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Renal Transplantation

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

Background

Renal transplantation is the treatment of choice for a minority of patients with end-stage renal disease (ESRD). Most adult patients with ESRD are never referred for evaluation for transplantation, and have a 70% 5-year mortality on dialysis. Marked improvements in early graft survival and long-term graft function have made kidney transplantation a more cost-effective alternative to dialysis. In the United States, over 375,000 kidney transplants have been performed, and in 2012, 191,400 patients were alive and with a functioning transplanted kidney; currently, more than 101,000 patients are waiting for kidney transplants.[1, 2]

Before the advent of immunosuppression, renal transplantation was limited to identical twins and was not applicable to the vast majority of patients with ESRD. The introduction of combined azathioprine-steroid therapy in 1963 produced encouraging results and became the mainstay of immunosuppression. Although this therapy improved the results of transplantation, acute rejection and complications associated with steroid therapy persisted.

The introduction of cyclosporine in 1983 significantly improved the outcomes of all solid-organ transplants by reducing the risk of rejection. Further innovations, including anti–T cell antibodies (both monoclonal and polyclonal preparations), as well as other maintenance immunosuppressants (eg, tacrolimus, mycophenolate, sirolimus), have made a significant impact on both patient and graft survival. Currently, 1-year patient and graft survival rates exceed 90% in most transplant centers.

For patient education information, see Kidney Transplant and the Mayo Clinic's kidney transplant information Web page.

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Indications

Indications for renal transplantation include chronic kidney disease (CKD) and renal tumors. Studies show that renal transplantation prolongs patient lifespan compared with dialysis. Although perhaps only 25% of adult patients on dialysis are being referred for transplant evaluation (probably 95% of pediatric patients with ESRD will be referred), the number of potential candidates has resulted in burgeoning waitlists and longer waiting times for patients in need of kidney transplants.   See Tables 1 through 4, below.

Table 1. Demographics of adult patients on the waiting list for kidney transplants, United States, 2012[2] (Open Table in a new window)

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] (Open Table in a new window)

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] (Open Table in a new window)

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] (Open Table in a new window)

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  

A resurgence of interest in living donation, possibly stimulated by the introduction of laparoscopic donor nephrectomy in 1994, has led to a substantial growth in the number of living-donor transplants, which is also associated with improved outcomes and significantly shorter waiting times.[3] In 2002, the number of living-donor transplants exceeded the number of deceased-donor transplants for the first time. Some conditions may recur in the transplanted kidney, including immunoglobulin A (IgA) nephropathy, certain glomerulonephritides, oxalosis, and diabetes. Generally, the rate of recurrence is low enough to justify transplantation. In some patients, renal transplantation alone is not optimal treatment. Combined kidney-pancreas transplantation is the treatment of choice for patients who have type 1 diabetes and ESRD. Candidates for this combined procedure are typically younger than 50 years and do not have significant coronary artery disease (CAD).  At present, pancreas graft survival is worse in recipients of pancreas-after-kidney transplants than in recipients of simultaneous kidney-pancreas transplants; however, this is more than offset by the reduced waiting time, better overall patient survival, and better renal allograft survival that living-donor kidney transplantation affords; thus, for diabetic patients with living donors, living-donor kidney transplantation followed by pancreas-after-kidney transplantation is a reasonable option. Combined kidney-pancreas transplantation is covered in greater detail elsewhere (see Pancreas Transplantation). The treatment of oxalosis is controversial. In some cases, renal transplantation in conjunction with pyridoxine therapy can produce good results, but combined liver-kidney transplantation is generally preferred; in some patients, staged liver-kidney transplantation may be preferable. Hemolytic-uremic syndrome (HUS), a not uncommon cause of renal failure in children, may recur after transplantation in response to cyclosporine-based or tacrolimus-based immunosuppression. Renal tumors (eg, Wilms tumor in children or renal cell carcinoma in adults) can be treated with transplantation. A 2-year disease-free interval before transplantation is strongly advised, except in adults with small asymptomatic renal cell cancers, where a waiting period after radical nephrectomy may not be needed.

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Contraindications

A number of contraindications exist for renal transplantation. Some are contraindications for surgery, others are contraindications for immunosuppression, and still others derive from various concomitant disorders and conditions.

Contraindications for surgery

Contraindications for surgery include the following:

  • Metastatic cancer
  • Ongoing or recurring infections that are not effectively treated
  • Serious cardiac or peripheral vascular disease
  • Hepatic insufficiency (patients may be candidates for simultaneous liver-kidney transplantation)
  • Serious conditions that are unlikely to improve after renal transplantation (ie, the patient’s life expectancy can be finitely measured)
  • Demonstrated and repeated episodes of medical noncompliance
  • Inability to perform rehabilitation adequately after transplantation

HIV seropositivity is NOT a contraindication for kidney transplantation,provided that the patient meets the following criteria[4] :

  • The CD4 count has been higher than 200/µL for at least 6 months
  • HIV-I RNA is undetectable
  • The patient has been stable on antiretroviral therapy for at least 3 months
  • The patient has no major infectious or neoplastic complications

Adverse effects of immunosuppressive drugs may exacerbate atherosclerosis, hypertension, diabetes, and lipid disorders and thus may increase cardiac risk after transplantation. Currently, patient death from cardiac disease (ie, death with a functioning kidney) is the most common cause of renal allograft failure, not direct failure of the graft.

Contraindications for immunosuppression

Infection and malignancy are the primary medical conditions to be considered. Acute infections should be fully resolved at the time of transplantation. As noted (see above), HIV infection is no longer an absolute contraindication for renal transplantation if certain conditions are met[4] ; with these conditions satisfied, outcomes are equivalent to those of patients without HIV infection.

In general, one should wait about 5 years after successful treatment of breast cancer, colorectal cancer, melanoma, diffuse bladder carcinoma, and non–in situ ovarian cancer. The risk of recurrence is about 50% if the transplant is performed within 2 years of such treatment, about 35% if it is performed between 2 and 5 years, and only about 10% if it is performed after 5 years.

Some tumors may permit shorter waiting times. For isolated nodules of prostatic carcinoma and focal bladder carcinoma, 1 year (or even less) is reasonable; for in situ uterine carcinoma, some renal tumors (eg, clear cell, Wilms, urothelioma), and basal cell carcinoma or squamous cell skin carcinoma, no waiting time at all may be reasonable.

Poor social support, substance abuse, and intractable financial problems can compromise postoperative management and immunosuppression, contraindicating transplantation.

Other contraindications

The risk of recurrent disease is not a contraindication for renal transplantation. In about 3% of transplants, evidence of recurrence is observed by 2 years, and it is observed in about 20% of transplants by 8 years.

Glomerulonephritides (eg, mesangiocapillary glomerulonephritis type 1 and IgA nephropathy) are most likely to recur. However, loss of the kidney generally occurs late; thus, these diseases are not contraindications for transplantation. Focal segmental glomerulosclerosis is associated with a highly variable rate of recurrence in the first allograft, which approaches 30% in some series; however, if the first allograft is lost to recurrent disease, the risk of recurrence in the second allograft is approximately 85%.

Similarly, patients with diabetes mellitus have poorer outcomes after transplantation than patients without diabetes; nearly all of them demonstrate histologic evidence of diabetic nephropathy within 4 years. However, the improved quality of life for patients with diabetes after transplantation justifies its use as the treatment of choice for these patients if they have ESRD.

Increasingly, the treatment of choice for patients with type 1 diabetes and renal failure is combined kidney-pancreas transplantation or pancreas-after-kidney transplantation. The latter option is particularly attractive when the patient can receive the initial kidney transplant from a living donor.

Hereditary oxalosis is associated with a high rate of recurrence after kidney transplantation and graft failure. Optimal management remains controversial, but it may involve (1) intensive preoperative dialysis to reduce the oxalate burden and (2) combined or staged liver-kidney transplantation.

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Outcomes

The prognosis after kidney transplantation is generally excellent, with 1-year graft survival rates ranging from 90% to 95%. Many factors influence the anticipated outcome. HLA-identical (HLA-ID) transplants from living related donors have the best overall graft survival rate, whereas transplants from complete-mismatch cadaveric donors have the worst. Complete-mismatch living-donor transplants have outcomes equivalent to those of zero-mismatch deceased-donor transplants. See Table 5, below.

Table 5. Five-year post-transplant survival with a functioning kidney graft: United States, 2012 (Open Table in a new window)

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

Other factors affect outcomes after kidney transplantation. One such factor is kidney preservation time. Prolonged cold ischemia can result in delayed graft function immediately after transplantation and may result in a somewhat shorter lifespan for the transplant. Another factor is donor age: older age in the donor can adversely affect both immediate graft function and long-term outcomes. In general, both delayed graft function after transplantation and early rejection episodes adversely affect the long-term outcome of the transplant.

Although advances in immunosuppression have led to significant decreases in the incidence and severity of posttransplant acute rejection, these decreases have not led to corresponding increases in long-term graft and patient survival. The most likely explanation for this discrepancy is that at present, the most common cause of kidney graft loss is death of the recipient with a functioning graft, and the nephrotoxicity of immunosuppression.

To achieve significant improvements in graft and patient survival, patients’ comorbid conditions must be addressed more effectively. Chief among these is cardiac disease, which can be exacerbated by complications of immunosuppression. Special attention should be paid to cardiac risk factors after transplantation, including hypertension, hyperlipidemia, and diabetes.

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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
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  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].

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  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].

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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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