RESULTS
A total of 13857 patients from 30 transplantation centers were screened. There were 248 cases (1.7%) with BKVN diagnosed in allograft biopsy. Of these cases, the pathologic diagnosis of 20 biopsy samples was uncertain, and 21 patients’ blood BKV-DNA levels or clinical data were missing and excluded from the analysis. 207 (1.4%) patients were included in the study (Flow diagram ).
The mean age was 46.4±13.1 and 146 (70.5%) cases were male. The most common primary kidney diseases were chronic glomerulonephritis [n=43 (21%)], hypertension [n=32 (15.6%)], and diabetic nephropathy [n=28 (13.7%)]. Baseline characteristics and laboratory data of the patients are given in Table 1.
Sixteen patients had fully matched HLA profiles with the donors, 34 patients had 1 HLA mismatch, 31 patients had 2 HLA mismatches, 50 patients had 3 HLA mismatches, 33 patients had 4 HLA mismatches, 31 patients had 5 HLA mismatches, and 12 patients had 6 HLA mismatches with their donors.
At the time of renal transplantation, 26 patients did not receive induction IS treatment, 144 patients had induction IS treatment with anti-T lymphocyte globulin (ATLG), and 37 patients had basiliximab. Thirty-six patients had delayed graft function (DGF).
The maintenance IS treatments at the time of discharge after transplantation were cyclosporine-A (CSA) + mycophenolate mofetil/mycophenolic acid (MMF/MFA) + steroid in 18 patients, tacrolimus (Tac) + MMF/MFA + steroid in 164 patients, Tac + MMF in 18 patients, a CSA + a mammalian target of rapamycin inhibitors (mTORi) in 4 patients, mTORi inhibitör + MMF/MFA + steroid in 2 patients, and a CSA + Azathioprine (AZA) + steroid in 1 patient.
While any acute rejection episodes did not develop in 158 patients, 49 patients were diagnosed with acute rejection within the first six months after transplantation.
BKV-DNA was screened monthly for nine months, then every three months from the serum samples in 110 patients and the urine samples in 25 patients.
The mean time to diagnosis of BKVN was 15.8±22.2 months after transplantation. At the time of diagnosis, the mean creatinine of the patients was 1.8±0.7 mg/dl (0.5-5.6), the mean eGFR was 45.8±19.6 ml/min (8-111), and the mean amount of daily urine protein excretion was 0,6±1,6 (0,01-19) g. The mean creatinine, eGFR, and proteinuria amounts in the first and six months are shown in the Table 2.
In the allograft biopsy specimens, 181 cases had only BKVN with typical basophilic nuclear bodies [SV40 (+) in the epithelial cells (renal tubular and Bowman’s capsule) and fibrosis with varying degrees of inflammatory infiltration], and 21 cases had BKVN + cellular rejection, and four patients had BKVN + humoral rejection findings.
After the diagnosis of BKVN, the antimetabolite dose was reduced in 18 patients; the antimetabolite treatment was discontinued in 45 patients; the antimetabolite was discontinued, and the CNI dose was reduced in 47 patients; the antimetabolite was discontinued and switched to AZA in 30 patients; the antimetabolite was discontinued, CNI dose was reduced, and AZA was added in 11 patients; CNI was discontinued and switched to mTORi in 56 patients (Table 3 ).
Pulse steroid was given to 10 patients with concomitant rejection, and steroid + IVIG treatment was given to 10 of the patients, while no additional treatment was given to the others.
For BKVN, 18 patients were treated with cidofovir, 11 patients with leflunomide, 17 patients with quinolones, 15 patients with intravenous immunoglobulin (IVIG), 5 patients with cidofovir + IVIG, and 12 patients with leflunomide+IVIG.
Allograft loss occurred in 7 (38%) of the patients receiving cidofovir, 1 (5%) of the patients receiving quinolones, 2 (13%) of the patients receiving IVIG, and 2 (40%) the patients receiving cidofovir + IVIG. No allograft loss was observed in any patients who received leflunomide and leflunomide+IVIG. Allograft loss was observed in 12 (15%) of 78 patients given antiviral or immunomodulatory therapy (Table 4 ).
When BKVN recovered, and non-recovered groups were compared, the patients in the recovered group were younger, the BKV diagnosis was earlier after transplantation, leflunomide usage, lower acute humoral rejection rate and the serum creatinine values were lower at the time of diagnosis (Table 5 ). No difference was found in other parameters (gender, proteinuri levels, BKV-DNA copy, etc).
Allograft loss occurred in 32 patients (15%) during mean 49.5±40.8 mo follow-up out of 207 patients. 5 patients had retransplantation, and none developed BK virus nephropathy during the follow-up.