Renale Anämie bei Kindern

ZUSAMMENFASSUNG

Kinder und Jugendliche sind durch eine Anämie bei chronischen Nierenerkrankungen besonders gefährdet. Eine nicht ausreichende Synthese von Erythropoietin, eine reduzierte Erythrozytenlebensdauer, Eisenmangel und Blutverluste steigern das Risiko einer renalen Anämie mit zunehmendem Grad der chronischen Niereninsuffizienz (CKD). Keiner der bislang verfügbaren diagnostischen Parameter reicht allein aus, um den Eisenstatus des Blutes exakt zu beurteilen. Daher sollte die Diagnose erweitert werden und der Retikulozyten-Hämoglobin-Gehalt bzw. das -Äquivalent (CHr/RET-He) gemessen werden. Die Werte spiegeln die aktuelle Bioverfügbarkeit von Eisen für die Erythropoese wider. Zur Standardbehandlung der renalen Anämie gehören seit wenigen Jahrzehnten die Erythropoese stimulierenden Wirkstoffe (ESAs). Diese Therapie schlägt jedoch nicht immer ausreichend an. Doch es gibt es neue Therapieansätze, die hier vorgestellt werden. Hierbei könnten v. a. die oral verabreichbaren HIF-Stabilisatoren (HIF: Hypoxie induzierbarer Faktor) bald eine vielversprechende Therapiealternative für Kinder bieten.

Publication History

Article published online:
17 December 2020

• Literatur

• 1 Atkinson MA, Martz K, Warady BA. et al Risk for anemia in pediatric chronic kidney disease patients: a report of NAPRTCS. Pediatr Nephrol 2010; 25: 1699-1706
• 2 Staples AO, Wong CS, Smith JM. et al Anemia and risk of hospitalization in pediatric chronic kidney disease. Clin J Am Soc Nephrol 2009; 4: 48-56
• 3 Atkinson MA, Warady BA. Anemia in chronic kidney disease. Pediatr Nephrol 2018; 33: 227-238
• 4 Naito M, Kawashima A, Akiba T. et al Effects of an angiotensin II receptor antagonist and angiotensin converting enzyme inhibitors on burst forming U-erythroid in chronic hemodialysis patients. Am J Nephrol 2003; 23: 287-293
• 5 Warady BA. Chapter 23: Anemia Management. In: Warady BA, Schaefer F, Alexander SR, Hrsg. Pediatric Dialysis Case Studies. A Practical Guide to Patient Care. Heidelberg: Springer; 2017
• 6 Schlieper G, Hess K, Floege J. et al The vulnerable patient with chronic kidney disease. Nephrol Dial Transplant 2015; 31: 382-390
• 7 Mitsnefes MM, Laskin BL, Dahhou M. et al Mortality risk among children initially treated with dialysis for end-stage kidney disease, 1990–2010. JAMA 2013; 8 309 1921-1929
• 8 Furth SL, Cole CR, Fadorowski JJ. et al The association of anemia and hypoalbuminemia with accelerated decline in GFR among adolescents with chronic kidney disease. Pediatr Nephrol 2007; 22: 265-271
• 9 Filler G, Mylrea K, Feber J. et al How to define anemia in children with chronic kidney disease?. Pediatr Nephrol 2007; 22: 702-707
• 10 Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int (2011) 2012; 2: 279-335
• 11 Hayes W. Measurement of iron status in chronic kidney disease Pediatr Nephrol. 2019; 34: 605-613
• 12 Macdougall IC, White C, Anker SD. et al Randomized Trial Comparing Proactive, High-Dose versus Reactive, Low-Dose Intravenous Iron Supplementation in Hemodialysis (PIVOTAL): Study Design and Baseline Data. Am J Nephrol 2018; 48: 260-268
• 13 Ganz T, Nemeth E. Iron sequestration and anemia of inflammation. Semin Hematol 2009; 46: 387-393
• 14 Atkinson M. Part F. Chapter 32: Anemia in chronic kidney disease. In: Kher KK, William HW, Greenbaum LA, eds. Clinical Pediatric Nephrology. 3rd ed. Florida (USA): Apple Academic Press Inc; 2016
• 15 Wish JB. Assessing iron status: beyond serum ferritin and transferin saturation. Clin J Am Soc Nephrol 2006; 1 (Suppl. 01) S4-S8
• 16 Kalantar-Zadeh K, Lee GH. The fascinating but deceptive ferritin: to measure it or not to measure it in chronic kidney disease?. Clin J Am Soc Nephrol 2006; 1 (Suppl. 01) S9-S18
• 17 Atkinson MA, Pierce CB, Fadrowski JJ. et al Association between common iron store markers and hemoglobin in children with chronic kidney disease. Pediatr Nephrol 2012; 27: 2275-2283
• 18 Davidkova S, Prestidge TD, Reed PW. et al Comparison of reticulocyte hemoglobin equivalent with traditional markers of iron and erythropoiesis in pediatric dialysis. Pediatr Nephrol 2016; 31: 819-826
• 19 Lopez-Ruzafa E, Vazquez-Lopez MA, Lendinez-Molinos F. et al Reference values of reticulocyte hemoglobin content and their relation with other indicators of Iron status in healthy children. J Pediatr Hematol Oncol 2016; 38: e207-212
• 20 Teixeira C, Barbot J, Freitas MI. Reference values for reticulocyte parameters and hypochromic RBC in healthy children. Int J Lab Hematol 2015; 37: 626-630
• 21 Thomas L, Thomas C, Heimpel H. Neue Parameter zur Diagnostik von Eisenmangelzuständen. Dtsch Ärztebl 2005; 102: A580-A586
• 22 Billing H, Sauerstein K, Melk A. Therapie der renalen Anämie. In: Schaefer F, Schmitt C, Melk A, Hrsg. SOPs Kinderdialyse: Standard Operating Procedures. 3. Aufl. Auerbach/Vogtland: Wissenschaftliche Scripten; 2018
• 23 Ambarsari CG, Trihono PP, Kadaristiana A. et al Low-Dose Maintenance Intravenous Iron Therapy Can Prevent Anemia in Children with End-Stage Renal Disease Undergoing Chronic Hemodialysis. Int J Nephrol 2020: 3067453
• 24 Coyne D, Kapoian T, Suki W. et al Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: results of the dialysis patients’ response to IV iron with elevated ferritin (DRIVE) study. J Am Soc Nephrol 2007; 18: 975-984
• 25 Fischbach M, Wühl E, Meyer Reigner SC. et al Efficacy and Long-Term Safety of C.E.R.A. Maintenance in Pediatric Hemodialysis Patients with Anemia of CKD. Clin J Am Soc Nephrol 2018; 13: 81-90
• 26 Singh AK, Szczech L, Tang KL. et al Investigators CHOIR Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006; 355: 2085-2098
• 27 Pfeffer MA, Burdmann EA, Chen CY. et al Investigators TREAT. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 2009; 361: 2019-2032
• 28 Tobu M, Iqbal O, Fareed D. et al Erythropoietin-induced thrombosis as a result of increased inflammation and thrombin activatable fibrinolytic inhibitor. Clin Appl Thromb Hemost 2004; 10: 225-232
• 29 Gilbertson DT, Peng Y, Arneson TJ. et al Comparison of methodologies to define hemodialysis patients hyporesponsive to epoetin and impact on counts and characteristics. BMC Nephrol 2013; 20: 14-44
• 30 Borzych-Duzalka D, Bilginer Y, Ha IS. et al Management of anemia in children receiving chronic peritoneal dialysis. J Am Soc Nephrol 2013; 24: 665-676
• 31 Malyszko J, Malyszko JS, Matuszkiewicz-Rowinska J. Hepcidin as a therapeutic target for anemia and inflammation associated with chronic kidney disease. Expert Opin Ther Targets 2019; 23: 407-421
• 32 Gluba-Brzózka A, Franczyk B, Olszewski R. et al The Influence of Inflammation on Anemia in CKD Patients. Int J Mol Sci 2020; 21: 725
• 33 Schmid H, Jelkmann W. Investigational therapies for renal disease-induced anemia. Expert Opin Investig Drugs 2016; 25: 901-916
• 34 Gupta N, Wish JB. Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients with CKD. Am J Kidney Dis 2017; 69: 815-826
• 35 Akizawa T, Macdougall IC, Berns JS. et al Long-Term Efficacy and Safety of Molidustat for Anemia in Chronic Kidney Disease: DIALOGUE Extension Studies. Am J Nephrol 2019; 49: 271-280
• 36 Schmitt CP, Nau B, Brummer C. et al Increased injection pain with darbepoetin-alpha compared to epoetin-beta in paediatric dialysis patients. Nephrol Dial Transplant 2006; 21: 3520-3524
• 37 Shah HH, Hazzan AD, Fishbane S. Ferric pyrophosphate citrate: a novel iron replacement agent in patients undergoing hemodialysis. Semin Nephrol 2016; 36: 124-129
• 38 TRIFERIC Prescribing Information. Wixom, MI: Rockwell Medical, Inc.; 2018
• 39 Fishbane SN, Singh AK, Cournoyer SH. et al Ferric pyrophosphate citrate (Triferic®) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients. Nephrol Dial Transplant 2015; 30: 2019-2026
• 40 Gupta A, Lin V, Guss C. et al Ferric pyrophosphate citrate administered via dialysate reduces erythropoiesis-stimulating agent use and maintains hemoglobin in hemodialysis patients. Kidney Int 2015; 88: 1187-1194
• 41 Pratt RD, Grimsberg S, Zaritsky JJ. et al Pharmacokinetics of ferric pyrophosphate citrate administered via dialysate and intravenously to pediatric patients on chronic hemodialysis. Pediatr Nephrol 2018; 33: 2151-2159
• 42 Yagil Y, Fadem SZ, Kant KS. et al Managing hyperphosphatemia in patients with chronic kidney disease on dialysis with ferric citrate: latest evidence and clinical usefulness. Ther Adv Chronic Dis 2015; 6: 252-263
• 43 Block GA, Fishbane S, Rodriguez M. et al A 12-week, double-blind, placebo-controlled trial of ferric citrate for the treatment of iron deficiency anemia and reduction of serum phosphate in patients with CKD Stages 3–5. Am J Kidney Dis 2015; 65: 728-736
• 44 Lewis JB, Sika M, Koury MJ. et al Ferric citrate controls phosphorus and delivers iron in patients on dialysis. J Am Soc Nephrol 2015; 26: 493-503
• 45 Ye Y, Liu H, Chen Y. et al Hemoglobin targets for the anemia in patients with dialysis-dependent chronic kidney disease: a meta-analysis of randomized, controlled trials. Ren Fail 2018; 40: 671-679