Campbell-Walsh Urology, 11th Edition

PART VII

Renal Physiology and Pathophysiology

47

Renal Transplantation

Hans Albin Gritsch; Jeremy Matthew Blumberg

Questions

  1. Which of the following renal diseases has a high probability of recurrence in patients with a kidney transplant, resulting in failure of the kidney graft?
  2. Chronic glomerulonephritis
  3. Focal segmental glomerulosclerosis
  4. IgA nephropathy
  5. Alport syndrome
  6. Autosomal dominant polycystic kidney disease
  7. Lymphoproliferative disorders are most commonly associated with which of the following viruses?
  8. Herpes simplex virus type 1
  9. Varicella-zoster virus
  10. Epstein-Barr virus (EBV)
  11. Cytomegalovirus (CMV)
  12. Cocksackie virus
  13. Pretransplant nephrectomy is indicated for:
  14. hypertension controlled with medication.
  15. prior renal infection.
  16. symptomatic renal stones.
  17. 200 mg/dL proteinuria.
  18. most polycystic kidneys.
  19. The best renal imaging protocol for a living renal donor to define renal anatomy and renal vasculature and to rule out renal stones is:
  20. kidney, ureter, bladder (KUB) radiography and selective renal arteriography.
  21. magnetic resonance nephrotomography and angiography.
  22. helical computed tomography (CT) without and with intravenous iodinated contrast.
  23. helical CT without and with intravenous iron contrast.
  24. renal ultrasonography and selective renal arteriography.
  25. After living donor nephrectomy, the renal donor is expected to have what level of total renal function?
  26. 50%
  27. 60%
  28. 75%
  29. 90%
  30. 95%
  31. Kidney transplant survival rates are poorest for which of the following donor categories?
  32. Sibling
  33. Parent
  34. Spouse
  35. Standard criteria deceased
  36. Expanded criteria deceased
  37. Which of the following is required for the cellular sodium-potassium pump to maintain a high intracellular concentration of potassium and a low intracellular concentration of sodium?
  38. ADP
  39. ATP
  40. CMP
  41. CTP
  42. Nitric oxide
  43. The best solution for preservation of all abdominal organs is:
  44. EuroCollins.
  45. Collins 2.
  46. Sach solution.
  47. University of Wisconsin (UW) solution.
  48. Histidine-tryptophan-ketoglutarate (HTK).
  49. A cadaver kidney transplant recipient receives points on the national waiting list for all of the following EXCEPT:
  50. time on the waiting list.
  51. age younger than 18 years.
  52. panel reactive antibody (PRA) level greater than 80%.
  53. histocompatibility.
  54. full-time employment.
  55. The standard method of urinary tract reconstruction during renal transplantation is:
  56. ureteropyelostomy.
  57. ureteroureterostomy.
  58. ureteroneocystostomy.
  59. vesicopyelostomy.
  60. cutaneous ureterostomy.
  61. A woman wishes to donate a kidney to her husband who has end-stage renal disease (ESRD). She is ABO blood type A, and he is ABO blood type O. Each of the following is a possible solution to this problem EXCEPT:
  62. plasmapheresis.
  63. immunoadsorption.
  64. immunoglobulin administration.
  65. anti CD-37 antibody administration.
  66. paired kidney exchange.
  67. The risk of a hyperacute rejection after kidney transplantation is high when which of the following is positive?
  68. B-cell flow cross match
  69. T-cell flow cross match
  70. B-cell complement-dependent cytotoxicity cross match
  71. T-cell complement-dependent cytotoxicity cross match
  72. DR-cell cross match
  73. Which of the following immunosuppressants inhibits cell cycle progression?
  74. Azathioprine
  75. Mycophenolate mofetil
  76. Cyclosporine
  77. Tacrolimus
  78. Sirolimus
  79. Which of the following paired immunosuppressants have similar mechanisms of action and toxicity?
  80. Azathioprine and cyclosporine
  81. Azathioprine and tacrolimus
  82. Basiliximab and mycophenolate mofetil
  83. Tacrolimus and cyclosporine
  84. OKT3 and mycophenolate mofetil
  85. Which of the following two drugs have been used to reduce calcineurin inhibitor dosing and cost while maintaining blood levels and immunosuppressive effect?
  86. Diltiazem and ketoconazole
  87. Prednisone and azathioprine
  88. Basiliximab and daclizumab
  89. Equine antilymphocyte globulin and azathioprine
  90. Mycophenolate mofetil and azathioprine
  91. Prophylaxis against Pneumocystisinfection is best achieved with:
  92. trimethoprim-sulfamethoxazole.
  93. erythromycin.
  94. ciprofloxacin.
  95. cephalexin.
  96. minocycline.
  97. Prophylaxis against cytomegalovirus infection is best done with:
  98. trimethoprim-sulfamethoxazole.
  99. erythromycin.
  100. ganciclovir.
  101. basiliximab.
  102. minocycline.
  103. Five years after successful renal transplantation, a 55-year-old man is referred to you because of total gross hematuria. Each of the following is an important part of the workup EXCEPT:
  104. urine cytology.
  105. urine PCA3 determination.
  106. images of the native kidneys.
  107. images of the kidney transplant.
  108. cystourethroscopy.
  109. Which of the following interferes with the tubular secretion of creatinine and can cause an increase in serum creatinine levels?
  110. Azathioprine
  111. Trimethoprim
  112. Mycophenolate mofetil
  113. Tacrolimus
  114. Basiliximab
  115. Oral fluconazole is prescribed to treat cystitis caused by yeast. Which of the following medications will need to have the dose reduced?
  116. Muromonab-CD3
  117. Prednisone
  118. Tacrolimus
  119. Azathioprine
  120. Mycophenolate mofetil
  121. Hemorrhagic cystitis in an immunosuppressed patient has been most commonly associated with which of the following viruses?
  122. Cytomegalovirus
  123. Adenovirus
  124. Herpes simplex virus type 1
  125. Herpes simplex virus type 2
  126. Polyoma virus
  127. The most common cancer after kidney transplantation is:
  128. skin.
  129. cervix.
  130. Kaposi sarcoma.
  131. thyroid.
  132. breast.
  133. Hyperlipidemia is most often associated with which of the following three-drug combinations?
  134. Prednisone, cyclosporine, sirolimus
  135. Equine antithymocyte globulin, tacrolimus, mycophenolate mofetil
  136. Mycophenolate mofetil, tacrolimus, basiliximab
  137. Cyclosporine, tacrolimus, mycophenolate mofetil
  138. Basiliximab, mycophenolate mofetil, azathioprine
  139. A kidney transplant patient with chronic rejection presents with constipation. The contraindicated treatment is:
  140. oral docusate calcium
  141. oral psyllium
  142. polyethylene glycol–electrolyte solution
  143. phospho-soda enema
  144. soap suds enema
  145. Patients with chronic renal insufficiency should be referred for kidney transplant evaluation when:
  146. the disease is confirmed by kidney biopsy.
  147. the estimated glomerular filtration rate is less than 20 mg/dL.
  148. the estimated glomerular filtration rate is less than 8 mg/dL.
  149. they are on dialysis.
  150. they have identified a living kidney donor.
  151. The peritoneal dialysis solution containing the following compound that may lead to false point-of-care glucose readings is:
  152. dextran.
  153. icodextrin.
  154. glucose.
  155. sucrose.
  156. d-xylose.
  157. A 52-year-old diabetic man with a solitary right kidney has a 7-cm mass noted on ultrasound in the lower pole. He is blood type O and has had multiple abdominal operations including previous partial nephrectomies with blood transfusions. His serum creatinine is 2.3 mg/dL and he is not aware of any potential kidney transplant donors. In preparation for partial nephrectomy he should have:
  158. referral to a vascular surgeon for creation of a dialysis fistula prior to surgery.
  159. consent for placement of a peritoneal dialysis catheter.
  160. magnetic resonance angiogram with gadolinium contrast.
  161. computed tomography with iodinated contrast.
  162. referral to a transplant surgeon.
  163. A frequent symptom associated with hyperphosphatemia is:
  164. seizures.
  165. flank pain.
  166. headache.
  167. diarrhea.
  168. conjunctival itching.
  169. The most common causes of death following kidney transplant in order are:
  170. kidney failure, sepsis, and cancer.
  171. cancer, sepsis, and heart disease.
  172. heart disease, sepsis, and stroke.
  173. sepsis, cancer, and heart disease.
  174. heart disease, cancer, and stroke.
  175. Which of the following has been associated with a higher incidence of mortality in living donor nephrectomies?
  176. Open donor nephrectomy
  177. Ligation of the renal vein with an Endo-GIA stapling device
  178. Ligation of the renal artery with a single Hem-o-Lok®clip
  179. Insufflation with a Veress needle during laparoscopic donor nephrectomy
  180. Retroperitoneoscopic donor nephrectomy
  181. A 54-year-old male with ESRD due to type 2 diabetes mellitus has been on hemodialysis for 2 years and is referred for transplant evaluation. Which of the following is an absolute contraindication to renal transplantation?
  182. Gleason 3 + 3 prostate cancer treated by radical prostatectomy 1 year ago
  183. Recent development of a gangrenous toe
  184. Gleason 3 + 4 prostate cancer treated with external beam radiation 3 years ago; prostate-specific antigen (PSA) currently 0.2 ng/mL
  185. A T1aN0Mx, Fuhrman grade 2 renal cell carcinoma treated by radical nephrectomy 1 year ago
  186. History of right below-the-knee amputation 4 years ago, currently using prosthesis and able to walk 100 yards with no difficulty
  187. All of the following place a deceased donor into the Centers for Disease Control’s "high-risk" category EXCEPT a:
  188. man who has had sex with another man during the previous month.
  189. donor who has smoked crack cocaine within the last year.
  190. history of intravenous heroin use 3 years ago.
  191. man who was released from prison after a 15-year sentence 5 days before the pronouncement of brain death.
  192. 23-year-old woman who was currently working as a prostitute.
  193. Regarding allograft nephrectomy, which of the following statements is TRUE?
  194. Allograft nephrectomy is indicated for all failed kidney transplants.
  195. Allograft nephrectomy is a relatively simple procedure and can be performed without significant prior experience.
  196. Levels of circulating anti-human leukocyte antigen (HLA) antibodies may be reduced by allograft nephrectomy if the transplant fails within the first year.
  197. Post-transplant gross hematuria arising from the transplant is an absolute indication for allograft nephrectomy.
  198. Allograft nephrectomy is mandatory if a patient is a candidate for a second renal transplant.
  199. The test that is most sensitive for finding donor-specific antibodies (DSA) is:
  200. complement dependent lymphocytotoxicity assay.
  201. B-cell flow-cytometric cross match.
  202. T-cell flow-cytometric cross match.
  203. solid-phase single-antigen bead testing.
  204. pronase-treated flow-cytometric cross match.
  205. A healthy 32-year-old female with no prior history of urolithiasis wishes to donate a kidney to her 33-year-old husband, who has ESRD due to congenital reflux nephropathy. On CT scan evaluation, she is found to have a 1.5-mm calculus in the right renal pelvis. The metabolic stone workup is normal. Which of the following statements is TRUE?
  206. She cannot donate her kidney because of her renal stone.
  207. She should be accepted as a donor, and the left kidney should be removed for donation.
  208. She may be considered for donation of the right kidney.
  209. She cannot donate because of her husband's etiology of ESRD.
  210. She must undergo treatment of her stone with a 5-year stone-free interval before being considered a suitable donor.

Answers

  1. b. Focal segmental glomerulosclerosis. Patients with focal segmental glomerulosclerosis, hemolytic-uremic syndrome, or primary oxalosis should be counseled about the significant probability of disease recurrence and the risk of secondary graft failure.
  2. c. Epstein-Barr virus (EBV).EBV titers are determined in children, and, for the EBV-seronegative child, a kidney from an EBV-seronegative donor is preferred to reduce the risk of a post-transplant lymphoproliferative disorder, the most common de novo malignancy in pediatric organ transplant recipients.
  3. c. Symptomatic renal stones. The generally accepted recommendations for pretransplant nephrectomy, as outlined in the table, include the following: renal stones not cleared by minimally invasive techniques or lithotripsy; solid renal tumors with or without acquired renal cystic disease; polycystic kidneys that are symptomatic, extend below the iliac crest, have been infected, or have solid tumors; persistent antiglomerular basement membrane antibody levels; significant proteinuria not controlled with medical nephrectomy or angio-ablation; recurrent pyelonephritis; and grade 4 or 5 hydronephrosis.
  4. c. Helical computed tomography (CT) with and without intravenous contrast.Three-dimensional CT angiography with and without intravenous contrast has been widely accepted for use with living renal donors because it satisfactorily excludes stone disease, demonstrates renal and vascular anatomy, and defines the urinary collecting system, all with minimal donor morbidity and at reasonable expense.
  5. c. 75%. Hyperfiltration injury has not been a problem for living renal donors.Endogenous creatinine clearance rapidly approaches 70% to 80% of the preoperative level, and this has been shown to be sustained for more than 10 years. The development of late hypertension is nearly the same as that for the general population, and the development of proteinuria is negligible.
  6. e. Expanded criteria deceased.Kidney transplant survival rates are poorest when the quality of the kidney is the worst. Expanded criteria deceased kidney donors are older than the age of 60 years or are older than the age of 50 years and have two of the following: death from cerebrovascular accident, hypertension, or serum creatinine greater than 1.5 mg/dL.
  7. b. ATP.ATP is required for the cellular sodium-potassium pump to maintain a high intracellular concentration of potassium and a low intracellular concentration of sodium.
  8. d. University of Wisconsin (UW) solution.The UW solution minimizes cellular swelling with the impermeable solutes lactobionate, raffinose, and hydroxyethyl starch. Phosphate is used for its hydrogen ion buffering qualities, adenosine is for ATP synthesis during reperfusion, glutathione is a free radical scavenger, allopurinol inhibits xanthine oxidase and the generation of free radicals, and magnesium and dexamethasone are membrane-stabilizing agents. A major advantage of this preservation solution has been its utility as a universal preservation solution for all intra-abdominal organs.
  9. e. Full-time employment.A point system that has evolved in the United States for the selection of cadaver kidney transplant recipients includes the following variables: waiting time; human leukocyte antigen panel reactive antibody greater than 80%; age younger than 18 years; donor of kidney, liver segment, lung segment, partial pancreas, or small bowel segment; and histocompatibility.
  10. c. Ureteroneocystostomy.Urinary tract reconstruction is usually by antireflux ureteroneocystostomy, of which there are several techniques.
  11. d. Anti-CD 37 antibody administration.Plasmapheresis and immunoadsorption are used to remove antibodies. Immunoglobulin administration and anti CD-20 antibody (not anti CD-37 antibody) are used to prevent antibody reformation. Paired kidney exchange is an inexpensive way to deal with the problem.
  12. d. T-cell complement dependent cytotoxicity cross match.Hyperacute rejection is rare when the T-cell microlymphocytotoxicity cross match between recipient serum and donor lymphocytes is negative.
  13. e. Sirolimus. Sirolimus (formerly called rapamycin) inhibits cell cycle progression. Azathioprine and mycophenolate mofetil are purine antagonists, and they prevent lymphocyte proliferation. Tacrolimus and cyclosporine are calcineurin inhibitors.They inhibit the production of calcineurin and interleukin-2.
  14. d. Tacrolimus and cyclosporine.These two drugs have similar mechanisms of action, effectiveness, and cost but slightly different side effect profiles, and they are not used together.
  15. a. Diltiazem and ketoconazole.Diltiazem and ketoconazole have been used to reduce calcineurin inhibitor dosing and cost while maintaining blood levels and immunosuppressive effect.
  16. a. Trimethoprim-sulfamethoxazole.Commonly used regimens to prevent infections and peptic ulcer disease include trimethoprim-sulfamethoxazole for 3 months for prophylaxis against Pneumocystispneumonia.
  17. c. Ganciclovir.Prophylaxis against cytomegalovirus disease is possible with ganciclovir, acyclovir, valacyclovir, or cytomegalovirus immune globulin.
  18. b. Urine PCA3 determination.Urine PCA3 determinations have been used to screen for prostate cancer, not renal cell carcinoma or urothelial carcinomas.
  19. b. Trimethoprim.Trimethoprim interferes with the tubular secretion of creatinine, and this can cause an increase in serum creatinine levels.
  20. c. Tacrolimus. Cyclosporine and tacrolimus doses usually have to be reduced when fluconazole or ketoconazole is given because these drugs interfere with the metabolism of both of those immunosuppressants via the cytochrome P450 system.
  21. b. Adenovirus.Hemorrhagic cystitis can be caused by adenovirus. The disease is usually self-limited and resolves within a few weeks.
  22. a. Skin.Immunosuppressed patients are more likely to develop cancer than age-matched control subjects in the general population. Among several thousand tumors that occurred in renal transplant recipients, the common cancers, in order, were skin, lymphoma, Kaposi sarcoma, carcinomas of the cervix, renal tumors, and carcinomas of the vulva and perineum.
  23. a. Prednisone, cyclosporine, sirolimus.Prednisone, cyclosporine, and sirolimus all result in hyperlipidemia.
  24. d. Phospho-soda enema.Patients with poor renal function cannot easily eliminate a large phosphate load. If the serum calcium × phosphorus product exceeds 60 mg2/dL2, vascular calcium deposits can lead to arterial thrombosis and calciphylaxis.
  25. b. The estimated glomerular filtration rate is less than 20 mg/dL.For many patients with end-stage renal disease, a kidney transplant is the optimal renal replacement. An evaluation can identify potential barriers to transplantation and facilitate the education of potential living kidney donors. The best outcomes are achieved with renal transplantation immediately prior to the need for dialysis. In the United States, a patient must have documentation of a glomerular filtration rate of less than 20 mg/dL to be placed on the national waiting list for deceased donors.
  26. b. Icodextrin. This glucose polymer and maltose can be detected by some point-of-care devices, leading to a falsely elevated glucose reading. Inappropriate treatment of this result could lead to severe hypoglycemia and altered mental status.
  27. a. Referral to a vascular surgeon for creation of a dialysis fistula prior to surgery.This patient is very likely to need hemodialysis because he has very marginal renal function. Early creation of a fistula is the safest vascular access for dialysis. With multiple previous abdominal operations, he is not a good candidate for peritoneal dialysis. Iodinated contrast is a relative contraindication due to the marginal renal function, and gadolinium contrast has a risk of nephrogenic fibrosis. Referral to the transplant surgeon is more appropriate once the pathology of the tumor is known.
  28. e. Conjunctival itching. The hyperphosphatemia due to renal failure leads to severe itching, conjunctival irritation, and alterations in bone metabolism.
  29. c. Heart disease, sepsis, and stroke.Based on the Annual Report of the United States Renal Data System in 2014, the most common causes of death in patients with renal failure are heart disease, sepsis, and stroke.
  30. c. Ligation of the renal artery with a single Hem-o-Lok®(Teleflex, Morrisville, NC) clip. Ligation of the renal artery with Hem-o-Lok® clips, particularly when used as a single clip in an effort to increase renal artery length, has been associated with donor mortality secondary to hemorrhage.
  31. b. Recent development of a gangrenous toe.Serious, active infection, such as a gangrenous toe or foot, is a contraindication to renal transplantation. Once the infection is completely treated, the patient may again be considered for transplantation.
  32. b. Donor who has smoked crack cocaine within the last year.The Centers for Disease Control (CDC) does not consider inhaled or smoked drug use to be higher risk for the contraction of transmissible disease. All the other scenarios listed would place the donor in a CDC higher risk category.
  33. c. Levels of circulating anti-human leukocyte antigen (HLA) antibodies may be reduced by allograft nephrectomy if the transplant fails within the first year.Allograft nephrectomy can be a technically challenging procedure and is reserved for few clinical situations. Removal of an allograft that has failed during the first year post-transplant can lower levels of anti-HLA antibodies that may make subsequent transplantation more difficult due to positive cross matches.
  34. d. Solid-phase single-antigen bead testing.Very low levels of specific anti-HLA antibodies are detected by single-antigen bead testing (SAB). Because SAB is so sensitive, an antibody detected by SAB does not necessarily produce a positive flow-cytometric or complement-dependent lymphocytotoxicity cross match.
  35. c. She may be considered for donation of the right kidney.Although urolithiasis is an important aspect of the living kidney donor evaluation, urinary stones are not an absolute contraindication to donation. Potential donors with a single, tiny stone may donate if they have a normal metabolic stone workup. In general, the kidney with the stone is used for donation.

Chapter review

  1. The most common causes of ESRD, in order, are diabetes, hypertension, glomerulonephritis, and renal cystic disease.
  2. ESRD in children may result in growth failure, poor nutrition, and psychiatric problems.
  3. The major causes of death for patients with ESRD who are on dialysis or who have received a transplant are heart disease, sepsis, and stroke. Patients older than the age of 50 years have a 20% mortality in the first year of dialysis.
  4. A defunctionalized bladder usually regains normal volume within weeks of transplantation.
  5. Clean intermittent catheterization when necessary has been successfully used in transplant recipients.
  6. Surgical treatment of the bladder outlet should not be performed in the anuric patient. If the native kidneys are producing no urine and a procedure on the bladder outlet is deemed necessary, bladder cycling should be instituted.
  7. The quality of early graft function is directly correlated with cold ischemia time.
  8. The routine use of a ureteral stent for all cases of renal transplantation has been shown to reduce the incidence of ureteral complications.
  9. The histocompatibility antigens of greatest importance are ABO blood group and the major histocompatibility complex (MHC).
  10. Class I antigens are HLA-A, HLA-B, and HLA-C. Class II antigens are HLA-DR, HLA-DQ, and HLA-DP. Class I antigens are on all nucleated cells. Class II antigens are expressed by antigen-presenting cells.
  11. Lymphoma may respond to a reduction in immunosuppression.
  12. Patients with focal segmental glomerulosclerosis, hemolytic-uremic syndrome, or primary oxalosis should be counseled about the significant probability of disease recurrence and the risk of secondary graft failure.
  13. The recommendations for pretransplant nephrectomy include the following: renal stones not cleared by minimally invasive techniques or lithotripsy; solid renal tumors with or without acquired renal cystic disease; polycystic kidneys that are symptomatic, extend below the iliac crest, have been infected, or have solid tumors; persistent antiglomerular basement membrane antibody levels; significant proteinuria not controlled with medical nephrectomy or angio-ablation; recurrent pyelonephritis; and grade 4 or 5 hydronephrosis.
  14. Hyperfiltration injury has not been a problem for living renal donors.
  15. Sirolimus (formerly called rapamycin) inhibits cell cycle progression. Azathioprine and mycophenolate mofetil are purine antagonists, and they prevent lymphocyte proliferation. Tacrolimus and cyclosporine are calcineurin inhibitors. They inhibit the production of calcineurin and interleukin-2.
  16. Cyclosporine and tacrolimus doses usually have to be reduced when fluconazole or ketoconazole is given because these drugs interfere with the metabolism of both of those immunosuppressants via the cytochrome P450 system.
  17. Immunosuppressed patients are more likely to develop cancer than age-matched control subjects in the general population. Among several thousand tumors that occurred in renal transplant recipients, the common cancers, in order, were skin, lymphoma, Kaposi sarcoma, carcinomas of the cervix, renal tumors, and carcinomas of the vulva and perineum.