A 45-year-old man comes to clinic for routine follow-up. He has a history of end-stage renal disease due to autosomal dominant polycystic kidney disease, and he underwent a deceased-donor kidney transplant 4 years ago. The patient has hypertension that initially resolved following the transplant but redeveloped 6 months ago. Review of his recent laboratory studies reveals a progressive increase in serum creatinine levels over the last few months. Urinalysis is within normal limits. On ultrasonography, the transplanted kidney is reduced in size. A biopsy of the graft is most likely to show which of the following?

Question

A 45-year-old man comes to clinic for routine follow-up.  He has a history of end-stage renal disease due to autosomal dominant polycystic kidney disease, and he underwent a deceased-donor kidney transplant 4 years ago.  The patient has hypertension that initially resolved following the transplant but redeveloped 6 months ago.  Review of his recent laboratory studies reveals a progressive increase in serum creatinine levels over the last few months.  Urinalysis is within normal limits.  On ultrasonography, the transplanted kidney is reduced in size.  A biopsy of the graft is most likely to show which of the following?

Quizplus · Accepted Answer

11ec160b_37c3_4ce2_9249_39a4ac7aae6a_MD0001_00 This kidney transplant recipient with progressive decline in renal function most likely has chronic allograft rejection. The process is a mixed cell-mediated and antibody-mediated response and can occur anytime from several months to years posttransplantation. Following transplant, T cells are activated and recipient antibodies are created against graft HLA and other antigens. The activated T cells can initially cause cell-mediated acute rejection, which is generally reversible via an increase in immunosuppression (eg, high-dose glucocorticoids). Chronic rejection represents progression of cell-mediated and antibody-mediated inflammation (eg, via activation of complement and recruitment of neutrophils) to the point that irreversible renal damage takes place; the kidney grossly decreases in size, and histopathology shows obliterative vascular wall thickening with tubular atrophy and interstitial fibrosis. Due to increased sodium retention, declining renal function in chronic rejection is also commonly accompanied by new or worsening hypertension. Chronic rejection is the most common cause of renal graft failure following transplant. (Choice A) A dense, interstitial, mononuclear (lymphocytic) infiltrate is characteristic of acute allograft rejection, which is most often a primarily T cell-mediated process. Acute rejection typically occurs <6 months after transplant but can occur later in a patient in whom posttransplant immunosuppression has been stopped. (Choice B) Glomerular injury in chronic rejection is predominantly ischemic, and crescent formation is not typically observed. Crescents develop mainly in anti-glomerular basement membrane antibody-mediated, antineutrophilic cytoplasmic autoantibody-associated, or immune complex-mediated glomerulonephritis. (Choice D) Muddy brown casts can be seen with acute tubular necrosis, which usually manifests as acute (rather than gradual) kidney injury. Tubular hypertrophy may be present during the recovery phase. These findings are not typical of chronic rejection. (Choice E) Vascular fibrinoid necrosis with capillary thrombotic occlusion occurs in hyperacute rejection, which is a rapid and profound form of antibody-mediated rejection caused by preformed antibodies to graft antigens. Chronic rejection is a more gradual antibody-mediated process resulting from sensitization that occurs after a transplant has taken place. Educational objective: Chronic renal allograft rejection manifests months to years after a transplant and presents with worsening hypertension and a gradual decline in renal function. It involves a chronic cell-mediated and antibody-mediated response against donor antigens and leads to obliterative vascular wall thickening, tubular atrophy, and interstitial fibrosis. The process is usually irreversible and eventually leads to graft failure.

A 45-Year-Old Man Comes to Clinic for Routine Follow-Up