A 52-year-old man comes to the clinic for follow-up. The patient has a history of diabetes mellitus type 2 and end-stage renal disease due to diabetic nephropathy. He underwent living donor kidney transplantation 5 months ago. The patient's immunosuppression regimen includes prednisone, tacrolimus, and mycophenolate sodium, and he also takes insulin. At his last clinic visit 3 months ago, he had good renal graft function with serum creatinine of 1.2 and trace proteinuria. In the interim, the patient has had no symptoms other than mild fatigue. Temperature is 37.3 C (99.1 F), blood pressure is 146/82 mm Hg, pulse is 78/min, and respirations are 12/min. Physical examination is unremarkable. Laboratory studies are as follows: Urinalysis shows 1+ glucose and 2+ protein and is otherwise unremarkable. Biopsy of the transplanted kidney reveals heavy lymphocyte infiltration with vascular involvement and swelling of the intima. Which of the following is the most likely cause of this patient's renal dysfunction?

Question

A 52-year-old man comes to the clinic for follow-up.  The patient has a history of diabetes mellitus type 2 and end-stage renal disease due to diabetic nephropathy.  He underwent living donor kidney transplantation 5 months ago.  The patient's immunosuppression regimen includes prednisone, tacrolimus, and mycophenolate sodium, and he also takes insulin.  At his last clinic visit 3 months ago, he had good renal graft function with serum creatinine of 1.2 and trace proteinuria.  In the interim, the patient has had no symptoms other than mild fatigue.  Temperature is 37.3 C (99.1 F), blood pressure is 146/82 mm Hg, pulse is 78/min, and respirations are 12/min.  Physical examination is unremarkable.  Laboratory studies are as follows:  Urinalysis shows 1+ glucose and 2+ protein and is otherwise unremarkable.  Biopsy of the transplanted kidney reveals heavy lymphocyte infiltration with vascular involvement and swelling of the intima.  Which of the following is the most likely cause of this patient's renal dysfunction?

Quizplus · Accepted Answer

This patient is most likely experiencing acute renal allograft rejection, which is predominantly a T-cell mediated response to antigens within the donor kidney. The use of immunosuppression with calcineurin inhibitors (eg, tacrolimus) and antiproliferative agents (eg, mycophenolate) markedly reduces the incidence of acute rejection; however, it is still a risk. When it occurs it is most commonly within the first 6 months following transplant. Patients with acute rejection are usually asymptomatic, but they may have fever, decreased urine output, or graft tenderness. The process is usually recognized by acutely increased serum creatinine, often accompanied by proteinuria. Diagnostic confirmation requires renal biopsy, which characteristically reveals lymphocytic infiltration of the intima with inflammatory tubular disruption. Intimal arteritis is often present as well. Acute rejection is mostly reversible, and treatment involves the administration of high-dose intravenous glucocorticoids, usually accompanied by increased dosing of the patient's maintenance immunosuppression regimen to help prevent further episodes. (Choice B) BK virus reactivation likely results from excessive immunosuppression in renal allograft recipients and leads to tubulointerstitial nephritis. Patients typically experience an asymptomatic, acute increase in serum creatinine just as they do in acute rejection; however, renal biopsy reveals intranuclear inclusions and a mixed lymphocytic and neutrophilic infiltrate. (Choice C) Pyelonephritis can affect a transplanted kidney and cause acute renal dysfunction, but it is expected to cause symptoms (eg, fever, dysuria, pelvic pain) and positive nitrates and/or leukocyte esterase on urinalysis. (Choice D) Acute toxicity to calcineurin inhibitors (eg, tacrolimus) involves vasoconstriction of the afferent and efferent renal arterioles, leading to prerenal acute kidney injury and hypertension. A blood urea nitrogen/creatinine ratio >20 is expected, and renal biopsy is typically unremarkable. (Choice E) Urinary obstruction can occur in renal transplant recipients due to ureteral stenosis, either from ureteral ischemia or as a complication of BK virus reactivation. Although ureteral obstruction can cause acute renal dysfunction, this patient's renal biopsy is most consistent with acute rejection. Educational objective: Acute renal allograft rejection is predominantly T-cell mediated and usually occurs within the first 6 months following transplant. Affected patients typically experience an asymptomatic rise in serum creatinine. The diagnosis is confirmed by renal biopsy showing lymphocytic infiltration of the intima, and treatment is with high-dose intravenous glucocorticoids. References: Completely reversed acute rejection is not a significant risk factor for development of chronic rejection in renal transplant recipients. (http://www.ncbi.nlm.nih.gov/pubmed/11052270)

A 52-Year-Old Man Comes to the Clinic for Follow-Up