Caribbean ethnicity	4/20 (20)	16/40 (40)	0.1536
Recipient age (yr)	49 (33.5-58)	48.5 (37.75-53)	0.8887
Pre-transplant diabetes	1/20 (5)	5/40 (12.5)	0.6532
Pre-transplant CVD	4/20 (20)	3/40 (7.5)	0.2077
Recipient CMV IgG positive	13/20 (65)	27/40 (67.5)	1.0000
Haemodialysis	9/20 (45)	19/40 (47.5)	1.0000
Peritoneal dialysis	6/20 (30)	7/40 (17.5)	0.3258
Pre-emptive transplant	2/20 (10)	6/40 (15)	0.7068
PRA test > 50%	6/20 (30)	12/40 (30)	1.0000
Primary transplant	17/20 (85)	36/40 (90)	0.6763
Deceased donor	13/20 (65)	25/40 (62.5)	1.0000
ABO-incompatible transplant	1/20 (5)	3/40 (7.5)	1.0000
Donor age (yr)	53.5 (42.25-62.75)	51 (40.75-57)	0.30302
Donor age ≥ 60 yr	8/20 (40)	9/40 (22.5)	0.2246
Donor CMV IgG positive	7/20 (35)	24/40 (60)	0.1004
CMV D⁺R^- immunization	1/20 (5)	3/40 (7.5)	1.0000
Cold ischemia time (h)	14.25 (4.3-21.5)	12 (4-15)	0.4413
Cumulative HLA mismatch	3 (3-4.25)	3 (2-5)	0.4654
HLA mismatch > 4	5/20 (25)	11/40 (27.5)	1.0000
HLA-A mismatch	1 (1-1.25)	1 (1-2)	0.78716
HLA-B mismatch	1 (1-2)	1 (1-2)	0.25014
HLA-DR mismatch	1 (0-1.25)	1 (0-1.25)	0.8181
Induction immunosuppression
Anti-IL2-receptor antagonist	15/20 (75)	28/40 (70)
Anti-thymocyte globulin	4/20 (20)	9/40 (22.5)
Rituximab	1/20 (5)	3/40 (7.5)
Maintenance immunosuppression
CyA-based scheme	14/20 (70)	26/40 (65)
Tacrolimus-based scheme	6/20 (30)	14/40 (35)
MMF-containing scheme	19/20 (95)	35/40 (87.5)
AZA-containing scheme	1/20 (5)	5/40 (12.5)
CNI-free scheme	0/20 (0)	0/40 (0)
Steroid-free scheme	0/20 (0)	1/40 (2.5)
CMV prophylaxis	4/20 (20)	13/40 (32.5)	0.3752
DGF	6/20 (30)	9/40 (22.5)	0.5424
BPR within 30 d of transplant	4/20 (20)	9/40 (22.5)	1.0000
Initial viremia ≥ 10000 copies/mL	3/20 (15)	37/40 (92.5)	< 0.00001
Initial viral load (copies/mL)	6000 (2975-7550)	134800 (28750-425000)	< 0.00001
BKV viremia ≥ 3 wk	5/20 (25)	38/40 (95)	< 0.00001

PVAN: Polyomavirus-associated nephropathy; IQR: Interquartile range; BMI: Body mass index; CVD: Cardiovascular disease; CMV: Cytomegalovirus; IgG: Immunoglobulin class G; PRA: Panel-reactive antibody; HLA: Human leukocyte antigen; CyA: Cyclosporine; MMF: Mycophenolate mofetil; AZA: Azathioprine; CNI: Calcineurin inhibitor; DGF: Delayed graft function; BPR: Biopsy-proven rejection.

Table 4 Final multivariable model for the risk of BK-viremia in a cohort of kidney transplant recipients

Variable	OR	95%CI	P
Afro-Caribbean ethnicity	2.882	1.549; 5.259	0.001
Panel-reactive antibody > 50%	3.352	1.737; 6.338	< 0.001
HLA mismatch > 4	2.585	1.303; 4.955	0.005
CMV Prophylaxis	0.467	0.244; 0.854	0.017
BPR within 30 d of transplant	2.342	1.117; 4.664	0.019

Table 5 Final multivariable model for the risk of Polyomavirus-associated nephropathy in a cohort of kidney transplant recipients

Variable	OR	95%CI	P
Afro-Caribbean ethnicity	2.717	0.705-12.458	0.164
Cardiovascular disease	0.235	0.034-1.42	0.117
Donor Age ≥ 60 yr	0.243	0.055-0.949	0.048
Recipient CMV IgG positive	4.371	1.261-17.968	0.027

Citation: Favi E, Puliatti C, Sivaprakasam R, Ferraresso M, Ambrogi F, Delbue S, Gervasi F, Salzillo I, Raison N, Cacciola R. Incidence, risk factors, and outcome of BK polyomavirus infection after kidney transplantation. World J Clin Cases 2019; 7(3): 270-290
URL: https://www.wjgnet.com/2307-8960/full/v7/i3/270.htm
DOI: https://dx.doi.org/10.12998/wjcc.v7.i3.270