Hepcidin serum levels and resistance to recombinant human erythropoietin therapy in hemodialysis patients
Abstract
1. Introduction
2. Materials and methods
3. Results
4. Discussion
5. Conclusions
Conflict of interest
Authors’ contributions
Acknowledgments
R E F E R E N C E S
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Ferritin (µg/L or ng/mL) | IV iron therapy |
---|---|
<100 | 100–500 mg per day, not exceed 1000 mg. |
Repeat ferritin test one week after the last dose of IV iron, if it is still less 100 mg/L, repeat the same treatment course | |
100–300 | 100 mg of iron per week. Measure ferritin concentration every 3 months |
>300–500 | 100 mg of iron every second week. Measure ferritin concentration every 3 months |
>500 | Suspend IV iron therapy. Measure ferritin concentration after 1–3 months |
Characteristic | Total population (n = 173) | Nonresponders, ERI > 15 (n = 20) | Responders, ERI ≤ 15 (n = 153) | P |
---|---|---|---|---|
Demographic and dialysis-related data | ||||
Age, years | 63.19 ± 15.60 | 62.19 ± 15.73 | 63.5 ± 15.59 | 0.082 |
Males, % | 51.2 | 43.2 | 53.7 | 0.475 |
Time on dialysis, min per week | 682.2 ± 79.66 | 667.50 ± 118.44 | 685.63 ± 67.92 | 0.668 |
UF, kg | 2.17 ± 0.84 | 2.04 ± 0.73 | 2.21 ± 0.87 | 0.404 |
Kt/V (single pool) | 1.42 ± 0.18 | 1.35 ± 0.17 | 1.43 ± 0.17 | 0.039 |
CVC versus fistula, % | 14.3 | 25 | 11.8 | 0.095 |
Diabetic patients, % | 22.2 | 13 | 24.3 | 0.242 |
Malignancy, % | 9.5 | 26.1 | 5.8 | 0.003 |
Treatment characteristics | ||||
ESA dose, IU/week | 6210.59 ± 5276.89 | 14,973.25 ± 4902.54 | 4168.80 ± 2588.68 | <0.001 |
ESA dose, IU/kg/week | 88.65 ± 77.31 | 216.75 ± 72.89 | 58.81 ± 37.74 | <0.001 |
ERI, IU/kg/week per 100 mL | 12.29 ± 10.9 | 23.9 ± 8.9 | 5.4 ± 3.6 | 0.001 |
Cardiovascular parameters | ||||
Systolic blood pressure, mmHg | 140.1 ± 17.06 | 141.10 ± 11.09 | 139.13 ± 17.65 | 0.617 |
Diastolic blood pressure, mmHg | 76.34 ± 11.02 | 77.25 ± 10.18 | 75.05 ± 11.17 | 0.399 |
LVMM, g | 260.36 ± 92.19 | 239.40 ± 50.37 | 264.47 ± 98.19 | 0.461 |
LVMI, g/m2 | 143.28 ± 51.57 | 141.51 ± 29.36 | 143.62 ± 55.11 | 0.912 |
LVEF, % | 49.60 ± 9.16 | 51.79 ± 9.58 | 49.16 ± 9.06 | 0.194 |
No. of antihypertensive medications | 2.09 ± 1.71 | 2.13 ± 1.56 | 2.08 ± 1.75 | 0.901 |
Prescription of RAS inhibitors, % | 48.2 | 53.8 | 47.1 | 0.657 |
Hematological data | ||||
Erythrocytes, ×1012/L | 3.31 ± 0.32 | 3.0 ± 0.38 | 3.37 ± 0.28 | <0.001 |
Hemoglobin, g/L | 98.8 ± 9.8 | 91.1 ± 9.8 | 103.9 ± 5.5 | <0.001 |
Hematocrit, % | 30.32 ± 3.23 | 28.24 ± 2.72 | 32.01 ± 2.92 | <0.001 |
MCV, fL | 94.86 ± 5.71 | 95.6 ± 5.9 | 94.34 ± 5.6 | 0.479 |
MCH, pg | 30.87 ± 2.2 | 31.11 ± 2.27 | 30.70 ± 2.21 | 0.556 |
Platelets, ×109/L | 223.66 ± 94.06 | 235.43 ± 81.82 | 220.95 ± 96.83 | 0.23 |
Iron metabolism | ||||
Cumulative iron dose, mg per year | 2668.04 ± 1300.69 | 3560.00 ± 1576.98 | 2504.88 ± 1183.62 | 0.003 |
Ferritin, µg/L | 283.1 ± 139.8 | 318.87 ± 168.8 | 260.16 ± 114.98 | 0.206 |
Hepcidin-25, ng/mL | 135.79 ± 115.52 | 158.51 ± 162.57 | 120.65 ± 67.28 | 0.33 |
Inflammatory and nutritional status | ||||
Body mass index, kg/m2 | 26.53 ± 6.37 | 24.83 ± 4.89 | 26.93 ± 6.62 | 0.067 |
Albumin, g/L | 36.39 ± 4.13 | 33.91 ± 4.12 | 37.98 ± 3.33 | 0.001 |
Protein, g/L | 66.10 ± 4.25 | 64.64 ± 5.19 | 66.44 ± 3.97 | 0.13 |
CRP, mg/L | 18.17 ± 21.67 | 27.16 ± 29.24 | 12.39 ± 12.50 | 0.048 |
Cholesterol, mmol/L | 4.89 ± 1.12 | 4.78 ± 1.17 | 4.95 ± 1.10 | 0.638 |
Calcium-phosphorus metabolism | ||||
Phosphorus, mmol/L | 1.78 ± 0.38 | 1.82 ± 0.41 | 1.76 ± 0.38 | 0.64 |
Calcium, mmol/L | 2.26 ± 0.17 | 2.29 ± 0.13 | 2.22 ± 0.22 | 0.27 |
PTH, pmol/L | 29.22 ± 25.67 | 25.44 ± 22.93 | 31.65 ± 27.41 | 0.412 |
Hepatic enzymes | ||||
AST, U/L | 20.15 ± 10.38 | 20.31 ± 11.96 | 20.12 ± 10.06 | 0.982 |
ALT, U/L | 19.89 ± 12.40 | 19.51 ± 12.16 | 19.99 ± 12.51 | 0.77 |
Alkaline phosphatase, U/L | 97.08 ± 55.85 | 93.32 ± 43.99 | 97.94 ± 58.39 | 0.647 |
Hospitalization | ||||
Hospitalization rate per year | 1.53 ± 1.5 | 2.35 ± 1.8 | 1.04 ± 1.04 | 0.011 |
Mean length of one hospitalization | 16.22 ± 19.90 | 25.12 ± 21.26 | 10.82 ± 17.25 | 0.012 |
Values are mean ± SD, unless otherwise stated. | ||||
UF, ultrafiltration; CVC, central venous catheter; LVMM, left ventricular myocardium mass; LVMI, left ventricular mass index; LVEF, left ventricular ejection fraction; RAS, rennin angiotensin aldosterone system; CRP, C-reactive protein; PTH, parathyroid hormone; AST, asparatate aminotransferase; ALT, alanine aminotransferase. |
Parameter | r | P | Unstandardized B coefficient (95% CI) |
---|---|---|---|
Demographic and dialysis-related data | |||
Age, years | −0.061 | 0.495 | |
Time on dialysis, min per week | −0.067 | 0.451 | |
Kt/V (single pool) | −0.048 | 0.598 | |
UF, kg | −0.102 | 0.284 | |
Hematological data | |||
Erythrocytes, ×1012/L | −0.444 | <0.001 | −12.84 (−16.98;−8.701) |
Hematocrit, % | −0.537 | <0.001 | −1.29 (−1.704;−0.876) |
Platelets, ×109/L | −0.031 | 0.732 | |
Iron metabolism | |||
MCV, fl | 0.028 | 0.779 | |
MCH, pg | −0.102 | 0.303 | |
Ferritin, µg/L | 0.057 | 0.524 | |
Hepcidin, ng/mL | 0.349 | 0.017 | 0.032 (0.006;0.059) |
Cumulative iron dose, mg per year | 0.1 | 0.442 | |
Inflammatory and nutritional status | |||
Body mass index, kg/m2 | −0.344 | <0.001 | −0.368 (−0.598;−0.137) |
CRP, mg/L | 0.217 | 0.015 | 0.148 (0.083;0.213) |
Protein, g/L | −0.09 | 0.32 | −0.640 (−0.994;−0.286) |
Albumin, g/L | −0.181 | 0.044 | |
Cholesterol, mmol/L | −0.04 | 0.661 | |
Calcium-phosphorus metabolism | |||
Calcium, mmol/L | −0.026 | 0.776 | |
Phosphorus, mmol/L | 0.144 | 0.109 | |
PTH, pmol/L | −0.077 | 0.398 | |
Hepatic enzymes | |||
AST, U/L | −0.067 | 0.461 | |
ALT, U/L | −0.06 | 0.508 | |
Alkaline phosphatase, U/L | −0.057 | 0.42 | |
Hospitalization | |||
Hospitalization rate per year | 0.459 | <0.001 | 3.725 (2.73;4.74) |
Mean length of one hospitalization | 0.406 | <0.001 | 0.25 (0.173;0.327) |
UF, ultrafiltration; CRP, C-reactive protein; PTH, parathyroid hormone; AST, aspartate aminotransferase; ALT, alanine aminotransferase. |
Independent variables | Unstandardized B coefficient (95% CI) | Standardized B coefficient | P |
---|---|---|---|
CRP | 0.078 (0.021;0.134) | 0.198 | 0.007 |
Albumin | −0.436 (−0.73;−0.142) | −0.209 | 0.004 |
Body mass index | −0.374 (−0.553;−0.195) | −0.28 | <0.001 |
Hospitalization rate per year | 3.017 (2.077;3.957) | 0.446 | <0.001 |
Constant | 30.959 (18.099;43.818) | <0.001 | |
r2 = 0.46. |
Variable | r | P | Unstandardized B coefficient (95% CI) |
---|---|---|---|
Hematological data | |||
Hemoglobin | −0.4 | 0.013 | −3.404 (−5.554;−1.255) |
Hematocrit | −0.382 | 0.008 | −11.976 (−18.945;−5.008) |
Erythrocytes | −0.3 | 0.041 | −78.895 (−136.14;−21.647) |
Platelets | 0.015 | 0.921 | |
MCV | 0.036 | 0.816 | |
MCH | 0.084 | 0.587 | |
EAS therapy | |||
ESA dose, IU/week | 0.4 | 0.008 | 0.006 (0.002;0.011) |
ERI, IU/kg/week per 100 mL | 0.349 | 0.017 | 3.756 (0.691;6.821) |
Iron metabolism | |||
Ferritin | 0.5 | <0.001 | 0.334 (0.212;0.457) |
TSAT | −0.43 | 0.025 | −4.642 (−9.101;−0.183) |
Cumulative iron dose, mg per month | −0.096 | 0.485 | |
Inflammatory and nutritional status | |||
Body mass index, kg/m2 | 0.11 | 0.25 | |
Albumin | −0.4 | 0.013 | −8.34 (−14.846;−1.833) |
Protein | 0.097 | 0.51 | |
Cholesterol | −0.11 | 0.607 | |
CRP | 0.213 | 0.15 | |
Calcium-phosphorus metabolism | |||
Calcium | −0.179 | 0.223 | |
Calcium corrected | 0.147 | 0.138 | |
Phosphorus | −0.138 | 0.351 | |
CaxP | −0.24 | 0.1 | |
PTH | 0.113 | 0.444 | |
Hepatic enzymes | |||
AST | 0.118 | 0.261 | |
ALT | 0.14 | 0.18 | |
Alkaline phosphatase | −0.034 | 0.745 | |
ESAs, erythropoiesis-stimulating agents; ERI, ESA resistance index; TSAT, transferrin saturation; CRP, C-reactive protein; PTH, parathyroid hormone; AST, aspartate aminotransferase; ALT, alanine aminotransferase. |
Independent variables | Unstandardized B coefficient (95% CI) | Standardized B coefficient | P |
---|---|---|---|
ERI, IU/kg/week per 100 mL | 4.869 (1.844;7.895) | 0.439 | 0.002 |
Ferritin | 0.242 (0.086;0.399) | 0.422 | 0.003 |
r2 = 0.64. |
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Petrulienė, K.; Žiginskienė, E.; Kuzminskis, V.; Nedzelskienė, I.; Bumblytė, I.A. Hepcidin serum levels and resistance to recombinant human erythropoietin therapy in hemodialysis patients. Medicina 2017, 53, 90-100. https://doi.org/10.1016/j.medici.2017.03.001
Petrulienė K, Žiginskienė E, Kuzminskis V, Nedzelskienė I, Bumblytė IA. Hepcidin serum levels and resistance to recombinant human erythropoietin therapy in hemodialysis patients. Medicina. 2017; 53(2):90-100. https://doi.org/10.1016/j.medici.2017.03.001
Chicago/Turabian StylePetrulienė, Kristina, Edita Žiginskienė, Vytautas Kuzminskis, Irena Nedzelskienė, and Inga Arūnė Bumblytė. 2017. "Hepcidin serum levels and resistance to recombinant human erythropoietin therapy in hemodialysis patients" Medicina 53, no. 2: 90-100. https://doi.org/10.1016/j.medici.2017.03.001
APA StylePetrulienė, K., Žiginskienė, E., Kuzminskis, V., Nedzelskienė, I., & Bumblytė, I. A. (2017). Hepcidin serum levels and resistance to recombinant human erythropoietin therapy in hemodialysis patients. Medicina, 53(2), 90-100. https://doi.org/10.1016/j.medici.2017.03.001