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Persistent C4d and antibody‐mediated rejection in pediatric renal transplant patients
Authors:Andrew M. South  Lynn Maestretti  Neeraja Kambham  Paul C. Grimm  Abanti Chaudhuri
Affiliation:1. Section of Nephrology, Department of Pediatrics, Wake Forest School of Medicine, Winston Salem, NC, USA;2. Cardiovascular Sciences Center, Wake Forest School of Medicine, Winston Salem, NC, USA;3. Pediatric Renal Transplant Program, Lucile Packard Children's Hospital at Stanford, Stanford, CA, USA;4. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA;5. Division of Nephrology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA
Abstract:Pediatric renal transplant recipient survival continues to improve, but ABMR remains a significant contributor to graft loss. ABMR prognostic factors to guide treatment are lacking. C4d staining on biopsies, diagnostic of ABMR, is associated with graft failure. Persistent C4d+ on follow‐up biopsies has unknown significance, but could be associated with worse outcomes. We evaluated a retrospective cohort of 17 pediatric renal transplant patients diagnosed with ABMR. Primary outcome at 12 months was a composite of ≥50% reduction in eGFR, transplant glomerulopathy, or graft failure. Secondary outcome was the UPCR at 12 months. We used logistic and linear regression modeling to determine whether persistent C4d+ on follow‐up biopsy was associated with the outcomes. Forty‐one percent reached the primary outcome at 12 months. Persistent C4d+ on follow‐up biopsy occurred in 41% and was not significantly associated with the primary outcome, but was significantly associated with the secondary outcome (estimate 0.22, 95% CI 0.19‐0.25, < .001), after controlling for confounding factors. Persistent C4d+ on follow‐up biopsies was associated with a higher UPCR at 12 months. Patients who remain C4d+ on follow‐up biopsy may benefit from more aggressive or prolonged ABMR treatment.
Keywords:C1q  donor‐specific antibody  graft failure  humoral rejection  proteinuria  transplant glomerulopathy
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