Characteristics, risk factors and outcome of BKV nephropathy in kidney transplant recipients: a case-control study.

BACKGROUND: Following kidney transplantation, BK virus associated nephropathy (BKVN) occurs in 1 to 10% of kidney transplant recipients (KTR) and represents a major cause of graft loss. We aim at identifying factors associated with biopsy proven BKVN among KTR. METHODS: We conducted a retrospective case-control study including all KTR with a biopsy-proven diagnosis of BKVN between 2005 and 2019. Clinical characteristics and outcome were described. For each case, one control KTR without BKV infection was identified and matched by age, transplant date, and donor status. Factors associated with BKVN diagnosis were identified using exact conditional logistic regression. Comparative survival was described using Kaplan-Meier estimator. RESULTS: Sixty-four cases of BKVN were identified among 1737 new kidney transplantation (3.7% prevalence). Clinical characteristics did not differ between groups, except for a higher c-PRA among cases. BKVN occurred in a median time of 11 (5-14.5) months after KT, and was associated with a significantly impaired graft function at diagnosis. Following BKVN, 61 (95%) of the patients had immunosuppression reduction, which led to BKV DNAemia resolution in 49% of cases. In multivariate analysis, factors associated with BKVN diagnosis were lymphopenia < 500/mm3 and a prednisone dose > 7.5 mg/day. Median duration of follow-up was 40 months for both groups. BKVN was associated with a significantly increased risk of graft rejection (P = 0.02) and return to dialysis (P = 0.01). CONCLUSIONS: BKVN remains a severe complication in KTR and is associated with an increased risk for acute rejection and return to dialysis. Lymphopenia below 500/mm3 and corticosteroid maintenance therapy are significantly associated with biopsy-proven BKVN diagnosis.

BK virus genotypes and humoral response in kidney transplant recipients with BKV associated nephropathy.

BACKGROUND: Among kidney transplant recipients (KTR) with BK virus associated nephropathy (BKVN), BKV genotypes' evolution and anti-BKV humoral response are not well established. We aim to analyze BKV replication and genetic evolution following transplantation, and characterize concomitant anti-BKV-VP1 humoral response. METHODS: We retrospectively analyzed 32 cases of biopsy-proven BKVN. Stored plasma and kidney biopsies were tested for BKV viral load, and VP1 sequencing performed on positive samples. BKV-VP1 genotype-specific neutralizing antibodies (NAbs) titers were determined at transplantation and BKVN. RESULTS: At the time of BKVN diagnosis, BKV viral load was 8.2 log10 IU/106 cells and 5.4 log10 IU/mL in kidney and plasma, respectively. VP1 sequencing identified the same BKV-subtype in both compartments in 31/32 cases. At the time of transplantation, 8/20 (40%) of biopsies tested positive for BKV detection, whereas concomitant BKV viremia was negative. VP1 sequencing identified a different subtype compared to BKVN in 5/6 of these samples. This was confirmed following transplantation: 8 patients had a BKV+ biopsy before BKV viremia, and VP1 sequencing identified a different subtype compared to BKVN in all of them. After the onset of BKV viremia and prior to BKVN diagnosis, the BKV subtype in BKV+ plasma and kidney biopsy was the same as the one isolated at BKVN. BKV-VP1 NAbs titers were significantly higher at the time of BKVN compared to transplantation (p = .0031), with similar titers across genotypes. CONCLUSION: Altogether, our data suggest that among some KTR with BKVN, the BKV genotype from the donor may not be responsible for BKVN pathogenesis.

Incidence, risk factors and outcome of BK virus hemorrhagic cystitis following allogenic hematopoietic cell transplantation: a retrospective cohort study.

BK polyomavirus (BKPyV) can cause hemorrhagic cystitis (HC) after allogeneic hematopoietic cell transplantation (allo-HCT). Recent evaluation of BKPyV HC (BKHC) incidence and risk factors are scarce. We conducted a retrospective single-center study on a recent allo-HCT cohort over 3 years in a referral academic hospital for hematological malignancies. Primary objective was to determine BKHC incidence using competitive risk analysis. Secondary objectives were the identification of HC risk factors using Fine and Gray models and the evaluation of mortality. Among 409 allo-HCT recipients (median age 47 years), 41 developed BKHC after a median delay of 41 [32-55] days. Incidence density of BKHC was 2.4 [1.8-3.1] events per 100 days post-allo-HCT. The proportion of BKHC after adjustment for time-dependent competing risk was 9.5 [9.5-9.6]% at 100 days. BK viremia was detected in 63 versus 20% in tested patients with and without BKHC, respectively. After adjustment for confounders, myeloablative conditioning regimen with and without cyclophosphamide and CMV seropositivity were independently associated with BKHC. Post-transplantation cyclophosphamide was not associated with BKHC. BKHC resolved in 90% of the patients. No difference in mortality was found between patients with or without BKHC. In parallel to the recent evolution of allo-HCT protocols, BKHC remains a frequent complication following allo-HCT.

Clostridioides difficile infection in solid organ and hematopoietic stem cell transplant recipients: A prospective multinational study.

BACKGROUND: Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality in recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT). In retrospective single center analyses, severe disease and relapse are common. We undertook an international, prospective cohort study to estimate the response to physician determined antibiotic treatment for CDI in patients with SOT and HSCT. METHODS: Adults with a first episode of CDI within the first 2 years of SOT or HSCT were enrolled. Demographics, comorbidities, and medication history were collected, and over 90 days of follow-up clinical cure, recurrences, and complications were assessed. Logistic regression was used to study associations of baseline predictors of clinical cure and recurrence. Odds ratios (ORs) and 95% confidence intervals (CIs) are cited. RESULTS: A total of 132 patients, 81 SOT and 51 HSCT (32 allogeneic), were enrolled with a median age of 56 years; 82 (62%) were males and 128 (97%) were hospitalized at enrollment. One hundred and six (80.3%) were diagnosed by DNA assay. CDI occurred at a median of 20 days post-transplant (interquartile range, IQR: 6-133). One hundred and eight patients (81.8%) were on proton pump inhibitors; 126 patients (95.5%) received antibiotics within the 6 weeks before CDI. The most common initial CDI treatments prescribed, on or shortly before enrollment, were oral vancomycin alone (50%) and metronidazole alone (36%). Eighty-three percent (95% CI: 76, 89) of patients had clinical cure; 18% (95% CI: 12, 27) of patients had recurrent CDI; global clinical cure occurred in 65.2%. Of the 11 patients who died, two (1.5% of total) were related to CDI. In multivariable logistic regression analyses, the type of initial treatment was associated with clinical cure (p = .009) and recurrence (p = .014). A history of cytomegalovirus (CMV) after transplant was associated with increased risk of recurrence (44% with versus 13% without CMV history; OR: 5.7, 95% CI: 1.5, 21.3; p = .01). CONCLUSIONS: Among adults who develop CDI after SOT or HSCT, despite their immunosuppressed state, the percentage with clinical cure was high and the percentage with recurrence was low. Clinical cure and recurrence varied by type of initial treatment, and CMV viremia/disease was associated with an increased risk of recurrence.