Epstein–Barr virus infection in children with renal transplantation: 17 years experience at a single center

Figures & data

Table 1. Characteristics of patients before transplantation.

	EBV seropositive N (%)	EBV seronegative N (%)	p Value
Patients	144 (86.7)	22 (13.3)
Median age at tx, year	13.2 (1.5–18)	10.2 (2–18)	0.05
Male/female	80 (55.5)/64 (44.5)	9 (40.9)/13 (59.1)	0.19
Live/deceased donor	121 (84)/23 (16)	18 (81.8)/4 (18.2	0.79
HLA mismatches ≥4 (n, %)	34 (23.6)	5 (22)	0.54
Time on dialysis, median (month)	12 (range: 1–108)	54 (16–108)	0.01
Follow-up duration, median (month)	29 (range: 3–137)	32.5 (7–81)	0.59
CMV seronegativity	6 (4.1)	5 (22.7)	0.007
Induction therapy, MP/MP-ATG	108 (75)/36 (25)	16 (72.7)/6 (27.3)	–
Primary immunosuppression			–
Prednisone-MMF/MYF-CSA	33 (22.9)	4 (18.1)	–
Prednisone-MMF/MYF-Tac	109 (75.6)	15 (68.2)	–
Prednisone-Sirolimus-CSA	2 (1.4)	1 (4.5)	–
Prednisone-AZA-Tac	–	2 (9.2)	–

Note: Tx, transplantation; MP, methylprednisolone; ATG, antithymocyte globulin; MMF, mycophenolate mofetil; MYF, mycophenoic acid; CSA, cyclosporine; Tac, tacrolimus; AZA, azathioprine.

Table 2. Primary renal disease of the patients.

Primary renal disease	Total 166, n (%)
Reflux nephropathy	24 (14.5)
Nephronophthisis/autosomal recessive  polycystic disease	22 (13.3)
PUV	20 (12.0)
Focal segmental glomerulosclerosis	18 (10.8)
Renal aplasia/hypoplasia/dysplasia	17 (10.2)
Chronic glomerulonephritis	15 (9.0)
Neurogenic bladder	8 (4.8)
Cystinosis	5 (3.0)
Bardet–Biedel syndrome	3 (1.8)
Congenital nephrotic syndrome	2 (1.2)
Primary hyperoxaluria	2 (1.2)
Atypical hemolytic uremic syndrome (HUS)	2 (1.2)
Other (Prune Belly syndrome, Bartter Syndrome,  Denys Drash Syndrome, Fanconi Syndrome)	4 (2.3)
Unknown	24 (14.5)

Table 3. Characteristics of patients with primary EBV infection.

Patient No/Sex	Age at Tx (Month)	Donor	Induction therapy	Primary* immunsup.	Number of acute rejection	Method	Presentation	First viremia (month)	EBV viral load at diagnosis	CNI levels*** ng/mL	Immunsup. intervention	Result/last GFR
1/F	66	Live	MP	Tac	–	PCR	PTLD	23	4.9 × 10^6	6.2	Stop all immunsup.	exitus
2/M	120	Live	MP	Tac	–	PCR	PTLD	9	2.9 × 10^5	11.6	Stop all immunsup. except steroids	88
3/M	48	Live	MP	CsA	–	PCR	subclinical	36	2.5 × 10^4	65/304	Decrease CsA dose	52
4/F**	162	Deceased	MP-ATG	Tac	–	PCR	subclinical	2	957	12.7	Decrease Tac dose	32
5/F	102	Live	MP	Tac	1	PCR	subclinical	2	4330	7.2	Decrease MMF dose	90
6/F	162	Live	MP	Tac	–	serological	subclinical	–	–	–	–	79
7/M	180	Live	MP	Tac	2	serological	subclinical	–	–	–	–	66
8/F	200	Live	MP	Tac	–	serological	subclinical	–	–	–	–	85
9/F	198	Live	MP	Sirolimus	–	serological	subclinical	–	–	–	–	82
10/F	72	Deceased	MP-ATG	Tac	–	serological	subclinical	–	–	–	–	92
11/M**	204	Live	MP	CsA	–	serological	subclinical	–	–	–	–	44

Note: GFR, glomerular filtration rate; F, female; M, male; PTLD, post-transplant lymphoproliferative disorder; tx, transplantation; MP, methylprednisolone; ATG, antithymocyte globulin; CSA, cyclosporine; Tac, tacrolimus.

*All patients received mycophenolate mofetil or mycophenoic acid except patient 9.

**Patients 4 and 11 with low GFR had also BK nephropathy and recurrent urinary infection due to vesicoureteral reflux, respectively.

***Tac-0 or CsA-0 and 2 h.

Table 4. EBV-related complications in Group 1 and 2 patients.

	Group 1 (n = 45, 27.1%)	Group 2 (n = 121, 72.9%)	p
EBV seropositivity (n, %)	40 (88.9)	104 (85.9)	0.001
Subclinical infection	12	9	0.01
Symptomatic infection	1	1	0.41
PTLD	–	–
EBV seronegativity (n, %)	5 (11.1)	17 (14.1)	0.8
Subclinical infection	1 (20)	8 (47)	0.79
Symptomatic infection	–	–
PTLD	1 (20)	1 (5.9)	0.44

Note: PTLD, post-transplant lymphoproliferative disorder.

Table 5. Characteristics of patients with primary EBV infection and EBV reactivation.

	Primary EBV infection (n = 11, 50%)	EBV reactivation (n = 23, 15.9%)	p
Mean age at tx (year)	11.4 ± 4.8	10.8 ± 3.9	0.69
Male/female, n (%)	4/7 (36.4/63.6)	12/11 (52.2/47.8)	0.38
Live/deceased donor, n (%)	9/2 (81.8/18.2)	20/3 (87/13)	0.69
Median follow-up duration (month)	29 (8–48)	48 (24–97)	0.01
First viremia, median (month)	9 (2–36)	23 (2–59)	0.47
EBV viral load at diagnosis median (copies/mL) (n/n)	2.5 × 10^4 (957–4.9 × 10^6) 5/11	600 (100–4604) 23/23	0.018
Viremia duration (median, month)	2.0 (1–3)	1.0 (1–7)	NA
Number of positive EBV results during EBV viremia	3 (range: 2–10)	2 (range: 1–5)	NA
Acute rejection, n (%)	2 (18.2)	7 (30.4)	NA
BK viremia, n (%)	2 (18.2)	2 (8.7)	NA
BK nephropathy, n (%)	1 (9.1)	0	NA
Recurrent urinary infection, n (%)	2 (18.2)	3 (13.0)	NA

Note: NA, not available because of low numbers.