Hematuria as a risk factor for progression of chronic kidney disease and death: findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

Abstract

Background: Hematuria is associated with chronic kidney disease (CKD), but has rarely been examined as a risk factor for CKD progression. We explored whether individuals with hematuria had worse outcomes compared to those without hematuria in the CRIC Study.

Methods: Participants were a racially and ethnically diverse group of adults (21 to 74 years), with moderate CKD. Presence of hematuria (positive dipstick) from a single urine sample was the primary predictor. Outcomes included a 50% or greater reduction in eGFR from baseline, ESRD, and death, over a median follow-up of 7.3 years, analyzed using Cox Proportional Hazards models. Net reclassification indices (NRI) and C statistics were calculated to evaluate their predictive performance.

Results: Hematuria was observed in 1145 (29%) of a total of 3272 participants at baseline. Individuals with hematuria were more likely to be Hispanic (22% vs. 9.5%, respectively), have diabetes (56% vs. 48%), lower mean eGFR (40.2 vs. 45.3 ml/min/1.73 m2), and higher levels of urinary albumin > 1.0 g/day (36% vs. 10%). In multivariable-adjusted analysis, individuals with hematuria had a greater risk for all outcomes during the first 2 years of follow-up: Halving of eGFR or ESRD (HR Year 1: 1.68, Year 2: 1.36), ESRD (Year 1: 1.71, Year 2: 1.39) and death (Year 1:1.92, Year 2: 1.77), and these associations were attenuated, thereafter. Based on NRIs and C-statistics, no clear improvement in the ability to improve prediction of study outcomes was observed when hematuria was included in multivariable models.

Conclusion: In a large adult cohort with CKD, hematuria was associated with a significantly higher risk of CKD progression and death in the first 2 years of follow-up but did not improve risk prediction.

Keywords: CKD; CKD progression; ESRD; Epidemiology; Hematuria; Mortality; Risk factors.

Fig. 1

Time-varying Hazard Ratios for CKD progression and death for participants with hematuria compared to those without hematuria. Solid lines indicate the time-varying Hazard Ratios for participants with hematuria compared to those without hematuria for each of the three studied outcomes (Halving of eGFR or ESRD, ESRD, and death). Dashed lines indicate 95% confidence intervals. The natural logarithm of analysis time using restricted cubic splines transformation with 3 knots and its interaction with hematuria was applied to all models above. Model for Halving of eGFR/ESRD was adjusted for age, race, sex, education, eGFR, albuminuria, diabetes, systolic blood pressure, BMI, BNP, HbA1c, FGF23, albumin. Model for ESRD was adjusted for age, race, sex, education, eGFR, albuminuria, diabetes, systolic blood pressure, BMI, BNP, FGF23, serum albumin, high-sensitivity CRP. Model for Death was adjusted for age, race, sex, education, eGFR, albuminuria, diabetes, systolic blood pressure, ankle-brachial index, smoking, history of cardiovascular disease, BNP, troponinT, calcium, FGF23, high-sensitivity CRP