Study Tips: USMLE® Step 1 Question of the Day: Acute transplant rejection
Study Tips

USMLE® Step 1 Question of the Day: Acute transplant rejection

Osmosis Team
May 31, 2023

This week, we are sharing another USMLE® Step 1-style practice question to test your knowledge of medical topics. Today's case focuses on a 55-year-old with a history of diabetic nephropathy and chronic kidney failure, who recently underwent a successful kidney transplant and is currently taking tacrolimus, presents with a 3-day fever. Physical examination reveals tenderness at the graft site. Lab results show a previous serum creatinine level of 1.1 mg/dL, a current temperature of 38.5°C (101.3°F), pulse rate of 88/minute, and blood pressure of 140/90 mmHg. The patient is referred for a biopsy of the transplanted kidney. What is the most likely finding on histological examination of the biopsy? Can you figure it out?

A 55-year-old individual comes to the physician due to fever for the last three days. The patient has a history of diabetic nephropathy and chronic kidney failure and underwent successful kidney transplantation one month ago. The patient is currently taking tacrolimus. Temperature is 38.5°C (101.3°F), pulse is 88/minute, and blood pressure is 140/90 mmHg. On physical examination, tenderness is noted in the graft site. Laboratory evaluation is shown below. Chart review from the previous visit two weeks ago shows a serum creatinine of 1.1 mg/dL. BK virus DNA PCR test is negative. The patient is referred for a biopsy from the transplanted kidney. Which of the following is most likely to be seen on histological examination of the biopsy?

Laboratory value

Result

Serum chemistry

Sodium

147 mEq/L

Potassium 

4.5 mEq/L

Blood urea nitrogen

30 mg/dL

Creatinine

2.3 mg/d



A. Interstitial fibrosis with tubular atrophy

B. Widespread thrombosis of the graft vessels

C. Interstitial inflammation, tubular fibrosis with basophilic intranuclear inclusions

D. Dense mononuclear infiltration of the interstitium and necrosis of the arterial wall

E. Interstitial fibrosis with arteriolar hyalinosis and tubular vacuolization


Scroll down to find the answer!                       

The correct answer to today's USMLE® Step 1 Question is...

D. Dense mononuclear infiltration of the interstitium and necrosis of the arterial wall

Before we get to the Main Explanation, let's look at the incorrect answer explanations. Skip to the bottom if you want to see the correct answer right away!

Incorrect answer explanations

The incorrect answers to today's USMLE® Step 1 Question are...

A. Interstitial fibrosis with tubular atrophy 

Incorrect: Interstitial fibrosis with tubular atrophy is seen in chronic transplant rejection, not acute transplant rejection. 

B. Widespread thrombosis of the graft vessels

Incorrect: Widespread thrombosis of the graft vessels is seen in patients with hyperacute transplant rejection, not acute transplant rejection.

C. Interstitial inflammation, tubular fibrosis with basophilic intranuclear inclusions

Incorrect: BK virus is an opportunistic infection of transplanted kidneys that can lead to nephritis and graft failure. On histology, viral basophilic intranuclear inclusions can be seen in addition to interstitial inflammation and varying degrees of tubular atrophy and fibrosis. However, this patient has a negative BK DNA PCR test, making BK virus infection less likely the cause.

E. Interstitial fibrosis with arteriolar hyalinosis and tubular vacuolization

Incorrect: Tacrolimus toxicity on histology is characterized by interstitial fibrosis, arteriolar hyalinosis, and tubular vacuolization. In addition, patients may show acute tubular necrosis. However, tacrolimus nephrotoxicity occurs due to vasoconstriction of the afferent arterioles of the kidney, causing prerenal kidney injury where the BUN:Cr ratio is >20 (unlike this patient).


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Main Explanation

This patient has fever, graft site tenderness, and abnormal kidney function test one month after kidney transplantation. This presentation is concerning for acute graft rejection. Although the incidence of acute renal graft rejection has decreased immensely after the introduction of immunosuppressant drugs, it is still one of the leading causes of rejection. 

Acute rejection develops due to recognition of the graft antigens by the immune system, and it results from two immunological immune responses that act in combination or alone: the cellular and the humoral immune responses. The cellular response is mediated by T-cells, which directly recognize MHC antigens on the graft and cause damage to the graft (T-cell dependent process), while the humoral response develops when B cells are recruited (by T-helper cells) and generate antibodies that cause acute humoral rejection (B-cell dependent process). Therefore, acute rejection is considered a type II (antibody-mediated) and type IV (cellular-mediated) hypersensitivity reaction.

Acute rejection develops from one week to three months after transplantation, and patients usually complain of fever and graft site tenderness. Additionally, there is typically decreased function of the transplanted organ; for example, patients with acute renal graft rejection develop anuria, metabolic abnormalities (e.g. hyperkalemia), and elevated serum creatinine, as seen in this patient.

A biopsy is needed to diagnose acute graft rejection and differentiate it from other diagnoses (e.g. tacrolimus toxicity). Histologically, acute graft rejection is characterized by mononuclear lymphocytic infiltrate in the interstitium of the graft tissue along with necrosis of the arterial walls (vasculitis).


image of Acute cellular rejection, renal graft biopsy

Reproduced from: Wikipedia

Major Takeaway

Acute graft rejection is mediated by both T-cells (type IV hypersensitivity reaction) and antibodies (type II hypersensitivity reaction) that recognize the graft antigens and cause damage to the transplanted organ. It is characterized by dense lymphocytic interstitial infiltration along with vasculitis of the arterial walls.

References

Justiz Vaillant AA, Misra S, Fitzgerald BM. Acute Transplantation Rejection. [Updated 2020 Aug 16]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK535410/ 

Naik RH, Shawar SH. Renal Transplantation Rejection. [Updated 2020 Dec 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553074/ 


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The United States Medical Licensing Examination (USMLE®) is a joint program of the Federation of State Medical Boards (FSMB®) and National Board of Medical Examiners (NBME®). Osmosis is not affiliated with NBME nor FSMB.