Hyperacute rejection is caused by A. Preformed antibodies

1. Hyperacute rejection is caused by A. Preformed antibodies B. B-cell–generated antidonor antibodies C. T-cell–mediated allorejection D. Nonimmune mechanism

2. Answer A. Explanation: Hyperacute rejection, which usually occurs within minutes after the transplanted organ is reperfused, is due to the presence of preformed antibodies in the recipient, antibodies that are specific to the donor. These antibodies may be directed against the donor's HLA antigens or they may be anti-ABO blood group antibodies. Either way, they bind to the vascular endothelium in the graft and activate the complement cascade, leading to platelet activation and to diffuse intravascular coagulation. The result is a swollen, darkened graft, which undergoes ischemic necrosis. This type of rejection is generally not reversible, so prevention is key. Prevention is best done by making sure the graft is ABO-compatible and by performing a pretransplant cross-match. The cross-match is an in vitro test that involves mixing the donor's cells with the recipient's serum to look for evidence of donor cell destruction by recipient antibodies. A positive cross-match indicates the presence of preformed antibodies in the recipient that are specific to the donor, thus a high risk of hyperacute rejection if the transplant is performed. (See Schwartz 8th ed., Chapter 10, Transplant Immunology.)

3. The mechanism of action of azathioprine is A. Inhibition of calcineurin B. Interference with DNA synthesis C. Binding of FK-506 binding proteins D. Inhibition of P7056 kinase

4. Answer B. Explanation: Azathioprine (AZA) acts late in the immune process, affecting the cell cycle by interfering with DNA synthesis, thus suppressing proliferation of activated B and T lymphocytes. AZA is valuable in preventing the onset of acute rejection, but is not effective in the treatment of rejection episodes themselves. Cyclosporine binds with its cytoplasmic receptor protein, cyclophilin, which subsequently inhibits the activity of calcineurin. Doing so impairs expression of several critical T-cell activation genes, the most important being for interleukin-2 (IL-2). As a result, T-cell activation is suppressed. The metabolism of cyclosporine is via the cytochrome P450 system, therefore several drug interactions are possible. Inducers of P450 such as phenytoin decrease blood levels; drugs such as erythromycin, cimetidine, ketoconazole, and fluconazole increase them. Tacrolimus, like cyclosporine, is a calcineurin inhibitor and has a very similar mechanism of action. Cyclosporine acts by binding cyclophilins, while tacrolimus acts by binding FK506-binding proteins (FKBPs). The tacrolimus-FKBP complex inhibits the enzyme calcineurin, which is essential for activating transcription factors in response to the rise in intracellular calcium seen with stimulation of the T-cell receptor (TCR). The net effect of tacrolimus is to inhibit T-cell function by preventing synthesis of IL-2 and other important cytokines. Sirolimus (previously known as rapamycin) is structurally similar to tacrolimus and binds to the same immunophilin (FKBP). Unlike tacrolimus, it does not affect calcineurin activity, and therefore does not block the calcium-dependent activation of cytokine genes. Rather, the active complex binds so-called target of rapamycin (TOR) proteins (Fig. 10-2), resulting in inhibition of P7056 kinase (an enzyme linked to cell division). The net result is to prevent progression from the G1 to the S phase of the cell cycle, halting cell division. Mycophenolate mofetil works by inhibiting inosine monophosphate dehydrogenase, which is a crucial, rate-limiting enzyme in de novo synthesis of purines. Specifically, this enzyme catalyzes the formation of guanosine nucleotides from inosine. Many cells have a salvage pathway and therefore can bypass this need for guanosine nucleotide synthesis by the de novo pathway. Activated lymphocytes, however, do not possess this salvage pathway and require de novo synthesis for clonal expansion. The net result is a selective, reversible antiproliferative effect on T and B lymphocytes. (See Schwartz 8th ed., Chapter 10, Clinical Immunosuppression.)

5. Lymphoceles occur how long after a renal transplant? A. Within 48 h B. ~1 week after surgery C. 2–4 weeks after surgery D. 3 months after surgery

6. Answer C. Explanation: The reported incidence of lymphoceles (fluid collections of lymph that generally result from cut lymphatic vessels in the recipient) is 0.6 to 18%. Lymphoceles usually do not occur until at least two weeks posttransplant. Symptoms are generally related to the mass effect and compression of nearby structures (e.g., ureter, iliac vein, allograft renal artery), and patients develop hypertension, unilateral leg swelling on the side of the transplant, and elevated serum creatinine. Ultrasound is used to confirm a fluid collection, although percutaneous aspiration may be necessary to exclude presence of other collections such as urinomas, hematomas, or abscesses. The standard surgical treatment is creation of a peritoneal window to allow for drainage of the lymphatic fluid into the peritoneal cavity where it can be absorbed. Either a laparoscopic or an open approach may be used. Another option is percutaneous insertion of a drainage catheter, with or without sclerotherapy; however, it is associated with some risk of recurrence or infection. (See Schwartz 8th ed., Chapter 10, Kidney Transplantaion.)

7. Which of the following is NOT a side effect of cyclosporine? A. Interstitial fibrosis of the renal parenchyma B. Gingival hyperplasia C. Headache D. Pancreatitis

8. Answer D Explanation: Adverse effects of cyclosporine can be classified as renal or nonrenal. Nephrotoxicity is the most important and troubling adverse effect of cyclosporine. Cyclosporine has a vasoconstrictor effect on the renal vasculature. This vasoconstriction (likely a transient, reversible, and dose-dependent phenomenon) may cause early posttransplant graft dysfunction or may exaggerate existing poor graft function. Also, long-term cyclosporine use may result in interstitial fibrosis of the renal parenchyma, coupled with arteriolar lesions. The exact mechanism is unknown, but renal failure may eventually result. A number of nonrenal side effects may also be seen with the use of cyclosporine. Cosmetic complications, most commonly hirsutism and gingival hyperplasia, may result in considerable distress, possibly leading to noncompliant behavior, especially in adolescents and women. Several neurologic complications, including headaches, tremor, and seizures, also have been reported. Other nonrenal side effects include hyperlipidemia, hepatotoxicity, and hyperuricemia. (See Schwartz 8th ed., Chapter 10, Clinical Immunosuppression.)

9. The 5-year graft survival rate after renal transplantation is A. 35–40% B. 50–55% C. 75–80% D. 90–95%

10. Answer C. Explanation: The incidence of acute rejection has declined steadily since the early 1990s. Most centers now report acute rejection rates of 10 to 20% at 1 year posttransplant. This decline has been a major factor in the improvement in graft survival rates, which are now about 75 to 80% at 5 years and 60 to 65% at 10 years posttransplant for all kidney recipients. Currently, the most common cause of graft loss is recipient death (usually from cardiovascular causes) with a functioning graft. The second most common cause is chronic allograft nephropathy. Characterized by a slow, unrelenting deterioration of graft function, it likely has multiple causes (both immunologic and nonimmunologic). The graft failure rate due to surgical technique has remained at about 2%. (See Schwartz 8th ed., Chapter 10, Kidney Transplantation.)

11. All of the following are absolute contraindications in considering a candidate for orthotopic cardiac transplantation EXCEPT A. Active infection B. Age over 65 years C. History of medical noncompliance D. Severe renal insufficiency

12. Answer A. Explanation: Active infection is considered a potentially reversible contraindication to cardiac transplantation. The other conditions listed are absolute contraindications to orthotopic cardiac transplantation. Heterotopic cardiac transplantation, in which the patient's right heart continues to work against the pulmonary hypertension while the donor heart supplies systemic circulation, is used for a certain number of patients with pulmonary hypertension. (See Schwartz 7th ed.)

13. After completion of the vascular anastomoses, drainage of a transplanted pancreas is accomplished by anastomosis to A. Right colon B. Left colon C. Duodenum D. Bladder or small bowel

14. Answer D Explanation: Once the pancreas is revascularized, a drainage procedure must be performed to handle the pancreatic exocrine secretions. Options include anastomosing the donor duodenum to the recipient bladder or to the small bowel, with the small bowel either in continuity or connected to a Roux-en-Y limb. Some centers always use enteric drainage, others always use bladder drainage, and others tailor the approach according to the recipient category. Both enteric drainage and bladder drainage now have a relatively low surgical risk. The main advantage of bladder drainage is the ability to directly measure enzyme activity in the pancreatic graft exocrine secretions by measuring the amount of amylase in the urine. A decrease in urine amylase is a sensitive marker for rejection, even though it is not entirely specific. Urine amylase always decreases before hyperglycemia ensues. A rise in serum amylase may precede a decrease in urine amylase, but serum amylase by itself is less sensitive (it does not always rise, but urine amylase always decreases), and is no more specific for the diagnosis of rejection. The leak rate is the same whether the pancreas is drained to the bladder or to the bowel, but the consequences of a bladder leak are much less severe than those associated with a bowel leak. The disadvantages of bladder drainage include complications such as dehydration and acidosis (from loss of alkalotic pancreatic secretions in the urine), and local problems with the bladder such as infection, hematuria, stones, and urethritis. Because of these chronic complications, between 10 and 20% of bladder-drained graft recipients are ultimately converted to enteric drainage. Enteric drainage is more physiologic and has fewer long-term complications. However, the ability to monitor for rejection is decreased, given the absence of urinary amylase. Rejection in simultaneous pancreas and kidney (SPK) transplant recipients almost always affects both the kidney and the pancreas; therefore, the serum creatinine level can be used as a marker for rejection of the pancreas. Hence, most centers now use enteric drainage for SPK transplants. If the kidney and the pancreas are from different donors, or if a pancreas transplant alone (PTA) is performed, then bladder drainage is preferred, so rejection of the pancreas can be detected earlier. (See Schwartz 8th ed., Chapter 10, Pancreas Transplantation.)

15. Absolute contraindications for donation of a heart include all of the following EXCEPT A. Carbon monoxide-hemoglobin level >20% B. Prolonged cardiac arrest C. Prolonged high-dopamine requirement D. Significant smoking history

16. Answer C. Explanation: The use of high doses of dopamine for more than 24 h before death is a relative contraindication to transplantation of the heart. The other listed items are all absolute contraindications to cardiac donation. Severe structural heart disease and human immunodeficiency virus seropositivity are other absolute contraindications. (See Schwartz 7th ed.)

17. The most common cause of renal failure in the United States is A. Chronic glomerulonephritis B. Chronic pyelonephritis C. Diabetes mellitus D. Obstructive uropathy

18. Answer C. Explanation: Because the life expectancy of patients with diabetes mellitus has dramatically lengthened by appropriate use of insulin, diabetes is now the leading cause of renal failure and contributes to blindness, neuropathies, and early atherosclerosis. These problems have led to the continued interest in the possibility of pancreatic transplantation as a form of disease control. (See Schwartz 7th ed.)

19. A 53-year-old man has long-standing liver cirrhosis secondary to hepatitis C infection. The most appropriate screening regimen should include I. yearly CT scan of the abdomen II. a liver biopsy III. liver ultrasound IV. AFP level V. diagnostic laparoscopy A. I, II B. III, V C. III, IV D. I, V E. II, III

20. Answer C. Explanation: The risk factors for developing HCC are well documented and include the presence of cirrhosis, chronic active viral hepatitis associated with elevated AFP, age >50, male gender, family history of HCC, and previously resected or ablated HCC. Once cirrhosis has developed, HCC is estimated to occur at the rate of 1–4% per year. This well-documented risk for developing HCC has led to the practice of screening and surveillance of high-risk patients for HCC. Although there are no randomized trials comparing surveillance with no surveillance, a National Institute of Health Consensus Panel currently recommends the use of ultrasonography and AFP levels for early detection of HCC in high-risk populations (Fig. 28-20). FIG. 28-20Routine screening for HCC has been demonstrated not to be cost-effective; however, the wide availability of color-flow or power Doppler imaging provides a rapid noninvasive modality to serially examine the liver in patients at risk for the development of HCC. The image depicted illustrates an HCC lesion with a hallmark arterial feeding vessel visualized by color-flow Doppler imaging.Serum markers other than AFP have no proven efficacy for early detection of HCC, and ultrasound has a reasonable sensitivity (60–78%) but is operator dependent. This combination should be done at 6 months intervals. The identification of HCC by screening has marginal cost effectiveness. Despite this, screening for HCC in high-risk patients has become the standard of care and should be recommended when applicable. When viewed from an individual patient's perspective, screening seems to be worthwhile for good surgical candidates who can undergo resection or transplantation. The use of CT scan for this purpose is not cost-effective, and it is not currently recommended as a screening tool although some physicians use it in addition to AFP levels and ultrasound. Liver biopsy and laparoscopy may establish the diagnosis of HCC in high-risk patients but should not be routinely obtained and have no role as screening tools.

21. Which of the following radiologic studies is not recommended for the diagnosis of Caroli's disease? A. magnetic resonance imaging (MRI) abdomen B. CT scan abdomen C. abdominal US D. HIDA scan E. ERCP

22. Answer D. Explanation: Caroli's disease is an abnormal development of the intrahepatic bile ducts without an obstructive cause, characterized by saccular dilatations, resembling a picture of multiple cyst-like structures of varying size. Two types have been described: a type with bile duct abnormalities alone and a type with bile duct abnormality combined with periportal fibrosis, similar to congenital hepatic fibrosis. This combined type is also known as Caroli's syndrome and has been reported more frequently than the pure type, or Caroli's disease. Caroli's disease is anatomically characterized for saccular dilatations of the bile ducts more frequently seen in the left side of the liver. In 30–40% of the cases this are confined to one segment of one side of the liver. Bilateral abnormalities are more common in the second type: Caroli's syndrome. The most common complications are cholangitis, septicemia, amyloidosis, and cholangiocarcinoma (7–10% of patients). Caroli's syndrome is associated with renal disorders such as renal cysts and nephrospongiosis seen in 30–40% of patients. These disorders have not been seen in Caroli's disease. The diagnosis is made by radiologic studies such as US, CT scan, ERCP, MRI where saccular or cystically dilated intrahepatic ducts are seen. Surgical treatment is indicated in order to reduce the risk of recurrent cholangitis, biliary cirrhosis, or cholangiocarcinoma. Hepatic lobectomy is indicated for localized bile duct abnormalities (Caroli's disease), while liver transplant should be considered in selected patients with generalized disease or concomitant liver fibrosis and portal hypertension (Caroli's syndrome).

23. Immunologic rejection is mediated by the recipient's A. Eosinophils B. Lymphocytes C. Neutrophils D. Plasma cells

24. Answer B. Explanation: Early work in the transplantation field showed that graft rejection was mediated by the recipient's white blood cells. Refinement of the techniques involved demonstrated that the lymphocytes played the major role in this phenomenon. The development of antilymphocyte serum was an early step in controlling the rejection process. (See Schwartz 7th ed.)

25. In the prevention of graft rejection, cyclosporine A. Blocks transcription of interleukin-1 (IL-1) and tumor necrosis factor- (TNF-) B. Inhibits lymphocyte nucleic acid metabolism C. Results in rapid decrease in the number of circulatory T lymphocytes D. Selectively inhibits T-cell activation

26. Answer D. Explanation: There are a number of different agents used to control graft rejection, and they function in different ways. Cyclosporine, the mainstay of immunosuppression, selectively inhibits T-cell activation. Corticosteroids block the transcription of IL-1 and TNF-. Azathioprine inhibits lymphocyte nucleic acid metabolism. Mycophenolate mofetil inhibits RNA and DNA synthesis. OKT3 results in a rapid decrease in circulatory T lymphocytes. (See Schwartz 7th ed.)

27. Required laboratory tests in evaluation of a patient under consideration for heart transplantation include all of the following EXCEPT A. Blood type B. Cardiac catheterization C. Complete blood count D. Prothrombin time and activated partial thromboplastin time

28. Answer B. Explanation: Cardiac catheterization may be indicated in some patients to evaluate cardiac function. The other tests are required in any patient under consideration for cardiac transplantation. (See Schwartz 7th ed.)

29. All of the following conditions in a potential donor are absolute contraindications to the use of a kidney for transplantation EXCEPT A. Age older than 70 years B. Chronic renal insufficiency C. Long-standing hypertension D. Presence of hepatitis C

30. Answer D. Explanation: Cadaveric kidneys make up 75% of all donor kidneys, and the demand far exceeds the supply. For this reason, donor criteria have been liberalized in recent years. Advanced age, chronic renal insufficiency, intravenous drug abuse, and long-standing hypertension remain absolute contraindications. Human immunodeficiency virus seropositivity and the presence of surface antigens against hepatitis B are also absolute contraindications. Although there is risk associated with using a kidney from a donor with evidence of hepatitis C, this condition is not considered an absolute contraindication to kidney use. (See Schwartz 7th ed.)

31. Absolute contraindications to renal transplantation for a patient with chronic renal failure include all of the following EXCEPT A. Chronic active hepatitis B. Human immunodeficiency virus infection C. Recent operation of cancer of the colon D. Sickle cell disease

32. Answer D. Explanation: Sickle cell disease is a relative contraindication to renal transplantation because of the associated high incidence of recurrence. The other listed conditions are considered absolute contraindications because of the patient's generally poor health prognosis. (See Schwartz 7th ed.)

33. The single most important factor in determining whether to perform a transplant between a specific donor and recipient is A. Mixed lymphocyte culture assays of the donor and recipient B. HLA types of the donor and recipient C. ABO blood types of the donor and recipient D. Peripheral T-cell count of the recipient

34. Answer C. Explanation: Although mixed lymphocyte culture assays and HLA typing of the donor and recipient to determine compatibility have been shown to enhance long-term graft survival, immediate graft function has been correlated to the absence of the presensitized state. This presensitization can be with respect to lymphocytotoxic antibodies or preformed isoagglutinins. ABO compatibility is essential in renal and cardiac transplantation because incompatibility leads to prompt destruction of the transplanted organ. In liver transplantation, the presensitized state is of less importance, but diminished graft survival has been demonstrated in ABO-incompatible combinations. (See Schwartz 7th ed.)

35. A 24-year-old woman is admitted to the intensive care unit for sudden collapse with progressive neurologic deficits. A computed tomography scan reveals an intracranial tumor with evidence of acute hemorrhage. Emergent craniotomy is done for decompression, and tissue obtained reveals high-grade malignant astrocytoma. On postoperative day 1, the patient is placed on large doses of phenobarbital for seizure activity but continues to deteriorate. On day 3, she requires dopamine support at 10 mg/kg/min to maintain a systolic blood pressure of 90 mm Hg. She develops diabetes insipidus, and her urine output is adequate, although her creatinine rises to 1.5 mg/dL and the blood urea nitrogen (BUN) is 40 mg/dL. A urine culture from a Foley specimen yields Escherichia coli at 100,000/mL. On day 4, she becomes unresponsive, without evidence of cortical or brainstem function. An electroencephalogram (EEG) is isoelectric. Which of the following is an absolute contraindication for consideration of this woman as a potential organ donor? A. Presence of high-grade intracranial malignancy B. Requirement of pressor support C. Elevated BUN and creatinine D. Presence of supratherapeutic phenobarbital levels

36. Answer D. Explanation: The presence of phenobarbital, narcotics or alcohol, or of hypothermia is a contraindication to organ donation, even with an isoelectric EEG. This is because these factors may suppress spontaneous electric activity of the brain. Intracranial tumors are not considered a contraindication, mainly because of their lack of systemic metastasis. Other malignancies do contraindicate donation. The need for pressor is not necessarily a contraindication, especially if these drugs are used in the terminal period to maintain blood pressure and urine output. Elevations of BUN and creatinine are not uncommon, especially in the face of diabetes insipidus with prerenal azotemia. Adequate urine output is the most important factor in consideration of renal organ donation. Lower urinary tract infection caused by instrumentation is not a contraindication to donation of kidneys, whereas systemic or peritoneal sepsis is. (See Schwartz 7th ed.)

37. All of the following are side effects of cyclosporine A administration for prevention of organ rejection EXCEPT A. Hepatotoxicity B. Hirsutism C. Tremor D. Bone marrow depression

38. Answer D. Explanation: Bone marrow depression has often been seen with azathioprine but is not seen in patients on cyclosporine. Hepatotoxicity, hirsutism, tremor, and nephrotoxicity are complications of prolonged use of cyclosporine A. Nephrotoxicity is the most clinically important and most frequently seen side effect and may limit the drug's use in some patients. (See Schwartz 7th ed.)

39. Currently, which of the following infectious illnesses is most likely to compromise patients after renal transplantation? A. Coli sepsis B. Pneumococcal sepsis C. Candidiasis D. Cytomegalovirus sepsis

40. Answer D. Explanation: Immunosuppression for transplantation increases the risk for all types of infection. Use of cyclosporine, along with broad-spectrum antibiotics, has reduced the incidence of bacterial infections. Most serious posttransplant infections arise when rejection is being treated, and in the past, these led to high mortality. Both Candida and Aspergillus infections can occur but are relatively rare compared with viral infection. Cytomegalovirus (CMV) can produce a spectrum of illness characterized by fever, neutropenia, arthralgias, malaise, gastrointestinal ulcerations, and decreased renal function. CMV itself produces a state of immunosuppression, and many serious infections are superinfections in patients already experiencing CMV infections. Treatment of CMV sepsis includes decreasing immunosuppression and administering ganciclovir, a new antiviral drug. (See Schwartz 7th ed.)

41. Postoperative indicators of primary nonfunction of a liver allograft include all of the following EXCEPT A. Hypokalemia B. Hypoglycemia C. Elevated prothrombin time D. Alkalosis

42. Answer A. Explanation: Primary graft failure is a very serious complication. The patient decompensates quickly, and urgent transplantation is indicated. Severe central nervous system changes, with acid-base changes (early alkalosis due to inability to metabolize citrate and acidosis as a terminal event), hyperkalemia, coagulopathy, hypoglycemia, and oliguria are often terminal events of this acute hepatic decompensation. (See Schwartz 7th ed.)

43. An absolute contraindication to cardiac transplantation is • Active peptic ulcer disease • Age older than 60 years • Fixed pulmonary vascular resistance • Heavy cigarette smoking

44. Answer C. Explanation: Although the other three items are relative contraindications to cardiac transplantation, fixed pulmonary vascular resistance is the only absolute contraindication among those listed. A heart accustomed to low pulmonary artery pressure and resistance will fail immediately if placed in a recipient with fixed pulmonary vascular resistance. (See Schwartz 7th ed.)

45. A 45-year-old female underwent a kidney transplant 6 months ago and has been taking cyclosporine and steroids. She developed cholelithiasis and requires a laparoscopic cholecystectomy. She wants to know if her chance to have a wound infection is increased. The best answer to her question is A. No, steroids and cyclosporine do not increase the chance to have wound infection when used chronically B. Yes, because of inhibition of collagen synthesis and fibroblast proliferation C. Yes, because of persistent vasoconstriction and hypoxia D. Yes, because of structural nuclear changes and decreased DNA synthesis E. Yes, mainly because of cyclosporine, which blocks IL-2 and decrease migration of macrophages

46. Answer B. Explanation: During the past two decades the survival rate of solid organ recipients has improved dramatically. The major factor in improved clinical outcome is the decline in death secondary to infection. Currently, 1-year mortality caused by infection has decreased to less than 5% for renal transplant patients. Better immunosuppression and understanding by the clinician of drug pharmacodynamics and pharmacokinetics are responsible for decrease morbidity and mortality after solid organ transplantation. Steroids reduce the inflammatory process blocking transcription of cytokine genes (especially IL-1) leading to nonspecific inhibition of T lymphocytes and macrophages. It is well documented that steroids decrease fibroblast migration and collagen synthesis. Topical steroids also inhibit wound healing. Cyclosporine is a potent immunosuppressant used to suppress transplant rejection. Experimental evidence suggests that the effectiveness of cyclo-sporine is because of specific and reversible inhibition of immunocompetent lymphocytes in the G0- or G1-phase of the cell cycle. T lymphocytes are preferentially inhibited. The T-helper cell is the main target, although the T-suppressor cell may also be suppressed. Cyclosporine also inhibits lymphokine production and release of IL-2. Cyclosporine does not significantly affect hydroxyproline content and macrophages migration, although there is some evidence that cyclosporine impairs wound healing. Studies in rats have shown that activin- expression and matrix metalloproteinases (MMPs) activity by fibroblast is reduced. BIBLIOGRAPHYMulder GD et al. Factors complicating wound repair. In: McCulloch JM, Kloth LC, Feedar JA (eds.), Wound Healing Alternatives in Management, 2nd ed. Philadelphia, PA: FA Davis, 1996, 51. Petri JB, Schurk S, Gebauer S, Haustein U. Cyclosporine A delays wound healing and apoptosis and suppresses activin BA expression in rats. Eur J Dermatol 1998;8(2):104–113.  [PubMed: 9649703]

47. The best method of monitoring the development of acute rejection in a patient after cardiac transplantation is A. Dipyridamole thallium study B. Electrocardiogram C. Endomyocardial biopsy D. Ultrasound examination of the heart

48. Answer C. Explanation: It would be desirable to follow possible rejection by some noninvasive procedure, but none has given timely results. Endomyocardial biopsies allow rejection to be diagnosed before significant organ damage and dysfunction occur. (See Schwartz 7th ed.)

49. You are caring for a 50-year-old man who is 3 years out from a cadaveric renal transplant for diabetic nephropathy. He had a single episode of vascular rejection 1 month after transplant, but otherwise has done well with a baseline serum Cr of 1.8 mg/dL. He is admitted to your service with increasing fatigue, dyspnea with exertion, and acute renal failure. His medications include cyclosporine, mycophenolate mofetil, prednisone, and nifedipine. On examination, he is pale and weak with a BP of 150/95 mmHg and a pulse of 110/min. He has a few scattered ecchymoses on his skin, but otherwise the examination is normal. Laboratory values 3 months ago Laboratory findings on admission Na+  142 Na+  144 K+  4.8 K+  6.7 Cl–  105 Cl–  110 HCO3–  25 HCO3–  17   BUN 30 BUN 68 Cr 1.8 Cr 5.8 LDH 150 LDH 650 Bili 0.7 Bili 2.9 Alb 3.9 Alb 3.5 AlkP 78 AlkP 80 WBC 8 WBC 14 Hb 11 Hb 5 Hct 33 Hct 15 Plts 221 Plts 45 U/A trace pro U/A 2+ protein No cells     20–30 RBC/Hpf Laboratory values 3 months ago Laboratory findings on admission Na+  142 Na+  144 K+  4.8 K+  6.7 Cl–  105 Cl–  110 HCO3–  25 HCO3–Which of the following is the most appropriate step in the evaluation of your patient? A. schedule a renal biopsy B. give IV pulse steroids C. order a renal ultrasound D. obtain a right upper quadrant (RUQ) ultrasound E. review the peripheral smear looking for schiztocytes

50. Answer E. Explanation: The patient has a hemolytic anemia (elevated LDH and bilirubin), thrombocytopenia, and renal failure. Therefore, the patient meets the criteria of HUS. The most important next step would be to obtain a peripheral smear to document the presence of schiztocytes. HUS is usually seen in children with bloody diarrhea associated with infection with verotoxin producing E. coli from undercooked meat; however, HUS is also seen in a variety of conditions including malignancy, scleroderma renal crises, bone marrow transplantation, and the administration of the immunosuppressants cyclosporine A and tacrolimus. In renal transplantation, cyclosporine associated HUS may develop in up to 10% of patients. Treatment is removal of the offending agent. Small case series suggest that plasma exchange may be helpful. Bibliography Zarifian A, Meleg-Smith S, O'Donovan R, et al. Cyclosporine-associated thrombotic microangiopathy in renal allografts. Kidney Int 1999;55:2457–2466.  [PubMed: 10354295]