Pretransplantation seroreactivity in kidney donors and recipients as a predictive factor for posttransplant BKPyV-DNAemia

Abstract

BK polyomavirus (BKPyV) often reactivates after kidney transplantation, causing BKPyV-associated nephropathy (BKPyVAN) in 1%-10% of cases with a potential detrimental effect on allograft survival. Kidney transplant recipients are regularly screened for BKPyV DNA in plasma. As this strategy may not always reduce the risk of BKPyVAN, other predictive markers are needed. To evaluate the role of pretransplant BKPyV-specific antibody, 210 kidney transplant recipients and 130 donors were screened for BKPyV DNA and BKPyV-specific antibodies. We found that the donor BKPyV immunoglobulin G (IgG) seroprevalence and antibody level were strongly associated with BKPyV-DNAemia and BKPyVAN, although multivariant analysis found the presence of anti-BKPyV-specific antibodies as a predictive factor only for BKPyV-DNAemia. The pretransplant recipient status had no effect on posttransplant BKPyV-DNAemia and BKVAN. BKPyV IgG levels remained stable in BKPyV-negative recipients during 1-year follow-up, while a considerable increase was observed in BKPyV-positive patients. The presence of anti-BKPyV-specific antibodies in kidney allograft donors is a good and reliable predictive marker for posttransplant BKPyV replication with relevance to risk stratification in transplant recipients.

Keywords: BK polyomavirus (BKPyV); BKPyV-associated nephropathy; kidney transplantation; seroprevalence; seroreactivity.

Figure 1

Prevalence of BK polyomavirus (BKPyV)-DNAemia in recipients during the follow-up. Presumptive BKPyVAN was defined as >10⁴ copies/ml, viral load <10⁴ copies/ml viremia as low BKPyV-DNAemia. Legend: BKPyV-DNAemia after transplantation at month 1 (M1), 3 (M3), 6 (M6), and 12 (M12).

Figure 2

BKPyV IgG seroreactivity among kidney transplant recipients according to BKPyV DNA detection before transplantation (baseline–bas) and at one-year follow-up (M12). Legend: ****p < 0.0001, ns non-significant difference p=0.623, OD INDEX—the ratio of the absorbance of a sample to the respective CO value. bas—baseline, before transplantation; M12—month 12 after transplantation.

Figure 3

BKPyV IgG seroreactivity among viremic kidney transplant recipients according to the viral load (A) and length of BKPyV DNA detection (B). (A). Legend: **** p < 0.0001, ns non-significant difference p=0.0527. OD INDEX - the ratio of the absorbance of a sample to the respective CO value, bas – baseline, before transplantation, M12 – month 12 after transplantation. Presumptive BKPyVAN was defined as >10⁴ copies/ml, viral load <10⁴ copies/ml viremia as low BKPyV-DNAemia, (B). Legend: **** p < 0.0001, ns, non-significant difference; p=0.0777. OD INDEX—the ratio of the absorbance of a sample to the respective CO value, bas—baseline, before transplantation, M12—month 12 after transplantation. Sustained DNAemia was defined as two or more consecutive positive plasma samples, while transient DNAemia refers to the detection of BKPyV DNA in a single sample.

Figure 4

Pretransplant BKPyV seroreactivity in kidney allograft donors stratified by posttransplant BKPyV-DNAemia. Legend: ** p=0.0011, * p=0.026. Donors’ OD INDEX represents the ratio of the absorbance of a sample to the respective CO value; donors were divided according to the posttransplant recipients’ BKPyV status.

Figure 5

Pretransplant BKPyV seroreactivity among kidney allograft donors of BKPyV- negative recipients and those with posttranplant BKPyVAN. Legend: p=0.058, donors’ OD INDEX represent the ratio of the absorbance of a sample to the respective CO value; donors were divided according to posttransplant BKVAN.

Figure 6

Seroreactivity during the follow-up in recipients with BKPyVAN, presumptive BKPyVAN, and low BKPyV-DNAemia. Legend: Presumptive BKPyVAN was defined as >10⁴ copies/ml, viral load <10⁴ copies/ml viremia as low BKPyV-DNAemia. BKVAN was a biopsy-proven disease.