Post-transplant immunosuppression protocols US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Post-transplant immunosuppression protocols. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Post-transplant immunosuppression protocols US Medical PG Question 1: A 31-year-old female receives a kidney transplant for autosomal dominant polycystic kidney disease (ADPKD). Three weeks later, the patient experiences acute, T-cell mediated rejection of the allograft and is given sirolimus. Which of the following are side effects of this medication?
- A. Nephrotoxicity, hypertension
- B. Hyperlipidemia, thrombocytopenia (Correct Answer)
- C. Nephrotoxicity, gingival hyperplasia
- D. Pancreatitis
- E. Cytokine release syndrome, hypersensitivity reaction
Post-transplant immunosuppression protocols Explanation: ***Hyperlipidemia, thrombocytopenia***
- **Sirolimus** (rapamycin) is an **mTOR inhibitor** commonly used in transplant immunology, which frequently causes **hyperlipidemia** (elevated cholesterol and triglycerides) and **thrombocytopenia** (low platelet count).
- Other common side effects include **myelosuppression** (leukopenia, anemia), **mouth ulcers**, and **impaired wound healing**.
*Nephrotoxicity, hypertension*
- **Nephrotoxicity** and **hypertension** are more characteristic side effects of **calcineurin inhibitors** like **tacrolimus** and **cyclosporine**, which are also used in transplant immunosuppression but have a different mechanism of action than sirolimus.
- While sirolimus can indirectly affect kidney function, it is generally considered less nephrotoxic than calcineurin inhibitors.
*Nephrotoxicity, gingival hyperplasia*
- **Gingival hyperplasia** is a hallmark side effect of **cyclosporine**, a calcineurin inhibitor, along with **hirsutism** and **nephrotoxicity**.
- Sirolimus does not typically cause gingival hyperplasia.
*Pancreatitis*
- While some immunosuppressants can rarely cause pancreatitis, it is not a common or characteristic side effect of **sirolimus**.
- **Azathioprine** is more frequently associated with pancreatitis among immunosuppressive agents.
*Cytokine release syndrome, hypersensitivity reaction*
- **Cytokine release syndrome** and acute **hypersensitivity reactions** are more often associated with **monoclonal antibodies** (e.g., **basiliximab**, **daclizumab**) used for induction therapy or treatment of acute rejection, particularly within hours or days of administration.
- Sirolimus is less likely to cause these immediate severe reactions.
Post-transplant immunosuppression protocols US Medical PG Question 2: A research team develops a new monoclonal antibody checkpoint inhibitor for advanced melanoma that has shown promise in animal studies as well as high efficacy and low toxicity in early phase human clinical trials. The research team would now like to compare this drug to existing standard of care immunotherapy for advanced melanoma. The research team decides to conduct a non-randomized study where the novel drug will be offered to patients who are deemed to be at risk for toxicity with the current standard of care immunotherapy, while patients without such risk factors will receive the standard treatment. Which of the following best describes the level of evidence that this study can offer?
- A. Level 1
- B. Level 3 (Correct Answer)
- C. Level 5
- D. Level 4
- E. Level 2
Post-transplant immunosuppression protocols Explanation: ***Level 3***
- A **non-randomized controlled trial** like the one described, where patient assignment to treatment groups is based on specific characteristics (risk of toxicity), falls into Level 3 evidence.
- This level typically includes **non-randomized controlled trials** and **well-designed cohort studies** with comparison groups, which are prone to selection bias and confounding.
- The study compares two treatments but lacks randomization, making it Level 3 evidence.
*Level 1*
- Level 1 evidence is the **highest level of evidence**, derived from **systematic reviews and meta-analyses** of multiple well-designed randomized controlled trials or large, high-quality randomized controlled trials.
- The described study is explicitly stated as non-randomized, ruling out Level 1.
*Level 2*
- Level 2 evidence involves at least one **well-designed randomized controlled trial** (RCT) or **systematic reviews** of randomized trials.
- The current study is *non-randomized*, which means it cannot be classified as Level 2 evidence, as randomization is a key criterion for this level.
*Level 4*
- Level 4 evidence includes **case series**, **case-control studies**, and **poorly designed cohort or case-control studies**.
- While the study is non-randomized, it is a controlled comparative trial rather than a case series or retrospective case-control study, placing it at Level 3.
*Level 5*
- Level 5 evidence is the **lowest level of evidence**, typically consisting of **expert opinion** without explicit critical appraisal, or based on physiology, bench research, or animal studies.
- While the drug was initially tested in animal studies, the current human comparative study offers a higher level of evidence than expert opinion or preclinical data.
Post-transplant immunosuppression protocols US Medical PG Question 3: A 10-year-old boy is presented to the hospital for a kidney transplant. In the operating room, the surgeon connects an allograft kidney renal artery to the aorta, and after a few moments, the kidney becomes cyanotic, edematous, and dusky with mottling. Which of the following in the recipient’s serum is responsible for this rejection?
- A. Macrophages
- B. CD4+ T cells
- C. IgA
- D. CD8+ T cells
- E. IgG (Correct Answer)
Post-transplant immunosuppression protocols Explanation: ***IgG***
- The rapid onset of tissue necrosis and the immediate signs of rejection (cyanotic, edematous, dusky with mottling) upon vascular anastomosis are characteristic of **hyperacute rejection**.
- **Hyperacute rejection** is mediated by pre-formed recipient antibodies, primarily **IgG**, targeting donor ABO or HLA antigens. These antibodies activate complement, leading to rapid thrombosis and graft destruction.
*Macrophages*
- While macrophages play a role in chronic allograft rejection and delayed type hypersensitivity, they are not the primary mediators of **hyperacute rejection**.
- Their involvement typically presents with a more delayed and less immediate profound tissue damage than seen in this scenario.
*CD4+ T cells*
- **CD4+ T cells** are central to acute cellular rejection, which typically manifests days to weeks after transplantation.
- They are not responsible for the immediate, pre-formed antibody-mediated response seen in **hyperacute rejection**.
*IgA*
- **IgA antibodies** are primarily involved in mucosal immunity and are generally not implicated in solid organ transplant rejection, especially hyperacute rejection.
- While IgA can contribute to immune complex formation, it's not the main antibody type driving hyperacute allograft destruction.
*CD8+ T cells*
- **CD8+ T cells** (cytotoxic T lymphocytes) are key players in acute cellular rejection, mediating direct lysis of donor cells.
- Their action is part of a cellular immune response that takes days to weeks to develop and is not responsible for the immediate, antibody-mediated hyperacute rejection.
Post-transplant immunosuppression protocols US Medical PG Question 4: A 56-year-old man comes to the emergency department because of progressively worsening shortness of breath and fever for 2 days. He also has a nonproductive cough. He does not have chest pain or headache. He has chronic myeloid leukemia and had a bone marrow transplant 3 months ago. His current medications include busulfan, mycophenolate mofetil, tacrolimus, and methylprednisolone. His temperature is 38.1°C (100.6°F), pulse is 103/min, respirations are 26/min, and blood pressure is 130/70 mm Hg. Pulse oximetry on room air shows an oxygen saturation of 93%. Pulmonary examination shows diffuse crackles. The spleen tip is palpated 4 cm below the left costal margin. Laboratory studies show:
Hemoglobin 10.3 g/dL
Leukocyte count 4,400/mm3
Platelet count 160,000/mm3
Serum
Glucose 78 mg/dL
Creatinine 2.1 mg/dL
D-dimer 96 ng/mL (N < 250)
pp65 antigen positive
Galactomannan antigen negative
Urinalysis is normal. An x-ray of the chest shows diffuse bilateral interstitial infiltrates. An ECG shows sinus tachycardia. Which of the following is the most appropriate pharmacotherapy?
- A. Levofloxacin
- B. Ganciclovir (Correct Answer)
- C. Valganciclovir
- D. Azithromycin
- E. Acyclovir
Post-transplant immunosuppression protocols Explanation: ***Ganciclovir***
- The patient's **positive pp65 antigen** confirms **cytomegalovirus (CMV) infection**, the most common viral infection in immunocompromised bone marrow transplant recipients.
- This patient has **severe, life-threatening CMV pneumonitis** evidenced by hypoxia (O2 sat 93%), tachypnea, and diffuse bilateral interstitial infiltrates.
- **Intravenous ganciclovir** is the **first-line treatment** for severe CMV disease due to its potent antiviral activity and reliable bioavailability in critically ill patients.
*Valganciclovir*
- **Valganciclovir** is an **oral prodrug of ganciclovir** with excellent bioavailability, but it is primarily reserved for **CMV prophylaxis** or **maintenance therapy** after initial IV treatment.
- In this patient with **acute, severe CMV pneumonitis** requiring urgent intervention (hypoxia, respiratory distress), **IV ganciclovir is strongly preferred** for faster, more reliable drug delivery and higher tissue concentrations.
*Levofloxacin*
- This **fluoroquinolone antibiotic** treats **bacterial infections**, not viral pathogens like CMV.
- The **positive pp65 antigen** specifically identifies CMV as the etiology, and negative galactomannan rules out invasive aspergillosis.
- While empiric antibacterial coverage might be considered in febrile neutropenic patients, the clear viral diagnosis directs therapy toward antivirals.
*Azithromycin*
- **Azithromycin** is a macrolide antibiotic effective against atypical bacteria (Mycoplasma, Chlamydophila) and some other bacterial pathogens.
- It has **no activity against CMV** and would not address the confirmed viral etiology.
*Acyclovir*
- **Acyclovir** is effective against **herpes simplex virus (HSV)** and **varicella-zoster virus (VZV)**, but has **poor activity against CMV** due to inadequate phosphorylation by CMV enzymes.
- The positive pp65 antigen specifically indicates CMV, for which ganciclovir (not acyclovir) is required.
Post-transplant immunosuppression protocols US Medical PG Question 5: 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?
- A. Granular immunofluorescence around the glomerular basement membrane
- B. Lymphocytic infiltrate of the tubules and interstitium (Correct Answer)
- C. Crescent formation in Bowman’s space
- D. Drug precipitation in the renal tubules
- E. Sloughing of proximal tubular epithelial cells
Post-transplant immunosuppression protocols Explanation: ***Lymphocytic infiltrate of the tubules and interstitium***
- **Acute cell-mediated rejection** is primarily characterized by the infiltration of **T lymphocytes** and macrophages into the allograft, leading to inflammation and damage.
- This cellular infiltrate is typically observed in the **interstitium and tubules** of the transplanted kidney.
*Granular immunofluorescence around the glomerular basement membrane*
- This finding is characteristic of **immune complex-mediated glomerulonephritis**, such as post-streptococcal glomerulonephritis, and signifies deposition of immune complexes.
- It is not typical of acute cell-mediated rejection, which is driven by T-cells rather than circulating immune complexes.
*Crescent formation in Bowman’s space*
- **Crescents** in Bowman's space are indicative of rapidly progressive glomerulonephritis (RPGN), a severe form of glomerular inflammation usually associated with conditions like Goodpasture syndrome or ANCA-associated vasculitis.
- While crescentic glomerulonephritis can cause acute kidney injury, it is not the primary histological hallmark of acute cell-mediated transplant rejection.
*Drug precipitation in the renal tubules*
- **Drug precipitation** can occur with certain medications, leading to acute kidney injury (e.g., sulfonamides, methotrexate), but it is a chemical injury, not an immune-mediated rejection process.
- The patient's symptoms of fever and arthralgia, along with elevated creatinine, point towards an inflammatory immune response rather than drug toxicity alone.
*Sloughing of proximal tubular epithelial cells*
- **Sloughing of proximal tubular epithelial cells** is a hallmark of **acute tubular necrosis (ATN)**, often caused by ischemia or nephrotoxic agents.
- While ATN can also lead to elevated creatinine, the presence of fever and arthralgia, plus the context of transplantation, makes acute cell-mediated rejection a more likely diagnosis.
Post-transplant immunosuppression protocols US Medical PG Question 6: A 40-year-old male with a history of chronic alcoholism recently received a liver transplant. Two weeks following the transplant, the patient presents with a skin rash and frequent episodes of bloody diarrhea. A colonoscopy is performed and biopsy reveals apoptosis of colonic epithelial cells. What is most likely mediating these symptoms?
- A. Donor T-cells (Correct Answer)
- B. Recipient T-cells
- C. Recipient B-cells
- D. Recipient antibodies
- E. Donor B-cells
Post-transplant immunosuppression protocols Explanation: ***Donor T-cells***
- This clinical presentation of **skin rash**, **bloody diarrhea**, and **colonic epithelial apoptosis** following an allogeneic transplant (like a liver transplant) is classic for **Graft-versus-Host Disease (GVHD)**.
- In GVHD, **immunocompetent T-cells from the donor** recognize the recipient's tissues as foreign and mount an immune attack, causing damage to organs like the skin, gastrointestinal tract, and liver.
*Recipient T-cells*
- **Recipient T-cells** are typically immunosuppressed following an organ transplant to prevent organ rejection.
- Furthermore, if activated, recipient T-cells would target the donor organ (the liver in this case), leading to **rejection**, rather than the systemic symptoms observed (skin rash, bloody diarrhea) which suggest an attack by donor cells on recipient tissues.
*Recipient B-cells*
- While recipient B-cells can be involved in **antibody-mediated rejection** of the transplanted organ, they are not the primary mediators of **cellular GVHD**.
- **Antibody-mediated rejection** would typically involve antibodies targeting the donor liver, leading to liver dysfunction, not the widespread GVHD symptoms described.
*Recipient antibodies*
- **Recipient antibodies** are primarily involved in **antibody-mediated rejection** of the transplanted organ, which would manifest as dysfunction of the transplanted liver.
- They do not mediate the symptoms of **Graft-versus-Host Disease (GVHD)**, which is a cell-mediated immune response.
*Donor B-cells*
- **Donor B-cells** are generally not the primary mediators of GVHD.
- While donor immune cells are crucial for GVHD, the major players are **donor T-cells**, which directly recognize and attack host tissues.
Post-transplant immunosuppression protocols US Medical PG Question 7: A 67-year-old man is seen on the surgical floor after a transplant procedure. The previous day, the patient had a renal transplant from a matched donor. He is currently recovering and doing well. The patient has a past medical history of IV drug use, diabetes mellitus, oral cold sores, hypertension, renal failure, and dyslipidemia. The patient's current medications include lisinopril, atorvastatin, insulin, and aspirin. Prior to the procedure, he was also on dialysis. The patient is started on cyclosporine. The patient successfully recovers over the next few days. Which of the following medications should be started in this patient?
- A. Azithromycin
- B. TMP-SMX (Correct Answer)
- C. Acyclovir
- D. Low dose acyclovir
- E. Penicillin
Post-transplant immunosuppression protocols Explanation: ***TMP-SMX***
- **TMP-SMX (trimethoprim-sulfamethoxazole)** is the **most critical** prophylactic medication for all solid organ transplant recipients on immunosuppression.
- It provides essential prophylaxis against **Pneumocystis jirovecii pneumonia (PJP)**, a life-threatening opportunistic infection with high mortality if not prevented.
- PJP prophylaxis is a **universal recommendation** for all transplant patients and is typically continued for 6-12 months post-transplant.
- Additionally offers protection against **Toxoplasma gondii**, **Nocardia**, and common urinary tract infections, making it particularly valuable in renal transplant recipients.
*Azithromycin*
- Azithromycin is a macrolide antibiotic used for specific bacterial infections and sometimes for **Mycobacterium avium complex (MAC)** prophylaxis in severely immunocompromised patients.
- It is not standard prophylaxis in routine post-transplant care and does not protect against PJP, the most critical opportunistic infection in this setting.
*Acyclovir*
- High-dose acyclovir is used to **treat active HSV or VZV infections**, not for routine prophylaxis.
- This patient has no active viral infection requiring treatment doses at this time.
*Low dose acyclovir*
- Low-dose acyclovir (or valacyclovir) is indeed used for **HSV/VZV prophylaxis** in transplant patients, especially those with a history of cold sores.
- Many transplant centers do initiate this medication alongside TMP-SMX in the post-transplant period.
- However, in a **single-best-answer** context, **TMP-SMX takes priority** as it prevents PJP, which is universally life-threatening and has higher incidence without prophylaxis compared to severe HSV reactivation.
- TMP-SMX is considered the **essential first-line** prophylaxis that all transplant patients must receive.
*Penicillin*
- Penicillin is a narrow-spectrum antibiotic effective against certain gram-positive bacteria.
- It has no role in post-transplant opportunistic infection prophylaxis and does not protect against PJP, HSV, or other transplant-related infections.
Post-transplant immunosuppression protocols US Medical PG Question 8: A 63-year-old HIV-positive man comes to the physician for a routine health maintenance examination. Four years ago, he was diagnosed with HIV and was started on cART therapy. He tells the physician that he has been having difficulty adhering to his medication regimen. He has been unemployed for the past couple of years and relies on unemployment benefits to cover the costs of daily living. His father died of lymphoma at the age of 60 years. He wants more information about his risk of developing DLBCL. Which of the following is the greatest risk factor for the development of DLBCL in HIV-positive patients?
- A. Poor adherence to cART (Correct Answer)
- B. Income below $30,000 per year
- C. Male sex
- D. Positive family history of cancer
- E. Age over 55 years
Post-transplant immunosuppression protocols Explanation: **Poor adherence to cART**
- **Poor adherence** to cART leads to **uncontrolled HIV replication** and persistent **immunosuppression**, which significantly increases the risk of developing **DLBCL**.
- **Immune dysregulation** caused by HIV directly contributes to a higher incidence of **AIDS-defining malignancies**, including DLBCL.
*Income below $30,000 per year*
- While **socioeconomic factors** can impact access to care and medication adherence, low income itself is not a direct biological risk factor for DLBCL.
- Its influence is secondary to its effect on adherence and overall health status, rather than a primary risk factor for the malignancy.
*Positive family history of cancer*
- Although a family history of cancer can increase the risk for some malignancies, it is generally **not a significant risk factor** for **HIV-associated DLBCL**.
- The primary drivers of HIV-associated DLBCL are linked to HIV-induced immunodeficiency, not specific inherited genetic predispositions for lymphoma.
*Age over 55 years*
- While the incidence of many cancers increases with **age**, for **HIV-associated DLBCL**, age is less prominent than the degree of **immunodeficiency** caused by HIV.
- The stronger prognostic factor remains the state of the immune system, particularly a **low CD4 count**, which is often exacerbated by poor cART adherence.
*Male sex*
- While there are minor differences in cancer incidence between sexes, **male sex** is not a primary or significant independent risk factor for **HIV-associated DLBCL**.
- The risk is predominantly driven by factors related to HIV infection itself and the resulting immune dysfunction.
Post-transplant immunosuppression protocols US Medical PG Question 9: A 38-year-old woman comes to the physician for a follow-up examination. Two years ago, she was diagnosed with multiple sclerosis. Three weeks ago, she was admitted and treated for right lower leg weakness with high-dose methylprednisone for 5 days. She has had 4 exacerbations over the past 6 months. Current medications include interferon beta and a multivitamin. Her temperature is 37°C (98.6°F), pulse is 90/min, and blood pressure is 116/74 mm Hg. Examination shows pallor of the right optic disk. Neurologic examination shows no focal findings. She is anxious about the number of exacerbations and repeated hospitalizations. She is counseled about the second-line treatment options available to her. She consents to treatment with natalizumab. However, she has read online about its adverse effects and is concerned. This patient is at increased risk for which of the following complications?
- A. Tuberculosis
- B. Syndrome of inappropriate antidiuretic hormone
- C. Parkinsonism
- D. Progressive multifocal leukoencephalopathy (Correct Answer)
- E. Aplastic anemia
Post-transplant immunosuppression protocols Explanation: ***Progressive multifocal leukoencephalopathy***
- **Natalizumab** is a monoclonal antibody that blocks the binding of leukocytes to endothelial cells, preventing their entry into the central nervous system. This immunosuppressive effect increases the risk of **progressive multifocal leukoencephalopathy (PML)**, especially in patients who are positive for the **JC virus**.
- PML is a serious and often fatal opportunistic infection of the brain caused by the **JC virus**, which demyelinates axons and leads to severe neurological deficits.
*Tuberculosis*
- While some immunosuppressants can reactivate **latent tuberculosis**, natalizumab is not typically associated with an increased risk of TB compared to other immunomodulatory drugs like TNF-alpha inhibitors.
- The mechanism of action of natalizumab (alpha-4 integrin blocker) does not directly impede the immune response responsible for containing mycobacterial infections to the same extent as other treatments.
*Syndrome of inappropriate antidiuretic hormone*
- **SIADH** is not a known adverse effect of natalizumab.
- SIADH is characterized by excessive secretion of **antidiuretic hormone**, leading to hyponatremia, and is often associated with certain medications (e.g., SSRIs, carbamazepine) or underlying conditions like malignancy or pulmonary disease.
*Parkinsonism*
- Parkinsonism involves symptoms like **bradykinesia**, rigidity, and tremor, and is a neurodegenerative disorder.
- There is **no evidence** suggesting a causal link between natalizumab treatment and the development of Parkinsonism.
*Aplastic anemia*
- **Aplastic anemia** is a rare but severe condition where the bone marrow fails to produce blood cells.
- This adverse effect is not associated with natalizumab; it is more commonly linked to certain **chemotherapeutic agents**, radiation, or specific antimicrobial drugs like chloramphenicol.
Post-transplant immunosuppression protocols US Medical PG Question 10: A 55-year-old woman recently underwent kidney transplantation for end-stage renal disease. Her early postoperative period was uneventful, and her serum creatinine is lowered from 4.3 mg/dL (preoperative) to 2.5 mg/dL. She is immediately started on immunosuppressive therapy. On postoperative day 7, she presents to the emergency department (ED) because of nausea, fever, abdominal pain at the transplant site, malaise, and pedal edema. The vital signs include: pulse 106/min, blood pressure 167/96 mm Hg, respirations 26/min, and temperature 40.0°C (104.0°F). The surgical site shows no signs of infection. Her urine output is 250 mL over the past 24 hours. Laboratory studies show:
Hematocrit 33%
White blood cell (WBC) count 6700/mm3
Blood urea 44 mg/dL
Serum creatinine 3.3 mg/dL
Serum sodium 136 mEq/L
Serum potassium 5.6 mEq/L
An ultrasound of the abdomen shows collection of fluid around the transplanted kidney with moderate hydronephrosis. Which of the following initial actions is the most appropriate?
- A. Re-operate and remove the failed kidney transplant
- B. Continue with an ultrasound-guided biopsy of the transplanted kidney (Correct Answer)
- C. Start on pulse steroid treatment or OKT3
- D. Supportive treatment with IV fluids, antibiotics, and antipyretics
- E. Consider hemodialysis
Post-transplant immunosuppression protocols Explanation: ***Continue with an ultrasound-guided biopsy of the transplanted kidney***
- The patient's symptoms (fever, malaise, abdominal pain, rising creatinine) and ultrasound findings (fluid collection, hydronephrosis) are highly suggestive of **acute renal allograft rejection** or an **obstructive uropathy**, necessitating a definitive diagnosis through biopsy.
- A biopsy will differentiate between rejection, drug toxicity, or other causes of allograft dysfunction, guiding appropriate and specific treatment.
*Re-operate and remove the failed kidney transplant*
- Removing the transplanted kidney is a drastic measure and premature at this stage, as the cause of dysfunction is not yet confirmed.
- The elevated creatinine and hydronephrosis could be reversible with proper treatment once the underlying cause is identified.
*Start on pulse steroid treatment or OKT3*
- While pulse steroids or OKT3 (muromonab-CD3) are used to treat acute rejection, administering them without a definitive diagnosis from a biopsy could be inappropriate and potentially harmful.
- The symptoms could also be due to infection or obstruction, which would not respond to these immunosuppressive therapies and could worsen with increased immunosuppression.
*Supportive treatment with IV fluids, antibiotics, and antipyretics*
- Supportive care alone is insufficient given the potential for acute allograft rejection or severe obstruction, which requires specific intervention.
- Although the patient has fever, there are no clear signs of infection, and empirical antibiotics may delay necessary diagnostic steps.
*Consider hemodialysis*
- While the patient's creatinine is elevated and potassium is high, these parameters alone do not immediately warrant hemodialysis without exploring the underlying cause of allograft dysfunction.
- Dialysis is typically considered when there are severe indications like refractory hyperkalemia, fluid overload, acidosis, or uremic symptoms that cannot be otherwise managed, and the primary goal should be to treat the cause of decreasing kidney function.
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