Ebbestad R., Sanaei Nurmi M., Lundberg S.: Long-Term Outcomes of Patients with IgA Nephropathy Categorized by the International IgAN Risk Prediction Tool and by the Degree of Hematuria at Diagnosis. Nephron DOI 10.1159/000525001
Accurate and reproducible prediction of the long-term (5–10 years) outcomes in individuals or groups of patients with biopsy-proven IgA nephropathy (IgAN) is a very desirable goal. Such prediction helps in treatment decisions and the design of interventional trials. Several well-validated prediction tools are now available, but few have incorporated hematuria as a controlling (or controllable) prognostic variable.
Ebbestad and co-workers attempt to fill this “gap” in a small cohort (n = 95) of Swedish patients with IgAN and a median follow-up of 12.5 years. Particular attention was placed on baseline hematuria defined as >10 erythrocytes per high-power field or a urine dipstick for hemoglobin of 2–3+. No attempt was made to quantify the severity of hematuria at baseline or during follow-up. The primary outcome metric was a 50% or greater decline in eGFR from baseline or ESKD, similar to that used in the IgA Risk Prediction Tool (IgAN-RPT), which was also used in this study.
In total, 2% of the cohort reached the endpoint. 77 of 95 patients had hematuria assessed at baseline. The 5-year risk quartiles were 0.95%, 2.6%, 5.9%, and 23.3%. Very-low and very-high risk primary outcome thresholds were defined as <4% and >11% at 5 years. High prevalence of hematuria (positive tests) was numerically associated with an increased risk of the primary outcome (8.8% vs. 5.7% at 5 years, increasing to 26.2% vs. 6.3% with continued follow-up). However, likely due to the small size of the cohort, these differences were not statistically significant. Unfortunately, the hematuria evaluation at baseline was nonquantitative, and no follow-up observations were made. Treatment with immunosuppression did not differentiate between the low- and high-risk groups, suggesting overtreatment of the low-risk group.
This study is largely confirmatory and not sufficiently powered to examine the influence of hematuria on outcome. Other uncontrolled studies have strongly suggested an adverse effect of continued high-grade hematuria on outcome, independent of other risk biomarkers. Very clearly, the variable of hematuria in risk prediction deserves further study. Standardization of methods to detect and quantify hematuria are greatly needed to foster incorporation of quantitative hematuria assessment into ongoing and future interventional trials of novel agents in IgAN.