Acute Renal Allograft Rejection

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:
Serum sodium 144 mEq/L

Serum potassium 5.2 mEq/L
Blood urea nitrogen30 mg/dL
Serum creatinine 2.4 mg/dL
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?
A. Acute rejection [59%]

B. BK virus reactivation [17%]
C. Pyelonephritis [1%]
D. Tacrolimus toxicity [19%]
E. Urinary obstruction [1%]
Correct
59% answered correctly
Explanation:
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.
Last updated:
Time spent: QID:4152
01/01/2024

Acute Renal Allograft Rejection

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A 52-year-old man comes to the clinic for follow-up.

The patient has a history of

Serum sodium 144 mEq/L

Urinalysis shows 1+ glucose and 2+ protein and is otherwise unremarkable. Biopsy

A. Acute rejection [59%]

(Choice B) BK virus reactivation likely results from excessive immunosuppression

(Choice D) Acute toxicity to calcineurin inhibitors (eg, tacrolimus) involves

(Choice E) Urinary obstruction can occur in renal transplant recipients due to

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