Biopsy findings after detection of de novo donor-specific antibodies in renal transplant recipients: a single center experience

Abstract

Background De novo donor-specific antibodies (DSA) are associated with an increased risk of antibody-mediated rejection and a substantial reduction of allograft survival. We hypothesized that detection of DSA should prompt a biopsy even in the absence of proteinuria and loss of estimated glomerular filtration rate (eGFR). However, data on a population without proteinuria or loss of kidney function is scant, and this is the main novelty of our study design. Methods Single center retrospective analysis on biopsy findings after detection of de novo DSA. One-hundred-thirty-two kidney and pancreas-kidney transplant recipients were included. Eighty-four of these patients (63.6%) underwent allograft biopsy. At the time of biopsy n = 50 (59.5%) had a protein/creatinine ratio (PCR) > 300 mg/g creatinine and/or a loss of eGFR ≥ 10 ml/min in the previous 12 months, whereas 40.5% did not. Diagnosis of rejection was performed according to Banff criteria. Results Seventy-seven (91.7%) of the biopsies had signs of rejection (47.6% antibody mediated rejection (ABMR), 13.1% cellular, 20.2% combined, 10.7% borderline). Among subjects without proteinuria or loss of eGFR ≥ 10 ml/min/a (n = 34), 29 patients (85.3%) showed signs of rejection (44.1% antibody mediated (ABMR), 14.7% cellular, 11.8% combined, 14.7% borderline). Conclusion The majority of subjects with de novo DSA have histological signs of rejection, even in the absence of proteinuria and deterioration of graft function. Thus, it appears reasonable to routinely perform an allograft biopsy after the detection of de novo DSA. Graphic abstract

The Clinical Utility of Post-Transplant Monitoring of Donor-Specific Antibodies in Stable Renal Transplant Recipients: A Consensus Report With Guideline Statements for Clinical Practice

“…Of those rejections, 60% were ABMR, 20% mixed rejections, and 20% were TCMR. Waldecker et al [ 81 ] retrospectively studied 84 German patients with indication biopsies or in case of dnDSA development from a single centre and found that out of 50 patients with subclinical dnDSA, 44% had ABMR, 15% had TCMR, 12% had mixed rejection and 15% had borderline rejection. Notably, only 14% of these patients had no histopathological signs of rejection at light microscopy.…”

“…While most studies only reported these biopsy results in terms of either positive or negative for ABMR, the studies by Schinstock et al [ 30 ], Parajuli et al [ 80 ] and Waldecker et al [ 81 ] interestingly further show that subclinical dnDSA can also be a signal for underlying TCMR. Unfortunately, no biopsies were performed in a DSA-negative control group in these studies, making it difficult to ascertain the precise odds of dnDSA to signal TCMR risk.…”

“…However, no control group was included and thus it cannot be concluded that improvement in outcome was due to treatment. Furthermore, irrespective of efficacy, subjecting all patients with subclinical dnDSA to such a strong and broadly targeting immunosuppressive regimen might be difficult to justify, considering that roughly half of this population have no underlying observable histological injury [30,57,78,[80][81][82][83]. In addition, transient spontaneous negativity of dnDSA has been observed in 24% of patients with subclinical dnDSA and complete clearance of dnDSA has been observed in around 10% of patients [29].…”