Abstract / Summary
Abstract Background Tubulointerstitial fibrosis is the principal determinant of long-term kidney graft outcome, but its assessment still relies on allograft biopsy, an invasive procedure subject to sampling variability. Proteinuria is associated with fibrosis but remains non-specific. Complement activation is increasingly implicated in tubular injury, and urinary soluble C5b-9 (sC5b-9) has been proposed as a marker of intrarenal complement activation. Whether it reflects genuine local complement activity or simply tracks proteinuria is unresolved, and data in pediatric transplant recipients are scarce. Methods We conducted a retrospective single-centre study of 31 pediatric kidney transplant recipients undergoing allograft biopsy; C4d-positive biopsies were excluded. Urinary and plasma sC5b-9 were measured by ELISA on first morning voids collected on the day of biopsy and related to proteinuria, estimated glomerular filtration rate (eGFR), interstitial fibrosis and tubular atrophy (IFTA), and intratubular C5b-9 deposition scored blinded to clinical data. Spearman rank correlation was the primary method; discrimination was assessed by ROC analysis and independence from proteinuria by multivariable logistic regression. Results Urinary sC5b-9 was detectable in 61% of patients and correlated with proteinuria (ρ = 0.48, p = 0.007) and with the proportion of tubules bearing C5b-9 deposits (ρ = 0.56, p = 0.001), supporting intratubular complement activation. Urinary sC5b-9 discriminated above-median intratubular C5b-9 deposition better than proteinuria (AUC 0.77 vs 0.54) and remained independently associated with it after adjustment for proteinuria (p = 0.023), improving model fit over proteinuria alone (p = 0.014). Urinary sC5b-9 was unrelated to eGFR and did not differ according to the presence of haematuria. Plasma sC5b-9 remained within normal ranges in all patients. No significant association was observed between urinary sC5b-9 and IFTA. Conclusion Urinary sC5b-9 is associated with proteinuria and intratubular complement activation in pediatric kidney transplant recipients, and provides information beyond proteinuria. With consistently normal plasma levels, these findings support a locally generated, complement-specific signal rather than passive leak of a urinary protein. No prognostic claim can be made from this cross-sectional cohort, in which no association with IFTA was found; longitudinal studies are needed to determine whether urinary sC5b-9 precedes and predicts fibrosis progression.