Kidney transplant rejection occurs when the recipient’s immune system identifies the new kidney as foreign tissue and launches an attack to destroy it. This serious complication is mediated by specialized white blood cells and circulating antibodies that target the proteins on the transplanted organ. Although modern immunosuppressive drugs have significantly lowered the risk, rejection remains a possibility that can occur at any point, from immediately following surgery to many years later. Successfully managing a rejection episode depends on early detection and prompt medical intervention to preserve the function of the new kidney.
Recognizing the Early Warning Signs
A patient’s awareness of subtle physical changes is often the first line of defense against a rejection episode. One of the most noticeable signs involves a change in fluid balance, manifesting as sudden, unexplained weight gain over a day or two. This fluid retention may also lead to swelling, known as edema, particularly around the ankles, feet, or face.
A general feeling of being unwell, similar to having a severe flu, frequently accompanies the onset of rejection. Symptoms include persistent fatigue, body aches, chills, and an elevated body temperature, typically a fever higher than 100.4 degrees Fahrenheit (38 degrees Celsius). Pain or tenderness in the lower abdomen or flank area, near where the transplanted kidney is located, is also a common sign.
Since the kidney filters waste and produces urine, a noticeable decline in output is a strong warning sign. Patients may observe they are urinating less frequently or producing a significantly reduced volume of urine, indicating compromised filtering capacity. Because these signs are non-specific, contacting the transplant team immediately upon noticing any combination of them is necessary.
The Different Categories of Rejection
Kidney rejection is categorized based on the timeline and the underlying immunological mechanism. The most immediate and severe form is hyperacute rejection, which occurs within minutes to hours after the blood supply is connected to the new kidney. This rare event is triggered by preformed antibodies in the recipient’s bloodstream that instantly attack the donor organ’s antigens, leading to rapid clotting and irreversible damage. Due to highly effective pre-transplant cross-matching procedures, hyperacute rejection is now largely avoided in clinical practice.
The most common type is acute rejection, which typically occurs within the first year, peaking in the first few weeks to months post-transplant. Acute rejection is classified as T-cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR). TCMR involves the recipient’s T-lymphocytes directly attacking the kidney tissue. ABMR involves newly produced antibodies targeting the donor’s blood vessel lining.
Acute rejection episodes, particularly TCMR, are often successfully treated, but they still pose a risk to long-term graft survival. Chronic rejection, also known as chronic allograft dysfunction, represents a slow, progressive decline in kidney function that develops months to years after the transplant. This gradual process is characterized by vascular damage, inflammation, and the accumulation of scar tissue (fibrosis) within the kidney structure. Chronic rejection is generally more difficult to reverse than acute rejection and remains a leading cause of long-term graft failure.
Diagnosing Kidney Rejection
When rejection is suspected based on symptoms or routine monitoring, diagnostic tests are performed to confirm the episode and determine its specific type and severity. The initial step involves monitoring blood work that measures the kidney’s filtering efficiency. A rise in serum creatinine and blood urea nitrogen (BUN) levels indicates a decrease in the kidney’s ability to clear waste products.
While these blood tests signal a problem with kidney function, they cannot definitively confirm rejection, as infection or medication toxicity can cause similar changes. Specialized blood tests can also measure the presence of donor-specific antibodies (DSA), which strongly suggest an antibody-mediated rejection process. However, the definitive procedure for diagnosing rejection remains the allograft biopsy.
During a biopsy, a small core of tissue is extracted from the transplanted kidney using a needle guided by ultrasound imaging. This tissue sample is then examined under a microscope by a pathologist to identify the presence and extent of immune cell infiltration and structural damage. The histological findings from the biopsy are crucial for distinguishing between cellular and antibody-mediated rejection and for guiding the specific therapeutic approach.
Immediate Treatment Protocols
Once a rejection episode is confirmed by biopsy, the immediate goal of treatment is to rapidly suppress the immune response attacking the kidney. The first-line strategy for acute cellular rejection involves administering high-dose corticosteroids, such as intravenous methylprednisolone, typically given daily for three to five days. This powerful anti-inflammatory treatment works quickly to dampen the T-cell activity damaging the graft.
If the rejection is severe or resistant to corticosteroid therapy, treatment may escalate to include stronger antibody-based therapies. Agents such as anti-thymocyte globulin (ATG) are designed to deplete or neutralize the circulating T-lymphocytes responsible for the attack.
For cases of antibody-mediated rejection (ABMR), the protocol shifts to directly addressing the harmful antibodies circulating in the blood. This involves plasmapheresis, which filters the patient’s blood to physically remove donor-specific antibodies. Plasmapheresis is often followed by intravenous immunoglobulin (IVIG) therapy, which helps block the production and effects of harmful antibodies. In some cases, additional medications like Rituximab, which targets the B-cells that produce antibodies, may be introduced to further suppress the humoral immune response.
Long-Term Management and Next Steps
Following the resolution of a rejection episode, long-term management focuses on preventing recurrence and preserving the remaining kidney function. The maintenance immunosuppression regimen is typically re-evaluated and adjusted, often by increasing the doses of existing medications or adding new agents like mycophenolate mofetil. This adjustment aims to maintain a higher level of immune suppression to protect the kidney without unduly compromising the patient’s overall immunity.
If the immediate treatment protocols are successful, kidney function stabilizes or improves, and the patient returns to routine post-transplant monitoring with a modified medication schedule. However, if the rejection was severe or if treatments were unsuccessful in fully reversing the damage, the kidney’s function may remain partially or permanently impaired. In these cases, the long-term outlook involves managing progressive chronic kidney disease.
A gradual but continuous decline in function means the patient may eventually require a return to maintenance dialysis to manage waste and fluid buildup. If the allograft fails completely, the patient will need to begin the process of planning for a second kidney transplant. This involves re-evaluation for surgical fitness and inclusion on the transplant waiting list, while remaining under close medical supervision.