Comparison of Recipients with Early and Later Presentation Polyomavirus Nephropathy (PVN) with Regard to Histological Findings and Graft Survival: What is the Influence of CD4/CD8 Ration on the Presenting Time of PVN

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Abstract

Introduction

PVN is a common complication occurring around 12 months after transplant (Tx). Although unusual, the number of patients with late-presenting PVN is too much to underestimate. Thus, we aimed to understand if there are any differences between early and late-presenting PVN with regard to histological findings and graft survival.

Materials and Methods

All indication and follow-up biopsies of 71 patients with PVN re-evaluated and examined for the development of interstitial fibrosis (IF). Interstitial plasma cells, neutrophils, and CD3, CD4, CD8, HLA-DR positive cells, and macrophages graded. Patients separated into four groups in regards to the time of the development of PVN after Tx [Group A: <12 months (n:35), Group B: 12-24 months (n:13), Group C: 24-48 months (n:15), Group D: >48 months (n:8)]. Also, recipients correlated in two groups as Group 1 (n:48) early PVN (≤12 months) and Group 2 (n: 23) late PVN (>12 months).

Results

The mean interval between the diagnosis of PVN and Tx was 17±22 months. Group 1 had higher mean hemodialysis (HD) time before Tx than Group 2 (p<.05). At the same time with PVN, CMV viremia was found in 27 patients. The mean viral load in urine and plasma at diagnosis was found higher in Group 1 than those Group 2 (p<0,01). Group 1 showed lower stages and higher degrees of polyoma viral load (Pvl) in biopsy compared to Group 2 (p<.05). Viral load in urine, plasma, and biopsy found to increase from Group A to Group D. Compared to Group 2; Group 1 showed higher degrees of interstitial neutrophil, plasma, macrophage, lymphocyte, DR-positive cell infiltration and lower degrees of the CD4/CD8 ratio (p<.01). All inflammatory cell types in interstitium found to increase from Group A to Group D. Interstitial CD4/CD8 ratio showed a significant negative correlation with Pvl (r=-0.320, p=.01), viremia (r=-0.602, p<.001) and viruria (r=-0.748, p<.001). Total 43 patients (60.6%) developed IF during follow-up, and 31 (43.7%) cases lost their graft at a mean time of 18±14 months after PVN. The risk of the development of IF increases from Group A to Group D (p<.01). Compared to Group 2 (28.7±16 months), the mean time of the graft loss after PVN was significantly early in Group 1 (13.3±9 months). The mean time of graft loss also decreases from group A to D (p<.05). Positive correlation found between the graft loss and CD4/CD8 ratio (r=0.391, p<.05).

Conclusion

This study pointed out that late-onset PVN is not uncommon. Recipients with late-onset PVN had a better prognosis than early-onset cases. Although the cause of late-onset PVN remains unclear, it is possible that host cells could influence the time of the onset of PVN. We showed that lower CD4 and higher CD8 proportions were risk factors for early-onset of PVN and poor graft survival. Contrarily patients who had high CD4/CD8 ratio developed late-onset PVN and better graft survival.

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