Surreal illustration of a healthy kidney with a glowing complement cascade

Kidney Transplants: New Monitoring Methods Could Improve Detection of Rejection

Beau Callahan in Health & Wellness December 2025 • 4 min read.

"Research shows that monitoring complement activation products in urine may offer insights into antibody-mediated rejection, improving long-term outcomes for kidney transplant recipients."

Kidney transplantation is a life-saving procedure for individuals with end-stage renal disease. However, the success of kidney transplants can be threatened by antibody-mediated rejection (ABMR), a major immunological complication that can lead to graft failure. Early detection of ABMR is crucial for timely intervention and improved long-term outcomes.

A new study published in Molecular Immunology explores the potential of monitoring the complement classical pathway (CP) in kidney transplant recipients to improve the detection of ABMR. The study investigates whether measuring complement activation products in urine and blood can provide an earlier and more accurate indication of ABMR compared to traditional methods.

The research highlights the significance of the complement system, a crucial part of the immune system, in the development of ABMR. Donor-specific antibodies (DSA) activate the classical pathway, leading to inflammation and tissue damage in the transplanted kidney. By monitoring the activity of the CP and the levels of complement proteins, clinicians may be able to identify ABMR earlier and implement appropriate treatment strategies.

Unlocking the Role of Complement Activation in Kidney Transplant Rejection

Surreal illustration of a healthy kidney with a glowing complement cascade

The complement system is a complex network of proteins that plays a vital role in the immune response. It can be activated through different pathways, including the classical pathway, which is triggered by antibodies binding to antigens on cell surfaces. In the context of kidney transplantation, donor-specific antibodies (DSA) can activate the classical pathway, leading to inflammation and damage to the transplanted kidney.

The study focused on monitoring the activity of the classical pathway and measuring the levels of complement proteins in both plasma and urine samples from kidney transplant recipients. The researchers aimed to determine whether these markers could provide an early indication of ABMR and improve the prediction of graft failure.

Complement Proteins: The study measured various complement proteins, including C1q, C3a, SC5b-9, C4d, and C5a, which are involved in different stages of the complement cascade.
Enzyme-Linked Immunosorbent Assay (ELISA): The levels of these complement proteins were measured using ELISA, a highly sensitive and specific technique.
DSA-Positive Patients: The analysis focused on 83 DSA-positive recipients who underwent protocol biopsy and had available data for IgG mean fluorescence intensity (MFI) and complement fixation.

The study found a significant positive correlation between the protein/creatinine ratio and the urinary levels of complement activation products, indicating that monitoring these markers in urine may provide valuable insights into ABMR. However, monitoring the complement classical pathway in blood and urine alone did not demonstrate an independent diagnostic advantage and did not improve the prediction of ABMR when used alone or combined with antibody characteristics. The research team emphasized the importance of detecting increasing complement activation products in urine, especially when associated with a higher protein/creatinine ratio and worsening renal function.

Future Directions in Kidney Transplant Monitoring

While the study did not find a definitive diagnostic advantage in monitoring the complement classical pathway in blood and urine alone, it did highlight the potential of using urinary complement activation products as an indicator of ABMR, especially when combined with other clinical parameters. Further research is needed to validate these findings and explore the optimal strategies for integrating complement monitoring into routine clinical practice. By improving the detection of ABMR, clinicians can intervene earlier and improve long-term outcomes for kidney transplant recipients, ultimately enhancing their quality of life.

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Everything You Need To Know

What is antibody-mediated rejection and why is it a concern in kidney transplants?

Antibody-mediated rejection (ABMR) is a major complication following kidney transplantation where the recipient's immune system attacks the transplanted kidney. This rejection is driven by antibodies, specifically donor-specific antibodies (DSA), which recognize and bind to antigens on the cells of the transplanted kidney. This antibody binding activates the complement system, leading to inflammation and damage to the kidney, potentially resulting in graft failure. Early detection of ABMR is critical to preserve the kidney's function. The process can be identified through monitoring the complement classical pathway.

What is the complement classical pathway, and how does it relate to kidney transplant rejection?

The complement classical pathway (CP) is a part of the immune system that gets activated by antibodies. In kidney transplantation, donor-specific antibodies (DSA) activate the classical pathway, leading to inflammation and damage to the transplanted kidney. Monitoring the activity of the complement classical pathway, by measuring levels of complement proteins like C1q, C3a, SC5b-9, C4d, and C5a may help in early detection of antibody-mediated rejection (ABMR) following kidney transplantation. Identifying this allows for timely intervention and better outcomes for the transplanted kidney.

What are donor-specific antibodies and how do they contribute to rejection after a kidney transplant?

Donor-specific antibodies (DSA) are antibodies produced by the recipient's immune system that target antigens present on the donor kidney. These antibodies play a crucial role in antibody-mediated rejection (ABMR). When DSA bind to the donor kidney, they activate the complement classical pathway (CP), leading to inflammation and tissue damage. The presence and characteristics of DSA, such as their concentration and ability to activate complement, are important factors in assessing the risk of rejection. Monitoring DSA levels and their activity helps clinicians to tailor immunosuppressive strategies and prevent ABMR.

What are complement proteins, and why are they important in monitoring kidney transplant recipients?

Complement proteins, such as C1q, C3a, SC5b-9, C4d, and C5a, are key components of the complement system. These proteins participate in a cascade of events that lead to inflammation and target destruction. In the context of kidney transplantation, measuring these proteins, specifically in urine samples, may offer insights into the presence and activity of antibody-mediated rejection (ABMR). Elevated levels of these proteins indicate that the complement classical pathway (CP) has been activated, suggesting ongoing immune attack on the transplanted kidney.

What is ELISA, and how is it used in monitoring kidney transplant patients?

An Enzyme-Linked Immunosorbent Assay (ELISA) is a highly sensitive and specific laboratory technique used to measure the concentration of proteins in biological samples, such as urine and blood. In kidney transplant monitoring, ELISA is used to quantify the levels of complement proteins, including C1q, C3a, SC5b-9, C4d, and C5a, which are indicators of complement activation. By accurately measuring these proteins, clinicians can gain insights into the activity of the complement classical pathway and identify patients who may be experiencing antibody-mediated rejection (ABMR).