Die Anämie bei einer chronischen Funktionseinschränkung der Niere ist multifaktoriell
bedingt. Der Erythropoetinmangel ist im Zentrum der Aufmerksamkeit und der Therapie.
Man muss aber die begleitenden Faktoren berücksichtigen. Ansonsten ist die EPO-Therapie
unwirksam. Häufig wird die renale Anämie von Eisenmangel, Eisenverwertungsstörungen
bei akuten oder chronischen Entzündungszuständen, sekundärem Hyperparathyreoidismus
und weiteren, seltenen Faktoren begleitet. Diese Komponenten muss man bei einem fehlenden
Ansprechen der renalen Anämie auf EPO-Gaben analysieren. Eine EPO-Hyporesponse ist
definiert als ein fehlendes Ansprechen über 4–6 Monate nach der Substitution von mehr
als 300 IE EPO pro kg Körpergewicht pro Woche. Die Differenzialdiagnose der EPO-Hyporesponse
und die Abklärung können schematisiert erfolgen. Unter einer danach erfolgenden gezielten
Behandlung ist die Substitution im Regelfall effektiv.
The causes of anemia in chronic renal failure are multiple. The deficiency of erthyropoetine
is in the centre of the awareness of the caregivers. However, the accompanying factors
also have to be put into account. Otherwise, failure of EPO therapy is the result.
Renal anemia often is combined with iron deficiencies, iron achrestic pictures seen
with acute or chronic inflammations, secondary hyperparathyreoidism and more, rare
factors. These components have to be analyzed if failure of EPO therapy is diagnosed.
The definition of EPO hyporesponse is as following: not reaching target hemoglobin
levels after the use of more than 300 IU EPO per kg bodyweight per week for 4–6 months.
The work-up of the differential diagnosis can be following a flow-sheet. With target-aimed
therapy, EPO becomes effective again.
Key words
erythropoetin - kidney - anemia - dialysis - iron deficiency - hyperparathyreoidism
- infection - inflammation
Literatur
1
Bradbury BD, Danese MD, Gleeson M, Critchlow CW..
Effect of Epoetin alfa dose changes on hemoglobin and mortality in hemodialysis patients
with hemoglobin levels persistently below 11 g/dL.
Clin J Am Soc Nephrol.
2009;
4
630-637
2
Zhang Y, Thamer M, Stefanik K et al..
Epoetin requirements predict mortality in hemodialysis patients.
Am J Kidney Dis.
2004;
44
866-876
3
Kausz AT, Solid C, Pereira BJ et al..
Intractable anemia among hemodialysis patients: a sign of suboptimal management or
a marker of disease?.
Am J Kidney Dis.
2005;
45
136-147
4
IV. NKF-K/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease:
update 2000.
Am J Kidney Dis.
2001;
37
182-238
5
Drueke TB, Locatelli F, Clyne N et al..
Normalization of hemoglobin level in patients with chronic kidney disease and anemia.
N Engl J Med.
2006;
355
2071-2084
6
Locatelli F, Aljama P, Barany P et al..
Revised European best practice guidelines for the management of anaemia in patients
with chronic renal failure.
Nephrol Dial Transplant.
2004;
19
(S 02)
1-47
7
Hutchinson FN, Jones WJ..
A cost-effectiveness analysis of anemia screening before erythropoietin in patients
with end-stage renal disease.
Am J Kidney Dis.
1997;
29
651-657
8
Loge JP, Lange RD, Moore CV..
Characterization of the anemia associated with chronic renal insufficiency.
Am J Med.
1958;
24
4-18
9
Silverberg DS, Iaina A, Peer G et al..
Intravenous iron supplementation for the treatment of the anemia of moderate to severe
chronic renal failure patients not receiving dialysis.
Am J Kidney Dis.
1996;
27
234-238
10
Erslev AJ, Besarab A..
Erythropoietin in the pathogenesis and treatment of the anemia of chronic renal failure.
Kidney Int.
1997;
51
622-630
11
Eschbach JW..
Iron requirements in erythropoietin therapy.
Best Pract Res Clin Haematol.
2005;
18
347-361
12
Fernandez-Rodriguez AM, Guindeo-Casasus MC, Molero-Labarta T, Dominguez-Cabrera C,
Hortal-Casc L n, Perez-Borges P, Vega-Diaz N, Saavedra-Santana P, Palop-Cubillo L..
Diagnosis of iron deficiency in chronic renal failure.
Am J Kidney Dis.
1999;
34
508-513
13
Kaufman JS, Reda DJ, Fye CL et al..
Diagnostic value of iron indices in hemodialysis patients receiving epoetin.
Kidney Int.
2001;
60
300-308
14
Danielson B..
R-HuEPO hyporesponsiveness -- who and why?.
Nephrol Dial Transplant.
1995;
10
(S 02)
69-73
15
Drueke TB..
R-HuEPO hyporesponsiveness -- who and why?.
Nephrol Dial Transplant.
1995;
10
(S 02)
62-68
16
Goicoechea M, Martin J, de Sequera P et al..
Role of cytokines in the response to erythropoietin in hemodialysis patients.
Kidney Int.
1998;
54
1337-1343
17
Gunnell J, Yeun JY, Depner TA, Kaysen GA..
Acute-phase response predicts erythropoietin resistance in hemodialysis and peritoneal
dialysis patients.
Am J Kidney Dis.
1999;
33
63-72
18
Lopez-Gomez JM, Perez-Flores I, Jofre R et al..
Presence of a failed kidney transplant in patients who are on hemodialysis is associated
with chronic inflammatory state and erythropoietin resistance.
J Am Soc Nephrol.
2004;
15
2494-2501
19
Alscher DM, Mettang T..
Procalcitonin in peritoneal dialysis--a useful marker of inflammation?.
Perit Dial Int.
2005;
25
441-444
20
Roberts TL, Obrador GT, St WL Peter et al..
Relationship among catheter insertions, vascular access infections, and anemia management
in hemodialysis patients.
Kidney Int.
2004;
66
2429-2436
21
Rao DS, Shih MS, Mohini R..
Effect of serum parathyroid hormone and bone marrow fibrosis on the response to erythropoietin
in uremia.
N Engl J Med.
1993;
328
171-175
22
Klemm A, Sperschneider H, Lauterbach H, Stein G..
Is folate and vitamin B12 supplementation necessary in chronic hemodialysis patients
with EPO treatment?.
Clin Nephrol.
1994;
42
343-345
23
Zachee P, Chew SL, Daelemans R, Lins RL..
Erythropoietin resistance due to vitamin B12 deficiency. Case report and retrospective
analysis of B12 levels after erythropoietin treatment.
Am J Nephrol.
1992;
12
188-191
24
Casadevall N, Dupuy E, Molho-Sabatier P et al..
Autoantibodies against erythropoietin in a patient with pure red-cell aplasia.
N Engl J Med.
1996;
334
630-633
25
Casadevall N, Nataf J, Viron B et al..
Pure red-cell aplasia and antierythropoietin antibodies in patients treated with recombinant
erythropoietin.
N Engl J Med.
2002;
346
469-475
26
McKoy JM, Stonecash RE, Cournoyer D et al..
Epoetin-associated pure red cell aplasia: past, present, and future considerations.
Transfusion.
2008;
48
1754-1762
27
Macdougall IC, Rossert J, Casadevall N et al..
A peptide-based erythropoietin-receptor agonist for pure red-cell aplasia.
N Engl J Med.
2009;
361
1848-1855
28
Tomson CR, Edmunds ME, Chambers K et al..
Effect of recombinant human erythropoietin on erythropoiesis in homozygous sickle-cell
anaemia and renal failure.
Nephrol Dial Transplant.
1992;
7
817-821
29
Griffing GT, Melby JC..
Enalapril (MK-421) and the white cell count and haematocrit.
Lancet.
1982;
1
1361
30
Fyhrquist F, Karppinen K, Honkanen T et al..
High serum erythropoietin levels are normalized during treatment of congestive heart
failure with enalapril.
J Intern Med.
1989;
226
257-260
31
Kamper AL, Nielsen OJ..
Effect of enalapril on haemoglobin and serum erythropoietin in patients with chronic
nephropathy.
Scand J Clin Lab Invest.
1990;
50
611-618
32
Kaiser L, Schwartz KA..
Aluminum-induced anemia.
Am J Kidney Dis.
1985;
6
348-352
33
Ifudu O, Feldman J, Friedman EA..
The intensity of hemodialysis and the response to erythropoietin in patients with
end-stage renal disease.
N Engl J Med.
1996;
334
420-425
34
Movilli E, Cancarini GC, Zani R et al..
Adequacy of dialysis reduces the doses of recombinant erythropoietin independently
from the use of biocompatible membranes in haemodialysis patients.
Nephrol Dial Transplant.
2001;
16
111-114
35
Locatelli F, Andrulli S, Pecchini F et al..
Effect of high-flux dialysis on the anaemia of haemodialysis patients.
Nephrol Dial Transplant.
2000;
15
1399-1409
36
Richardson D, Lindley EJ, Bartlett C, Will EJ..
A randomized, controlled study of the consequences of hemodialysis membrane composition
on erythropoietic response.
Am J Kidney Dis.
2003;
42
551-560
37
Opatrny Jr. K, Reischig T, Vienken J et al..
Does treatment modality have an impact on anemia in patients with chronic renal failure?
Effect of low- and high-flux biocompatible dialysis.
Artif Organs.
2002;
26
181-188
38
Locatelli F, Andrulli S, Memoli B et al..
Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis
patients.
Nephrol Dial Transplant.
2006;
21
991-998
39
Hurot JM, Cucherat M, Haugh M, Fouque D..
Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic
review.
J Am Soc Nephrol.
2002;
13
708-714
40
Priyadarshi A, Shapiro JI..
Erythropoietin resistance in the treatment of the anemia of chronic renal failure.
Semin Dial.
2006;
19
273-278
Korrespondenz
Prof. Dr. Mark Dominik Alscher
Abteilung für Allgemeine Innere Medizin und Nephrologie Zentrum für Innere Medizin
Robert-Bosch-Krankenhaus
Auerbachstraße 110
70376 Stuttgart
Email: dominik.alscher@rbk.de