Predictive Value of Urinary Inflammatory Biomarkers for IgAN

An increase in urinary protein concentration is the only clinical urinary biomarker for immunoglobulin A nephropathy (IgAN). Because definitive biomarkers remain elusive, Soo-Young Yoon and others conducted a study with the goal of verifying the predictive value of urinary inflammatory biomarkers at the time of biopsy, as well as the predictive value of noninvasive cytokine biomarkers. Their results were published in BMC Nephrology.

The study enrolled 320 patients, of whom 191 were diagnosed with biopsy-proven IgAN; 53 were disease controls with minimal change disease, membranous glomerulonephri­tis, and focal segmental glomerulosclerosis; and 76 were healthy controls. Median patient age was 41.5 ± 15.9 years, and 47.2% were male.

The researchers utilized a multiplex enzyme-linked immunosorbent assay to measure 16 selected urinary inflammatory cytokines, then evaluated the correlation between clinical and pathological features following regression analysis on progression.

The IgAN group demonstrated significantly different levels of urinary cytokines versus the disease control and healthy control groups. Urinary levels of the following significantly correlated with both the estimated glomerular filtration rate and urine protein-to-creatinine ratio: B-cell–activating factor, vascular endothelial growth factor receptor-2, monocyte chemoattractant protein-1, C–X–C motif chemokine 10, C–X–C motif ligand 16, epidermal growth factor (EGF), endocan, endostatin, growth/differentiation factor-15 (GDF-15), interleukin-6 (IL-6), mannose-binding lectin, transferrin receptor, and kidney injury molecule-1.

In addition, a multivariate Cox regression analysis found that urinary EGF (hazard ratio [HR], 0.40; 95% CI, 0.17-0.95; P=.04), GDF-15 (HR, 2.45; 95% CI, 1.01-5.94; P=.048), and IL-6 (HR, 3.02; 95% CI, 1.05-8.64; P=.04) were associated with IgAN progression.

The authors acknowledged that the number of participants in the study was small, requiring that results be validated in a large-scale cohort. They suggested that repeated long-term follow-up studies could yield more clinically meaningful outcomes. Considering the long prognosis of IgAN, a 1-year follow-up period may be insufficient for assessing chronic kidney disease progression. The authors acknowledged a few other limitations to the study as well.

In sum, urinary inflammatory biomarkers may be considered as alternative predictive biomarkers in patients with IgAN. “The urinary inflammatory biomarkers in the IgAN group were dysregulated compared with those in the disease control and healthy control groups. Specific urinary cytokines, such as GDF-15, IL-6, and EGF, significantly strengthened the predictability of IgAN prognosis. These candidates, as early prognostic biomarker candidates, may assist in the formulation of therapeutic strategies for patients with IgAN,” the researchers concluded.

Source: BMC Nephrology