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Renal Transplantation (Medical)
Updated: Jun 12, 2009
Introduction
Background
Kidney transplantation should be strongly considered for all patients who are medically suitable with chronic and end-stage renal disease (ESRD).1 A successful kidney transplant offers enhanced quality and duration of life and is more effective (medically and economically) than chronic dialysis therapy. Transplantation is the renal replacement modality of choice for patients with diabetic nephropathy and pediatric patients.
Currently in the United States, more than 100,000 persons are living with a functioning kidney transplant. This number represents 27% of the nearly 350,000 persons enrolled in the US ESRD program.
In 1973, Congress enacted Medicare entitlement for ESRD treatment to provide equal access to dialysis and transplantation for all patients with ESRD in the Social Security system by removing the financial barrier to care.2 Currently, the main obstacle is donor organ shortage.
History
Early experimentsExperimental intra-abdominal renal grafts were being performed in animals in the 1930s and 1940s. Autografts generally survived, although homografts were rejected. On December 25, 1952, Hamburger performed the world's first renal transplantation in a 15-year-old roofer who injured his solitary kidney. The donor of the graft was the patient's mother. The graft functioned immediately following surgery, but it unfortunately ceased to function on the 22nd postoperative day. The patient died 10 days later due to the unavailability of hemodialysis. However, this event had a considerable impact on the scientific community. Surgical inspection of the graft revealed that immunological rejection, rather than stenosis or thrombosis of the renal artery, led to graft failure.
Successful kidney transplantation
Joseph Murray and Hartwell Harrison performed the first transplantation of a kidney graft between identical twins on December 23, 1954. This success was followed by subsequent attempts by Murray and Merrill that led to 7 successful transplantations between identical twins in Boston. Most of the recipients of identical twin kidney grafts performed by Joseph Murray did well; some still have functioning kidneys more than 30 years after transplantation. However, the attempts at cadaveric renal transplantation universally resulted in graft failure due to rejection.
The first attempts to control the immune system used total body irradiation. In 1958, a Boston-area woman who was accidentally irradiated with 6 Gy received a functional renal graft, although the patient died from bone marrow aplasia. In 1959, Hamburger and Merrill irradiated 2 transplant recipients with a total dose of 4.5-4.8 Gy; the donors were nonidentical twins. Both of these recipients had successful outcomes. The patients survived 20 and 26 years, respectively. In June 1960, Kuss and colleagues were faced with rejection in a kidney transplant recipient who received the graft from an unselected donor. The use of 6-mercaptopurine in this patient, an immunosuppressive agent previously studied in animals, reversed the rejection process and ushered in the era of medications for the prevention and treatment of rejection. In 1964, Crosnier performed another cadaveric transplantation with long-term successful function.
In the early 1960s, the pioneering work of Thomas Starzl led to further advancements. His contributions were systematic studies using azathioprine and prednisone therapy to prolong graft survival. Following the demonstration of antilymphocyte serum efficacy by Waksman, Starzl conducted the first clinical trial of antilymphocyte globulin as an adjunct to azathioprine and prednisone in human kidney transplantation.
Long-term graft survival
At present, the 1-year patient survival rate for living donor transplants is 98%, and the 1-year patient survival rate for deceased donor transplants is 94%.3 The graft half-life for living donors is approximately 20 years, and the graft half-life for deceased donors is 12 years.
Data from the Organ Procurement and Transplantation Network for transplants performed in 2002-2004 show that the 1-year survival rate for grafts from living donors is approximately 95% and the rate for deceased donor grafts is approximately 89%.3 The half-life for grafts from living donors increased steadily from 12.7 to 21.6 years, and that for deceased donor grafts increased from 7.9 to 13.8 years. Kidney graft failure occurs because of chronic rejection, graft dysfunction, and nephrotoxicity, causing the patient to need dialysis and often a new organ. The development of new therapeutic approaches to prevent chronic rejection is needed to prolong the long-term survival of kidney transplants.
Pathophysiology
An increasing rise in ESRD coupled with a lack of donor organs has resulted in an average waiting time of more than 4 years for a deceased donor renal transplant.
Frequency
United States
The overall rate of ESRD is approximately 735/1,000,000. As the end-stage population continues to increase, projections estimate that the current population of 372,407 will exceed 660,000 by the year 2010.
In 2007, 6,037 kidney transplants from living donors and 10,082 deceased-donor kidney transplants were performed in the United States.4
Mortality/Morbidity
The 1-year life expectancy after kidney transplantation is 95-98%. The standardized mortality rate for patients on dialysis who are awaiting kidney transplantation is 6.3/100 patient-years. The standardized mortality rate with each treatment per 100 patient-years is as follows:
- Dialysis - 6.3
- Cadaveric transplant - 3.8
- Living donor transplant - 2.0
Age
The proportion of patients either waiting for a kidney transplant or receiving a kidney transplant according to age is as follows:5
Open table in new window
Table
| Age, Years | Wait List, % | Transplant, % |
| 0-19 | 2.8 | 3.7 |
| 20-39 | 31.2 | 33.6 |
| 40-59 | 15.0 | 13.0 |
| 60-70 | 39.5 | 37.2 |
| Age, Years | Wait List, % | Transplant, % |
| 0-19 | 2.8 | 3.7 |
| 20-39 | 31.2 | 33.6 |
| 40-59 | 15.0 | 13.0 |
| 60-70 | 39.5 | 37.2 |
Clinical
History
Candidates for renal transplantation undergo an extensive evaluation to identify factors that may have an adverse effect on outcome. Virtually all transplant programs have a formal committee that meets regularly to discuss the results of evaluation and select medically suitable candidates to place on the waiting list. Most programs perform the evaluation in the outpatient setting and possess a relatively uniform approach to the diagnosis and treatment of the pertinent medical and psychosocial issues affecting candidacy.
- Preexisting morbidities of the transplant candidate with renal disease
- Hematologic abnormalities, such as anemia and platelet-hemostatic dysfunction
- Upper and lower gastrointestinal track abnormalities, such as gastritis, peptic ulcer disease, diverticulosis, diverticulitis, spontaneous colonic perforation, and prolonged adynamic ileus (pseudo-obstruction)
- Hepatic abnormalities, such as viral hepatitis B and C (For more information, see Emerging Issues in Hepatitis C Virus–Positive Liver Kidney Transplant Recipients.)
- The cardiovascular system is profoundly affected in patients with chronic or end-stage renal failure. The increased mortality is related to hypertension, atherosclerotic heart disease with myocardial infarction, congestive heart failure, and left ventricular hypertrophy.
- Bone and joint disease is common in these patients because of low calcium levels, high phosphorus concentrations, and elevated serum parathyroid hormone (PTH) levels.
Causes
- A diverse array of diseases destroys renal function in all age groups. The most common etiologies of renal disease leading to kidney transplantation are the following:
- Diabetes – 31%
- Chronic glomerulonephritis – 28%
- Polycystic kidney disease – 12%
- Nephrosclerosis (hypertensive) – 9%
- Systemic lupus erythematosus (SLE) – 3%
- Interstitial nephritis – 3%
- Understanding the etiology of renal disease is important because the primary renal pathology may influence the outcome based on the propensity for recurrence of disease and the association of comorbidities.
More on Renal Transplantation (Medical) |
 Overview: Renal Transplantation (Medical) |
| Differential Diagnoses & Workup: Renal Transplantation (Medical) |
| Treatment & Medication: Renal Transplantation (Medical) |
| Follow-up: Renal Transplantation (Medical) |
| References |
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References
Suthanthiran M, Strom TB. Renal transplantation. N Engl J Med. Aug 11 1994;331(6):365-76. [Medline].
Nissenson AR, Rettig RA. Medicare's end-stage renal disease program: current status and future prospects. Health Aff (Millwood). Jan-Feb 1999;18(1):161-79. [Medline].
Organ Procurement and Transplantation Network (OPTN). National Data, Kidney Graft/Patient Survival. OPTN Web site. Available at http://optn.transplant.hrsa.gov/latestData/viewDataReports.asp. Accessed June 12, 2009.
McCullough KP, Keith DS, Meyer KH, Stock PG, Brayman KL, Leichtman AB. Kidney and pancreas transplantation in the United States, 1998-2007: access for patients with diabetes and end-stage renal disease. Am J Transplant. Apr 2009;9(4 Pt 2):894-906. [Medline].
Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. Dec 2 1999;341(23):1725-30. [Medline].
Meyers CM, Kirk AD. Workshop on late renal allograft dysfunction. Am J Transplant. Jul 2005;5(7):1600-5. [Medline].
Zarifian A, Meleg-Smith S, O'Donovan R, Tesi RJ, Batuman V. Cyclosporine-associated thrombotic microangiopathy in renal allografts. Kidney Int. Jun 1999;55(6):2457-66. [Medline].
Cornell LD, Colvin RB. Chronic allograft nephropathy. Curr Opin Nephrol Hypertens. May 2005;14(3):229-34. [Medline].
Wong W, Venetz JP, Tolkoff-Rubin N, Pascual M. 2005 immunosuppressive strategies in kidney transplantation: which role for the calcineurin inhibitors?. Transplantation. Aug 15 2005;80(3):289-96. [Medline].
Further Reading
Keywords
renal transplantation, allotransplantation, kidney transplantation, kidney transplant, renal transplant, end stage renal disease, end-stage renal disease, end stage kidney disease, end-stage kidney disease, ESRD, renal replacement, diabetic nephropathy, nephrectomy, organ transplant, organ transplantation, renal disease, kidney disease, diabetes, chronic glomerulonephritis, polycystic kidney disease, PKD, nephrosclerosis, hypertensive nephrosclerosis, systemic lupus erythematosus, SLE, interstitial nephritis, renal allograft, kidney allograft
