THE GRAFT THAT BECAME A GRANULOMA: RENAL ALLOGRAFT TUBERCULOSIS

Tuberculosis (TB) remains one of the most significant opportunistic infections in kidney transplant recipients, often presenting with atypical manifestations that can mimic rejection. Renal allograft involvement is uncommon but may lead to irreversible graft injury or loss. We report a case of renal allograft tuberculosis characterized by complete replacement of the graft parenchyma with granulomatous inflammation, clinically resembling antibody-mediated rejection.

A 30-year-old male with end-stage renal disease of undetermined etiology underwent a deceased-donor kidney transplant in 2013. Induction therapy included basiliximab, and prophylaxis was provided with valganciclovir and TMP-SMX due to high CMV risk. Maintenance therapy consisted of tacrolimus, mycophenolate mofetil, and prednisone. His baseline serum creatinine was 0.9 mg/dL, and a one-year protocol biopsy revealed no rejection.

Between 2015 and 2016, he developed a perianal abscess and a community-acquired pneumonia, both treated successfully. In 2019, he presented with recurrent diarrhea, fever, and lumbar pain, initially treated as urinary tract infections despite persistently sterile cultures. Serum creatinine increased to 1.3 mg/dL, accompanied by microscopic hematuria and sterile pyuria. Viral PCRs for BK, CMV, and adenovirus were negative. The presence of anti-donor HLA antibodies (B6, DR4, DQ8, DR53) and rising panel-reactive antibodies (PRA) suggested possible antibody-mediated rejection; however, a renal biopsy showed only mild interstitial fibrosis and chronic vascular changes without active rejection.

In 2020, renal function deteriorated further (creatinine 2.7 mg/dL) with episodes of macroscopic hematuria and negative autoimmune markers. Ultrasound showed graft enlargement, segmental hydronephrosis, ureteral thickening, and grade II vesicoureteral reflux. MRI of the spine revealed vertebral destruction at T11–L1 with paravertebral and psoas abscesses suggestive of tuberculous spondylitis. Bacilloscopy and GeneXpert MTB from sputum were negative, but urine culture was positive for Mycobacterium tuberculosis.

In 2021, the patient presented with further deterioration of renal function (creatinine 4.0 mg/dL). A new determination of donor-specific antibodies revealed increased mean fluorescence intensity (MFI) levels, raising concern for antibody-mediated rejection. As part of the diagnostic protocol, a repeat renal allograft biopsy was performed, revealing 26 glomeruli with chronic hypoperfusion and complete interstitial replacement by numerous tuberculoid granulomas containing Langhans-type multinucleated giant cells (Figure 1). Ziehl–Neelsen staining was positive for acid-fast bacilli, while Grocott staining was negative. Due to these findings consistent with active Mycobacterium tuberculosis infection, anti-rejection therapy  could not be administered. The patient subsequently experienced progressive graft failure and returned to maintenance dialysis.

This case illustrates a rare and destructive manifestation of renal allograft tuberculosis that clinically mimicked antibody-mediated rejection due to rising donor-specific antibodies and PRA levels. Despite immunologic evidence suggestive of rejection, anti-rejection therapy was withheld because the biopsy demonstrated diffuse granulomatous inflammation consistent with Mycobacterium tuberculosis. This case underscores the importance of including tuberculosis in the differential diagnosis of graft dysfunction with sterile pyuria, particularly in endemic areas, to prevent misdiagnosis, inappropriate immunosuppression, and irreversible graft loss.