Abstract
BackgroundAnemia status may be transient. Causal associations between changes in anemia status over time and adverse outcome development are not well characterized in community-dwelling subjects at the beginning of impaired kidney function.MethodsThis retrospective cohort study used annual health checkup and medical and pharmacy claims data from the JMDC between January 2005 and June 2019. Community-dwelling subjects in Japan with a pre-index estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 followed by a subsequent eGFR < 60 mL/min/1.73 m2 (index) were included. The composite renal outcome was ≥ 30% eGFR reduction over 3 years from baseline, serum creatinine doubling, progression to chronic dialysis, kidney transplantation, or eGFR < 15 mL/min/1.73 m2. The composite cardiovascular outcome was fatal and non-fatal unstable angina, myocardial infarction, heart failure, or cerebrovascular event. Time-dependent anemia risk was evaluated using Breslow’s estimator and marginal structural Cox models (MSM).ResultsIn 32,870 included subjects, 1,396 had anemia at baseline. Adverse outcome incidence was higher in the baseline anemic group, but absolute differences in renal and cardiovascular outcomes between groups were diminished after adjusting for baseline characteristics. In MSM, time-dependent anemia status was associated with higher risk of renal (hazard ratio [95% confidence interval]; 2.6 [1.7–3.8]) and cardiovascular (1.6 [1.2–2.2]) outcomes and mortality (2.8 [1.8–4.3]). Absolute differences in survival probabilities were retained over time but were clinically marginal (1.1–2.7% over 6 years).ConclusionsEven in subjects at the very early stage of impaired kidney function, early detection and treatment of anemia may help reduce the development of negative sequelae.
Highlights
The prevalence of chronic kidney disease (CKD) in the Japanese adult population is approximately 13%, with most of these individuals in stage 3 [1]
We identified the first consecutive pair of estimated glomerular filtration rate (eGFR) for a subject, within a 2-year timeframe, in which an eGFR ≥ 60 mL/min/1.73 m 2 was followed by an eGFR < 60 mL/min/1.73 m2
Subjects were excluded because they started chronic dialysis before enrollment (n = 2), experienced kidney transplantation before enrollment (n = 2), had eGFR < 6 ml/min/1.73m2 at enrollment (n = 5), or had no serum creatinine (SCr) record within 38 months from the index date (n = 900)
Summary
The prevalence of chronic kidney disease (CKD) in the Japanese adult population is approximately 13%, with most of these individuals in stage 3 [1]. Undertreatment of anemia of CKD, in patients with CV diseases and/or DM, is associated with increased rates of blood transfusions, hospitalization, and death [14,15,16]. Recognition and treatment of anemia of CKD in patients who progress to stage 3 CKD can improve clinical outcomes, including delaying the need for renal replacement therapy [12, 13, 17,18,19]. Causal associations between changes in anemia status over time and adverse outcome development are not well characterized in community-dwelling subjects at the beginning of impaired kidney function. In MSM, time-dependent anemia status was associated with higher risk of renal (hazard ratio [95% confidence interval]; 2.6 [1.7–3.8]) and cardiovascular (1.6 [1.2–2.2]) outcomes and mortality (2.8 [1.8–4.3]). Conclusions Even in subjects at the very early stage of impaired kidney function, early detection and treatment of anemia may help reduce the development of negative sequelae
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