*Purpose: Describing the nuances in treatment of Angiotensin receptor II Type I antibody mediated rejection

*Methods: Complement-independent Angiotensin receptor II Type I antibodies (AT1R-Ab) have been identified in kidney transplant recipients at high risk of allograft rejection and loss, independent of the HLA system. AT1R-Ab are associated with a specific histo-molecular phenotype of kidney allograft rejection, characterized by microvascular and arterial inflammation, expression of endothelial cell associated transcripts and low prevalence of complement deposition in capillaries, independent of the presence of HLA-DSAs. We present a difficult case of antibody mediated rejection due to AT1R antibodies and delayed onset proteinuria.

*Results: 62 y/o Caucasian male with h/o HTN, DM, ESRD secondary to IgA nephropathy, received a 2nd living unrelated kidney transplant CMV +/+, induction with Alemtuzumab, maintenance immunosuppression with Tacrolimus, Mycophenolic acid and prednisone. Nadir creatinine was 1.8. 1st allograft lost due to chronic allograft nephropathy. CPRA 0% at the time of transplant. 2 months post-transplant he had persistent elevated blood pressure and a raise in creatinine to 2.3. No proteinuria or hematuria were noted. Allograft ultrasound did not reveal evidence of obstruction, collection or vascular abnormality. Viral studies and HLA DSAs were negative. Allograft biopsy reveled diffuse peritubular capillaritis and glomerulitis. C4D was negative in peritubular capillaries. Further testing revealed presence of non-HLA DSA – AT1R-Ab titers of 12. Endothelial cell cross match was negative. He was treated with IV steroids, Rituximab, plasma exchange and IV Ig. Creatinine improved to 1.7. He was also initiated on treatment with ARB – Telmisartan 40mg/d. 1.5 months after discharge he developed nephrotic range proteinuria and AKI with creatinine up to 2.1. Re-biopsy reveled marked ongoing transplant glomerulitis and mild peritubular capillaritis. He was re-treated with steroids, plasma exchange and IV Ig. Telmisartan dose increased to maximum tolerated dose 80mg/d. CD 19 levels were undetectable showing adequate response to Rituximab. AT1R antibodies were still present with titers at 11. Creatinine was stable at 2.0.

*Conclusions: Our case confirms that AMR with AT1R-Ab has a distinct phenotype and is difficult to treat. Onset of proteinuria after initiating treatment with an ARB is an unusual occurrence, but it can be explained by the presence of severe glomerulitis. Longer treatment course, close monitoring of AT1R Ab titers and proteinuria are critical in treating AMR mediated by AT1R-Ab.

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