Complications of Transplantation — MCQs
A man has undergone renal transplant and is taking immunosuppressant drug. On biopsy there was presence of budding cells with pseudohyphae. Identify the organism?
Which of the following drugs shows nephrotoxicity during administration?
Post transplant lymphoma most commonly associated with:
Sirolimus is more likely than cyclosporine to cause which of the following?
What is the most common type of graft rejection?
In discussing the treatment of a 42-year-old man with severe liver cirrhosis, the possibility of heterotopic transplantation is considered. Which statement about heterotopic liver transplantation is TRUE?
After the first postoperative year of cardiac transplantation, what is the most common cause of death?
Infection in a renal transplant patient is usually caused by which pathogen?
Which of the following should be avoided in the long-term follow-up of a renal transplant recipient on ciclosporin?
Which type of transplant has the lowest chance of recipient failure?
Complications of Transplantation Indian Medical PG Practice Questions and MCQs
Question 1: A man has undergone renal transplant and is taking immunosuppressant drug. On biopsy there was presence of budding cells with pseudohyphae. Identify the organism?
- A. Invasive candidiasis (Correct Answer)
- B. Pneumocystis
- C. Invasive aspergillosis
- D. Histoplasmosis
Explanation: ***Invasive candidiasis*** - The presence of **budding cells** and **pseudohyphae** on biopsy is a classic histological finding for *Candida* species. - Individuals who have undergone **renal transplant** and are on **immunosuppressant drugs** are at high risk for opportunistic fungal infections, including invasive candidiasis. *Pneumocystis* - *Pneumocystis jirovecii* typically causes pneumonia and is characterized by cysts or trophic forms in lung tissue, not budding cells and pseudohyphae. - While common in immunocompromised patients, its microscopic morphology is distinctly different from *Candida*. *Invasive aspergillosis* - *Aspergillus* species are characterized by **septate hyphae with acute angle branching** (typically 45-degree angles) on microscopy. - They do not form budding cells or pseudohyphae, which are characteristic of *Candida*. *Histoplasmosis* - *Histoplasma capsulatum* appears as **small, oval-shaped yeast cells** (2-4 µm) often found within macrophages. - It does not form pseudohyphae or large budding cells as described in the question.
Question 2: Which of the following drugs shows nephrotoxicity during administration?
- A. Azathioprine
- B. Tacrolimus (Correct Answer)
- C. Mycophenolate mofetil
- D. Leflunomide
Explanation: ***Tacrolimus*** - **Tacrolimus** is a calcineurin inhibitor and a well-known cause of **nephrotoxicity**, which can manifest as acute kidney injury or chronic renal dysfunction [1], [4]. - Its mechanism involves vasoconstriction of afferent arterioles and direct tubular toxicity, leading to reduced glomerular filtration. *Azathioprine* - **Azathioprine** is an immunosuppressant primarily associated with **bone marrow suppression** (leukopenia, thrombocytopenia) and **hepatotoxicity**, not typically nephrotoxicity [2]. - While it can cause renal impairment in rare cases, it is not a primary mechanism of action. *Mycophenolate mofetil* - **Mycophenolate mofetil (MMF)** is an immunosuppressant that primarily causes **gastrointestinal side effects** (diarrhea, nausea) and **myelosuppression**. - It is generally considered **renal-sparing** and is often used in situations where calcineurin inhibitors are contraindicated due to nephrotoxicity. *Leflunomide* - **Leflunomide** is an immunosuppressant used in rheumatoid arthritis, known for causing **hepatotoxicity**, **hypertension**, and **teratogenicity** [3]. - While it can affect various organ systems, direct and significant nephrotoxicity is not a prominent adverse effect.
Question 3: Post transplant lymphoma most commonly associated with:
- A. Epstein-Barr virus (Correct Answer)
- B. HHV-6
- C. Herpes simplex
- D. Cytomegalo virus
Explanation: ***Epstein-Barr virus*** - **EBV** is strongly implicated in the pathogenesis of **post-transplant lymphoproliferative disorder (PTLD)**, especially in patients receiving immunosuppressive therapy [1]. - The immune suppression post-transplant allows for uncontrolled B-cell proliferation driven by latent EBV infection, leading to lymphoma [2]. *HHV-6* - While HHV-6 can cause reactivation and complications in transplant recipients, it is **not commonly associated** with lymphoma development. - Its clinical manifestations usually include **fever, rash, encephalitis**, and bone marrow suppression. *Herpes simplex* - **HSV** infections are common in transplant patients due to immunosuppression, presenting as mucocutaneous lesions [3]. - However, HSV is **not a known oncogenic virus** that directly contributes to the development of post-transplant lymphoma. *Cytomegalo virus* - **CMV** is a significant pathogen in transplant recipients, causing various syndromes like pneumonitis, colitis, and retinitis [3]. - Although CMV can cause **indirect immunomodulatory effects**, it is not a primary cause of post-transplant lymphoma, unlike EBV.
Question 4: Sirolimus is more likely than cyclosporine to cause which of the following?
- A. Osteoporosis
- B. Renal insufficiency
- C. Thrombocytopenia (Correct Answer)
- D. Hypertension
Explanation: ***Thrombocytopenia*** - **Sirolimus** frequently causes **myelosuppression**, leading to **thrombocytopenia** and leukopenia. - While both sirolimus and cyclosporine can have side effects, **thrombocytopenia** is a more prominent and distinguishing adverse effect of sirolimus. *Hypertension* - **Cyclosporine** is well-known for causing **hypertension** due to its effect on the renin-angiotensin-aldosterone system and endothelial dysfunction. - While sirolimus can cause hypertension, it is generally less pronounced compared to cyclosporine. *Osteoporosis* - **Corticosteroids** are the primary immunosuppressants associated with **osteoporosis** due to their effects on bone metabolism. - Neither sirolimus nor cyclosporine is a major direct cause of osteoporosis. *Renal insufficiency* - **Cyclosporine** is distinctively associated with **nephrotoxicity**, leading to acute and chronic **renal insufficiency** through vasoconstriction and tubular damage. - While sirolimus can impact renal function indirectly or in combination with calcineurin inhibitors, cyclosporine's direct nephrotoxic effect is more significant.
Question 5: What is the most common type of graft rejection?
- A. Hyperacute
- B. Acute (Correct Answer)
- C. Chronic
- D. Acute on chronic
Explanation: ***Acute*** - **Acute rejection** is the most common type of graft rejection, occurring in **10-40% of transplant recipients**. [1] - It typically occurs **days to weeks to months** after transplantation (most commonly within the first 6 months). [1] - Mediated primarily by **T-lymphocytes** (cellular rejection) or **antibodies** (antibody-mediated rejection) reacting against donor antigens. [1] - Usually **responsive to immunosuppressive therapy** when detected early. *Hyperacute* - **Hyperacute rejection** is rare (occurs in <1% of cases) due to routine **pre-transplant cross-matching**. - Occurs within **minutes to hours** after transplantation due to **pre-existing circulating antibodies** against donor antigens. [1] - Results in immediate thrombosis and graft necrosis, requiring **immediate graft removal**. [1] *Chronic* - **Chronic rejection** (chronic allograft dysfunction) develops **months to years** after transplantation. - It is the **most common cause of late graft failure**, but not the most common type of rejection episode. - Characterized by **gradual, progressive loss of graft function** with vascular and fibrotic changes. - **Largely irreversible** and poorly responsive to treatment. *Acute on chronic* - This is **not a primary category** of graft rejection but represents an **acute rejection episode superimposed** on a graft already undergoing chronic changes. - Reflects exacerbation in a chronically rejecting graft. **References:** [1] Kumar V, Abbas AK, et al.. Robbins and Cotran Pathologic Basis of Disease. 9th ed. Diseases of the Immune System, pp. 239-242.
Question 6: In discussing the treatment of a 42-year-old man with severe liver cirrhosis, the possibility of heterotopic transplantation is considered. Which statement about heterotopic liver transplantation is TRUE?
- A. It is preferable to orthotopic liver transplantation.
- B. It is rarely associated with long-term survival.
- C. It implies removal of the recipient's liver.
- D. It should be done in the iliac vessels. (Correct Answer)
Explanation: ***It should be done in the iliac vessels.*** - **Heterotopic liver transplantation** involves placing the donor liver in an ectopic location (typically in the right lower abdomen or pelvis) while the native liver remains in situ. - Vascular anastomosis is commonly performed using the **iliac vessels** (external or common iliac artery and vein) or infrarenal IVC and aorta for blood supply to the graft. - This is a **largely historical procedure** that has been mostly abandoned due to technical complexity, high complication rates, and poor long-term outcomes compared to orthotopic transplantation. *It is preferable to orthotopic liver transplantation.* - **Orthotopic liver transplantation (OLT)**, where the diseased liver is completely removed and replaced, is the **gold standard** for end-stage liver disease. - OLT provides superior long-term outcomes, complete removal of the diseased organ, and eliminates competition between native and donor liver function. - Heterotopic transplantation is **not preferable** and has been largely abandoned in modern practice. *It is rarely associated with long-term survival.* - This statement has historical validity—heterotopic liver transplantation was indeed associated with **poor long-term outcomes**, which is a major reason the procedure was largely discontinued. - Complications included vascular thrombosis, competition between native and donor liver, portal hypertension, and technical difficulties. - However, in the context of this question, the statement about iliac vessels is more specifically correct regarding the technical aspect of the procedure. *It implies removal of the recipient's liver.* - **Incorrect**—the defining feature of **heterotopic transplantation** is that the **native liver is left in place**. - Removal of the recipient's liver is characteristic of **orthotopic liver transplantation**, where the diseased organ is excised and replaced in the same anatomical location.
Question 7: After the first postoperative year of cardiac transplantation, what is the most common cause of death?
- A. Infection
- B. Arrhythmia
- C. Accelerated graft arteriosclerosis (Correct Answer)
- D. Acute rejection episode
Explanation: **Explanation:** The survival of cardiac transplant recipients is divided into two distinct phases: the early postoperative period (within the first year) and the late postoperative period (after one year). **Why 'Accelerated Graft Arteriosclerosis' is correct:** Also known as **Cardiac Allograft Vasculopathy (CAV)**, this is a unique, progressive form of chronic rejection. Unlike typical atherosclerosis, CAV is characterized by diffuse, concentric intimal proliferation affecting the entire length of the coronary arteries. It remains the leading cause of late mortality (after 1 year) because the denervated heart does not experience typical angina, often leading to silent myocardial infarction, heart failure, or sudden death. **Why the other options are incorrect:** * **Infection:** This is the **most common cause of death within the first year** (specifically the first 30 days to 6 months) due to intense induction immunosuppression. * **Acute Rejection:** This typically occurs within the first 3–6 months. While it remains a risk, its incidence decreases significantly after the first year due to maintenance therapy. * **Arrhythmia:** While arrhythmias can occur due to surgical trauma or acute rejection in the early phase, they are rarely the primary cause of late-term mortality unless secondary to CAV. **High-Yield Clinical Pearls for NEET-PG:** 1. **Most common cause of death (<1 year):** Infection. 2. **Most common cause of death (>1 year):** Cardiac Allograft Vasculopathy (CAV) / Graft Arteriosclerosis. 3. **Gold Standard for CAV diagnosis:** Annual coronary angiography with **Intravascular Ultrasound (IVUS)**, as angiography alone may underestimate the diffuse narrowing. 4. **Malignancy:** The risk of lymphomas (PTLD) and skin cancers increases significantly in the late phase due to long-term immunosuppression.
Question 8: Infection in a renal transplant patient is usually caused by which pathogen?
- A. Cytomegalovirus (CMV) (Correct Answer)
- B. Human Immunodeficiency Virus (HIV)
- C. Herpes Simplex Virus (HSV)
- D. Salmonella
Explanation: **Explanation:** **Cytomegalovirus (CMV)** is the most common clinically significant opportunistic viral pathogen in renal transplant recipients. It typically manifests between **1 to 6 months post-transplant**, coinciding with the period of maximal immunosuppression. The infection occurs due to primary infection (seronegative recipient receiving a seropositive organ), reactivation of latent virus, or superinfection. CMV is high-yield because it not only causes systemic symptoms (fever, leukopenia) and organ-specific disease (pneumonitis, hepatitis, colitis) but also acts as an immunomodulator, increasing the risk of graft rejection and other opportunistic infections. **Analysis of Incorrect Options:** * **HIV (Option B):** While HIV is a significant viral pathogen, it is not a common "post-transplant infection." In fact, HIV-positive status was previously a contraindication to transplant, though "HIV-to-HIV" transplants are now performed in specific protocols. * **HSV (Option C):** Herpes Simplex Virus can cause mucocutaneous lesions in the early post-operative period, but its incidence has significantly decreased due to routine prophylactic use of Acyclovir/Valacyclovir. It is less common and less severe than CMV. * **Salmonella (Option D):** While transplant patients are at higher risk for intracellular bacterial infections like Salmonella, it is far less frequent than viral pathogens like CMV. **High-Yield Clinical Pearls for NEET-PG:** * **Timeline of Infection:** * *<1 month:* Bacterial infections (UTI, wound infection) and donor-derived infections. * *1–6 months:* **CMV (Peak incidence)**, BK virus, and opportunistic infections (PJP). * *6+ months:* Community-acquired pneumonia or chronic viral infections (HCV, HBV). * **Diagnosis:** Quantitative PCR for CMV DNA is the gold standard. * **Treatment:** Intravenous **Ganciclovir** or oral Valganciclovir. * **Prophylaxis:** Most centers use Valganciclovir for 3–6 months post-transplant to prevent CMV.
Question 9: Which of the following should be avoided in the long-term follow-up of a renal transplant recipient on ciclosporin?
- A. Administer live vaccines
- B. Prescribe drugs that inhibit cytochrome P450 activity
- C. Prescribe NSAIDs
- D. All of the above (Correct Answer)
Explanation: In renal transplant recipients on long-term immunosuppression with Ciclosporin, management focuses on preventing graft rejection, avoiding nephrotoxicity, and managing drug-drug interactions. **Explanation of Options:** * **A. Live Vaccines:** Immunosuppressed patients (on Ciclosporin, Tacrolimus, or Mycophenolate) have a diminished immune response. Administering live-attenuated vaccines (e.g., BCG, MMR, Yellow Fever) carries a significant risk of causing disseminated infection from the vaccine strain itself. * **B. Cytochrome P450 (CYP3A4) Inhibitors:** Ciclosporin is extensively metabolized by the hepatic CYP3A4 enzyme system. Drugs that inhibit this system (e.g., Erythromycin, Ketoconazole, Diltiazem) decrease Ciclosporin metabolism, leading to toxic blood levels. Conversely, CYP inducers (e.g., Rifampicin, Phenytoin) lower levels, risking graft rejection. * **C. NSAIDs:** Ciclosporin causes vasoconstriction of the afferent arterioles, reducing renal blood flow. NSAIDs inhibit prostaglandins, which are necessary to maintain afferent arteriolar vasodilation. Combining the two leads to synergistic pre-renal vasoconstriction and acute-on-chronic nephrotoxicity. **Clinical Pearls for NEET-PG:** * **Gingival Hyperplasia:** A classic side effect of Ciclosporin (also seen with Phenytoin and Nifedipine). * **Monitoring:** Therapeutic Drug Monitoring (TDM) is essential for Ciclosporin due to its narrow therapeutic index. * **Metabolic Profile:** Ciclosporin is associated with "H" side effects: **H**ypertension, **H**yperlipidemia, **H**yperglycemia, **H**irsutism, and **H**yperkalemia. * **Tacrolimus vs. Ciclosporin:** Tacrolimus is more potent and lacks hirsutism/gingival hyperplasia but has a higher incidence of New-Onset Diabetes After Transplantation (NODAT).
Question 10: Which type of transplant has the lowest chance of recipient failure?
- A. Allograft
- B. Isograft (Correct Answer)
- C. Xenograft
- D. Heterotropic graft
Explanation: **Explanation:** The success of a transplant is primarily determined by the **Major Histocompatibility Complex (MHC)** or Human Leukocyte Antigen (HLA) compatibility between the donor and the recipient. **Why Isograft is correct:** An **Isograft** (also known as a syngeneic graft) is a transplant between genetically identical individuals, such as **monozygotic (identical) twins**. Because the donor and recipient share identical genetic material and HLA antigens, the recipient’s immune system recognizes the graft as "self." This results in a negligible risk of rejection, requiring little to no immunosuppression, and thus carries the lowest chance of failure. **Analysis of Incorrect Options:** * **Allograft:** This is a transplant between genetically different members of the same species (e.g., human to human). This is the most common clinical transplant type but carries a significant risk of rejection due to HLA mismatch. * **Xenograft:** This involves a transplant between different species (e.g., porcine heart valve to human). These carry the highest risk of hyperacute rejection due to pre-existing antibodies and significant genetic disparity. * **Heterotopic graft:** This refers to the **anatomical position** of the graft (placed in a different site than the original organ, like a kidney transplant in the iliac fossa) rather than the genetic relationship. It does not inherently determine the immunological failure rate. **High-Yield Clinical Pearls for NEET-PG:** * **Autograft:** Transplant within the same individual (e.g., skin graft, CABG). This has zero rejection risk and is technically the most successful, but among the options provided (comparing donor types), Isograft is the standard answer for "lowest failure." * **Hyperacute Rejection:** Occurs within minutes/hours; mediated by pre-formed Type II hypersensitivity antibodies. * **Order of Rejection Risk:** Autograft/Isograft < Allograft < Xenograft.
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