Anemia of Renal Tubular Damage and Mortality in the General Population: The Yamagata (Takahata) study

Objective Anemia is reportedly associated with all-cause mortality in elderly individuals. Kidney dysfunction is a major cause of anemia in the elderly. Kidney dysfunction is characterized by glomerular and renal tubular damage (RTD). We aimed to examine the association between RTD and anemia, and the impact of anemia on all-cause mortality in the general population. Methods This prospective cohort study included 3,464 participants aged ≥ 40 years who participated in a community-based health checkup. The estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and urinary β2-microglobulin to creatinine ratio (UBCR) were measured. The primary endpoint was all-cause mortality rate. Results The prevalence of anemia, but not albuminuria, increased with a reduced eGFR and advanced RTD (UBCR ≥ 300 μg/gCr). A multivariate logistic analysis demonstrated that UBCR was significantly associated with the presence of anemia in the general population, but not with eGFR or UACR. RTD anemia was defined as comorbid anemia and RTD. Anemia in the RTD group showed a lower eGFR and higher brain natriuretic peptide and heart-type fatty acid-binding protein levels than those without. During the median follow-up period of 6,794 days, 772 all-cause deaths occurred. Univariate and multivariate Cox proportional hazards regression analyses demonstrated that anemia of the RTD was independently associated with all-cause mortality in the general population. Anemia of the RTD significantly improved the C-statistic with a significant net reclassification index and integrated discrimination improvement. Conclusion RTD was closely associated with anemia. RTD anemia could be a novel risk factor for all-cause mortality in the general population.