A 38-year-old kidney transplant recipient maintained on tacrolimus presents with a 2-week history of progressive confusion, ataxia, and visual disturbances. MRI shows multifocal white matter lesions without mass effect or enhancement. CSF analysis reveals mild pleocytosis with elevated protein. JC virus DNA is detected in CSF by PCR. Serum tacrolimus level is therapeutic at 8 ng/mL. Apply knowledge of this condition to determine the appropriate management strategy.
Q2
A 41-year-old heart transplant recipient (5 years post-transplant) on cyclosporine, azathioprine, and prednisone develops progressive dyspnea on exertion. Echocardiogram shows preserved ejection fraction but abnormal diastolic dysfunction. Right heart catheterization reveals elevated filling pressures. Endomyocardial biopsy shows interstitial fibrosis without significant cellular infiltration. Coronary angiography shows diffuse, concentric narrowing of distal vessels. Synthesize these findings to determine the underlying pathophysiology and evaluate management options.
Q3
A 52-year-old man with hepatocellular carcinoma (single 4.5 cm lesion) within Milan criteria is listed for liver transplantation with MELD exception points. While waiting, alpha-fetoprotein increases from 125 to 850 ng/mL over 3 months despite locoregional therapy. Repeat imaging shows the tumor has grown to 6 cm with possible vascular invasion. He has no extrahepatic disease. His wife offers to be a living donor. Synthesize the clinical data and evaluate the most appropriate management decision.
Q4
A 29-year-old woman with polycystic kidney disease receives a living-related kidney transplant from her brother (5/6 HLA match). Induction immunosuppression with basiliximab was given, and she is maintained on tacrolimus, mycophenolate, and prednisone. On postoperative day 4, urine output suddenly decreases from 200 mL/hr to 30 mL/hr. Doppler ultrasound shows normal vasculature and a moderate fluid collection. Creatinine rises from 1.1 to 3.8 mg/dL over 12 hours. Evaluate the clinical scenario and synthesize the most likely diagnosis requiring urgent intervention.
Q5
A 48-year-old kidney transplant recipient (3 years post-transplant) on tacrolimus, mycophenolate, and prednisone presents with a progressively enlarging neck mass and B symptoms (fever, night sweats, weight loss). Biopsy reveals Epstein-Barr virus-positive diffuse large B-cell lymphoma. CT staging shows localized disease (stage I). PET scan confirms single site involvement. Analyze the pathophysiology and determine the optimal initial management strategy.
Q6
A 55-year-old man with alcoholic cirrhosis (Child-Pugh C, MELD score 28) presents for liver transplant evaluation. He has been abstinent from alcohol for 4 months and actively participates in AA meetings. His wife is supportive. Medical comorbidities include obesity (BMI 38), well-controlled diabetes, and hypertension. Psychosocial evaluation reveals good insight and motivation. Analyze the factors to determine transplant candidacy.
Q7
A 34-year-old woman with autoimmune hepatitis underwent liver transplantation 18 months ago. She presents with jaundice, dark urine, and fatigue for 2 weeks. She admits to missing several doses of tacrolimus recently. Laboratory studies show: AST 450 U/L, ALT 520 U/L, total bilirubin 6.8 mg/dL, alkaline phosphatase 250 U/L. Liver biopsy shows portal inflammation with lymphocytic infiltration and endotheliitis. Tacrolimus trough level is 2.3 ng/mL (therapeutic range 5-15). Analyze the findings to determine the type of rejection.
Q8
A 62-year-old man undergoes renal transplantation and is maintained on tacrolimus, mycophenolate mofetil, and prednisone. Six months post-transplant, he presents with progressive dyspnea and fever. Chest CT shows bilateral interstitial infiltrates. Bronchoalveolar lavage reveals intracellular inclusion bodies on Giemsa stain. Serum creatinine has increased from 1.2 to 2.8 mg/dL. What is the most appropriate management?
Q9
A 58-year-old man with type 1 diabetes mellitus and end-stage renal disease on hemodialysis is being evaluated for kidney transplantation. His panel reactive antibody (PRA) level is 85%. A potential living donor kidney becomes available with a 3/6 HLA mismatch. Flow cytometry crossmatch is positive. Which immunologic intervention would be most appropriate to proceed with transplantation?
Q10
A 45-year-old woman with end-stage liver disease due to primary sclerosing cholangitis undergoes orthotopic liver transplantation. On postoperative day 3, she develops fever (38.9°C), tachycardia, and increased abdominal pain. Laboratory studies show: AST 850 U/L, ALT 920 U/L, total bilirubin 4.2 mg/dL, alkaline phosphatase 380 U/L. Doppler ultrasound shows absent flow in the hepatic artery. What is the most appropriate next step in management?
Transplant medicine US Medical PG Practice Questions and MCQs
Question 1: A 38-year-old kidney transplant recipient maintained on tacrolimus presents with a 2-week history of progressive confusion, ataxia, and visual disturbances. MRI shows multifocal white matter lesions without mass effect or enhancement. CSF analysis reveals mild pleocytosis with elevated protein. JC virus DNA is detected in CSF by PCR. Serum tacrolimus level is therapeutic at 8 ng/mL. Apply knowledge of this condition to determine the appropriate management strategy.
A. Significantly reduce or discontinue immunosuppression and provide supportive care (Correct Answer)
B. Switch from tacrolimus to sirolimus to preserve graft while treating infection
C. Continue current immunosuppression and administer IVIG therapy
D. Maintain immunosuppression and start cidofovir antiviral therapy
E. Reduce tacrolimus by 50% and start high-dose corticosteroids
Explanation: ***Significantly reduce or discontinue immunosuppression and provide supportive care***
- The patient presents with **Progressive Multifocal Leukoencephalopathy (PML)** caused by **JC virus** reactivation; the primary treatment is **immune reconstitution** to allow the body to fight the virus.
- Reducing or stopping agents like **tacrolimus** is critical for survival, even though it carries a high risk of **allograft rejection**.
*Switch from tacrolimus to sirolimus to preserve graft while treating infection*
- While **sirolimus** has some antiproliferative effects, it is still an **immunosuppressant** and will not allow for the aggressive immune recovery needed to halt **JC virus** replication.
- Managing the life-threatening neurological condition takes precedence over **graft preservation** in the acute phase of PML.
*Continue current immunosuppression and administer IVIG therapy*
- Maintaining current levels of **tacrolimus** prevents the T-cell mediated response necessary to clear the **JC virus** from the CNS.
- **IVIG therapy** has not been proven effective in clinical trials for the treatment of PML and does not address the underlying **immunosuppressed state**.
*Maintain immunosuppression and start cidofovir antiviral therapy*
- **Cidofovir** was previously studied for PML, but it has failed to show significant clinical benefit and is associated with severe **nephrotoxicity**.
- Antiviral therapy without addressing the **cellular immune deficiency** is insufficient to treat this opportunistic infection.
*Reduce tacrolimus by 50% and start high-dose corticosteroids*
- Adding **high-dose corticosteroids** is contraindicated as it further suppresses the immune system, potentially accelerating the progression of **PML**.
- Steroids are typically reserved only for patients who develop **Immune Reconstitution Inflammatory Syndrome (IRIS)** after immunosuppression is withdrawn.
Question 2: A 41-year-old heart transplant recipient (5 years post-transplant) on cyclosporine, azathioprine, and prednisone develops progressive dyspnea on exertion. Echocardiogram shows preserved ejection fraction but abnormal diastolic dysfunction. Right heart catheterization reveals elevated filling pressures. Endomyocardial biopsy shows interstitial fibrosis without significant cellular infiltration. Coronary angiography shows diffuse, concentric narrowing of distal vessels. Synthesize these findings to determine the underlying pathophysiology and evaluate management options.
A. Cardiac allograft vasculopathy requiring consideration for retransplantation evaluation (Correct Answer)
B. Restrictive cardiomyopathy from previous rejection episodes requiring diuretic therapy
C. Drug-induced cardiomyopathy from calcineurin inhibitor toxicity requiring switch to mTOR inhibitor
D. Acute cellular rejection requiring pulse steroids and optimization of immunosuppression
E. Antibody-mediated rejection requiring plasmapheresis and rituximab therapy
Explanation: ***Cardiac allograft vasculopathy requiring consideration for retransplantation evaluation***
- **Cardiac allograft vasculopathy (CAV)** is the leading cause of late graft failure, characterized by **diffuse, concentric intimal hyperplasia** and narrowing of the distal coronary vessels.
- The presentation of **progressive dyspnea**, diastolic dysfunction, and **interstitial fibrosis** on biopsy—without acute cellular or antibody-mediated rejection—is pathognomonic for advanced CAV, where **retransplantation** remains the definitive surgical option.
*Restrictive cardiomyopathy from previous rejection episodes requiring diuretic therapy*
- While **interstitial fibrosis** can mimic a restrictive phenotype, this option overlooks the specific **angiographic finding** of distal concentric narrowing which points directly to CAV.
- **Diuretic therapy** may provide symptomatic relief for heart failure but does not address the underlying **progressive vasculopathy** and graft failure.
*Drug-induced cardiomyopathy from calcineurin inhibitor toxicity requiring switch to mTOR inhibitor*
- **Cyclosporine** (a calcineurin inhibitor) primarily causes **nephrotoxicity** and hypertension rather than direct cardiomyopathy with concentric vascular narrowing.
- While **mTOR inhibitors** (like Sirolimus) are used to slow the progression of CAV, they do not resolve established diffuse vascular disease with hemodynamic compromise.
*Acute cellular rejection requiring pulse steroids and optimization of immunosuppression*
- **Acute cellular rejection** is excluded by the endomyocardial biopsy, which specifically showed **no significant cellular infiltration**.
- This condition typically occurs earlier in the post-transplant period and would show **lymphocytic infiltration** and myocyte necrosis rather than concentric vessel narrowing.
*Antibody-mediated rejection requiring plasmapheresis and rituximab therapy*
- **Antibody-mediated rejection (AMR)** is characterized by **capillary endothelial injury** and C4d deposition on biopsy, which were not described in this patient.
- AMR typically presents with more acute graft dysfunction rather than the **slowly progressive** course and distal vessel pruning seen in this case.
Question 3: A 52-year-old man with hepatocellular carcinoma (single 4.5 cm lesion) within Milan criteria is listed for liver transplantation with MELD exception points. While waiting, alpha-fetoprotein increases from 125 to 850 ng/mL over 3 months despite locoregional therapy. Repeat imaging shows the tumor has grown to 6 cm with possible vascular invasion. He has no extrahepatic disease. His wife offers to be a living donor. Synthesize the clinical data and evaluate the most appropriate management decision.
A. Remove from transplant list and pursue systemic therapy with sorafenib (Correct Answer)
B. Perform surgical resection then relist if recurrence occurs within criteria
C. Downstage with aggressive locoregional therapy then reassess for transplantation
D. Proceed with living donor transplantation given no extrahepatic disease
E. Continue locoregional therapy and maintain listing with exception points
Explanation: ***Remove from transplant list and pursue systemic therapy with sorafenib***
- This patient no longer meets the **Milan criteria** due to the lesion size exceeding 5 cm and the presence of suspected **vascular invasion**, which significantly increases the risk of recurrence.
- A rapid rise in **alpha-fetoprotein (AFP)** to >400 ng/mL is a strong predictor of poor post-transplant survival and biological aggressiveness, necessitating **delisting** and alternative systemic management.
*Perform surgical resection then relist if recurrence occurs within criteria*
- **Surgical resection** is generally contraindicated in cases of suspected **vascular invasion** as it is associated with extremely high rates of early systemic metastasis.
- This approach does not address the underlying biological aggressiveness evidenced by the soaring **AFP** and likely poor outcome.
*Downstage with aggressive locoregional therapy then reassess for transplantation*
- While **downstaging** is an option for tumors just outside criteria, the combination of **vascular invasion** and a rapidly rising **AFP** suggests the disease is no longer localized or controllable by these methods.
- Failure of previous **locoregional therapy** to control the AFP and tumor growth indicates a resistant phenotype that is unlikely to respond to further local intervention.
*Proceed with living donor transplantation given no extrahepatic disease*
- Even with a **living donor**, transplanting a patient with suspected **vascular invasion** and high **AFP** is ethically controversial due to the very high risk of rapid disease recurrence.
- **Living donor liver transplantation (LDLT)** does not bypass the need for favorable tumor biology to ensure a successful long-term oncologic outcome.
*Continue locoregional therapy and maintain listing with exception points*
- National matching rules generally require patients to stay within **Milan criteria** to maintain **MELD exception points**; exceeding 5 cm and vascular invasion disqualifies the patient.
- Maintaining the current status ignores the clear radiographic and biochemical evidence of **tumor progression**, which would result in a waste of a donor organ.
Question 4: A 29-year-old woman with polycystic kidney disease receives a living-related kidney transplant from her brother (5/6 HLA match). Induction immunosuppression with basiliximab was given, and she is maintained on tacrolimus, mycophenolate, and prednisone. On postoperative day 4, urine output suddenly decreases from 200 mL/hr to 30 mL/hr. Doppler ultrasound shows normal vasculature and a moderate fluid collection. Creatinine rises from 1.1 to 3.8 mg/dL over 12 hours. Evaluate the clinical scenario and synthesize the most likely diagnosis requiring urgent intervention.
A. Ureteral obstruction from surgical complication requiring stent placement
B. Renal vein thrombosis requiring anticoagulation and possible thrombectomy
C. Urinary leak from ureteral anastomosis requiring surgical repair (Correct Answer)
D. Hyperacute rejection despite HLA compatibility requiring nephrectomy
E. Acute tubular necrosis requiring supportive care and dialysis
Explanation: ***Urinary leak from ureteral anastomosis requiring surgical repair***
- A sudden drop in **urine output** accompanied by a rapid rise in **serum creatinine** and a **perigraft fluid collection** on day 4 is highly suggestive of a **urine leak**.
- This complication typically occurs due to **ureteral ischemia** or technical failure; diagnosis is confirmed by finding a **fluid-to-serum creatinine ratio** much greater than 1.0.
*Ureteral obstruction from surgical complication requiring stent placement*
- While **ureteral obstruction** causes decreased urine output, it usually presents with **hydronephrosis** on ultrasound, which is not mentioned here.
- A **fluid collection** (urinoma) is less common in pure obstruction compared to a full dehiscence or leak at the **ureteroneocystostomy** site.
*Renal vein thrombosis requiring anticoagulation and possible thrombectomy*
- **Renal vein thrombosis** would typically show **reversed diastolic flow** or absent venous flow on **Doppler ultrasound**, whereas this patient has normal vasculature.
- It often presents with **graft tenderness** and swelling, but the Doppler findings in this scenario specifically rule out major vascular compromise.
*Hyperacute rejection despite HLA compatibility requiring nephrectomy*
- **Hyperacute rejection** occurs within **minutes to hours** of reperfusion in the operating room, not on postoperative day 4.
- It is caused by **preformed donor-specific antibodies** (Type II hypersensitivity) and would result in immediate graft cyanosis and failure.
*Acute tubular necrosis requiring supportive care and dialysis*
- **Acute tubular necrosis (ATN)** usually manifests as delayed graft function immediately after transplant, rather than a **sudden drop** in output after initial high flow.
- While ATN causes rising creatinine, it does not explain the presence of a **moderate fluid collection** surrounding the kidney graft.
Question 5: A 48-year-old kidney transplant recipient (3 years post-transplant) on tacrolimus, mycophenolate, and prednisone presents with a progressively enlarging neck mass and B symptoms (fever, night sweats, weight loss). Biopsy reveals Epstein-Barr virus-positive diffuse large B-cell lymphoma. CT staging shows localized disease (stage I). PET scan confirms single site involvement. Analyze the pathophysiology and determine the optimal initial management strategy.
A. Discontinue all immunosuppression and initiate rituximab monotherapy (Correct Answer)
B. Surgical excision followed by radiotherapy without changing immunosuppression
C. Maintain current immunosuppression and add rituximab to CHOP regimen
D. Continue immunosuppression and start CHOP chemotherapy immediately
E. Reduce immunosuppression by 50% and observe for tumor regression
Explanation: ***Discontinue all immunosuppression and initiate rituximab monotherapy***
- The primary driver of **Post-Transplant Lymphoproliferative Disorder (PTLD)** is **EBV-driven B-cell proliferation** due to suppressed T-cell surveillance; thus, **reduction of immunosuppression (RIS)** is the fundamental first step.
- For CD20+ localized disease, combining **RIS** with **Rituximab** (an anti-CD20 monoclonal antibody) provides a superior response rate compared to RIS alone and avoids the toxicity of systemic chemotherapy.
*Surgical excision followed by radiotherapy without changing immunosuppression*
- While surgery or radiation may be used for symptom control, they do not address the underlying **systemic immune deficiency** and EBV-positive cell proliferation.
- Modifying **immunosuppressive therapy** is mandatory in all cases of PTLD to restore the host's natural **T-cell response** against the tumor.
*Maintain current immunosuppression and add rituximab to CHOP regimen*
- Maintaining full immunosuppression while giving **CHOP chemotherapy** leads to extreme myelosuppression and an unacceptably high risk of **opportunistic infections**.
- Standard guidelines recommend a stepped approach starting with **RIS** rather than jumping straight to aggressive **cytotoxic chemotherapy** for localized disease.
*Continue immunosuppression and start CHOP chemotherapy immediately*
- Starting **CHOP** (Cyclophosphamide, Doxorubicin, Vincristine, Prednisone) immediately is reserved for aggressive, disseminated, or rapidly progressing disease that failed initial **RIS/Rituximab**.
- Failure to reduce **Tacrolimus and Mycophenolate** allows the PTLD to continue growing by preventing the patient's own immune system from recognizing the **EBV-infected cells**.
*Reduce immunosuppression by 50% and observe for tumor regression*
- While **RIS** is the first step, mere 50% reduction may be insufficient for a histology of **Diffuse Large B-cell Lymphoma (DLBCL)** which is an aggressive subtype.
- Current management protocols for aggressive DLBCL-type PTLD favor the immediate addition of **monoclonal antibodies** like Rituximab rather than passive observation alone.
Question 6: A 55-year-old man with alcoholic cirrhosis (Child-Pugh C, MELD score 28) presents for liver transplant evaluation. He has been abstinent from alcohol for 4 months and actively participates in AA meetings. His wife is supportive. Medical comorbidities include obesity (BMI 38), well-controlled diabetes, and hypertension. Psychosocial evaluation reveals good insight and motivation. Analyze the factors to determine transplant candidacy.
A. Deny transplantation due to morbid obesity and multiple comorbidities
B. List but designate as low priority due to alcohol etiology
C. Require weight loss to BMI <35 then list if abstinence maintained (Correct Answer)
D. List immediately as he meets MELD criteria and has adequate abstinence
E. Defer listing until 6 months of documented abstinence is achieved
Explanation: ***Require weight loss to BMI <35 then list if abstinence maintained***
- A **BMI >35** is associated with significantly higher risks of **perioperative complications**, wound infections, and decreased **graft survival**, making weight management a necessary criterion for listing.
- While the patient is showing progress, demonstrating **sustained weight loss** and professional management of **metabolic comorbidities** ensures better outcomes post-transplantation.
*Deny transplantation due to morbid obesity and multiple comorbidities*
- **Obesity** and controlled **diabetes/hypertension** are relative contraindications that can often be managed; they do not warrant an absolute denial if the patient is motivated.
- Denying care ignores the patient's strong **psychosocial support** and high **MELD score**, which indicates a critical need for intervention.
*List but designate as low priority due to alcohol etiology*
- Allocation of livers is based on medical urgency via the **MELD score**, not the etiology of the underlying liver disease.
- Patients with **alcoholic cirrhosis** who meet abstinence and psychosocial criteria have similar **post-transplant survival** rates compared to other etiologies.
*List immediately as he meets MELD criteria and has adequate abstinence*
- Immediate listing is premature because many centers enforce a strict **six-month abstinence rule** to predict long-term sobriety.
- Listing without addressing a **BMI of 38** ignores significant surgical risks and the potential for **post-transplant metabolic syndrome**.
*Defer listing until 6 months of documented abstinence is achieved*
- While the **six-month rule** is a common guideline, the **morbid obesity** (BMI 38) and the need for **weight optimization** are equally critical hurdles that must be addressed concurrently.
- Simply waiting for two more months of abstinence does not solve the **high-risk surgical profile** created by his current weight and comorbidities.
Question 7: A 34-year-old woman with autoimmune hepatitis underwent liver transplantation 18 months ago. She presents with jaundice, dark urine, and fatigue for 2 weeks. She admits to missing several doses of tacrolimus recently. Laboratory studies show: AST 450 U/L, ALT 520 U/L, total bilirubin 6.8 mg/dL, alkaline phosphatase 250 U/L. Liver biopsy shows portal inflammation with lymphocytic infiltration and endotheliitis. Tacrolimus trough level is 2.3 ng/mL (therapeutic range 5-15). Analyze the findings to determine the type of rejection.
A. Chronic rejection requiring retransplantation evaluation
B. Recurrent autoimmune hepatitis requiring increased immunosuppression
C. Antibody-mediated rejection requiring plasmapheresis
D. Hyperacute rejection requiring immediate re-transplantation
E. Acute cellular rejection treatable with corticosteroids (Correct Answer)
Explanation: ***Acute cellular rejection treatable with corticosteroids***
- The biopsy findings of **portal inflammation**, **lymphocytic infiltration**, and **endotheliitis** constitute the classic triad of **Acute Cellular Rejection (ACR)**.
- It is frequently triggered by **medication non-compliance**, evidenced here by the subtherapeutic **tacrolimus trough level** of 2.3 ng/mL.
*Chronic rejection requiring retransplantation evaluation*
- **Chronic rejection** is characterized histologically by **vanishing bile duct syndrome** and obliterative arteriopathy, not acute inflammatory endotheliitis.
- While it presents with jaundice, it typically occurs over months to years and is often **irreversible**, eventually requiring **retransplantation**.
*Recurrent autoimmune hepatitis requiring increased immunosuppression*
- While **autoimmune hepatitis** can recur post-transplant, the specific finding of **endotheliitis** is pathognomonic for rejection rather than disease recurrence.
- Recurrence usually shows **plasma cell-rich** infiltrates and **interface hepatitis**, which are distinct from the cellular rejection patterns seen here.
*Antibody-mediated rejection requiring plasmapheresis*
- **Antibody-mediated rejection (AMR)** is less common in liver transplants and is diagnosed via **C4d staining** on biopsy and the presence of **donor-specific antibodies (DSA)**.
- The clinical scenario of missing calcineurin inhibitors strongly favors **T-cell mediated (cellular)** rejection over a primary humoral process.
*Hyperacute rejection requiring immediate re-transplantation*
- **Hyperacute rejection** occurs within **minutes to hours** of graft reperfusion due to preformed antibodies (ABO incompatibility or HLA sensitization).
- It presents with **rapid graft necrosis** or thrombosis immediately post-surgery, which is impossible 18 months after the procedure.
Question 8: A 62-year-old man undergoes renal transplantation and is maintained on tacrolimus, mycophenolate mofetil, and prednisone. Six months post-transplant, he presents with progressive dyspnea and fever. Chest CT shows bilateral interstitial infiltrates. Bronchoalveolar lavage reveals intracellular inclusion bodies on Giemsa stain. Serum creatinine has increased from 1.2 to 2.8 mg/dL. What is the most appropriate management?
A. Reduce immunosuppression and start ganciclovir (Correct Answer)
B. Initiate plasmapheresis for antibody-mediated rejection
C. Start high-dose corticosteroids for organizing pneumonia
D. Increase tacrolimus levels to treat presumed rejection
E. Start trimethoprim-sulfamethoxazole for Pneumocystis pneumonia
Explanation: ***Reduce immunosuppression and start ganciclovir***
- The presence of **intracellular inclusion bodies** (owl’s eye) on bronchoalveolar lavage and systemic symptoms indicates a **Cytomegalovirus (CMV)** infection, which is a common post-transplant complication.
- Management requires **ganciclovir** to treat the virus and **reduction of immunosuppression** (especially mycophenolate) to enable the body's immune response to fight the infection.
*Initiate plasmapheresis for antibody-mediated rejection*
- **Plasmapheresis** is indicated for **antibody-mediated rejection** (AMR), which is typically diagnosed by C4d staining and donor-specific antibodies (DSA).
- This patient's symptoms and lung findings specifically point toward an **infectious etiology** rather than a primary immunological rejection.
*Start high-dose corticosteroids for organizing pneumonia*
- While **cryptogenic organizing pneumonia** can present with infiltrates, the visualization of **Giemsa-stained inclusion bodies** confirms a viral infection.
- Giving high-dose steroids would be contraindicated as it would further suppress the immune system and worsen the **CMV pneumonitis**.
*Increase tacrolimus levels to treat presumed rejection*
- Increasing tacrolimus would aggravate the viral replication and potentially lead to fatal **disseminated CMV disease**.
- The rise in creatinine (renal dysfunction) is likely due to **CMV-related nephropathy** or systemic illness rather than straightforward rejection requiring more suppression.
*Start trimethoprim-sulfamethoxazole for Pneumocystis pneumonia*
- **Pneumocystis jirovecii** (PCP) presents with interstitial infiltrates but would show **crushed ping-pong ball** cysts on silver stain, not intracellular inclusion bodies.
- While PCP is a differential for post-transplant dyspnea, the specific finding of **inclusions** on Giemsa stain is pathognomonic for **CMV**.
Question 9: A 58-year-old man with type 1 diabetes mellitus and end-stage renal disease on hemodialysis is being evaluated for kidney transplantation. His panel reactive antibody (PRA) level is 85%. A potential living donor kidney becomes available with a 3/6 HLA mismatch. Flow cytometry crossmatch is positive. Which immunologic intervention would be most appropriate to proceed with transplantation?
A. Rituximab monotherapy
B. High-dose corticosteroids alone
C. Increased maintenance immunosuppression only
D. Plasmapheresis with intravenous immunoglobulin (IVIG) (Correct Answer)
E. Decline transplantation and wait for better HLA match
Explanation: ***Plasmapheresis with intravenous immunoglobulin (IVIG)***
- A high **Panel Reactive Antibody (PRA)** and a **positive flow cytometry crossmatch** indicate the presence of **Donor-Specific Antibodies (DSAs)**, requiring desensitization to prevent **antibody-mediated rejection**.
- **Plasmapheresis** physically removes circulating antibodies, while **IVIG** suppresses further antibody production and helps modulate the **complement system**.
*Rituximab monotherapy*
- While this **anti-CD20 monoclonal antibody** depletes B-cells, it is insufficient as a standalone therapy to clear existing pre-formed **DSAs**.
- It is generally used as an adjunct to **plasmapheresis** rather than a primary tool for rapid desensitization in acute crossmatch-positive settings.
*High-dose corticosteroids alone*
- Steroids primarily target **T-cell mediated inflammation** and cytokines but do not effectively reduce the titer of pre-formed **humoral antibodies**.
- Relying on steroids alone in a highly sensitized patient with a **positive crossmatch** carries an extremely high risk of **hyperacute rejection**.
*Increased maintenance immunosuppression only*
- Standard maintenance agents like tacrolimus and mycophenolate prevent new immune responses but cannot clear the **pre-existing antibodies** identified by the crossmatch.
- Transplanting without active **antibody removal** (desensitization) ensures immediate graft failure in the presence of a positive immunologic crossmatch.
*Decline transplantation and wait for better HLA match*
- For highly sensitized patients (PRA >80%), waiting for a perfectly matched kidney can lead to years on dialysis with significant **morbidity and mortality**.
- Though an option, **desensitization protocols** allow for successful transplantation from **living donors** when a compatible deceased donor is unlikely to be found soon.
Question 10: A 45-year-old woman with end-stage liver disease due to primary sclerosing cholangitis undergoes orthotopic liver transplantation. On postoperative day 3, she develops fever (38.9°C), tachycardia, and increased abdominal pain. Laboratory studies show: AST 850 U/L, ALT 920 U/L, total bilirubin 4.2 mg/dL, alkaline phosphatase 380 U/L. Doppler ultrasound shows absent flow in the hepatic artery. What is the most appropriate next step in management?
A. Percutaneous transhepatic cholangiography
B. Increase immunosuppression to prevent rejection
C. Immediate surgical exploration for hepatic artery thrombosis (Correct Answer)
D. Start broad-spectrum antibiotics for cholangitis
E. Continue observation with serial liver function tests
Explanation: ***Immediate surgical exploration for hepatic artery thrombosis***
- Sudden post-operative fever, elevated transaminases, and **absent flow on Doppler ultrasound** are diagnostic of **Hepatic Artery Thrombosis (HAT)**.
- HAT is a surgical emergency requiring **urgent exploration** for thrombectomy or arterial revision to prevent graft loss and biliary necrosis.
*Percutaneous transhepatic cholangiography*
- This procedure is used to evaluate **biliary ductal anatomy** but does not address the underlying vascular obstruction.
- While biliary complications occur secondary to HAT, diagnosing localized ischemia is secondary to managing the **arterial blood supply**.
*Increase immunosuppression to prevent rejection*
- **Acute cellular rejection** typically presents with elevated liver enzymes but would show preserved vascular flow on Doppler.
- Increasing immunosuppressants is contraindicated here as HAT carries a high risk of **infarction and abscess**, which would be worsened by immunosuppression.
*Start broad-spectrum antibiotics for cholangitis*
- While fever and pain suggest infection, the **absent hepatic artery flow** confirms a primary mechanical/vascular etiology rather than simple bacterial cholangitis.
- Antibiotics are supportive, but they will not resolve the **ischemic damage** to the graft or the biliary system.
*Continue observation with serial liver function tests*
- Delaying intervention in the setting of HAT leads to rapid **graft failure** and high patient mortality.
- Serial LFTs are useful for monitoring recovery but are inappropriate as a primary strategy for an **acute vascular occlusion**.
