Renal Transplantation Periprocedural Care
- Author: Bradley H Collins, MD; Chief Editor: Ron Shapiro, MD more...
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
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
Studies of bladder capacity and function (if indicated)
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.
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
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. 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 :
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.
Another strategy involves the use of sirolimus, an immunosuppressant that targets T cells at a different site in the activation pathway. 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. 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. 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.
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- Table 1. Demographics of adult patients on the waiting list for kidney transplants, United States, 2012
- Table 2. Primary causes of ESRD in adult patients on the kidney transplant waiting list: United States, 2012
- Table 3. Demographics of pediatric patients awaiting kidney transplant: United States, 2012
- Table 4. Primary causes of end-stage renal disease in pediatric patients on the kidney transplant waiting list: United States, 2012
- Table 5. Five-year post-transplant survival with a functioning kidney graft: United States, 2012
|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|
|Cause of ESRD||Number of Patients||Percentage|
|Other or unknown cause||17||18.5|
|ESRD = End-stage renal disease|
|Age <1 y||1.0|
|Age 1-5 y||15.9|
|Age 6-10 y||14.1|
|Age 11-17 y||69.0|
|Other or unknown||1.8|
|Cause of Renal Failure||Percentage|
|Focal segmental glomerulosclerosis||12.0|
|Other or unknown||50.3|
|ESRD = End-stage renal disease|
|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|