What are the signs of kidney transplant rejection?

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Kidney transplant rejection occurs when the body’s immune system recognizes the transplanted kidney as a foreign entity and attacks it. Rejection must be identified early to prevent damage to the transplanted kidney. Rejection may be acute rejection, chronic rejection, or hyperacute rejection. The signs of kidney transplant rejection may vary depending on the type of rejection and the phase of rejection, but there are some common signs.

Symptoms of Rejection of Kidney Transplant:
1. Systemic Rejection Symptoms:
Fever: Mild or moderate fever, along with other symptoms of rejection, may indicate the body’s reaction against the new kidney.
Fatigue: Persistent fatigue or tiredness, even after resting, may be a sign of rejection.
Swelling: Swelling in the hands, feet, or legs may occur if the new kidney is not functioning properly.
Pain or Tenderness over the Kidney: Pain or tenderness over the area of the transplanted kidney, normally near the lower back or abdomen, can be a sign of rejection. The pain can either be mild or severe.
Flu-like Symptoms: Experiencing body aches, chills, or a general feeling of not being well may result, much like the flu.
2. Urinary Changes:
Decreased Urine Output: Acute decrease in urine quantity or lack of urination can be a sign of kidney failure or rejection.
Dark or Cloudy Urine: Protein or blood in the urine, causing the urine to be darker or cloudier, can be a sign of rejection.
Painful Urination: Burning or pain on urination, not necessarily specific for rejection but can be a sign of infection or rejection.
3. Hypertension (High Blood Pressure):
High blood pressure is a common expression of renal failure and can be due to rejection, especially early post-transplant.
4. Rising Serum Creatinine:
A rise in the serum creatinine level (a waste product filtered by the kidneys) is a significant marker of renal function. A rise in the creatinine level can indicate that the transplanted kidney is not functioning properly, which can be due to rejection.
Blood tests are performed routinely after a transplant to monitor the kidney function and diagnose any early sign of rejection.
5. Electrolyte Imbalance:
Potassium, sodium, or other electrolytes can get imbalanced. This can result from kidney dysfunction and also can be a sign of rejection or complications.
6. Weight Gain:
Sudden weight gain, particularly from fluid retention, may occur if the transplanted kidney is not effectively removing waste and fluids. It may be accompanied by swelling in the abdomen, face, or legs.
7. Rise in WBC Count (Leukocytosis):
An increase in the white blood cell count (WBC) can indicate an immune response, which may be the result of acute rejection or infection.
Types of Kidney Transplant Rejection and Their Symptoms:
Acute Rejection:

This type occurs in the first few weeks to months after transplant and is the most common form of rejection. It can exhibit many of the symptoms listed above (i.e., fever, pain, swelling, fatigue).
Acute rejection can be effectively treated with immunosuppressive therapy, but the sooner it is diagnosed, the better, to prevent damage to the kidney from becoming permanent.
Chronic Rejection:

This form of rejection happens over months or years and is characterized by a gradual loss of kidney function.
Symptoms might not necessarily be as severe or acute as in acute rejection but can instead consist of persistent fatigue, swelling, and gradual decline in urine output over a period of time.
Chronic rejection can lead to fibrosis or scarring of the transplanted kidney, which is harder to treat.
Hyperacute Rejection:

Hyperacute rejection is a rare, immediate reaction that occurs within hours to minutes after transplantation. It occurs when the body’s immune system already contains pre-formed antibodies against the donor kidney.
The symptoms of hyperacute rejection include severe pain, swelling, and abrupt reduction in kidney function. It is generally irreversible and normally leads to loss of the transplanted kidney.
Monitoring and Diagnosis:
Kidney biopsy: If rejection is suspected, a kidney biopsy may be performed to make the diagnosis. A tiny sample of kidney tissue is examined under a microscope to determine if there is any evidence of immune activity or damage to the kidney.
Blood tests: Routine tests, including serum creatinine levels and urine tests, are performed to check kidney function. A rise in the creatinine level may indicate rejection or other renal difficulties.
Ultrasound: One may perform an ultrasound to assess the size of the kidney, blood flow to the kidney, and for signs of swelling or other changes.
When to Call a Doctor:
If any of the above signs or symptoms of rejection are noticed, it is critical to call a health provider immediately. With rejection detected early, measures can be taken that can improve the outcome and prevent long-term injury to the transplanted kidney.

Conclusion:
Rejection of the kidney transplant is a serious but treatable condition if it is diagnosed early. Fever, fatigue, tenderness over the transplant, decrease in urine output, and swelling are all signs that must be monitored carefully. Frequent follow-up appointments, blood tests, and urine tests are necessary to diagnose rejection and other issues early.
Rejection is managed by managing the immune response to prevent further damage to the transplanted organ. The treatment differs depending on the type and extent of the rejection (hyperacute, acute, or chronic), but in general, an attempt is made to suppress the immune system to the point where the rejection is stopped but the body’s defense mechanisms are not compromised.

1. Immunosuppressive Medications:
Immunosuppressive drugs are the primary treatment for transplant rejection. These medications suppress the activity of the immune system, preventing it from rejecting the transplanted organ. The drugs used and their dosages may vary depending on the type of rejection and the response of the individual.
Some of the immunosuppressive drugs used are:

Calcineurin inhibitors (e.g., cyclosporine, tacrolimus): These drugs prevent the activation of T-cells and their attack on the transplanted organ.
Antiproliferative agents (for example, mycophenolate mofetil, azathioprine): These drugs suppress the formation of new immune cells, including those that would attack the transplant.
Corticosteroids (for example, prednisone): Steroids are used to reduce inflammation and suppress immune responses.
mTOR inhibitors (for example, sirolimus, everolimus): These drugs prevent immune cells from growing and block rejection.
Biological agents (for example, alemtuzumab, basiliximab): These medications can help target specific parts of the immune system and more specifically reduce immune response.
Induction therapy: It is a more intensive initial therapy, typically in the first days or weeks after transplant. It can involve monoclonal antibodies or polyclonal antibodies that deplete certain immune cells (e.g., thymoglobulin, basiliximab) to reduce the risk of rejection.

Maintenance therapy: It is a long-term therapy, often a combination of calcineurin inhibitors, antiproliferative agents, and steroids to provide long-term immune suppression.

2. Treatment of Acute Rejection:
Acute rejection can generally be managed with a change in immunosuppressive therapy, sometimes with higher doses or short courses of steroids. High-dose corticosteroids are generally the first treatment to manage acute rejection. It may be given intravenously (IV) for rapid action.
If steroids alone are not effective, other treatments may be used, such as antithymocyte globulin (ATG), a medication that depletes T-cells.
In some cases, plasmapheresis (a procedure during which antibodies are removed from the blood) or IV immunoglobulin therapy may be necessary in acute severe rejection, particularly if antibodies are involved in the rejection.
3. Treatment of Hyperacute Rejection:
Hyperacute rejection occurs early (within minutes to hours) after transplant and is almost always due to pre-existing antibodies against the donor organ.
Unfortunately, hyperacute rejection is irreversible and most commonly leads to the loss of the transplanted organ right away. When this happens, the transplanted kidney is usually removed to prevent further complications.
To prevent hyperacute rejection, crossmatching tests are done before the transplant to ensure that the recipient’s immune system will not reject the donor kidney as foreign.
4. Treatment of Chronic Rejection:
Chronic rejection occurs over months or years and is typically the result of a mixture of immune-mediated damage along with non-immune factors (e.g., drug-induced complications, insufficient blood flow to the transplant).
There is no direct treatment that can reverse chronic rejection, but the goal is to slow its progress and maintain the function of the transplanted organ. This may include adjustment of immunosuppressive therapy, and also management of risk factors (such as blood pressure and diabetes control).
5. Other Supportive Treatments:
Dialysis is required if there is a decrease in kidney function due to rejection, particularly in acute or chronic rejection when kidney function worsens severely.
Long-term immunosuppression can prevent ongoing immune injury to the transplanted kidney, but chronic rejection is generally progressive, and the transplant can ultimately fail, necessitating a second transplant.
Monitoring: Regular tests (blood tests, urine tests, and biopsies) are required to catch rejection early. The creatinine level is monitored regularly to assess kidney function.
Management of Side Effects: Immunosuppressive drugs do have side effects, such as an increased risk of infections, cancer, high blood pressure, and bone loss. Management of these side effects is a critical part of the overall treatment plan.
6. Other Treatments for Severe Rejection:
In the context of severe or refractory rejection not responsive to standard immunosuppressive drugs, experimental therapies may be attempted, such as:

Stem cell therapy for immune modulation.
Gene therapy for modification of immune system behavior.
Targeted immune-modulation therapy for specific pathways implicated in rejection.
Conclusion:
Treatment of transplant rejection is largely with immunosuppressive medications to control the immune response and prevent injury to the transplanted kidney. The nature of the rejection (hyperacute, acute, or chronic) will guide the exact treatment. Acute rejection may usually be reversed by therapy, but chronic rejection necessitates long-term treatment and may ultimately lead to the necessity for a second transplant. The monitoring of kidney function and immune response on a regular basis is instrumental in controlling rejection and assuring the long-term success of the transplant.