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Key Clinical Message In addition to post‐transplant lymphoproliferative disorders, it is necessary to be alert to the drug‐resistant bacteria or fungal infection, especially Talaromyces marneffei, in kidney transplant patients who have failed antibiotic treatment and whose PET‐CT indicates high metabolic mass in the transplanted kidney with a large number of other organs and lymph nodes. Abstract Talaromyces marneffei (TM) is a rare pathogenic fungus that primarily affects individuals with compromised immune systems. Post‐transplant lymphoproliferative disorders (PTLD) are serious complications that can occur after solid organ and cell transplantation. Both TM infection and PTLD can invade the monocyte–macrophage system and often manifest as extranodal masses. This case report describes a kidney transplant patient who presented with symptoms of frequent, urgent, and painful urination over 6 months. Pulmonary CT scans revealed multiple nodules, and PET‐CT demonstrated enlarged lymph nodes in the lungs and the transplanted kidney. The clinical manifestations closely mimicked those of PTLD. The confirmation of TM was achieved through pathogen metagenomic next‐generation sequencing and renal biopsy. Unfortunately, despite receiving treatment with antifungal agents, anti‐infective therapy, the patient's condition did not respond favorably, ultimately resulting in their unfortunate demise due to COVID‐19.

Mitochondria are essential organelles that possess their own DNA. Mitochondrial dysfunction has been revealed in many kidney diseases, including BK polyomavirus-associated nephropathy (BKPyVAN). In this study, we introduce an innovative approach for non-invasive monitoring of mitochondrial impairment through urinary donor-derived cell-free mitochondrial DNA (ddcfmtDNA), addressing the crucial challenge of BKPyVAN diagnosis. Urinary samples were collected at the time of biopsy from a total of 60 kidney transplant recipients, comprising 12 with stable function, 22 with T cell-mediated rejection, and 21 with biopsy-proven BKPyVAN. Our findings reveal that the ddcfmtDNA-to-ddcfDNA ratio exhibits superior capability in distinguishing BKPyVAN from other conditions, with a cutoff value of 4.96% (area under curve = 0.933; sensitivity: 71.4%; and specificity: 97.1%). Notably, an elevation of ddcfmtDNA levels is associated with mitochondrial damage, as visualized through electron microscopy. These results underscore the promise of non-invasive monitoring for detecting subtle mitochondrial damage and its potential utility in BKPyVAN diagnosis. Further investigations are required to advance this field of research.