A 62-year-old female with a history of uncontrolled hypertension undergoes kidney transplantation. One month following surgery she has elevated serum blood urea nitrogen and creatinine and the patient complains of fever and arthralgia. Her medications include tacrolimus and prednisone. If the patient were experiencing acute, cell-mediated rejection, which of the following would you most expect to see upon biopsy of the transplanted kidney?

Lymphocytic infiltrate of the tubules and interstitium

Granular immunofluorescence around the glomerular basement membrane

Crescent formation in Bowman’s space

Drug precipitation in the renal tubules

Sloughing of proximal tubular epithelial cells

A 50-year-old man with a history of stage 4 kidney disease was admitted to the hospital for an elective hemicolectomy. His past medical history is significant for severe diverticulitis. After the procedure he becomes septic and was placed on broad spectrum antibiotics. On morning rounds, he appear weak and complains of fatigue and nausea. His words are soft and he has difficulty answering questions. His temperature is 38.9°C (102.1°F), heart rate is 110/min, respiratory rate is 15/min, blood pressure 90/65 mm Hg, and saturation is 89% on room air. On physical exam, his mental status appears altered. He has a bruise on his left arm that spontaneously appeared overnight. His cardiac exam is positive for a weak friction rub. Blood specimens are collected and sent for evaluation. An ECG is performed (see image). What therapy will this patient most likely receive next?

Send the patient for hemodialysis

Perform a STAT pericardiocentesis

Prepare the patient for renal transplant

Treat the patient with cyclophosphamide and prednisone

Twelve days after undergoing a cadaveric renal transplant for adult polycystic kidney disease, a 23-year-old man has pain in the right lower abdomen and generalized fatigue. During the past 4 days, he has had decreasing urinary output. Creatinine concentration was 2.3 mg/dL on the second postoperative day. Current medications include prednisone, cyclosporine, azathioprine, and enalapril. His temperature is 38°C (100.4°F), pulse is 103/min, and blood pressure is 168/98 mm Hg. Examination reveals tenderness to palpation on the graft site. Creatinine concentration is 4.3 mg/dL. A biopsy of the transplanted kidney shows tubulitis. C4d staining is negative. Which of the following is the most likely cause of this patient's findings?

Allorecognition with T cell activation

Irreversible fibrosis of the glomerular vessels

Preformed cytotoxic antibodies against class I HLA

A 46-year-old man comes to the physician because of a 4-month history of progressively worsening fatigue and loss of appetite. Five years ago, he received a kidney transplant from a living family member. Current medications include sirolimus and mycophenolate. His blood pressure is 150/95 mm Hg. Laboratory studies show normocytic, normochromic anemia and a serum creatinine concentration of 3.1 mg/dL; his vital signs and laboratory studies were normal 6 months ago. Which of the following is the most likely underlying mechanism of this patient’s increase in creatinine concentration?

CD4+ T cell-mediated intimal smooth muscle proliferation

Drug-induced tubular vacuolization

CD8+ T cell-mediated parenchymal cell damage

Donor T cell-mediated epithelial cell damage

Donor endothelial cell damage by preformed host antibodies

Several weeks following a kidney transplantation, a 50-year-old Caucasian female presents for evaluation of the transplanted organ. Biopsy shows inflammation involving the endothelial cells of the kidney vasculature and the presence of mononuclear cells in the interstitium. Which cells are most likely responsible for this presentation?

Deposition of antibody immune complexes

An 18-year-old man is brought to the emergency department due to the confusion that started earlier in the day. His parents report that the patient had recovered from vomiting and diarrhea 3 days ago without medical intervention. They mention that although nausea and vomiting have resolved, the patient continued to have diffuse abdominal pain and decreased appetite. Past medical history is unremarkable, except for a recent weight loss and increased thirst. The patient does not use tobacco products or alcohol. He is not sexually active and does not use illicit drugs. He appears lethargic but responds to questions. His mucous membranes appear dry. Temperature is 36.9°C (98.4°F), blood pressure is 105/60 mm Hg, pulse is 110/min, and respiratory rate is 27/min with deep and rapid respiration. There is diffuse abdominal tenderness without guarding, rebound tenderness or rigidity. Which of the following is the next best step in the management of this patient?

Capillary blood glucose measurement

Kidney transplantation for USMLE Step 1: High-Yield Internal Medicine Lessons

Indications & Evaluation - The Kidney Waitlist

Indication: End-Stage Renal Disease (ESRD), typically with GFR < 20 mL/min/1.73m².
Evaluation: A multidisciplinary team assesses suitability, focusing on contraindications.
Absolute Contraindications:
- Active malignancy (requires disease-free interval).
- Active, untreated systemic infection.
- Severe, irreversible extra-renal organ damage (e.g., severe CAD, advanced liver disease).
- Active substance abuse.
- Persistent non-adherence to medical care.
Relative Contraindications:
- Morbid obesity (BMI > 40).
- Active smoking.
- Poorly controlled psychiatric conditions.

⭐ Most solid-organ cancers require a 2-5 year disease-free interval before a patient can be listed, as immunosuppression can accelerate recurrence.

Immunosuppression - Taming the Defenses

Goal: Prevent and treat rejection while minimizing drug toxicity and infection risk.
Phases:
- Induction: High-dose agents (e.g., basiliximab, anti-thymocyte globulin) at time of transplant.
- Maintenance: Lifelong triple therapy is common (e.g., CNI + antimetabolite + steroid).
- Rejection Treatment: High-dose steroids (pulses) or antibody therapy.

Class	Mechanism of Action (MOA)	Key Adverse Effects (AEs)
Calcineurin Inhibitors (Tacrolimus, Cyclosporine)	Block IL-2 transcription → ↓ T-cell activation	Nephrotoxicity, neurotoxicity, hypertension, hyperglycemia
Antimetabolites (Mycophenolate, Azathioprine)	Inhibit purine synthesis → ↓ lymphocyte proliferation	GI distress (diarrhea), bone marrow suppression
mTOR Inhibitors (Sirolimus, Everolimus)	Block IL-2 signal transduction → ↓ T-cell proliferation	Hyperlipidemia, proteinuria, poor wound healing, pancytopenia
Corticosteroids (Prednisone)	Broad anti-inflammatory; inhibit cytokine genes	Cushingoid features, osteoporosis, hyperglycemia, avascular necrosis

Transplant Rejection - The Body Fights Back

Type	Timing	Pathophysiology	Key Histologic Findings	Management
Hyperacute	Mins-hours	Pre-formed anti-donor Abs (Type II HSR)	Widespread thrombosis, fibrinoid necrosis	Immediate graft removal
Acute	< 6 months	Cellular (T-cell) or Antibody-mediated (B-cell)	Cellular: Lymphocytic infiltrate, tubulitis Antibody: C4d deposition	Corticosteroids, anti-lymphocyte Abs
Chronic	> 6 months	Mixed cellular/humoral; chronic inflammation	Interstitial fibrosis, tubular atrophy (IF/TA)	Supportive, eventual re-transplantation

⭐ C4d deposition in peritubular capillaries is a key marker for antibody-mediated rejection, indicating complement activation against the graft endothelium.

Post-Transplant Complications - More Than Just Rejection

Infections: Prophylaxis for CMV is key. Screen for BK virus to prevent graft loss.
Malignancies: ↑ risk of skin cancers (SCC > BCC) and PTLD (EBV-driven).
Cardiovascular Disease: The primary cause of long-term mortality.

⭐ BK virus nephropathy presents with a rising creatinine, mimicking acute rejection. Biopsy is required to differentiate as treatment differs (reduce immunosuppression vs. increase).

High‑Yield Points - ⚡ Biggest Takeaways

Standard triple immunosuppression includes a calcineurin inhibitor (e.g., tacrolimus), an antimetabolite, and corticosteroids.

Acute rejection, the most common type, is T-cell mediated and typically responds to high-dose steroids.

Chronic allograft nephropathy is the primary cause of late graft failure, marked by irreversible fibrosis.

Calcineurin inhibitors are highly effective but carry a major risk of nephrotoxicity and hypertension.

Post-transplant risks include opportunistic infections (CMV, BK virus) and malignancy (skin cancer, PTLD).

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