Effect of atorvastatin on iron metabolism regulation in patients with chronic kidney disease – a randomized double blind crossover study

Figures & data

Figure 1. Study design.

Table 1. Baseline clinical and biochemical characteristics of the study group.

	Mean ± SD	Median [IQR]	Range
Age (years)	57 ± 10	59 [15.7]	33–70
BMI (kg/m^2)	25.9 ± 4.5	25.4 [5.9]	17.8–34.8
Creatinine (mg/dl)	2.8 ± 0.8	2.3 [0.2]	1.41–3.87
Estimated GFR (ml/min/1.73 m^3)^a	22.7 ± 9.4	17.4 [13.1]	15.3–47.3
Hemoglobin (g/dl)	11.6 ± 1.6	11.5 [2.5]	9.1–14.7
Total cholesterol (mg/dl)	232.9 ± 47.6	225 [50]	154–367
HDL-cholesterol (mg/dl)	56.9 ± 16.7	56 [28.2]	32–89
LDL-cholesterol (mg/dl)	146 ± 29	146 [28.3]	72–201
Triglycerides (mg/dl)	170 ± 60	163 [46.7]	68–297
Uric acid (mg/dl)	7.5 ± 1.2	7.4 [2.1]	5–9.7
Total protein (g/l)	61.5 ± 8.7	63.9 [13.2]	50.2–75.4
Albumin (g/l)	37.8 ± 6.8	37.7 [9.3]	26.1–54.9
Iron (μg/dl)	69.1 ± 19.4	67 [31.5]	37–99
Ferritin (ng/ml)	177 ± 22.8	173 [19]	151–252
UIBC (μg/dl)	187 ± 49	195 [61]	64–296
TSAT (%)	25.3 ± 4.8	24 [5.7]	20–39
TIBC (μg/dl)	255 ± 43	262 [57]	131–335
Serum CRP (mg/l)	5.1 ± 2.9	4.7 [4.0]	0.27–9.87
AspAT (U/L)	25.4 ± 10.9	24.5 [10.7]	9–59
AlAT (U/L)	29.4 ± 12.4	31 [17]	12–34
Serum hepcidin (pg/ml)	244 ± 334	102 [307]	22.3–546.8
Serum hemojuvelin (ng/ml)	36.7 ± 14.3	37.6 [14.3]	14.9–80.3
Serum IL-6 (pg/ml)	15.1 ± 16.5	8.7 [12.0]	0.23–40.75

Results are expressed as mean ± SD [median (IQR)].

^aeGFR: estimated glomerular filtration rates – calculated using the MDRD abbreviated formula; UIBC: unsaturated iron binding capacity; TSAT: transferrin saturation; TIBC: total iron binding capacity; CRP: C-reactive protein; AspAT: aspartate aminotransferases; AlAT: alanine aminotransferases; IL-6: interleukin-6.

Table 2. Hematological and inflammatory parameters and kidney function during the study.

	Before statin	After statin	Δ after–before statin 95% CI	p Value	Before placebo	After placebo	Δ after–before placebo 95% Cl	p Value	Δ Statin/placebo 95% CI	Statin/placebo therapy p value
Hemoglobin (g/dl)	11.6 ± 1.6	11.9 ± 1.5	0.24 ± 0.44 (95% CI: 0.1–0.4)	.002	11.7 ± 1.3	11.8 ± 1.3	0.18 ± 0.89 (95% CI: –0.12 to 0.48)	.2	0.06 ± 0.9 (95% CI: –0.24 to 0.36)	.7
Iron (μg/dl)	67 [31.5]	68 [30.7]	3.2 ± 12.4 (95% CI: –0.9 to 7.3)	.2	68.5 [23.5]	67 [18]	2.7 ± 22.5 (95% CI: –4.8 to 10.2)	.9	0 ± 9.2 (95% CI: –3.09 to 3.09)	.4
Ferritin (ng/ml)	173 [19]	140 [65]	–3.19 ± 77.2 (95% CI: –29.1 to 22.7)	.06	163 [19]	157 [51]	–2.5 ± 50.3 (95% CI: 19.4–14.4)	.7	–0.68 ± 64.3 (95% CI: 22.3–20.9)	.2
UIBC (μg/dl)	187 ± 49	198 ± 50	11.3 ± 28.2 (95% CI: 1.9–20.7)	.02	205 ± 53	201 ± 44	–4.1 ± 39.2 (95% CI: –17.2 to 9)	.5	15.3 ± 47.9 (95% CI: –0.8 to 31.4)	.07
TSAT (%)	24 [5.7]	25.5 [6.7]	0.14 ± 5.6 (95% CI: –1.66 to 1.94)	.6	25 [7.5]	25 [5.7]	0.4 ± 4.6 (95% CI: –1.14 to 1.94)	.8	0.3 ± 7.4 (95% CI: –2.1 to 2.7)	.9
TIBC (μg/dl)	267 [57]	272 [96]	13.1 ± 26.1 (95% CI: 4.4–21.8)	.04	272 ± 49	270 ± 44	–1.6 ± 32.5 (95% CI –12.5 to 9.3)	.7	14.8 ± 44.7 (95% Cl 0.2–29.8)	.8
Hepcidin (pg/ml)	102 [307]	63 [170]	–85 ± 188.7 (95% Cl –148.4 to 21.6)	>.001	173 [256]	153 [204]	–21.1 ± 137.6 (95% Cl 67.3–25.1)	.9	–63.9 ± 171.8 (95% Cl 121.6–6.2)	.005
Hemojuvelin (ng/ml)	37.6 [14.3]	40.1 [10.6]	0.7 ± 10.8 (95% Cl –2.9 to 4.3)	.8	35.5 ± 10.5	35.4 ± 10.1	–1.2 ± 7.1 (95% Cl 1.1–5.9)	.3	1.95 ± 13.2 (95% Cl –2.4 to 6.3)	.4
RDW (%)	14.6 ± 1.3	14.3 ± 1.3	–0.35 ± 1.3 (95% Cl –0.75 to 0.05)	.6	14.3 [1.4]]	14.2 [1.7]	0.06 ± 1.1 (95% Cl –0.3 to 0.42)	.8	–0.4 ± 1.7 (95% Cl –0.9 to 0.1)	.8
MCH (pg)	27.9 [1.1]	28.6 [1.0]	0.4 ± 0.8 (95% Cl 0.14–0.66)	.01	28.5 [1.1]	28.4 [1.0]	0.16 ± 1 (95% Cl –0.14 to 0.46)	.5	0.22 ± 1.2 (95% Cl –0.18 to 0.62)	.2
MCHC (g/dl)	32.7 ± 1.5	33.1 ± 1.5	0.3 ± 1 (95% Cl 0–0.6)	.04	33.0 [3.2]	33.2 [3.2]	–0.2 ± 1.2 (95% Cl –0.6 to 0.2)	.4	0.5 ± 1.5 (95% Cl 0–1.0)	.08
hsCRP (mg/l)	4.7 [4.0]	4.0 [3.6]	–0.5 ± 1.5 (95% Cl 1.0–0)	.4	4.5 ± 2.3	4.5 ± 1.8	0.01 ± 0.9 (95% Cl 0.29–0.31)	.9	–0.5 ± 1.7 (95% Cl 1.0–0)	.06
IL-6 (pg/ml)	8.7 [12.0]	8.1 [13.9]	2.6 ± 7.4 (95% Cl 0.2–5.0)	.04	7.4 [9.4]	6.3 [6.6]	–2.5 ± 8.9 (95% Cl –5.4 to 0.4)	.4	–0.1 ± 5.5 (95% Cl 1.9–1.7)	.9
eGFR (ml/min/1.73 m^3)	17.4 [13.1]	17.3 [10.8]	–1.6 ± 3.7 (95% Cl –2.8 to 0.6)	.05	17.8 [11.2]	17.4 [9.2]	–0.9 ± 1.8 (95% Cl –1.5 to –0.3)	.03	0.7 ± 3.9 (95% Cl –0.6 to 2.0)	.5

Results are expressed as mean ± SD in the case of non-normally distributed variables or [median (IQR)] in the case of non-normally distributed variables.

eGFR: estimated glomerular filtration rates – calculated using the MDRD abbreviated formula; UIBC: unsaturated iron binding capacity; TSAT: transferrin saturation; TIBC: total iron binding capacity; IL-6: interleukin-6.

Figure 2. Changes of UIBC, TIBC, hepcidin, hemoglobin, MCHC, and IL-6 after placebo and atorvastatin treatment.

Table 3. Serum concentration of cholesterol, HDL, LDL, triglycerides, uric acid, as well as aspartate and alanine aminotransferase during the study.

	Before statin	After statin	Δ after–before statin 95% CI	p Value	Before placebo	After placebo	Δ after–before placebo 95% CI	p Value	Δ Statin/placebo 95% CI	Statin/placebo therapy p value
Total cholesterol (mg/dl)	225.5 [50]	195 [41]	–34.0 ± 32.8 (95% CI –45 to –23)	<.001	218 [55]	212 [49]	–5.3 ± 24.1 (95% CI –13.4 to 2.8)	.9	–28.6 ± 37.8 (95% CI –41.3 to –15.9)	<.001
HDL-cholesterol (mg/dl)	56.9 ± 16.7	63.7 ± 17.9	6.7 ± 12.5 (95% CI 2.5–10.9)	.003	56 [27]	56 [31.3]	0.6 ± 10.8 (95% CI –3.0 to 4.2	.8	6.1 ± 13.3 (95% CI 1.7–10.5)	.04
LDL-cholesterol (mg/dl)	146 ± 28	107 ± 26	–38.4 ± 29.1 (95% CI –48.2 to –28.6)	<.001	146 [24]	144 [40]	–5.2 ± 20.2 (95% CI –11.9 to 1.5)	.9	–32.3 ± 31.0 (95% CI –42.7 to –21.9)	<.001
Triglyceride (mg/dl)	165 [36]	145 [43]	–23.8 ± 36.9 (95% CI 36.2 to –11.4)	.02	154 [25]	149 [31]	–5.3 ± 17.8 (95% CI –11.2 to 0.6)	.03	–18.5 ± 36.9 (95% CI –30.8 to –6.1)	.01
Uric acid (mg/dl)	7.5 ± 1.3	7.1 ± 1.2	–0.4 ± 0.9 (95% CI –0.7 to 0.1)	.01	7.2 ± 1.4	7.1 ± 1.2	–0.2 ± 0.8 (95% CI –0.4 to 0)	.1	–0.2 ± 1.2 (95% CI –0.6 to 1.0)	.3
AspAT (U/L)	24.5 [10.7]	28 [11.7]	4.5 ± 11.8 (95% CI 2.1–6.9)	.003	21 [6.7]	21 [9]	1.1 ± 5.1 (95% CI –0.6 to 2.8)	.1	3.4 ± 13.5 (95% CI –1.1 to 7.9)	.3
AlAT (U/L)	29.4 ± 12.5	32.3 ± 12.5	2.1 ± 7.8 (95% CI –0.5 to 4.7)	.04	26.1 ± 8.9	27.1 ± 9.4	0,8 ± 2.7 (95% CI –0.1 to 1.7)	.09	–2.9 ± 9.2 (95% CI –5.9 to 0.1)	.2

Results are expressed as mean ± SD in the case of non-normally distributed variables or [median (IQR)] in the case of non-normally distributed variables.

AspAT: aspartate aminotransferase; AlAT: alanine aminotransferase.