Acute rejection remains a formidable impediment to long-term renal allograft survival despite significant therapeutic advancements. We report a case of a 36-year-old female, post ABO-compatible living-related renal transplantation, who presented with insidious graft dysfunction. Histopathological evaluation revealed features consistent with acute T-cell mediated rejection (TCMR) Grade 1B, accompanied by moderate acute tubular injury. The patient was managed with pulse corticosteroids followed by anti-thymocyte globulin (ATG). This case underscores the deceptive subtlety of clinical presentation and emphasizes the indispensable role of early biopsy and prompt immunosuppressive escalation in preserving graft integrity.
Renal transplantation is widely regarded as the definitive therapeutic modality for end-stage renal disease; however, acute rejection episodes continue to jeopardize graft longevity. Among these, T-cell mediated rejection (TCMR) represents a predominant immunological insult characterized by cellular infiltration and tubulointerstitial injury. Contemporary guidelines proposed by KDIGO advocate for early recognition and decisive intervention to mitigate irreversible allograft damage. Notably, clinical manifestations may often be muted, rendering histopathological evaluation indispensable.
A 36-year-old female, with a history of hypertension for one year, underwent an ABO-compatible living-related renal transplant in December 2022 and maintained stable graft function until the present episode. She presented with a biochemical profile suggestive of graft dysfunction, with serum creatinine elevated to 2.24 mg/dL and blood urea of 66 mg/dL. Hematological evaluation revealed hemoglobin of 12.3 g/dL, leukocytosis (12,800/µL), and platelet count of 3.55 lakh/µL. There were no clinical or laboratory indicators of infection, drug toxicity, or post-renal obstruction, thereby warranting further evaluation with a renal allograft biopsy.
Examination of the allograft biopsy demonstrated an adequate core comprising both cortex and medulla with six glomeruli. The glomeruli were unremarkable, with no evidence of mesangial expansion, glomerulitis, or transplant glomerulopathy. However, there was conspicuous peritubular capillaritis (ptc2), accompanied by marked interstitial inflammation (i3) and severe tubulitis (t3). Tubular epithelial vacuolations and features consistent with moderate acute tubular injury were noted. The vasculature revealed mild arteriolar hyalinosis (ah1) without evidence of vasculitis (v0).
The specimen was inadequate for evaluation due to absence of glomeruli.
The constellation of histopathological findings was diagnostic of acute T-cell mediated rejection (TCMR), Grade 1B, as per the Banff classification, with coexistent moderate acute tubular injury and mild arteriolar hyalinosis.
In accordance with established therapeutic protocols, the patient was initiated on high-dose pulse intravenous corticosteroids. Given the severity of histological involvement and anticipated steroid resistance, therapy was escalated to anti-thymocyte globulin (ATG) administered at a dose of 50 mg on alternate days, of which three doses have been completed to date. The patient remains under close clinical and biochemical surveillance to assess therapeutic response and guide дальнейшее immunosuppressive modulation.
TCMR represents a complex alloimmune response mediated predominantly by recipient T lymphocytes recognizing donor antigens, culminating in interstitial inflammation and tubular injury. The Banff classification serves as the cornerstone for histological grading, with Grade 1B denoting moderate rejection characterized by significant interstitial infiltration (i≥2) and tubulitis (t≥2).
In the present case, the presence of severe interstitial inflammation (i3) and tubulitis (t3) substantiates the diagnosis. Although peritubular capillaritis was observed, the absence of C4d deposition argues against concurrent antibody-mediated rejection. Additionally, the notable presence of plasma cells and eosinophils within the interstitium introduces a potential diagnostic confounder, necessitating exclusion of drug-induced interstitial nephritis; however, in the appropriate clinical and histological context, these findings may also reflect heightened immunological activity in severe rejection.
Therapeutically, current KDIGO recommendations advocate corticosteroids as first-line therapy, with lymphocyte-depleting agents such as ATG reserved for steroid-resistant or severe cases. Early and aggressive intervention remains pivotal in averting progression to chronic allograft dysfunction.
This case exemplifies the often-subtle clinical presentation of acute rejection, wherein minimal biochemical perturbations may conceal significant histopathological injury. It reinforces the critical importance of timely allograft biopsy, meticulous interpretation using Banff criteria, and prompt escalation of immunosuppressive therapy in optimizing graft survival and patient outcomes.
Dr. S. Farhan Ali DrNB Nephrology, Final Year Resident Kauvery Hospital, Chennai.
Dr. R. Balasubramaniyam Chief Nephrologist Kauvery Hospital, Chennai.
