An Unusual Case of Late-Onset Profound Granulomatous Interstitial Nephritis Due to Adenovirus in a Kidney Allograft

Introduction: Adenovirus (AV) is a common infection in transplant recipients with wide clinical presentations, ranging from subclinical and self-limiting to lethal disease. Most often, AV infection occurs within weeks to months after transplantation, suggesting reactivation of a latent AV in the immunosuppressed recipient as the source of infection. This report describes a case of AV infection in the renal allograft 19 years after transplantation. Case Description: A 71 year old male with analgesic nephropathy, status post DDKT was seen for annual f/u 19 yrs later. Immunosuppression included MMF and Sirolimus. Recently had AKI of unclear etiology and 1g proteinuria which was stable. UA showed hematuria, BK blood/uine and Adenovirus PCR in blood were negative. Urine Adenovirus DNA was barely detected. DSA, non-invasive gene expression profile, and donor-derived cell-free DNA were negative. Kidney biopsy showed granulomatous interstitial nephritis. Adenovirus immunohistochemistry was equivocal. PCR testing for Adenovirus on the paraffin embedded block was positive. Patient's wife was treated for large B cell lymphoma with chemotherapy and had hemorrhagic cystitis 2/2 Adenovirus and was receiving Cidofovir. Given the negative PCR test in the blood and low level of Adenovirus in the urine, no intervention was done. Cr is stable and back to baseline, UA is bland and proteinuria is stable at 6 month follow up. Discussion: Asymptomatic AV viremia is common in solid organ transplant recipients, estimated at 7.2% of patients and it was estimated that AV is excreted by 11% of patients with renal transplant. Since most AV infections occur during childhood, it is believed to be reactivation of an endogenous latent infection. This late onset of AV infection suggests that this is a de novo infection. In addition, this case highlights the perseverance that may be required to make a definitive diagnosis. Identification of AV contact tracing, prompted us for PCR testing for AV on the paraffin embedded block after immunohistochemical staining for the AV antigen on the biopsy was equivocal. A negative serological test and the absence of diagnostic viral cytopathic changes in a renal biopsy do not rule out AV infection and hence both the clinician and the pathologist need to remain alert to the possibility of this diagnosis.