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Renal Transplantation Periprocedural Care

  • Author: Bradley H Collins, MD; Chief Editor: Ron Shapiro, MD  more...
 
Updated: Oct 01, 2015
 

Preprocedural Evaluation

The pretransplant evaluation must address potential contraindications, should include baseline immunologic studies, and should assess the patient’s likelihood of success with transplantation.

Basic pretransplant studies

Either a need for dialysis or a creatinine clearance below 20 mL/min is generally an accepted definition of end-stage renal disease (ESRD). In the United States, a documented creatinine clearance of 20 mL/min or less is necessary to qualify for listing for transplantation. Typically, basic pretransplant studies are required, including the following:

  • Echocardiography and a stress study
  • Chest radiography
  • Pulmonary studies
  • Colonoscopy or barium enema (dependent on patient age)
  • Mammography, Papanicolaou (Pap) smear, and prostate-specific antigen (PSA) test, as indicated (depending on patient age)
  • Noninvasive vascular studies
  • Abdominal and renal ultrasonography
  • Serologic tests for HIV infection, hepatitis B and hepatitis C, cytomegalovirus (CMV) infection, and other viral infections
  • Studies of bladder capacity and function (if indicated)

Immunologic studies

Immunologic studies should include human leukocyte antigen (HLA) typing and measurement of the panel-reactive antibody (PRA) titer. The panel-reactive antibody titer approximates the likelihood that a randomly chosen kidney donor has a positive cytotoxic lymphocyte crossmatch with the potential recipient, thereby ruling out that particular donor-recipient combination. Screening for donor-specific antibodies in the potential recipient by using HLA-coated beads is currently becoming routine at many transplant centers.

Evaluation of potential living donors

Evaluation of potential living donors may involve some of the studies detailed above. The choice of studies in this setting is subject to great variation among programs; however, assessment of renal function, evaluation of general health, imaging of the renal vasculature, HLA typing, and crossmatching are essential in all cases. Most centers require a donor to have a glomerular filtration rate (GFR) of at least 80 mL/min. The authors find that spiral computed tomography (CT) allows evaluation of the renal vasculature and parenchymal abnormalities.

All donors should be in good health and should not have conditions that may compromise their renal function in the future, such as hypertension or diabetes. Some centers require potential donors to undergo 24-hour ambulatory blood pressure monitoring.

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Monitoring and Follow-up

Postoperative management involves two key tasks. The first task is to manage the dynamic fluid balance of a new kidney that is capable of responding to the high urea nitrogen load with an osmotic diuresis but is less capable of concentrating urine or reabsorbing sodium. With improving renal function, fluid balance must be maintained, hypertension management may need modification, and electrolyte abnormalities may require correction.

The second task is the administration of immunosuppression. Current immunosuppressive therapy can be divided into two phases: induction and maintenance. For some patients, a state of immunosuppression is induced just before the operation. This induction phase is continued during and after transplantation and is carried out by using either antibody- or nonantibody-based regimens.

Typical antibody-based induction immunosuppression uses either monoclonal or polyclonal antibody preparations directed at T cells in combination with calcineurin inhibitors (eg, cyclosporine and tacrolimus), antiproliferative agents (eg, azathioprine and mycophenolate), and corticosteroids. Maintenance therapy includes various combinations of a calcineurin inhibitor, an antiproliferative agent, and prednisone.

The choice of induction strategy depends on several factors. Some centers routinely use antibody induction. Of the centers that do not, most agree that antibody induction should still be used in immunologically higher-risk transplant cases, such as the following:

  • Repeat transplants, especially when the first kidney was lost to acute or chronic rejection
  • African-American patients
  • Patients with evidence of significant prior sensitization to HLAs, as evidenced by a high panel-reactive antibody titer

Calcineurin inhibitors have been the mainstay of clinical immunosuppression since the introduction of cyclosporine in the early 1980s. Calcineurin inhibitors were the first agents to target proliferating T cells by blocking the elaboration of cytokines (eg, interleukin [IL]–2) essential for proliferation. Both cyclosporine and tacrolimus are naturally occurring products and have significant toxicities. In particular, they have a significant dose-related nephrotoxicity.

This nephrotoxicity, combined with erratic absorption and complex pharmacokinetics, necessitates ongoing monitoring to maintain therapeutic drug levels while avoiding toxicities. Although most centers follow drug trough levels, some have used pharmacokinetic modeling to good effect.[5] Both cyclosporine and tacrolimus are metabolized in the liver by the cytochrome P-450 (CYP-450) system. Drugs that alter CYP-450 metabolism can result in higher blood levels (eg, fluconazole or verapamil) or lower drug levels (eg, rifampin or phenytoin).

The adverse consequences of long-term cyclosporine use for solid-organ transplant rejection (eg, hypertension and renal impairment) have prompted exploration of various treatment regimens. Gallagher et al studied long-term graft survival by comparing the following three immunosuppressive regimens in 489 patients with a median follow-up of 20.6 years[6] :

  • Azathioprine and prednisolone (AP)
  • Long-term cyclosporine alone (Cy)
  • Cyclosporine initiation followed by withdrawal at 3 months and azathioprine and prednisolone replacement (WDL)

Mean graft survival (with deaths censored) was longer in the WDL group (14.8 y) than in the AP group (12.4 y) or the Cy group (12.5 y). Without deaths censored, graft survival was again longer in the WDL group (9.5 y) than in the AP group (6.7 y) or the Cy group (8.5 y). Patient survival was comparable in the 3 groups. Renal function was superior in the AP group at 1, 10, and 15 years after transplantation and in the WDL group at 1, 5, 10, 15, and 20 years in comparison with the Cy group.[6]

Another strategy involves the use of sirolimus, an immunosuppressant that targets T cells at a different site in the activation pathway.[7] Sirolimus can be used in conjunction with reduced doses of calcineurin inhibitors or as a replacement for these agents in immunologically low-risk recipients. Although it lacks the nephrotoxicity of calcineurin inhibitors, it reduces wound healing and may cause myelosuppression.[8] Patients at high immunologic risk (see above) may be maintained on a combination of mycophenolate or sirolimus, tacrolimus or cyclosporine, and steroids for the first year after transplantation.

Mycophenolate reversibly inhibits de novo synthesis of purines during the S phase. Because the salvage pathway of purine synthesis is less active in lymphocytes than in other tissues, lymphocytes depend more on this pathway. Mycophenolate is far more selective than its predecessor, azathioprine, and it inhibits proliferation of both B and T cells. When used in conjunction with other agents (usually calcineurin inhibitors), mycophenolate significantly reduces the incidence of acute cellular rejection.

Mycophenolate can be administered either as a mofetil ester or as a sodium salt in enteric-coated form. It also reportedly reduces interstitial fibrosis associated with chronic rejection in animal models. Mycophenolate’s principal toxicities involve the gastrointestinal (GI) tract and principally manifest as nausea and diarrhea. These toxicities may limit its use, but patients who can tolerate them may experience significant reductions in allograft rejection.

Although steroids play a key role in induction and maintenance of immunosuppression and in treatment of rejection, they are associated with many complications of immunosuppression (eg, bone disease, hypertension, peptic ulcer disease, glucose intolerance, growth retardation, infection, obesity, and lipid abnormalities). Efforts to reduce steroid exposure have involved minimizing or completely avoiding their use. Steroids have been completely avoided in a few carefully selected cases, albeit with some increase in the rejection rate (but no long-term deterioration in graft survival).

Steroid doses have been reduced and rapidly tapered without significant increasing the risk of rejection.[9] Steroid reduction has been associated with decreases in hypertension, diabetes, and other adverse events associated with steroid therapy. Patients with stable graft function and no significant rejection episodes can often be weaned off steroids within the first 3-12 months and maintained on either combination therapy with a calcineurin inhibitor and an antiproliferative agent or, occasionally, monotherapy with a calcineurin inhibitor.[10]

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Contributor Information and Disclosures
Author

Bradley H Collins, MD Associate Professor, Department of Surgery, Division of Transplantation, Surgical Director of Kidney Transplantation, Surgical Director of Pancreas Transplantation, OPTN/UNOS Program Director of Kidney Transplantation and Pancreas Transplantation, Duke University Medical Center

Bradley H Collins, MD is a member of the following medical societies: American College of Surgeons, American Society of Transplant Surgeons, Society of University Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Ron Shapiro, MD Professor of Surgery, Robert J Corry Chair in Transplantation Surgery, Associate Clinical Director, Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center

Ron Shapiro, MD is a member of the following medical societies: American Society of Transplantation, American Surgical Association, American College of Surgeons, Transplantation Society, International Pediatric Transplant Association, American Society of Transplant Surgeons, Association for Academic Surgery, Central Surgical Association, Society of University Surgeons

Disclosure: Nothing to disclose.

Acknowledgements

Thomas D Johnston, MD Director, Renal and Pediatric Transplantation, Associate Professor, Department of Surgery, University of Kentucky

Thomas D Johnston, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Surgeons, American Society of Transplant Surgeons, Association for Academic Surgery, International College of Surgeons US Section, and Kentucky Medical Association

Disclosure: Nothing to disclose.

Edward David Kim, MD, FACS Professor of Surgery, Division of Urology, University of Tennessee Graduate School of Medicine; Consulting Staff, University of Tennessee Medical Center

Edward David Kim, MD, FACS is a member of the following medical societies: American College of Surgeons, American Society for Reproductive Medicine, American Society of Andrology, American Urological Association, Sexual Medicine Society of North America, and Tennessee Medical Association

Disclosure: Lilly Consulting fee Advisor; Astellas Consulting fee Speaking and teaching; Watson Consulting fee Speaking and teaching; Allergan Consulting fee Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
  1. United Network for Organ Sharing (UNOS). Data. UNOS. Available at http://www.unos.org/donation/index.php?topic=data. August 28, 2015; Accessed: September 3, 2015.

  2. Matas AJ, Smith JM, Skeans MA, Thompson B, Gustafson SK, Schnitzler MA, et al. OPTN/SRTR 2012 Annual Data Report: kidney. Am J Transplant. 2014 Jan. 14 Suppl 1:11-44. [Medline]. [Full Text].

  3. Bartlett ST, Farney AC, Jarrell BE, et al. Kidney transplantation at the University of Maryland. Clin Transpl. 1998. 177-85. [Medline].

  4. Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009 Oct. 5(10):582-9. [Medline].

  5. Oellerich M, Shipkova M, Schutz E, et al. Pharmacokinetic and metabolic investigations of mycophenolic acid in pediatric patients after renal transplantation: implications for therapeutic drug monitoring. German Study Group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipient. Ther Drug Monit. 2000 Feb. 22(1):20-6. [Medline].

  6. Gallagher M, Jardine M, Perkovic V, Cass A, McDonald S, Petrie J, et al. Cyclosporine withdrawal improves long-term graft survival in renal transplantation. Transplantation. 2009 Jun 27. 87(12):1877-83. [Medline].

  7. Kahan BD, Julian BA, Pescovitz MD, et al. Sirolimus reduces the incidence of acute rejection episodes despite lower cyclosporine doses in caucasian recipients of mismatched primary renal allografts: a phase II trial. Rapamune Study Group. Transplantation. 1999 Nov 27. 68(10):1526-32. [Medline].

  8. Yakupoglu YK, Kahan BD. Sirolimus: a current perspective. Exp Clin Transplant. 2003 Jun. 1(1):8-18. [Medline].

  9. Oberholzer J, John E, Lumpaopong A, et al. Early discontinuation of steroids is safe and effective in pediatric kidney transplant recipients. Pediatr Transplant. 2005 Aug. 9(4):456-63. [Medline].

  10. Kramer BK, Krager B, Mack M, et al. Steroid withdrawal or steroid avoidance in renal transplant recipients: focus on tacrolimus-based immunosuppressive regimens. Transplant Proc. 2005 May. 37(4):1789-91. [Medline].

  11. Berney T, Malaise J, Mourad M, et al. Laparoscopic and open live donor nephrectomy: a cost/benefit study. Transpl Int. 2000. 13(1):35-40. [Medline].

  12. Ratner LE, Montgomery RA, Kavoussi LR. Laparoscopic live donor nephrectomy: the four year Johns Hopkins University experience. Nephrol Dial Transplant. 1999 Sep. 14(9):2090-3. [Medline].

  13. Matas AJ, Smith JM, Skeans MA, Thompson B, Gustafson SK, Stewart DE, et al. OPTN/SRTR 2013 Annual Data Report: kidney. Am J Transplant. 2015 Jan. 15 Suppl 2:1-34. [Medline].

  14. Magee CC. Transplantation across previously incompatible immunological barriers. Transpl Int. Jan 2006. 19:87-97. [Medline]. [Full Text].

  15. Huh KH, Kim MS, Ju MK, Chang HK, Ahn HJ, Lee SH, et al. Exchange living-donor kidney transplantation: merits and limitations. Transpl. Aug 2008. 86:430-435. [Medline].

  16. Slagt I, Klop K, Ijzermans J. Intravesical versus extravesical ureteroneocystostomy in kidney transplantation: A systematic review and meta-analysis. Transplantation. October 2012.

  17. Isoniemi H, Lehtonen S, Salmela K, Ahonen J. Does delayed kidney graft function increase the risk of chronic rejection?. Transpl Int. 1996. 9 Suppl 1:S5-7. [Medline].

  18. Johnston TD, Thacker LR, Jeon H, et al. Sensitivity of expanded-criteria donor kidneys to cold ischaemia time. Clin Transplant. 2004. 18 Suppl 12:28-32. [Medline].

  19. al-Aasfari R, Hadidy S, Yagan S. Infectious complications of kidney transplantation. Transplant Proc. 1999 Dec. 31(8):3204. [Medline].

  20. Varon NF, Alangaden GJ. Emerging trends in infections among renal transplant recipients. Expert Rev Anti Infect Ther. 2004 Feb. 2(1):95-109. [Medline].

  21. Adamska Z, Karczewski M, Cichańska L, Więckowska B, Małkiewicz T, Mahadea D, et al. Bacterial Infections in Renal Transplant Recipients. Transplant Proc. 2015 Jul-Aug. 47 (6):1808-12. [Medline].

 
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End-to-side anastomosis between donor main renal artery just above its bifurcation and recipient external iliac artery.
Laparoscopic donor nephrectomy.
Table 1. Demographics of adult patients on the waiting list for kidney transplants, United States, 2012 [2]
Patient Characteristic Number of Patients Percentage
Age 18-34 y 8811 9.5
Age 35-49 y 24,799 26.7
Age 50-64 y 40,523 43.6
Age 65-74 y 16,779 18.1
Age >75 y 1973 2.1
Male 55,104 59.3
Female 37,781 40.7
White 35,189 37.9
Black 31,607 34.0
Hispanic 17,536 18.9
Asian 7218 7.8
Table 2. Primary causes of ESRD in adult patients on the kidney transplant waiting list: United States, 2012 [2]
Cause of ESRD Number of Patients Percentage
Diabetes 31,801 34.2
Hypertension 23,209 25.0
Glomerulonephritis 13,068 14.1
Cystic kidney 7591 8.2
Other or unknown cause 17 18.5
ESRD = End-stage renal disease    
Table 3. Demographics of pediatric patients awaiting kidney transplant: United States, 2012 [2]
Patient Characteristic Percentage
Age <1 y 1.0
Age 1-5 y 15.9
Age 6-10 y 14.1
Age 11-17 y 69.0
White 40.8
Black 25.4
Hispanic 28.6
Asian 3.5
Other or unknown 1.8
Table 4. Primary causes of end-stage renal disease in pediatric patients on the kidney transplant waiting list: United States, 2012 [2]
Cause of Renal Failure Percentage
Focal segmental glomerulosclerosis 12.0
Glomerulonephritis 10.8
Structural 26.9
Other or unknown 50.3
ESRD = End-stage renal disease  
Table 5. Five-year post-transplant survival with a functioning kidney graft: United States, 2012
Patient Characteristics Percentage
Age <11 y, deceased donor 75
Age <11 y, living donor 89
Age 11-17 y, deceased donor 67
Age 11-17, live donor 77
Adults, deceased donor 73
Adults, living donor 84
Adults transplanted for diabetes 71
Adults transplanted for hypertension 70
Adults transplanted for glomerulonephritis 77
Adults transplanted for cystic kidney disease 82
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