[Risk factors for anemia in the early stages of chronic kidney disease]

To identify the early markers of anemia in chronic kidney disease (CKD) in patients with chronic glomerulonephritis (CGN) and glomerulonephritis (GN) in systemic diseases.

Seventy-nine patients with some male preponderance who were aged 21 to 65 years (45.3±11.1 years) and had CKD (CGN and GN) in systemic diseases (systemic lupus erythematosus and Wegener's granulomatosis) in the early stages (Stages I-II) of CKD were examined. GN was diagnosed by a lifetime renal biopsy. Systemic diseases were diagnosed according to the criteria for each nosological entity. The stages of CKD were defined according to the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) criteria; the glomerular filtration rate (GFR) was calculated using the CKD EPI equation (2012). According to the presence or absence of anemia, all the patients included in the study were divided into 2 groups: 1) 43 (54.4%) anemic patients; 2) 36 (45.6%) non-anemic patients (a control group). In addition to general clinical examination adopted for a nephrology department, special studies, such as determination of the serum levels of hepcidin, interferon-γ (IFN-γ), soluble Klotho protein (s-Klotho), as well as iron, ferritin, and transferrin saturation (TSAT) ratio, were performed to solve the set tasks.

Forty-three anemic patients who had a hemoglobin level of 110 (100; 119) g/l and 36 control patients who had the similar values were noted to have statistically significantly (p<0.001) higher levels of IFN-γ (11 (10; 14) and 0.2 (0.09; 0.6) ng/ml), hepcidin (26 (25; 27) and 5.1 (3.8; 5.9) ng/ml) and C-reactive protein (1.5 (1.1; 2.1) and 0.3 (0.2; 0.6) mg/dl), and lower levels of s-Klotho protein (12 (10; 18) pg/ml) and TSAT (18 (14; 19)%. Forty-three patients with anemia were also found to have a statistically significantly (p<0.01) lower GFR (65 (62; 87) and 80.5 (62; 90) ml/min) and higher systolic blood pressure (145 (125; 160) and 120 (115; 16) mm Hg) as compared with those in 36 control patients. At the same time, the compared groups displayed no statistically significant differences in serum ferritin levels (123 (110; 150) and 115 (100; 140) µg/l). Among 43 CKD patients with anemia, its detection rate in the presence of systemic diseases was 3.2 times higher than that in CGN patients (41.7 and 12.7%). ROC analysis revealed that in the CKD patients with CGN and GN, the serum hepcidin level ≥ 25 ng/ml, with the sensitivity and specificity being of 89.7% and 74%, respectively (p > 0.001), was associated with the development of anemia. Moreover, the hemoglobin level of<120 g/ l was found to have an independent impact on the risk of reducing serum s-Klotho production.

In Stage I-II CKD patients with CGN and GN in the presence of systemic diseases, elevated serum hepcidin levels should be regarded as a predictor for anemia of chronic disease (ACD). Herewith, the decrease in hemoglobin levels <120 g/l is associated with the reduced production of the nephroprotective factor s-Klotho. The treatment of ACD for Stages I-II CKD should encompass intravenous administration of iron in order to increase its content and availability for erythropoiesis.