How Do You Assess Graft Function? A Comprehensive Guide to Post-Transplant Monitoring

September 30, 2025 •

5 min read

Approximately 12.5–16.5% of kidney transplant recipients in the United States have required a second transplant due to graft failure, underscoring the critical need for diligent post-operative monitoring. So, how do you assess graft function effectively and proactively following an organ transplant?

Quick Summary

Assessing graft function involves combining routine blood and urine tests, physical examinations, and imaging with invasive and advanced molecular diagnostics like biopsy and dd-cfDNA. Different protocols and monitoring methods are used depending on the specific organ transplanted and the post-operative timeline. Timely and accurate assessment is crucial for detecting rejection, guiding treatment, and ensuring long-term graft survival.

Key Points

Multi-Method Approach: Assessing graft function involves a combination of routine blood tests, imaging, and advanced molecular diagnostics, tailored to the specific organ.
Blood and Urine Tests: Lab work is the most common form of monitoring, tracking key markers like creatinine (kidney), liver enzymes (liver), and blood sugar (pancreas) to spot declines in function.
Biopsy as Gold Standard: Despite its invasive nature, a biopsy remains the most definitive way to diagnose organ rejection and other graft pathologies.
Non-Invasive Diagnostics: Newer technologies like donor-derived cell-free DNA (dd-cfDNA) and molecular profiling offer minimally invasive ways to screen for rejection and organ injury.
Continuous Monitoring: Patients undergo frequent and lifelong surveillance, as clinical signs of rejection are often unreliable and appear too late for effective intervention.
Immunosuppression Balance: Monitoring is crucial for balancing immunosuppressant drug levels—ensuring enough medication to prevent rejection while avoiding toxicity and infection.

The Importance of Graft Function Assessment

After an organ transplant, the recipient's immune system recognizes the new organ, or graft, as foreign and will attempt to attack and reject it. To counteract this, transplant recipients are prescribed immunosuppressive drugs for life. However, balancing the prevention of rejection with minimizing side effects and infection risk requires continuous and meticulous monitoring of the graft's function. Early detection of problems, often before the patient experiences any symptoms, is vital for long-term success. A proactive, multi-faceted approach is the cornerstone of post-transplant care.

Standard Non-Invasive Assessment Methods

Laboratory Blood and Urine Tests

Regular laboratory tests are the most common and frequent method for monitoring graft function. These tests act as an early warning system, though they often only signal a problem after some damage has already occurred.

Blood tests: These typically include comprehensive metabolic panels. For kidney recipients, serum creatinine and blood urea nitrogen (BUN) levels are key indicators, as rising levels can signal declining kidney function. For liver recipients, liver function tests (LFTs), including AST, ALT, bilirubin, and INR, are essential for monitoring performance. Pancreas transplant patients are monitored for blood sugar control.
Urine tests: A urinalysis can detect changes in kidney function and potential infections. In kidney transplant patients, measuring the urinary protein-to-creatinine ratio is a routine practice.
Therapeutic Drug Monitoring: Immunosuppressant drug levels are routinely checked in the blood to ensure they are within a therapeutic range, which helps prevent both rejection and toxicity.
Infection Screening: Because of immunosuppression, patients are monitored for common post-transplant viral infections like BK virus (for kidney transplants), Epstein-Barr virus (EBV), and Cytomegalovirus (CMV).

Imaging Techniques

Non-invasive imaging provides visual information on the graft's anatomy and blood flow.

Doppler Ultrasound: This is a crucial tool for evaluating blood flow in the transplant's arteries and veins. For kidney and liver transplants, it can quickly detect blockages or narrowing (stenosis). It can also identify fluid collections or anatomical abnormalities. For heart transplants, echocardiography assesses heart muscle function and valves.
Computed Tomography (CT) and Magnetic Resonance Imaging (MRI): These provide more detailed anatomical information, especially for complex issues. Their use is often limited by the nephrotoxic nature of contrast agents in CT for kidney patients, though non-contrast imaging is still valuable. Advanced functional MRI techniques are emerging but are largely experimental.
Nuclear Medicine Scintigraphy: This can evaluate perfusion and function, particularly useful for kidneys in the early post-operative period.

Advanced and Invasive Assessment Methods

The Role of Biopsy

Despite advances in non-invasive monitoring, a tissue biopsy remains the gold standard for definitively diagnosing most cases of allograft dysfunction.

Procedure: A small piece of tissue is removed from the graft, typically guided by ultrasound.
Pathology: The sample is examined by a pathologist for histological signs of rejection (e.g., inflammation) or other issues.
Protocol vs. Indication Biopsies: Some centers perform routine surveillance biopsies at set intervals, even without signs of rejection, to catch subclinical issues. More commonly, a biopsy is performed when clinical signs or other tests indicate a problem.

Novel Blood-Based Markers

Newer, less invasive molecular tests are gaining traction to improve monitoring and reduce the need for biopsies.

Donor-Derived Cell-Free DNA (dd-cfDNA): This test measures the percentage of DNA in the recipient's blood that comes from the donor organ. Elevated levels indicate organ injury, which can be caused by rejection. It has a high negative predictive value, making it useful for ruling out rejection.
Gene Expression Profiling: Assays like the Molecular Microscope Diagnostic System (MMDx) analyze gene expression patterns from a biopsy, while others like TruGraf use blood samples to assess for rejection. These help distinguish between different types of rejection and injury.
Urinary Biomarkers: Assays analyzing mRNA from urinary exosomes can help screen for kidney allograft rejection.

Organ-Specific Assessment Considerations

The monitoring protocol is tailored to the specific organ transplanted due to different functions and rejection patterns.

Kidney Graft Assessment

Early Phase (Initial Weeks): Frequent blood tests (creatinine, BUN, eGFR) and physical exams are performed. Doppler ultrasounds are used to ensure proper blood flow. Delayed graft function (DGF) is common, where the kidney is slow to start working, and may require temporary dialysis.
Late Phase (Ongoing): Ongoing monitoring focuses on maintaining stable creatinine and eGFR, checking for proteinuria, and watching for signs of chronic rejection, which may not cause symptoms initially.

Liver Graft Assessment

Early Phase: Blood tests for liver enzymes (ALT, AST), bilirubin, and coagulation factors (INR) are monitored closely. Physical examination looks for signs like jaundice or bleeding.
Late Phase: Regular labs continue. Imaging and biopsy are used to investigate causes of rising liver enzymes, which can include rejection or other complications like biliary issues.

Heart and Lung Graft Assessment

Heart Transplants: Regular echocardiograms and sometimes cardiac biopsies are required, especially in the first few months. Gene expression profiling tests from blood can help reduce the need for invasive biopsies. Signs of rejection can include fatigue, swelling, or shortness of breath.
Lung Transplants: Lung function tests and imaging like chest X-rays or CT scans are used to check for primary graft dysfunction (PGD), which appears as hypoxemia and pulmonary infiltrates. Bronchoscopy with biopsy may be performed to diagnose rejection or infection.

Comparing Assessment Methods


Method	Invasive?	Strengths	Limitations	Applications
Physical Exam	No	Quick, identifies external signs (swelling, tenderness)	Subjective, signs often appear late or are non-specific	Routine, initial screening tool
Blood/Urine Tests	No	Routine, objective, and quantitative	Non-specific indicators, can lag behind actual injury	Frequent surveillance, early screening
Imaging (Ultrasound)	No	Non-invasive, visualizes blood flow, anatomy	Operator-dependent, less sensitive than biopsy for rejection	Routine screening, investigation of specific issues
Donor-Derived cfDNA	Minimally	Non-invasive, sensitive for organ injury	High cost, can be elevated by non-rejection issues (e.g., infection)	For-cause testing, surveillance in higher-risk patients
Biopsy	Yes	Gold standard for definitive diagnosis	Invasive, risks bleeding/infection, sampling error possible	Confirmation of rejection, rule out other causes of dysfunction

Conclusion

Assessing graft function is a multi-layered, lifelong process for organ transplant recipients. It begins with routine monitoring using blood and urine tests, physical exams, and non-invasive imaging. For more definitive diagnosis or in cases where non-invasive tests indicate a potential issue, more advanced methods like dd-cfDNA or a biopsy are utilized. The protocol varies significantly depending on the transplanted organ, but the core principle remains consistent: to proactively detect and address issues like rejection as early as possible. A dedicated, personalized approach to monitoring, guided by the latest diagnostic technologies, is the key to ensuring the long-term health of both the patient and the new graft. Regular follow-up with the transplant team is essential for managing immunosuppression and addressing any issues promptly. Source: The Lancet

Frequently Asked Questions

Graft function refers to how well a transplanted organ is working. After an organ transplant, regular monitoring is necessary to ensure the new organ is healthy and not being damaged by the recipient's immune system or other complications.

Signs of rejection can be non-specific and vary by organ, but often include a decline in the organ's function, a general feeling of being unwell, fever, and flu-like symptoms. For kidneys, decreased urine output and increased creatinine are key indicators.

The frequency of monitoring is highest in the early post-transplant period, sometimes several times a week. Over time, monitoring becomes less frequent but is always lifelong. The exact schedule depends on the patient and the type of organ.

A tissue biopsy involves removing a small sample of the transplanted organ for microscopic analysis. It is considered the 'gold standard' for diagnosing rejection because it provides a definitive diagnosis by revealing what is happening at the cellular level within the graft.

Donor-derived cell-free DNA (dd-cfDNA) is a non-invasive blood test that measures the amount of DNA from the donor organ circulating in the recipient's blood. An increase can signal organ injury, potentially indicating rejection.

No, lab tests are crucial for screening and surveillance but are not specific enough to confirm rejection definitively. They can alert the transplant team to a potential problem, but further investigation, such as a biopsy, is often needed for a definitive diagnosis.

Imaging, such as Doppler ultrasound, is used to check for proper blood flow and identify physical complications like blockages or fluid collections. It provides valuable visual information but is not typically diagnostic for rejection itself.

If a potential problem is found, the transplant team will conduct further tests. If rejection is confirmed, medications are adjusted, often with higher doses or different types of immunosuppressants, to reverse the process and protect the organ.