A 44-year-old man with diabetic nephropathy undergoes a renal transplant. One week later, he develops low-grade fever, body aches, and decreased urine output. Temperature is 37.2 C (99 F), blood pressure is 124/76 mm Hg, and pulse is 88/min. Physical examination shows mild tenderness over the graft on palpation. Serum creatinine is 2.2 mg/dL, an increase from 1.2 mg/dL two days ago. Arterial and venous Doppler studies reveal adequate graft perfusion. Graft biopsy demonstrates dense interstitial infiltration by mononuclear cells. Which of the following is the most likely cause of this patient's current condition?

Question

A 44-year-old man with diabetic nephropathy undergoes a renal transplant.  One week later, he develops low-grade fever, body aches, and decreased urine output.  Temperature is 37.2 C (99 F), blood pressure is 124/76 mm Hg, and pulse is 88/min.  Physical examination shows mild tenderness over the graft on palpation.  Serum creatinine is 2.2 mg/dL, an increase from 1.2 mg/dL two days ago.  Arterial and venous Doppler studies reveal adequate graft perfusion.  Graft biopsy demonstrates dense interstitial infiltration by mononuclear cells.  Which of the following is the most likely cause of this patient's current condition?

Quizplus · Accepted Answer

11ec160b_37c2_1460_9249_693e11ae4f29_MD0001_00 This patient with impaired renal function within the first few weeks following renal transplant likely has acute rejection. This process is mostly cell-mediated and results from sensitization of recipient T cells to donor graft MHC antigens (human leukocyte antigens). Humoral (antibody-mediated) immunity may also be involved in acute rejection, but it typically plays a smaller role. Acute rejection usually occurs within the first 6 months following transplantation. Patients often have an asymptomatic rise in serum creatinine, but they may also have low-grade fever, malaise, joint pains, and graft tenderness. Histology reveals a dense lymphocytic infiltrate sometimes accompanied by vascular inflammation. Acute rejection is typically reversible and usually treated with high-dose glucocorticoids. Chronic immunosuppression with a calcineurin inhibitor-based regimen (eg, tacrolimus plus mycophenolate and low-dose prednisone) helps prevent acute rejection episodes. (Choices A and B) Graft versus host disease (GVHD) primarily involves activation of donor T cells within grafted tissue against recipient (host) antigens. B cells are also involved to a lesser extent. GVHD typically occurs only when the recipient lacks a competent immune response (eg, in the setting of bone marrow transplant). (Choice C) Host B-cell sensitization against donor antigens results in a humoral antibody response and is sometimes involved in acute rejection. Histology is expected to show deposition of complement (eg, C4d), neutrophilic infiltrate, and necrotizing vasculitis; this patient's mononuclear (lymphocytic) infiltrate is consistent with a cell-mediated T-cell response. Although it can occur acutely, the humoral response tends to be more involved in chronic rejection, which occurs months to years following transplant. (Choice E) Preformed antibodies against graft ABO or other antigens can lead to hyperacute graft rejection. Because the antibodies are already present in the recipient circulation, there is rapid response against the donor graft, leading to arterial fibrinoid necrosis and vascular thrombosis with graft mottling and cyanosis. Thorough crossmatching prior to transplant makes hyperacute rejection a rare occurrence. Educational objective: Organ rejection can be hyperacute, acute, or chronic. Acute rejection most often occurs within weeks or up to 6 months after transplant and is predominantly cell-mediated, involving sensitization of host T lymphocytes against donor MHC antigens. There is typically graft dysfunction with histology showing a dense, mononuclear (ie, lymphocytic) infiltrate.

A 44-Year-Old Man with Diabetic Nephropathy Undergoes a Renal Transplant