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Impact Of Nonspecific Allograft Biopsy Findings In Symptomatic Kidney Transplant Recipients – Scientific Reports –

Our study showed that 31.9% (83 out of 263) of patients who underwent a for-cause biopsy had nonspecific allograft biopsy findings in kidney transplantation. The graft outcome in recipients with nonspecific biopsy findings was comparable to that in recipients who did not require the for-cause biopsy. Interestingly, 28% and 25% of patients with nonspecific findings in the first for-cause biopsy showed a nonspecific allograft biopsy finding at the second and third for-cause biopsy, respectively. Our findings offer a better understanding of the ambiguous graft biopsy results occasionally encountered in clinical practice.

In this study, nonspecific allograft biopsy findings were defined as other findings excluding ABMR, TCMR, borderline rejection, CNI toxicity, infection, glomerulonephritis, and diabetic nephropathy. They included pathologic findings like acute tubular necrosis, tubulointerstitial nephritis, or interstitial inflammation that did not satisfy rejection. These findings were present in 31.9% of patients who underwent a for-cause biopsy. Recent studies showed that 29% of the 412 for-cause biopsies had biopsy results with “no major abnormalities”10 and that 25% of the 1371 kidney transplantation recipients who took a for-cause graft biopsy had “minor abnormalities”, including acute tubular injuries and tubular interstitial nephritis11. One domestic study revealed that 20% of 410 for-cause biopsies had pathologic findings characterized by “others”, excluding major abnormalities12. In addition, a previous study showed that histological diagnosis of “minor abnormalities” has comparable graft survival with “normal biopsy findings”11. Correspondingly, our study showed that nonspecific allograft biopsy findings might not be a poor prognostic factor even in symptomatic recipients.

In our study, patients with nonspecific allograft biopsy findings were more likely to have received a kidney from a deceased donor than patients without a for-cause biopsy. DGF is a common complication that occurs after kidney transplantation from deceased donors13. Nonspecific allograft biopsy findings include pathologic results such as acute tubular injury and minor vessel injury, which are often seen in DGF. Therefore, the type of donor may influence the occurrence of nonspecific allograft biopsy findings in kidney transplant recipients. Additionally, the subgroup analysis by 1-month time point of biopsy implies that graft survival may be favorable in recipients with nonspecific allograft findings, regardless of DGF. We found a significant difference in the use of ATG induction therapy between patients with nonspecific allograft biopsy findings and patients with no for-cause biopsy. ATG induction therapy is commonly used in high immunologic risk patients to reduce the incidence and severity of acute rejection14. Recipients with nonspecific allograft biopsy findings were at a relatively lower immunologic risk; thus, their graft survival was potentially comparable to those without a for-cause biopsy, even if they needed a for-cause biopsy.

Several studies have examined the histological diagnosis of allografts at different biopsy time points after kidney transplantation. Acute tubular injury, including CNI toxicity, was the most common finding within 14 days after kidney transplantation, accounting for 40% of all biopsies, but it decreased thereafter. On the other hand, rejection was the second most common finding within 14 days, accounting for 28% of all biopsies, and it tended to increase over time11. In a recent study, the histological diagnosis of “no major abnormalities” accounted for 62% of all biopsies during 0–6 weeks after kidney transplantation, 39% of biopsies during 6 weeks–6 months, 22% of biopsies during 6–12 months, and 16% of biopsies after 12 months10. These findings, observed relatively early after transplantation, are mainly associated with ischemic injury and acute kidney injury related to drugs or various causes. In our study, the mean biopsy time point after kidney transplantation was 15.4 months. This may be due to the inclusion of biopsy findings such as acute tubular necrosis and tubulointerstitial nephritis, which are not considered major abnormalities in other studies. Interestingly, we found that more than a quarter of patients who had nonspecific findings at the previous biopsy also had nonspecific findings at the subsequent biopsy. This suggests that these nonspecific biopsy findings may not indicate future major abnormalities, such as rejection, but rather reflect minor or transient changes in the allograft.

This study has limitations due to its retrospective observational study design, which relies on the review of electronic medical records. Regrettably, a comprehensive review of every confirmed pathologic finding was not feasible. We could not reassess histologic findings, thus not reflecting the latest Banff criteria. However, we did not include borderline rejection in nonspecific allograft findings. Therefore, we could minimize the potential variability introduced by the evolving definitions of allograft rejections over time. Variations in descriptions among pathologists were inevitable. Moreover, the decision to perform an allograft biopsy in cases of acute allograft dysfunction following kidney transplantation could vary depending on the healthcare professionals involved. The maximum follow-up period for kidney transplants in our study was 13 years, with most recipients having a follow-up duration shorter than this. Therefore, our results may not reflect a long-term graft survival beyond 10 years. Finally, there remained uncertainty concerning the definition of the nonspecific allograft biopsy findings.

In conclusion, there was no significant difference in graft survival between patients with nonspecific biopsy findings and patients with no for-cause biopsy. This study can provide more information about ambiguous graft biopsy results occasionally encountered in clinical practice. A better understanding of the minor abnormality in the allograft for-cause biopsy may help improve the management of kidney transplant recipients.