What are the treatment considerations for a patient with end-stage renal disease (ESRD) undergoing a kidney transplant?

Treatment Considerations for Kidney Transplantation in End-Stage Renal Disease

Kidney transplantation should be the primary treatment goal for patients with end-stage renal disease (ESRD), as it provides superior survival and quality of life compared to maintenance dialysis. 1

Referral and Timing

• Refer patients for transplant evaluation when creatinine clearance reaches 25 mL/min or serum creatinine is 4 mg/dL to expedite the transplantation process and minimize time on dialysis. 2
• Preemptive transplantation (before dialysis initiation) or short dialysis therapy before transplantation (<6 months) is associated with better patient and graft survival, lower cardiovascular complications, and improved quality of life. 3
• The American Society of Hematology recommends referral for kidney transplantation in children and adults with advanced or end-stage renal disease, despite very low certainty in evidence. 1

Pre-Transplant Evaluation

Absolute Contraindications to Screen For

• Uncontrolled active malignancy 1
• Severe active infection 1
• Very limited life expectancy due to comorbidities 1
• Patient noncompliance (which usually contraindicates kidney transplantation) 4

Immunological Assessment

• Perform panel of reactive antibodies (PRA) testing to determine the degree of HLA sensitization. 1
• Identify donor-specific antibodies (DSA). 1
• Consider desensitization strategies if the patient is highly sensitized. 1

Cardiovascular Evaluation

• Collect clinical data, perform physical examination, electrocardiography, chest X-ray, measure lipid profile and fasting glycemia. 3
• Perform cardiac ultrasonography after a hemodialysis session to avoid hypervolemia effects. 3
• Do not perform exercise tolerance tests as they have low sensitivity and are difficult to perform and interpret in this population. 3
• Consider coronary angiography in patients with positive exercise tolerance test results, history of acute coronary syndrome, unstable coronary artery disease, or high cardiovascular risk. 3

Obesity and Metabolic Assessment

• Recommend weight reduction to a BMI <30 kg/m² for renal transplant candidates, as obesity is associated with higher rates of delayed graft function, surgical complications including wound infections, prolonged hospital stays, increased costs, and higher incidence of post-transplant diabetes mellitus. 5
• For diabetic patients with Type 1 diabetes and ESRD, pancreas transplantation should be considered as an alternative to insulin therapy for those who have undergone or plan to undergo renal transplantation. 5

Post-Transplant Management

Immunosuppression

• Tacrolimus-based immunosuppression in conjunction with mycophenolate mofetil (MMF) and corticosteroids is a standard regimen, with or without induction therapy using daclizumab. 6
• During the first 3 months post-transplant, maintain tacrolimus trough concentrations between 7 to 20 ng/mL, then between 5 to 15 ng/mL through 1 year. 6
• Use corticosteroids judiciously in patients with sickle cell disease due to the potential relationship between steroid exposure and vaso-occlusive pain episodes. 5

Monitoring Protocol

• Monitor serum creatinine every 2-3 months to assess renal function. 1
• Monitor proteinuria every 3 months during the first year post-transplant. 1
• Surveillance biopsies and close monitoring of renal function are necessary, especially with certain immunosuppressive regimens. 1
• Increase the frequency of immunosuppressant level monitoring if any new medication must be started, as drug interactions with calcineurin inhibitors metabolized through the cytochrome P450 pathway are critical concerns. 7

Blood Pressure Management

• Control blood pressure with preferential initial use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for patients with proteinuria. 5
• Avoid calcium channel blockers in patients receiving protease inhibitors due to drug interactions. 5

Infection Prevention

• Vaccinate against seasonal influenza, tetanus, hepatitis B, human papillomavirus (through 26 years of age), and Streptococcus pneumoniae. 8
• HIV-infected patients requiring hemodialysis should have antibody to hepatitis B surface antigen (anti-HBs) titers checked after receiving a standard primary series of 3 hepatitis B vaccinations, and should receive a fourth injection if levels are <10 IU/L. 5

Mental Health Screening

• Include direct questioning about depression and anxiety as part of routine follow-up care after kidney transplantation. 5

Expected Outcomes

• One-year patient survival post-transplant is approximately 88% (95% CI, 80.1-95.5). 5, 1
• One-year graft survival is approximately 89.6%. 6
• Transplant outcomes in ESRD patients are comparable to those of patients with diabetes and end-stage renal disease who receive a transplant. 5, 1
• Five-year graft survival rates range from 72% to 99%, with the best rates seen in patients receiving kidneys from living donors. 5

Common Pitfalls to Avoid

• Do not withhold HAART from HIV-infected patients simply because of the severity of their renal dysfunction. 5
• Do not withhold dialysis and placement of arteriovenous fistulae for patients solely because of HIV infection. 5
• Do not extrapolate safety data from non-transplant populations to transplant recipients, as pharmacokinetics and risks are fundamentally different. 7
• Recognize that patients scheduled for kidney transplant may experience changes in their condition after several years on the waiting list, necessitating cardiac reevaluation. 3
• Protect arm veins from venipuncture and intravenous catheters, particularly the cephalic veins of the nondominant arm, to preserve future vascular access sites. 2

Special Populations

Sickle Cell Disease

• Adhere strictly to general guidelines for perioperative transfusion requirements for surgery in adults with sickle cell disease. 5, 1
• Despite very low certainty of evidence, renal transplant is justified given the high burden associated with dialysis and comparable outcomes to diabetic patients with ESRD. 5

Hepatitis C

• Treatment should be performed in expert centers with close monitoring. 1

Medication Safety

• Consult the transplant team before initiating therapy with any new medication, particularly those without established safety profiles in transplant recipients. 7
• Even "natural" or "nutritional" compounds can have profound drug interactions with immunosuppressants. 7