Complement Markers in Blood and Urine: No Diagnostic Value in Late Silent Antibody-Mediated Rejection
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Cross-sectional study of complement markers for diagnosing antibody-mediated kidney rejection; a clinical diagnostic question.
It evaluates diagnostic markers for kidney-transplant rejection, not research itself.
Diagnostic value of complement markers in kidney transplant rejection; clinical nephrology.
Abstract
Background. Antibody-mediated rejection (AMR) is a major cause of kidney allograft failure. Its molecular mechanisms are multifaceted and may include a role of complement activation via the classical pathway. Here, we investigated whether noninvasive complement monitoring adds predictive power to the diagnosis of AMR in the setting of donor-specific antibody (DSA) positivity. Methods. In this cross-sectional study, 741 kidney transplant recipients with stable graft function ≥180 days posttransplantation were screened for the presence of human leukocyte antigen (HLA) alloantibodies. Eighty-three of 111 DSA-positive recipients underwent protocol biopsies and were tested for blood and urinary levels of complement proteins (C1q, C4, C3) and activation products (C4d, C3a, C5a, C5b-9). Results. Forty-seven recipients were diagnosed with AMR, and 21 were C4d-positive. While biopsy-confirmed AMR (and C4d) associated with DSA-binding strength (IgG mean fluorescence intensity of the immunodominant DSA versus AMR; area under the receiver operating characteristic curve: 0.76), tested complement markers did not have any predictive value for rejection (area under the receiver operating characteristic curve: 0.49–0.56). There were, however, tight correlations between complement activation products in urine and protein/creatinine ratio ( ρ = 0.44–0.64; P < 0.001). Analysis of death-censored graft survival over a median of 60 months revealed no independent associations with levels of complement markers in blood or urine. Conclusions. Complement patterns in blood and urine failed to identify AMR in late biopsies and may have no relevant diagnostic value in this particular context.
Stored with the screening record, where it is evidence for the labels above.
The record
- Venue
- Transplantation Direct
- Topic
- Renal Transplantation Outcomes and Treatments
- Field
- Medicine
- Canadian institutions
- The Metabolomics Innovation CentreUniversity of Alberta
- Funders
- Nemzeti Kutatási Fejlesztési és Innovációs HivatalAustrian Science FundSemmelweis EgyetemEmberi Eroforrások MinisztériumaFonds National de la Recherche Luxembourg
- Keywords
- MedicineReceiver operating characteristicComplement systemContext (archaeology)AntibodyArea under the curveAlternative complement pathwayDonor specific antibodiesHuman leukocyte antigenUrineRenal functionCreatinineUrinary systemInternal medicineImmunologyGastroenterologyAntigenBiology
- Has abstract in OpenAlex
- yes