Abstract
Background and Aims
Anemia is a well-know complication of Chronic Kidney Disease (CKD) and it seems to contribute for deterioration of kidney function. Experimental data suggest that anemia produces hypoxia of tubular cells which leads to tubulointerstitial damage resulting on CKD progression. Other mechanism described is that red blood cells have antioxidant properties that prevent the damage of tubulointerstitial cells and glomerulosclerosis from oxidative stress. There aren’t many observational studies that evaluated the association between anemia and progression of CKD. Therefore, our aim was to evaluate the association of anemia and CKD progression and its association outcomes in an outpatient ND-CKD population.
Method
We conduct a retrospective, patient-level, cohort analysis of all adult ND-CKD patients evaluated in an outpatient nephrology clinic over a 6 years period. The follow up time was at least 12 months. Anemia was defined according to the WHO definition (hemoglobin [hb] < 13.0 g/dL in men and 12.0 g/dL in women). Progression of CKD was defined by one of the following criteria: decline in eGFR (CKD-EPI) superior to 5 ml/min/1.73 m2/year; duplication of serum creatinine or the need renal replacement therapy. Demographics and clinical data were also accessed.
Results
Out of 3008 patients referred to the nephrology clinic, 49.9% had anemia (mean age 71.9±15.9 years; 50.4% male; 92% white; mean follow-up time of 2.3±1.2 years). The mean Hb was 11.8 ±1.9 g/dL. Important cardiovascular comorbidities in patients with anemia were arterial hypertension (86.7%), obesity (65.5%), Diabetes Mellitus (DM) (52%) and dyslipidemia (46%). In univariate analysis, mortality was associated with anemia (36.9 vs 13.0%, p<0.001), obesity (30.1 vs 21.8%, p<0.001) and DM (30.1 vs 21.1%, p<0.001). Of the patients with anemia, 738 met the criteria for CKD progression. In univariate analysis, CKD progression was associated with anemia (49.6 vs 43.9%, p=0.002), male gender (49.5 vs 43.6% p= 0.001); DM (49.6 vs 44.8 % p=0.009) and hypertension (47.9 vs 42.3% p=0.0018). In multivariate logistic regression analysis, anemia emerged was an independent predictor of CKD progression (OR 1.435, CI 95% 1.21-1.71, p<0,001). Comparing hb values intervals (hb ≤10g/dl; hb10-12 g/dL; hb ≥12 g/dL), in the multivariate logistic regression analysis, hb ≤10g/dl was not associated with CKD progression and hb value between 10-12 g/dL was associated (OR 1,486, CI 95% 1.23-1.80, p<0,001), when compared with the group with hb ≥12g/dL. In multivariate logistic regression analysis, the independent predictors of mortality were: older age (OR per 1 year increase: 1.048, 95% CI 95% 1.04-1.06, p<0.001); arterial hypertension (OR 0.699 CI 95% 0.51-0.96, p=0.0029); obesity (OR 0.741, CI 95% 0.60-0.91, p=0.004) and hb value (OR per 1 g/dL decrease: 1.301, CI 95% 1.23-1.38, p<0.001). Cardiovascular events were correlated with Hb levels between 10-12 g/dL (univariate analysis: OR 2.021, CI 95% 1.27-3.22, P=0.003), but not with the group with hb≤10 g/dL (univariate analysis: OR 1.837, CI 95% 0.96-3.51, P=0.066), having the group with hb ≥12g/dL was reference. Anemia was strongly associated with hospitalizations (multivariate logistic regression analysis: OR per 1 g/dL of Hb decrease: 1.256 CI 95% 1.12-1.32 p<0.001), and this strong association was also observed on the groups with hb hb≤10 g/dL (multivariate logistic regression analysis: OR 3.591 CI 95% 32.67-4.84 p<0.001) and between 10-12 g/dL (multivariate logistic regression analysis: OR 1.678 CI 95% 1.40-2.02, p<0.001)
Conclusion
Our study suggests that anemia, at first consultation, increases the risk for rapid CKD progression and global mortality. This study could guide us on the development of futures studies in order to prove if anemia correction can slow the progression of CKD.
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