A kidney transplantation involves surgically implanting a kidney from a donor into a recipient to restore kidney function. A successful kidney transplant can fully restore renal function, offering better quality of life, lower maintenance costs, and higher survival rates compared to dialysis. It has become the preferred treatment for patients with end-stage renal disease. Advances in surgical techniques have made kidney transplantation a well-established procedure, with effective management of related medical issues being key to improving long-term survival.
Donor and Recipient Evaluation
Kidneys for transplantation can come from deceased donors or living donors. Transplants from living donors generally have better short- and long-term outcomes for both the individual and graft. This is attributable to factors such as shorter ischemic time of the donor kidney, shorter waiting times, the ability to schedule transplantation at an optimal time, better potential for achieving ideal tissue matching with living-related donors, and lower rates of postoperative rejection. All donor kidneys must be screened for infectious diseases or malignancies that could be transmitted to the recipient, with a comprehensive evaluation of the anatomy and function of the kidney.
Kidney transplantation is suitable for patients with end-stage renal disease caused by various conditions. Preoperative assessment of the recipient must be thorough, including evaluation of cardiovascular and pulmonary function, life expectancy, and the presence of active infections (such as viral hepatitis or tuberculosis), newly developed or recurrent malignancies, active gastrointestinal ulcers, or progressive metabolic diseases (e.g., oxalate deposition disease). Patients with severe chronic dysfunction of other organs (e.g., heart, lung, liver, pancreas) may need to be considered for combined organ transplantation.
Immunosuppressive Therapy
Kidney transplant recipients require lifelong immunosuppressive therapy to suppress rejection. The mechanisms underlying rejection are complex, and no single immunosuppressive agent can completely prevent or suppress all aspects of the immune response. Consequently, immunosuppressive agents targeting different points in the immune response are commonly combined to achieve complementary effects, effectively inhibiting rejection while minimizing the side effects associated with high-dose monotherapy.
Immunosuppressive therapies for kidney transplantation include:
Prophylactic Therapy
Prophylactic immunosuppression often involves dual or triple therapy anchored by calcineurin inhibitors (cyclosporine or tacrolimus) in combination with low-dose corticosteroids, mycophenolate mofetil, azathioprine, or sirolimus for long-term maintenance. Belatacept has also been approved to prevent rejection, reducing the long-term toxicity associated with calcineurin inhibitors.
Treatment or Reversal of Rejection
Treatment for rejection episodes typically involves high-dose methylprednisolone or agents like anti-thymocyte globulin (ATG) or anti-lymphocyte globulin (ALG), administered via "pulse" therapy.
Induction Therapy
Induction therapy is used in recipients at high risk for rejection, those experiencing delayed graft function, and during repeat transplantation. It often includes agents such as ATG or anti-CD25 monoclonal antibodies, followed by maintenance with calcineurin inhibitors like cyclosporine or tacrolimus.
Graft Rejection
Rejection is the primary complication of kidney transplantation and can be categorized into hyperacute, accelerated, acute, and chronic rejection.
Hyperacute Rejection
Hyperacute rejection occurs when pre-existing antibodies in the recipient target the donor kidney. This reaction typically happens immediately after vascular anastomosis or within 48 hours of transplantation. Pathological findings include thrombosis in glomerular capillaries and small arteries, which may lead to extensive cortical necrosis. There is no effective treatment for hyperacute rejection, which highlights the importance of preoperative screening for panel-reactive antibodies and donor-recipient lymphocytotoxicity.
Accelerated Rejection
The mechanisms underlying accelerated rejection remain unclear, although it is thought to involve pre-existing donor-specific antibodies. Accelerated rejection typically manifests 24 hours to 7 days after transplantation, presenting as fever, hypertension, hematuria, graft swelling with tenderness, and rapid deterioration of renal function. Pathological findings mainly include glomerular and arteriole lesions, along with complement deposition (C4d) in peritubular capillaries. Treatment includes intensified immunosuppressive therapy (e.g., ATG, ALG), combined with intravenous immunoglobulin (IVIG) or plasma exchange to remove antibodies, though the efficacy is generally limited.
Acute Rejection (AR)
Acute rejection is the most common form of rejection, usually occurring within 1–3 months post-transplantation, though it can occur at any time. Clinical manifestations include decreased urine output, graft swelling, and impaired renal function. Pathologically, acute rejection is classified into T-cell-mediated AR and antibody-mediated AR, necessitating graft biopsy for accurate diagnosis. Treatment for T-cell-mediated AR involves corticosteroid pulse therapy, often combined with ATG or ALG. Antibody-mediated AR requires additional use of IVIG or plasma exchange to remove antibodies.
Chronic Rejection
Chronic rejection often develops months to years after transplantation, characterized by progressively declining renal function, frequently accompanied by proteinuria and hypertension. The main mechanism involves humoral immune responses, with donor-specific antibodies present in the recipient. No highly effective treatment is currently available. Treatment focuses on escalating immunosuppressive therapy as appropriate, and managing symptoms such as hypertension. IVIG or plasma exchange may be used to remove donor-specific antibodies when present.
Prognosis
The postoperative survival rate for kidney transplant recipients exceeds 95% at 1 year, 80% at 5 years, and approximately 60% at 10 years, which is significantly higher than survival rates for patients on maintenance hemodialysis or peritoneal dialysis. The leading causes of death after transplantation include cardiovascular complications, infections, and malignancies.