Biomarkers of fibrosis, kidney tissue injury and inflammation may predict severity and outcome of renal ANCA – associated vasculitis

Abstract

BackgroundActivity and chronicity of kidney involvement in ANCA-associated vasculitis (AAV) can be currently reliably evaluated only by kidney biopsy. In this study, we measured a panel of serum and urinary biomarkers collected at the time of kidney biopsy and hypothesized that they could reflect specific histopathological parameters in the biopsy and help to predict prognosis.MethodsWe examined a cohort of 45 patients with AAV and 10 healthy controls. Biomarker levels (DKK-3, CD163, EGF, PRO-C6 and C3M) were measured in this study by ELISA. Biopsies were scored with a scoring system for AAV (focal x crescentic x sclerotic x mixed class) and interstitial fibrosis was quantified.ResultsLevels of urinary DKK-3, CD163, EGF, PRO-C6 and C3M significantly differed among biopsy classes in AAV, with urinary DKK-3 and PRO-C6 levels being highest in the sclerotic class and lowest in the focal class, urinary CD163 levels highest in the crescentic class and urinary C3M levels highest in the focal class. Moreover, the urinary biomarkers were able to discriminate focal biopsy class from the other classes. Urinary DKK-3, EGF, PRO-C6 and C3M levels measured at the time of biopsy were also significantly related to the extent of fibrosis and to the final kidney function at the end of follow-up.ConclusionsThis small pilot study suggests that selected urinary biomarkers of fibrosis and inflammation may reflect changes in the kidney biopsy and be prognostic of kidney outcome in patients with AAV.

Urinary Endotrophin and Long-term Outcomes in Kidney Transplant Recipients

“…Outliers were defined as values deviating >2 SD from the mean of the log 2 24-h urinary endotrophin excretion. 27 Furthermore, since urinary endotrophin has been shown to reflect the degree of fibrosis in nontransplant patients with kidney disease, 14,15 we reevaluated the association of 24-h urinary endotrophin excretion with study endpoints after excluding KTR with recurrent kidney disease as the cause of graft failure. Next to that, we repeated the Cox regression analyses with urinary endotrophin concentration and urinary endotrophin concentration indexed for creatinine (urinary endotrophin/creatinine ratio).…”

“…Previously, urinary endotrophin has been shown to reflect the degree of kidney fibrosis in patients with IgA nephropathy and ANCA-associated vasculitis, 14,15 and it can also be used as a prognostic marker to identify patients with a higher risk of worse kidney function. 15,16 Furthermore, urinary endotrophin has also been shown to be associated with disease progression in patients with chronic kidney disease (CKD). 12 In the KTR population, a recent study reported that urinary endotrophin at 3 mo posttransplantation was associated with lower kidney function at 12 mo.…”

Systemic vasculitis: one year in review 2024

“…However, biopsy may not always be feasible or may carry risks. In a pilot study by Satrapova et al urinary levels of five inflammation and kidney fibrosis biomarkers were collected from 45 AAV patients with renal involvement at biopsy (76). DKK-3 and PRO-C6 levels predicted renal fibrosis extent, peaking in the sclerotic class and lowest in the focal class, while C3M was higher in focal classes (76).…”

“…In a pilot study by Satrapova et al urinary levels of five inflammation and kidney fibrosis biomarkers were collected from 45 AAV patients with renal involvement at biopsy (76). DKK-3 and PRO-C6 levels predicted renal fibrosis extent, peaking in the sclerotic class and lowest in the focal class, while C3M was higher in focal classes (76). These biomarkers correlated with renal function at follow-up; higher DKK-3 and PRO-C6 levels were associated with worse renal function, while higher C3M levels correlated with better function.…”

“…Urinary CD163 levels were elevated in all cases of crescentic GN. Combining urinary biomarkers with serum creatinine distinguished biopsy classes with 92.5% accuracy (76). Furthermore, urinary levels of various T cell subpopulations have been examined alongside proteins like MCP-1, CD163, and CD25 to differentiate between active AAV and remission (77).…”