Urinary C5b-9 as a Prognostic Marker in IgA Nephropathy

Abstract

C5b-9 plays an important role in the pathogenesis of immunoglobin A nephropathy (IgAN). We evaluated C5b-9 as a prognostic marker for IgAN. We prospectively enrolled 33 patients with biopsy-proven IgAN. We analyzed the correlation between baseline urinary C5b-9 levels, posttreatment changes in their levels, and clinical outcomes, including changes in proteinuria, estimated glomerular filtration rate (eGFR), and treatment response. Baseline urinary C5b-9 levels were positively correlated with proteinuria (r = 0.548, p = 0.001) at the time of diagnosis. Changes in urinary C5b-9 levels were positively correlated with changes in proteinuria (r = 0.644, p < 0.001) and inversely correlated with changes in eGFR (r = −0.410, p = 0.018) at 6 months after treatment. Changes in urinary C5b-9 levels were positively correlated with time-averaged proteinuria during the follow-up period (r= 0.461, p = 0.007) but were not correlated with the mean annual rate of eGFR decline (r = −0.282, p = 0.112). Baseline urinary C5b-9 levels were not a significant independent factor that could predict the treatment response in logistic regression analyses (odds ratio 0.997; 95% confidence interval, 0.993 to 1.000; p = 0.078). Currently, urinary C5b-9 is not a promising prognostic biomarker for IgAN, and further studies are needed.

Systematic Review of the Link Between Oxford MEST-C Classification and Complement Activation in IgA Nephropathy

“…, 19 2020 C5b9 Canada Pediatric 67 IF 10.9 61 NA NA Yu et al. , 43 2022 C5b9 Korea Adult 33 urine, ELISA 40 52 79.7 ± 22.7 1.0 ± 1.0 Stefan et al. , 44 2020 IgA/C3 ratio Romania Adult 95 serum, turbidmetric 41 70 39.4 (25.2–56.5) 1.7 (0.8–3.0) Karahisar Sirali and Buberci, 45 2022 IgA/C3 ratio Turkey Adult 43 serum, turbidmetric 43 40 77 ± 22.0 NA Pan et al.…”

“…, 34 2019 No relationship with MEST-C classes c Yu et al. , 43 2022 No relationship with MEST-C classes b Stefan et al. , 44 2020 IgA/C3 ratio No relationship with MEST-C classes b Lang et al.…”

Challenges in IgA Nephropathy Management: An Era of Complement Inhibition

“…In terms of the terminal pathway markers, urinary C5b-9 levels have been explored as a prognostic biomarker in IgAN and have been shown to correlate positively with proteinuria. 75 , 80 As a note of caution, increased urinary excretion of complement proteins has been shown to correlate with levels of proteinuria in several kidney disorders and it has been suggested that this might be related to chronic injury and proximal tubule dysfunction as opposed to active glomerular disease 78 , 81 ; therefore, studies to clarify the pathological mechanisms underlying urinary C5b-9 and factor H excretion in IgAN are warranted.…”

Alternative pathway diagnostics

“…50 A similar study demonstrated that uC5b-9 decreased in treated patients, even those with persistent proteinuria, indicating that uC5b-9 was more reflective of immunologic activity than proteinuria. 51 Less is known about the significance of uC5b-9 in other glomerular diseases, but there is evidence that it is a useful biomarker in IgA nephropathy 42,52 and focal segmental glomerulosclerosis. 53 Nevertheless, many questions remain regarding the significance of uC5b-9 levels, the optimal methods of collecting and processing the urine, and whether the results should be corrected using either urine creatinine or an index of glomerular permeability to large proteins (e.g., albumin).…”