Renal Allograft Tuberculosis Diagnosed by Tissue GeneXpert in a Smear-Negative Granulomatous Lesion: A Case Report from a TB-Endemic Setting

Abstract Tuberculosis (TB) is a major opportunistic infection after kidney transplantation, particularly in high-burden regions. While pulmonary and disseminated forms predominate, isolated renal allograft TB is rare and can be difficult to distinguish from rejection or drug-induced interstitial nephritis. Diagnostic uncertainty is further compounded by the frequent absence of microbiological confirmation in smear-negative extrapulmonary disease. We report a 48-year-old woman who developed renal allograft TB three and a half years after a living-donor kidney transplant for diabetic kidney disease. She presented with malaise, anorexia, evening fevers, graft pain, and acute allograft dysfunction (serum creatinine 6.4 mg/dL), with markedly elevated inflammatory markers and sterile pyuria. Chest imaging was normal, and mycobacterial smears and cultures were negative. Allograft biopsy demonstrated florid granulomatous tubulointerstitial nephritis with severe interstitial inflammation and tubulitis (Banff i3/t3), without microvascular injury. Granulomas were well formed but non-caseating. C4d and SV40 were negative, donor-specific antibodies were absent, and special stains showed no acid-fast bacilli or fungi. Tissue GeneXpert MTB/RIF performed on the biopsy confirmed rifampicin-sensitive Mycobacterium tuberculosis, establishing the diagnosis. The patient received rifampicin-based quadruple anti-TB therapy. As rifabutin was unavailable, tacrolimus doses were increased approximately threefold with close monitoring. Symptoms resolved within 2 weeks, and serum creatinine improved to 1.6 mg/dL by 5 months. A 12-month treatment course was planned. This case highlights the decisive role of tissue GeneXpert in resolving diagnostic ambiguity in granulomatous allograft lesions and supports its use in smear-negative extrapulmonary disease.