AUTHOR AND EDITOR INFORMATION

Section 1 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Kidney transplantation should be strongly considered for all patients who are medically suitable with chronic and end-stage renal disease (ESRD). 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 300,000 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.¹ Currently, the main obstacle is donor organ shortage.

For further information, see Mayo Clinic - Kidney Transplant Information.

Pathophysiology

An increasing rise in ESRD coupled with a lack of donor organs has resulted in an average waiting time of more than 2 years for a cadaveric 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.

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:²

CLINICAL

Section 3 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

WORKUP

Section 4 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Pretransplantation recipient laboratory evaluation: Emphasize identifying and treating all coexisting medical problems that may increase the morbidity and mortality rates of the surgical procedure and adversely impact the posttransplant course. In addition to a thorough medical evaluation, evaluate the social issues of the patient to determine conditions that may jeopardize the outcome of transplantation, such as financial and travel restraints or a pattern of noncompliance.
• Pertinent components include the following:
• • Blood chemistries
  • Liver function tests
  • Complete blood count
  • Coagulation profile
• Infectious profile
• • Hepatitis B and C serologies
  • Epstein-Barr virus serologies (immunoglobulin M [IgM] and immunoglobulin G [IgG])
  • Cytomegalovirus (CMV) serologies (IgM and IgG)
  • Varicella-zoster serologies (IgM and IgG)
  • Rapid plasma reagin (RPR) test for syphilis
  • HIV
  • Purified protein derivative (PPD) - Tuberculosis skin test with anergy panel, when indicated
• Urinalysis, urine culture, and cytospin (when indicated)

Imaging Studies

• A complete cardiac workup including angiography is not necessary in every patient. However, individuals with a significant history, symptoms, type I diabetes, or hypertensive renal disease should undergo a thorough evaluation to rule out significant coronary artery disease.
• • ECG (12 lead)
  • Chest radiograph (posteroanterior [PA] and lateral)
  • Exercise and dipyridamole thallium scintigraphy
  • Two-dimensional echocardiography with Doppler (+/- dobutamine)
  • Coronary arteriogram (if indicated)
• Special procedures in selected patients are dictated by findings revealed on history and physical examination.
• • Upper GI endoscopy
  • Colonoscopy
  • Ultrasound of native kidneys
  • Peripheral arterial Doppler studies
  • Pulmonary function tests
  • Carotid duplex studies
  • Voiding cystourethrogram
  • Urodynamic pressure-flow studies

Other Tests

• Recipients of kidney transplants undergo an extensive immunological evaluation that primarily serves to avoid transplants that are at risk for antibody-mediated hyperacute rejection. The immunologic evaluation consists of 4 components.
• ABO blood group determination: This test is used to determine if the patient is a potential target of recipient circulating preformed cytotoxic anti-ABO antibody. Transplantation across incompatible blood groups may result in humoral-mediated hyperacute rejection.
• Human leukocyte antigen (HLA) typing: All transplant recipients are tissue typed to determine the HLA class I and class II loci. Six HLA antigens are determined. The kidney donors also are HLA typed, and the degree of incompatibility between the donor and recipient is defined by the number of antigens that are mismatched at each of the HLA loci.
• Serum screening for antibody to HLA phenotypes
• • Sensitization to histocompatibility antigens is of great concern in certain populations of transplantation candidates. This occurs when the recipient is sensitized because of receiving multiple blood transfusions, a previous kidney transplant, or from pregnancy.
  • Transplantation of a kidney into a recipient who is sensitized against donor class I HLA antigens puts the recipient at high risk of developing hyperacute antibody-mediated rejection. All transplantation candidates are screened to determine the degree of humoral sensitization to HLA antigens.
• Crossmatching: This is an in vitro assay method that determines whether a potential transplant recipient has preformed anti-HLA class I antibodies against those of the kidney donor. This immunologic test is conducted prior to transplantation. A negative crossmatch must be obtained prior to accepting a kidney for transplantation.

Procedures

• The medical workup may reveal circumstances that require surgical intervention to prepare the patient for kidney transplantation.
• Pretransplant native kidney nephrectomy/nephroureterectomy: This is no longer a routine pretransplantation procedure. The native kidneys are left in place because they may still produce significant volumes of urine, secrete erythropoietin, and activate vitamin D. Nephrectomy/nephroureterectomy is reserved for specific indications, such as large polycystic kidneys, significant proteinuria, and chronic reflux disease.
• Pretransplant cholecystectomy: Ultrasonographic evidence of symptomatic or asymptomatic gallstones is an indication. The mortality and morbidity of acute cholecystitis is significant in transplant recipients who are immunosuppressed.
• Splenectomy: This is no longer a requisite pretransplantation surgical procedure. However, splenectomy may be indicated as part of a protocol for ABO-incompatible kidney transplantations.
• Multiple random blood transfusions: Once, this was associated with improved kidney transplant graft survival in the precyclosporine era. Currently, transfusion offers no clinical benefit, and the risk of sensitization is significant. In the setting of living kidney transplantation, donor-specific transfusion therapy also has been almost completely eliminated.

TREATMENT

Section 5 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The primary goal of short-term and long-term medical follow-up is enabling surveillance for signs and symptoms of renal allograft dysfunction.

Renal parenchymal dysfunction has many etiologies. The clinical manifestation is typically an increase in serum creatinine level. Causes are numerous, and the differential diagnosis must be approached systematically.

The greatest considerations are rejection, nephrotoxicity of calcineurin inhibitors, and recurrence of native kidney disease. The time interval between transplantation and the rise in serum creatinine level is often helpful in determining the etiology of graft dysfunction.

• Delayed graft function immediately posttransplantation is usually due to acute tubular necrosis (ATN). Frequency is variable among the different transplant centers and is approximated at roughly 20-30% of cadaver transplants.
• The nephrotoxicity of calcineurin inhibitors cyclosporine and tacrolimus is dose-related. Occasionally, performing a renal allograft biopsy is necessary if the serum creatinine level does not respond to a reduction in dose.
• Hemolytic uremic syndrome (HUS) and thrombotic microangiopathy (TMA) may be associated with endothelial injury associated with calcineurin inhibitors and the occurrence of CMV. A systemic process reveals anemia, reduced haptoglobin levels, rising lactic dehydrogenase (LDH) levels, and a peripheral blood smear with schistocytes, all of which are consistent with the diagnosis. At times, HUS and TMA can be confined to the kidney and not show any systemic findings. The definitive diagnosis, whether local or systemic, is made with the aid of renal allograft biopsy that shows glomerular microthrombi.
• Recurrent renal disease in patients who have had kidney transplants accounts for less than 2% of all graft losses, though it affects as many as 10% of transplant recipients. A few diseases have a high risk of renal allograft loss, such as focal segmental glomerulosclerosis, HUS oxalosis, and membranoproliferative glomerulonephritis. Diabetic nephropathy can recur in renal allografts, but the time to onset is similar to that seen in native kidneys and is an uncommon cause of graft loss.
• Rejection
• • Hyperacute rejection of the renal allograft happens within hours of the transplant, and it occurs when circulating, preformed, cytotoxic, antidonor antibodies directed to the ABO blood group antigens or to the donor HLA class I antigens are present. No treatment exists, and nephrectomy is indicated.
  • Accelerated acute rejection is a very early, rapidly progressive, aggressive rejection reaction. It can occur within the first week of transplantation. Immediate therapy with anti–T-cell antibodies and pulse corticosteroids may reverse the process. Approximately 50% of cases can be salvaged.
  • Acute tubular interstitial cellular rejection is the most common type of rejection reaction, with an incidence of approximately 20-25%. Typically, it occurs between 1-3 months posttransplantation. It is T-cell mediated, and injury is directed to the renal tubules. The criterion standard for diagnosis is renal allograft biopsy. Mild rejections may be successfully reversed with corticosteroids alone, whereas moderate or severe rejections may require the use of anti–T-cell antibodies, either polyclonal or monoclonal.
  • Chronic rejection is a slow and progressive deterioration in renal function characterized by histologic changes involving the renal tubules, capillaries, and interstitium. The precise mechanism of this disease is poorly defined and is an area of intense study. Application of conventional antirejection agents, such as corticosteroids or anti–T-cell antibodies, does not appear to alter the progressive course. Unfortunately, this is a major cause of kidney allograft loss, occurring later than 2 years posttransplantation.

Surgical Care

• Wound complications: In patients who have undergone transplantation, risk factors for and the morbidity of wound complications are significant.
• Bleeding: Kidney transplantation is a vascular surgery procedure; however, it is not an operation associated with much blood loss. Postoperatively, a life-threatening bleeding complication is very rare but could result from rupture of the arterial anastomosis from a mycotic aneurysm.
• Vascular thrombosis: Acute arterial thrombosis occurs in 1% of all kidney transplantations. Salvage of the renal allograft is possible if diagnosed within the first one half hour of occurrence (during recovery in the postanesthesia recovery room). Rarely, venous thrombosis occurs. If it occurs, the kidney is usually unsalvageable. Often, the cause is never satisfactorily identified.
• Urine leak: Leaks occur at the ureterovesical junction or through a ruptured calyx secondary to acute ureteral obstruction. Often, the etiology of early urine leak is due to necrosis of the tip of the ureter. Urine leaks manifest as diminished urine output, an increase in creatinine levels, and lower abdominal or suprapubic discomfort. Repair with minimal intervention may be attempted with either a percutaneous nephrostomy and drainage with internal stenting or through a cystoscopic retrograde approach. More aggressive treatment involves operative intervention with reimplantation of the ureter or a ureteroureterostomy, utilizing the ipsilateral native ureter.
• Ureteral stenosis and obstruction: This is a relatively late complication, occurring months or years posttransplantation, that could result from ischemia of the ureter or a tight ureteroneocystostomy. Ureteral stenosis is manifested by elevated creatinine and hydronephrosis.
• Lymphocele: This is a circumscribed collection of retroperitoneal lymph that originates from lymphatic vessels about the iliac vasculature and the hilum of the kidney. Significant secondary problems may arise if external compression of the iliac vein (causing leg swelling and discomfort) or compression of the transplant ureter (causing hydronephrosis and renal dysfunction) occurs. The standard principle is that intraperitoneal drainage of the lymphocele should be accomplished with either a laparoscopic or an open surgical approach, with marsupialization of the edges of the lymphocele.

MEDICATION

Section 6 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medications are used in renal transplantation for immunosuppression.

All kidney transplant recipients require life-long immunosuppression to prevent a T-cell alloimmune rejection response. Several new immunosuppressive agents have been approved by the Federal Drug Administration (FDA), and several others are in clinical trials.

Two broad classifications of immunosuppressive agents exist: intravenous induction of antirejection agents and maintenance immunotherapy agents. No consensus exists about which is the single best immunosuppressive protocol, and each transplantation program uses various combinations of agents slightly differently.

The goals are to prevent acute and chronic rejection, to minimize drug toxicity and rates of infection and malignancy, and to achieve the highest possible rates of patient and graft survival.

Drug Category: Antirejection induction agents

Induction immunotherapy consists of a short course of intensive treatment with intravenous agents. Antilymphocyte antibody induction therapeutics vary and include polyclonal antisera, mouse monoclonals, and so-called humanized monoclonals. Polyclonal antisera, such as antilymphocyte globulin (ALG), antilymphocyte serum (ALS), and antithymocyte globulin (ATG), are equine, goat, or rabbit antisera directed against human lymphoid cells. The effect is to significantly lower and almost abolish the circulating lymphoid cells that are critical to the rejection response.

The agents are very effective at prophylaxis against early acute rejection, which is especially beneficial in managing the recipient with delayed graft function. The agents provide an effective immunologic cover during a period in which the calcineurin inhibitors are either delayed or given in subtherapeutic doses until graft function improves. Induction agents are used less often if immediate graft function occurs, such as in recipients of kidneys from living donors, especially HLA-ID grafts.

Drug Category: Maintenance Immunosuppression

Several immunosuppressive agents are currently in use for maintenance immunotherapy in kidney transplant recipients. Optimal maintenance immunosuppressive protocol has not been developed. Maintenance immunosuppressive agents are required for the patient's entire life.

FOLLOW-UP

Section 7 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Outpatient Care

• Improvements in surgical technique and the advent of more potent immunosuppressive agents have reduced early complications of renal transplantation. Greater emphasis is now placed on preventing late complications. This is accomplished in the outpatient setting by routine assessment of patients with transplants.
• Possible complications include the following:
• • Hypertension
  • Hyperlipidemia
  • Metabolic bone disease
  • Chronic allograft nephropathy

Complications

• Chronic systemic immunosuppression is a double-edged sword. The same immunosuppressive effects that prevent rejection of the allograft pose a risk for development of malignancy and infectious diseases. Routine cancer surveillance is mandatory to assure rapid diagnosis and treatment of any malignancy.

Prognosis

• Some of the most useful data on kidney transplantation has been collected by the Scientific Registry of Transplant Recipients (SRTR) of the United Network for Organ Sharing (UNOS). The outcome of kidney transplantation is superior in recipients receiving a kidney from a living donor. Within this category, recipients of sibling HLA-identical grafts do best.
• UNOS percent graft survival data from 2002
• • Deceased donor kidneys (N = 8288)
    • 1 year (89%)
    • 3 years (77%)
  • Living donor kidneys (N = 6236)
    • 1 year (95%)
    • 3 years (87%)

Patient Education

• For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education article Kidney Transplant.

MISCELLANEOUS

Section 8 of 9  

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Special Concerns

• Pregnant women have special obstetric considerations.
• Newborns also have special considerations because they are more often born premature and have lower birth weights for expected ages.

REFERENCES

Section 9 of 9

• Authors and Editors
• Introduction
• Clinical
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. 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].
2. 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].
3. Cornell LD, Colvin RB. Chronic allograft nephropathy. Curr Opin Nephrol Hypertens. May 2005;14(3):229-34. [Medline].
4. Kaufman DB, Shapiro R, Lucey MR, et al. Immunosuppression: practice and trends. Am J Transplant. 2004;4 Suppl 9:38-53. [Medline].
5. Meyers CM, Kirk AD. Workshop on late renal allograft dysfunction. Am J Transplant. Jul 2005;5(7):1600-5. [Medline].
6. Suthanthiran M, Strom TB. Renal transplantation. N Engl J Med. Aug 11 1994;331(6):365-76. [Medline].
7. 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].
8. 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].

Article Last Updated: Dec 3, 2007