Long-Term Outcomes of Patients with IgA Nephropathy Categorized by the International IgAN Risk Prediction Tool and by the Degree of Hematuria at Diagnosis

Abstract

Introduction: Within 30 years, 20-50% of IgA nephropathy (IgAN) patients progress to end-stage kidney disease (ESKD). Identifying these patients can be difficult since renal function may deteriorate after being stable for years. The International IgAN Risk Prediction tool (IgAN-RPT) combines histologic lesions and clinical risk factors to predict renal outcome up to 5 or 7 years of follow-up. The clinical value beyond 7 years is unknown and microhematuria data has not been assessed.

Methods: We studied the long-term renal outcome of 95 Swedish IgAN patients from the derivation cohort for the IgAN-RPT. The median follow-up was 11.2 years. Microhematuria at baseline was defined as high-degree by microscopy measurement of >10 red blood cell/high-power field of view or urine dipstick grading of 2-3. Primary outcome was defined as a 50% decrease in estimated glomerular filtration rate or ESKD.

Results: The mean predicted 5-year risk for increasing quartiles was 0.95%, 2.57%, 5.88%, and 23.31% and the observed 5-year-outcome was 0%, 0%, 0%, and 33.33%. During continued follow-up, 0%, 4.2%, 21.7%, and 75.0% of patients reached the primary outcome. ROC curve analysis identified the 5-year risk thresholds of under 4% and over 11% for very low and very high-risk patients, respectively. High-degree microhematuria was not significantly associated with renal outcome (p = 0.14).

Conclusions: The IgAN-RPT identifies long-term high- and low-risk patients, which can guide decisions on the frequency of clinical control visits and the selection of patients for clinical trials. Patients with intermediate risk remain a clinical challenge with an urgent need for novel biomarkers and treatments. Microhematuria could be a valuable marker of inflammatory activity, but measurement needs to be standardized for implementation in risk prediction tools.

Keywords: Hematuria; IgA nephropathy; Prediction model; Prognosis; Progression.

Fig. 1

Comparison of renal survival by risk of renal outcome. The graph illustrates the renal survival with regards to the outcome comparing patients in different quartiles of risk for the outcome. Risk quartiles were determined using the full model with race from the International Risk Prediction tool [19]. Survival curves were created using Kaplan-Meier estimation. The p value was obtained through log-rank test.

Fig. 2

ROC curve for the IgAN-RPTs prediction of the renal outcome. The graph illustrates time-independent ROC curve analyses using the predicted 5-year risk as the discriminatory variable and the outcome recorded at 7-year, 10-year, and full-length follow-up as stated in respective graph.

Fig. 3

Comparison of renal survival by degree of microhematuria. The graph illustrates the renal survival with regards to the outcome comparing patients with high-degree microhematuria and low-degree microhematuria. Survival curves were created using Kaplan-Meier estimation. The p value was obtained through log-rank test. The gray zone adjacent to the survival curves indicate the 95% confidence interval.

Fig. 4

Comparison of renal survival by history of macrohematuria. The graph illustrates the renal survival with regards to the outcome comparing patients with and without a history of macrohematuria. Survival curves were created using Kaplan-Meier estimation. The p value was obtained through log-rank test. The gray zone adjacent to the survival curves indicate the 95% confidence interval.