Immunosuppressants in Kidney Transplantation

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Questions and Answers

What is a primary characteristic of chronic allograft injury (CAI)?

Immediate graft failure post-transplant

Slow deterioration of renal function over months to years (correct)

Rapid decline of renal function within days

Complete recovery of graft function over time

Which of the following is an immunologic factor increasing the likelihood of chronic allograft injury?

Obesity

A history of acute rejection (correct)

Donor age

Recipient hyperlipidemia

Which treatment is used for antibody-mediated rejection?

Calcinorin inhibitors

Methyl prednisone

Rabbit anti-thymocyte globulin

Plasmapheresis with IVIG (correct)

What role does nonadherence to immunosuppressive therapy play in chronic allograft injury?

It increases the likelihood of chronic allograft injury. Signup and view all the answers

What is indicated by biopsy findings in chronic rejection?

Fibrosis of hollow structures and vessels Signup and view all the answers

Which of the following is not a treatment for T cell-mediated rejection?

Bortezomib Signup and view all the answers

Which medication is NOT part of the maintenance therapy for transplant recipients?

IVIG Signup and view all the answers

What is the significance of optimizing the dose of immunosuppressive medication?

To lower the risk of chronic allograft injury. Signup and view all the answers

What distinguishes acute rejection from chronic rejection in kidney transplantation?

Acute rejection happens primarily within the first week to months. Signup and view all the answers

Which of the following statements best describes chronic rejection?

It leads to progressive renal function decline over years. Signup and view all the answers

What is a common consequence of nonadherence to medications after kidney transplantation?

Increased likelihood of acute rejection. Signup and view all the answers

Which type of rejection can occur almost immediately after transplantation, often within minutes to hours?

Hyperacute rejection Signup and view all the answers

Which immunosuppressive therapy is primarily used for T-cell depletion?

Thymocyte globulin Signup and view all the answers

What is a significant characteristic of accelerated rejection?

It often occurs in recipients with previous transplants. Signup and view all the answers

What clinical manifestations are commonly seen in acute rejection episodes?

Anuria, hyperkalemia, and pulmonary edema. Signup and view all the answers

Which of the following is NOT a characteristic effect of chronic rejection?

Rapid development of acute renal failure. Signup and view all the answers

What is a major cause of chronic rejection in transplant patients?

Antibody-mediated rejection Signup and view all the answers

Which patients are considered at high immunological risk of rejection for ATG induction therapy?

Patients with over 80% calculated panel-reactive antibodies Signup and view all the answers

What is a common therapeutic use for basiliximab?

Post-transplant prophylaxis in low and intermediate risk patients Signup and view all the answers

Why might azathioprine be used instead of mycophenolic acids?

Gastrointestinal intolerance to mycophenolic acids Signup and view all the answers

Which drug is known for having a narrow therapeutic index and requires monitoring?

Tacrolimus Signup and view all the answers

What is a significant side effect associated with sirolimus?

Delayed wound healing Signup and view all the answers

What should be available during the administration of basiliximab due to potential adverse reactions?

Medications for hypersensitivity reactions Signup and view all the answers

What condition can chronic rejection lead to in transplant recipients?

Chronic allograft injury Signup and view all the answers

Study Notes

Immunosuppressants Use in Kidney Transplantation

Recipient recognition of the transplanted graft is based on the recipient's reaction to histocompatibility antigens.
Grafts can be recognized as 'self' or 'foreign'.
Immunosuppressive therapy is crucial for preventing rejection.

Histocompatibility Antigens

HLA Class I and HLA Class II are vital cellular components involved in the immune response in the body
HLA Class I antigens are found on virtually all nucleated cells and play a crucial role in displaying peptides derived from intracellular pathogens and in recognizing self-MHC-associated peptides.
HLA Class II antigens are primarily expressed on antigen-presenting cells (APCs), including macrophages, dendritic cells, and B cells.

The Immune Response to Grafts

In a kidney transplant, T cells play a vital role in the process.
After transplantation, the recipient's immune system can recognize the donated kidney as foreign tissue and initiate an attack.
To reduce the risk of rejection or prevent rejection, immunosuppressive drugs, like the ones mentioned in later sections, are prescribed.

Panel-Reactive Antibody (PRA)

This test assesses the recipient's serum against HLA specificities of potential donors.
The percentage of cell reactions determines the recipient's PRA.
A higher PRA (>20%-50%) indicates greater risk of rejection.

Lymphocyte Cross-Match

Cytotoxic and/or flow cytometry cross-matches the recipient's serum to assess preformed antibodies against donor lymphocytes.
A positive cross-match, where recipient cytotoxic IgG antibodies are present, may need to be considered a contraindication for kidney transplantation.

ABO Blood Typing

ABO blood typing is an essential evaluation for organ transplantation, especially for kidneys.
Transplantation with ABO incompatibility usually results in hyperacute rejection of the graft.

Desensitization Strategies

Desensitization strategies aim to reduce HLA antibodies in potential recipients, lessening the risk of a positive crossmatch.
This involves methods like plasmapheresis and rituximab to address existing antibodies.
Such protocols increase the chance of successful transplantations.

Immunosuppressives

Many drugs are used, categorized based on their mechanism of action e.g., antireceptor antibodies, calcineurin inhibitors, and mTOR inhibitors.
These drugs prevent the immune system from rejecting the transplanted kidney.

Drugs that Inhibit T-cell Activation

Several drugs are used to inhibit T-cell activation, preventing the rejection of the transplanted kidney, including Cyclosporine Tacrolimus, Belatacept, Basiliximab, Daclizumab.
These drugs target specific components of the T-cell activation pathway.

T-cell Depleting Drugs

T-cell depleting drugs, such as Muromonab-CD3 and Anti-thymocyte globulin, directly target and eliminate T cells, minimizing the risk of rejection.

Rejection

Rejection episodes can be acute or chronic.
Acute rejection commonly occurs within the first 60 days post transplant
Chronic rejection is a slower process, often spanning several years.
Cellular or antibody-mediated rejection are two major types of rejection.

Hyperacute Rejection

This type of rejection happens within minutes to hours after transplantation.
Improved HLA typing and ABO matching have reduced its occurrence.

Accelerated Rejection

Accelerated rejections can occur primarily in recipients who have undergone prior kidney transplants, multiple pregnancies, or blood transfusions.
This type is often resistant to standard rejection therapies.

Acute Rejection

Acute rejection often arises within the initial week or months after transplantation.
It's often linked to patient noncompliance with medications and monitoring.

Chronic Rejection

Chronic rejection occurs gradually, typically over several years.
It usually leads to gradual decline in renal function and kidney failure.
It can be either cellular- or antibody-mediated.

Chronic Allograft Injury (CAI)

CAI is a diagnosis of exclusion.
It points to a progressive decline in renal function.
It typically involves several factors including previous infection, immunosuppression therapy and nonimmunological factors like hypertension or recipient comorbidities.

Immunosuppressive Therapy

Induction and maintenance therapies are crucial post-transplantation.
Common induction therapies include ATG and Basiliximab.
Common maintenance therapies include calcineurin inhibitors, antimetabolites, and corticosteroids.

Antibody-Mediated Rejection

Plasma exchange, IVIG, Rituximab, and Bortezomib are some of the therapies used for antibody-mediated rejection.
These treatments aim to remove antibodies that target the donor kidney.

T-cell-Mediated Rejection

Methylprednisone is used to treat these cases.
Rabbit antithymocyte globulin is also helpful along certain maintenance therapies.

Chronic Rejection Therapy

Chronic antibody-mediated rejection is treated using therapies that have been used in other antibody-mediated rejection cases.
However, these measures aren't consistently effective.

Therapeutic Use of ATG

ATG is used for induction immunosuppression to reduce transplant rejection risk.
It's highly effective for cases where recipients have a high risk, including repeat transplants.

Basiliximab: Therapeutic Use

Basiliximab is used as prophylaxis post transplant especially in cases where the risk is 'low' and 'intermediate'.

Mycophenolic Acids

Mycophenolic acids are immunosuppressants used in combination with other medications to assist in preventing the rejection of transplanted organs.

Azathioprine: Therapeutic Use

Azathioprine is used in conjunction with other immunomodulatory agents to reduce the risk of rejection in patients with unsuitable mycophenolic acid therapies or pregnancies.

Cyclosporine

Approved for prevention and treatment of solid organ transplant rejection.
Can be used alone or in combination with other immunosuppressants.

Tacrolimus

Tacrolimus immediate-release formulations are widely used for prophylaxis and treatment post-transplant in various solid organ cases when paired with other immunosuppressants.

Sirolimus

Sirolimus has side effects like delayed wound healing and affecting the lipid profile.

Prednisone

Prednisone is used with other immunosuppressive drugs for transplant rejection.

Special Outpatient Medications

Many medications are used to maintain a healthy transplant function and to avoid rejection.
Erythropoiesis stimulating agents, and anti-viral agents are crucial components.

Screening and Graft Monitoring

Routine screening and monitoring is needed after transplantation to detect any signs of dysfunction, and optimize graft health.
This includes various tests that assess kidney function and other relevant factors.

Management of Comorbidities

Managing comorbidities is crucial for kidney transplant recipients.
Special focus on bone disease, hyperuricemia, and infection management to help prevent, monitor, and adjust treatment for potential issues.

Management of Infection

Appropriate treatment methods, such as antiviral drugs and antifungal agents.
Close monitoring for infections is crucial as they could negatively impact the health condition of the patient.

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Description

This quiz explores the role of immunosuppressants in kidney transplantation, focusing on the immune response to grafts and histocompatibility antigens. Understand the significance of HLA Class I and II in preventing rejection of transplanted kidneys and the importance of immunosuppressive therapy for transplant recipients.