Kidney Transplantation

Kidney 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.

Since 1988, over 515,000 kidney transplants have been performed in the United States. ^[1]  During 2019, a record 24,502 kidney transplants were performed in the US, 6915 from living donors and 17,586 from deceased-donors. ^[2] In 2019, 244,000 patients (pediatric and adult) were alive and with a functioning transplanted kidney; at the end of 2019, 101,337 adult patients were waiting for kidney transplants. ^[3] Although the spring 2020 wave of the COVID-19 pandemic severely disrupted kidney transplantation, rates subsequently recovered; however, kidney transplant recipients have experienced excess mortality through the pandemic, possibly due to lower vaccine efficacy in this population. ^{[4, 5, 6]}

Before the advent of immunosuppression, kidney 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.

Indications for kidney transplantation include chronic kidney disease (CKD) and renal tumors. Studies show that kidney 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, 2019 ^[3] (Open Table in a new window)

Table 2. Primary causes of ESRD in adult patients on the kidney transplant waiting list: United States, 2019 ^[3] (Open Table in a new window)

Table 3. Demographics of pediatric patients awaiting kidney transplant: United States, 2019 ^[3] (Open Table in a new window)

Table 4. Primary causes of end-stage renal disease (ESRD) in pediatric patients on the kidney transplant waiting list: United States, 2019 ^[3] (Open Table in a new window)

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. ^[7]   However, the rate of living-donor transplants began to decline in 2004 and has reached a plateau representing approximately 30% of all kidney transplantations. ^[2]

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, kidney 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 in Kidney-Pancreas Transplantation.

The treatment of oxalosis is controversial. In some cases, kidney 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 kidney failure in children, may recur after transplantation in response to cyclosporine-based or tacrolimus-based immunosuppression. Kidney 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.

A number of contraindications exist for kidney 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 kidney transplantation (ie, the patient’s life expectancy can be finitely measured)
• Demonstrated and repeated episodes of medical noncomplianceInability to perform rehabilitation adequately after transplantation

HIV seropositivity is NOT a contraindication for kidney transplantation, provided that the patient meets the following criteria ^[8] :

• 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 kidney transplantation if certain conditions are met ^[8] ; with these conditions satisfied, outcomes are equivalent to those of patients without HIV infection. ^[9]

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 kidney 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 kidney 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 kidney 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.

The prognosis after kidney transplantation is generally excellent, with 1-year graft survival rates ranging from 93% to 98% and 5-year survival rates from 83% to 92%. ^[1] 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.

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. The risk of cardiovascular events in kidney transplant recipients is 3.5–5% per year, which is 50-fold higher than that of the general population, and the prevalence of hypertension is greater than 80%. ^[10] Thus, special attention should be paid to cardiac risk factors after transplantation, including hypertension, hyperlipidemia, and diabetes.

Clinical practice guidelines on the management of blood pressure (BP) in kidney transplant recipients recommend maintaining BP at 130/80 mmHg or less. However, office BP measurements may be unreliable: a longitudinal study in kidney transplant recipients that compared routinely measured office BPs with 24-h ambulatory BPs (ABPs) found white coat hypertension in 25% of kidney transplant recipients and masked hypertension in 12%. ^[10]