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Background Previous studies highlighted the utility of individual urinary biomarkers in the prediction of interstitial fibrosis in IgA Nephropathy patients. However, it´s uncertain which biomarker or combination of biomarkers provides a more accurate estimation of renal interstitial fibrosis Surface. Herein, we measured the urinary excretion of a set of seven tubular injury biomarkers in a group of patients with primary IgA Nephropathy and analyzed their utility as non-invasive estimators of interstitial fibrosis area found on kidney biopsy. Methods Two hundred forty-seven adults with primary IgA Nephropathy diagnosed by kidney biopsy and a control group of 50 healthy control were included. The urinary excretion of EGF, MCP-1, NGAL, KIM-1, L-FABP, β2-microglobulin and DKK-3 was measured in urine samples collected at the day of the renal biopsy. Estimated glomerular filtration rate was measured by the CKD-EPI formula. Interstitial fibrosis area was quantified using a quantitative morphometric procedure and graded according to Oxford Classification. Predictive multivariate models were developed to predict the interstitial fibrosis surface. Results Patients with primary IgA Nephropathy showed significantly higher urinary levels of DKK-3, L-FABP and β2-microglobulin, and lower EGF levels than healthy controls. Interstitial fibrosis was negatively correlated with urinary EGF levels and positively with age, proteinuria, eGFR and urinary DKK-3, L-FABP and β2-microglobulin. The best model to predict interstitial fibrosis area accounted for > 60% of its variability and included age, eGFR, proteinuria, DKK-3, EGF, L-FABP and β2-microglobulin. Conclusions Our study provides a model to estimate the IFS in IgA Nephropathy which could be useful to monitor the progression of chronic kidney injury.

ABSTRACT Background In anti-phospholipase A2 receptor (PLA2R) membranous nephropathy (MN) there is controversy whether spontaneous remission (SR) can be predicted using a single titre or by assessing the dynamic changes in anti-PLA2R antibody (ab) titres. The study objective was to identify the optimal dynamics of anti-PLA2Rab titres to predict SR in MN. Methods A total of 127 nephrotic patients with anti-PLA2R-MN were prospectively followed up for 6 months under conservative treatment. Anti-PLA2Rabs and proteinuria were assessed at diagnosis and monthly thereafter. The primary endpoint (PEP) was a reduction of proteinuria ≥50% at 6 months. Logistic models with baseline and evolutive anti-PLA2Rab titres were developed to predict the PEP. Results A total of 28 patients (22%) reached the PEP. These patients were more frequently female and had significantly lower baseline proteinuria and anti-PLA2Rab titres. An anti-PLA2R titre ≤97.5 RU/mL at diagnosis had a sensitivity of 71% and a specificity of 81% to predict the PEP. The model including baseline anti-PLA2Rabs and a reduction ≥15% at 3 months predicted the PEP with a sensitivity of 93% and a specificity of 80%, with an area under the curve that was significantly greater than that obtained with relative changes of proteinuria in the same period of time {odds ratio [OR] 0.95 [95% confidence interval (CI) 0.91–0.98 versus OR 0.79 [95% CI 0.70–0.88], respectively; P = 0.0013}. Conclusions Combining the baseline anti-PLA2Rab titres with their relative changes at 3 months after diagnosis gives the earliest prediction for achieving a reduction of urinary protein excretion ≥50% at 6 months in MN, thereby shortening the observation period currently recommended to make individualized decisions to start immunosuppressive therapy. Graphical Abstract Graphical Abstract