Situation: A 45-year-old man is on day 5 after a living-donor kidney transplant. He takes tacrolimus at 8:00 AM and 8:00 PM, mycophenolate, and prednisone. He has an indwelling urinary catheter, and his urine output over the past day was 150–200 mL/h. Four months later, at a clinic visit, his serum creatinine has risen from 1.2 mg/dL (106 µmol/L) to 1.9 mg/dL (168 µmol/L) over 1 week. His urine output has decreased, his temperature is 37.9 °C, and the graft site is tender. His tacrolimus trough level is within the target range, and he has no tremor. How should the nurse classify this problem?

Acute rejection occurs over days to months, most often in the first 6 months, and shows a rising creatinine, falling urine output, fever, and graft tenderness; it is usually reversible with prompt treatment. Hyperacute rejection occurs within minutes to hours of transplant, and chronic rejection causes slow loss of function over months to years without fever or tenderness. A trough level within range and no tremor make calcineurin inhibitor toxicity unlikely.

Clinical classification of graft dysfunction

The presentation points to acute rejection. The timing—4 months after transplantation—falls within the highest-risk window for acute rejection, which is most common during the first 6 months after kidney transplantation ^[1]. The clinical picture is classic: a rise in serum creatinine from 1.2 mg/dL to 1.9 mg/dL over 1 week, decreased urine output, low-grade fever (37.9 °C), and graft tenderness. Acute rejection typically presents as unexplained graft dysfunction with fever and graft site pain, and it is often reversible when recognized and treated promptly.

The differential diagnosis can be narrowed by the tacrolimus trough level. Because the trough is within the target range and there is no tremor, calcineurin inhibitor toxicity is unlikely as the primary cause of the creatinine rise. Toxicity from tacrolimus is generally associated with supratherapeutic trough levels and neurologic findings such as tremor, which are absent here.

Watch out! Hyperacute rejection occurs within minutes to hours after reperfusion, not at 4 months. Chronic rejection develops over months to years as a slow, progressive decline in graft function, typically without fever or graft tenderness. The acute onset of fever and tenderness in this patient makes chronic rejection less consistent with the findings.

Feature	Acute rejection	Hyperacute rejection	Chronic rejection	Tacrolimus toxicity
Typical onset	Days to months, peak in first 6 months	Minutes to hours after transplant	Months to years, slow progression	Any time, related to drug level
Creatinine trend	Rising over days to weeks	Immediate graft failure	Slowly rising over months	Rising, often dose-dependent
Fever and graft tenderness	Common	Graft is lost rapidly	Usually absent	Usually absent
Trough level	Often within range	Not relevant	Often within range	Elevated
Reversibility	Often reversible with prompt treatment	Generally irreversible	Generally progressive, less responsive	Reversible with dose reduction

Key point! Acute rejection should remain high on the differential diagnosis for any unexplained graft dysfunction, because early recognition and treatment can preserve long-term graft survival. Tissue biopsy remains the gold standard for confirming the type and severity of rejection, including distinguishing T-cell–mediated from antibody-mediated processes ^[1]. Antibody-mediated rejection is increasingly recognized as a major cause of graft loss and can occur even when trough levels are therapeutic, particularly in the setting of nonadherence or HLA sensitization . In this patient, the clinical pattern of fever, graft tenderness, rising creatinine, and decreased urine output at 4 months post-transplant is most consistent with acute rejection, which is often reversible with prompt immunosuppressive escalation ^[1].