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Erschienen in: Pediatric Nephrology 10/2014

01.10.2014 | Original Article

Association of higher erythropoiesis stimulating agent dose and mortality in children on dialysis

verfasst von: Rachel M. Lestz, Barbara A. Fivush, Meredith A. Atkinson

Erschienen in: Pediatric Nephrology | Ausgabe 10/2014

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Abstract

Background

Higher doses of erythropoiesis-stimulating agents (ESA) have been associated with an increased risk of adverse outcomes in adults with chronic kidney disease (CKD) and end-stage kidney disease (ESRD), but to our knowledge no trials have been performed in children. We examined the association between ESA dose and all-cause mortality in a prevalent pediatric dialysis population.

Methods

Retrospective cohort study utilizing national data on all prevalent dialysis patients aged <18 years from the Centers for Medicare and Medicaid Services’ 2005 ESRD Clinical Performance Measures (CPM) project, linked to 18-month mortality records from the United States Renal Data System. Multivariate Cox proportional hazards regression was performed to determine the risk of mortality by mean weekly ESA dose.

Results

Eight-hundred and twenty-nine children were included in the analysis; 7 % died during follow-up. A higher proportion of patients receiving ESA doses in the highest category (erythropoietin ≥350 units/kg/week or darbepoetin ≥1.5 units/kg/week) died (50 % vs 28 %, p = 0.002), and also demonstrated a trend toward lower hemoglobin (11.0 vs 11.4 g/dL, p = 0.05). In multivariate analysis, patients receiving the highest dose of ESA demonstrated an increased risk of mortality (hazard ratio 3.37; p value <0.01).

Conclusion

Higher ESA dose is independently associated with mortality in children on chronic dialysis.
Literatur
1.
Zurück zum Zitat Amaral S, Hwang W, Fivush B, Neu A, Frankenfield D, Furth S (2006) Association of mortality and hospitalization with achievement of adult hemoglobin targets in adolescents maintained on hemodialysis. J Am Soc Nephrol 17:2878–2885PubMedCrossRef Amaral S, Hwang W, Fivush B, Neu A, Frankenfield D, Furth S (2006) Association of mortality and hospitalization with achievement of adult hemoglobin targets in adolescents maintained on hemodialysis. J Am Soc Nephrol 17:2878–2885PubMedCrossRef
2.
Zurück zum Zitat Borzych-Duzalka D, Bilginer Y, Ha IS, Bak M, Rees L, Cano F, Munarriz RL, Chua A, Pesle S, Emre S, Urzykowska A, Quiroz L, Ruscasso JD, White C, Pape L, Ramela V, Printza N, Vogel A, Kuzmanovska D, Simkova E, Muller-Weifel DE, Sander A, Warady BA, Schaefer F (2013) Management of anemia in children receiving chronic peritoneal dialysis. J Am Soc Nephrol 24:665–676PubMedCrossRefPubMedCentral Borzych-Duzalka D, Bilginer Y, Ha IS, Bak M, Rees L, Cano F, Munarriz RL, Chua A, Pesle S, Emre S, Urzykowska A, Quiroz L, Ruscasso JD, White C, Pape L, Ramela V, Printza N, Vogel A, Kuzmanovska D, Simkova E, Muller-Weifel DE, Sander A, Warady BA, Schaefer F (2013) Management of anemia in children receiving chronic peritoneal dialysis. J Am Soc Nephrol 24:665–676PubMedCrossRefPubMedCentral
3.
Zurück zum Zitat Collins AJ, Ma JZ, Ebben J (2000) Impact of hematocrit on morbidity and mortality. Semin Nephrol 20:345–349PubMed Collins AJ, Ma JZ, Ebben J (2000) Impact of hematocrit on morbidity and mortality. Semin Nephrol 20:345–349PubMed
4.
Zurück zum Zitat Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A, CREATE Investigators (2006) Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 355:2071–2084PubMedCrossRef Drueke TB, Locatelli F, Clyne N, Eckardt KU, Macdougall IC, Tsakiris D, Burger HU, Scherhag A, CREATE Investigators (2006) Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 355:2071–2084PubMedCrossRef
5.
Zurück zum Zitat Foley RN, Parfrey PS, Morgan J, Barre PE, Campbell P, Cartier P, Coyle D, Fine A, Handa P, Kingma I, Lau CY, Levin A, Mendelssohn D, Muirhead N, Murphy B, Plante RK, Posen G, Wells GA (2000) Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy. Kidney Int 58:1325–1335PubMedCrossRef Foley RN, Parfrey PS, Morgan J, Barre PE, Campbell P, Cartier P, Coyle D, Fine A, Handa P, Kingma I, Lau CY, Levin A, Mendelssohn D, Muirhead N, Murphy B, Plante RK, Posen G, Wells GA (2000) Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy. Kidney Int 58:1325–1335PubMedCrossRef
6.
Zurück zum Zitat Furuland H, Linde T, Ahlmen J, Christensson A, Strombom U, Danielson BG (2003) A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients. Nephrol Dial Transplant 18:353–361PubMedCrossRef Furuland H, Linde T, Ahlmen J, Christensson A, Strombom U, Danielson BG (2003) A randomized controlled trial of haemoglobin normalization with epoetin alfa in pre-dialysis and dialysis patients. Nephrol Dial Transplant 18:353–361PubMedCrossRef
7.
Zurück zum Zitat Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D, CHOIR Investigators (2006) Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355:2085–2098PubMedCrossRef Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D, CHOIR Investigators (2006) Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355:2085–2098PubMedCrossRef
8.
Zurück zum Zitat Besarab A, Bolton WK, Browne JK, Egrie JC, Nissenson AR, Okamoto DM, Schwab SJ, Goodkin DA (1998) The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 339:584–590PubMedCrossRef Besarab A, Bolton WK, Browne JK, Egrie JC, Nissenson AR, Okamoto DM, Schwab SJ, Goodkin DA (1998) The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 339:584–590PubMedCrossRef
9.
Zurück zum Zitat KDOQI (2007) KDOQI clinical practice guideline and clinical practice recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis 50:471–530CrossRef KDOQI (2007) KDOQI clinical practice guideline and clinical practice recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis 50:471–530CrossRef
10.
Zurück zum Zitat Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, Feyzi JM, Ivanovich P, Kewalramani R, Levey AS, Lewis EF, McGill JB, McMurray JJ, Parfrey P, Parving HH, Remuzzi G, Singh AK, Solomon SD, Toto R, TREAT Investigators (2009) A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 361:2019–2032PubMedCrossRef Pfeffer MA, Burdmann EA, Chen CY, Cooper ME, de Zeeuw D, Eckardt KU, Feyzi JM, Ivanovich P, Kewalramani R, Levey AS, Lewis EF, McGill JB, McMurray JJ, Parfrey P, Parving HH, Remuzzi G, Singh AK, Solomon SD, Toto R, TREAT Investigators (2009) A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 361:2019–2032PubMedCrossRef
11.
Zurück zum Zitat Kliger AS, Foley RN, Goldfarb DS, Goldstein SL, Johansen K, Singh A, Szczech L (2013) KDOQI US commentary on the 2012 KDIGO clinical practice guideline for anemia in CKD. Am J Kidney Dis 62:849–859PubMedCrossRef Kliger AS, Foley RN, Goldfarb DS, Goldstein SL, Johansen K, Singh A, Szczech L (2013) KDOQI US commentary on the 2012 KDIGO clinical practice guideline for anemia in CKD. Am J Kidney Dis 62:849–859PubMedCrossRef
12.
Zurück zum Zitat Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group (2012) KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl 2:279–335CrossRef Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group (2012) KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl 2:279–335CrossRef
13.
Zurück zum Zitat Neu AM, Frankenfield DL (2009) Clinical outcomes in pediatric hemodialysis patients in the USA: lessons from CMS’ ESRD CPM project. Pediatr Nephrol 24:1287–1295PubMedCrossRefPubMedCentral Neu AM, Frankenfield DL (2009) Clinical outcomes in pediatric hemodialysis patients in the USA: lessons from CMS’ ESRD CPM project. Pediatr Nephrol 24:1287–1295PubMedCrossRefPubMedCentral
15.
Zurück zum Zitat Amaral S, Hwang W, Fivush B, Neu A, Frankenfield D, Furth S (2008) Serum albumin level and risk for mortality and hospitalization in adolescents on hemodialysis. Clin J Am Soc Nephrol 3:759–767PubMedCrossRefPubMedCentral Amaral S, Hwang W, Fivush B, Neu A, Frankenfield D, Furth S (2008) Serum albumin level and risk for mortality and hospitalization in adolescents on hemodialysis. Clin J Am Soc Nephrol 3:759–767PubMedCrossRefPubMedCentral
16.
Zurück zum Zitat Morgenstern B, Nair KS, Lerner G, Neu A, Quan A, Warady BA, Pediatric Peritoneal Dialysis Study Consortium (2001) Impact of total body water errors on kt/V estimates in children on peritoneal dialysis. Adv Perit Dial 17:260–263PubMed Morgenstern B, Nair KS, Lerner G, Neu A, Quan A, Warady BA, Pediatric Peritoneal Dialysis Study Consortium (2001) Impact of total body water errors on kt/V estimates in children on peritoneal dialysis. Adv Perit Dial 17:260–263PubMed
17.
Zurück zum Zitat Hemodialysis Adequacy 2006 Work Group (2006) KDOQI clinical practice guidelines for hemodialysis adequacy, update 2006. Am J Kidney Dis 48:S2–S90CrossRef Hemodialysis Adequacy 2006 Work Group (2006) KDOQI clinical practice guidelines for hemodialysis adequacy, update 2006. Am J Kidney Dis 48:S2–S90CrossRef
18.
Zurück zum Zitat KDOQI (2006) KDOQI clinical practice guidelines for peritoneal dialysis adequacy, update 2006. Am J Kidney Dis 48:S91–S158CrossRef KDOQI (2006) KDOQI clinical practice guidelines for peritoneal dialysis adequacy, update 2006. Am J Kidney Dis 48:S91–S158CrossRef
19.
Zurück zum Zitat Zhang Y, Thamer M, Stefanik K, Kaufman J, Cotter DJ (2004) Epoetin requirements predict mortality in hemodialysis patients. Am J Kidney Dis 44:866–876PubMedCrossRef Zhang Y, Thamer M, Stefanik K, Kaufman J, Cotter DJ (2004) Epoetin requirements predict mortality in hemodialysis patients. Am J Kidney Dis 44:866–876PubMedCrossRef
20.
Zurück zum Zitat Port RE, Mehls O (2009) Erythropoietin dosing in children with chronic kidney disease: based on body size or on hemoglobin deficit? Pediatr Nephrol 24:435–437PubMedCrossRef Port RE, Mehls O (2009) Erythropoietin dosing in children with chronic kidney disease: based on body size or on hemoglobin deficit? Pediatr Nephrol 24:435–437PubMedCrossRef
21.
Zurück zum Zitat Atkinson MA, Furth SL (2011) Anemia in children with chronic kidney disease. Nat Rev Nephrol 7:635–641PubMedCrossRef Atkinson MA, Furth SL (2011) Anemia in children with chronic kidney disease. Nat Rev Nephrol 7:635–641PubMedCrossRef
22.
Zurück zum Zitat Foley RN (2008) Erythropoietin: physiology and molecular mechanisms. Heart Fail Rev 13:405–414PubMedCrossRef Foley RN (2008) Erythropoietin: physiology and molecular mechanisms. Heart Fail Rev 13:405–414PubMedCrossRef
23.
Zurück zum Zitat Badve SV, Hawley CM, Johnson DW (2011) Is the problem with the vehicle or the destination? does high-dose ESA or high haemoglobin contribute to poor outcomes in CKD? Nephrol (Carlton) 16:144–153CrossRef Badve SV, Hawley CM, Johnson DW (2011) Is the problem with the vehicle or the destination? does high-dose ESA or high haemoglobin contribute to poor outcomes in CKD? Nephrol (Carlton) 16:144–153CrossRef
24.
Zurück zum Zitat Staples AO, Wong CS, Smith JM, Gipson DS, Filler G, Warady BA, Martz K, Greenbaum LA (2009) Anemia and risk of hospitalization in pediatric chronic kidney disease. Clin J Am Soc Nephrol 4:48–56PubMedCrossRefPubMedCentral Staples AO, Wong CS, Smith JM, Gipson DS, Filler G, Warady BA, Martz K, Greenbaum LA (2009) Anemia and risk of hospitalization in pediatric chronic kidney disease. Clin J Am Soc Nephrol 4:48–56PubMedCrossRefPubMedCentral
25.
Zurück zum Zitat Goodkin DA, Fuller DS, Robinson BM, Combe C, Fluck R, Mendelssohn D, Akizawa T, Pisoni RL, Port FK (2011) Naturally occurring higher hemoglobin concentration does not increase mortality among hemodialysis patients. J Am Soc Nephrol 22:358–365PubMedCrossRefPubMedCentral Goodkin DA, Fuller DS, Robinson BM, Combe C, Fluck R, Mendelssohn D, Akizawa T, Pisoni RL, Port FK (2011) Naturally occurring higher hemoglobin concentration does not increase mortality among hemodialysis patients. J Am Soc Nephrol 22:358–365PubMedCrossRefPubMedCentral
26.
Zurück zum Zitat Koulouridis I, Alfayez M, Trikalinos TA, Balk EM, Jaber BL (2013) Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: a metaregression analysis. Am J Kidney Dis 61:44–56PubMedCrossRefPubMedCentral Koulouridis I, Alfayez M, Trikalinos TA, Balk EM, Jaber BL (2013) Dose of erythropoiesis-stimulating agents and adverse outcomes in CKD: a metaregression analysis. Am J Kidney Dis 61:44–56PubMedCrossRefPubMedCentral
27.
Zurück zum Zitat Goodnough LT, Nemeth E, Ganz T (2010) Detection, evaluation, and management of iron-restricted erythropoiesis. Blood 116:4754–4761PubMedCrossRef Goodnough LT, Nemeth E, Ganz T (2010) Detection, evaluation, and management of iron-restricted erythropoiesis. Blood 116:4754–4761PubMedCrossRef
28.
Zurück zum Zitat Atkinson MA, White CT (2012) Hepcidin in anemia of chronic kidney disease: review for the pediatric nephrologist. Pediatr Nephrol 27:33–40PubMedCrossRef Atkinson MA, White CT (2012) Hepcidin in anemia of chronic kidney disease: review for the pediatric nephrologist. Pediatr Nephrol 27:33–40PubMedCrossRef
29.
Zurück zum Zitat Zaritsky J, Young B, Wang HJ, Westerman M, Olbina G, Nemeth E, Ganz T, Rivera S, Nissenson AR, Salusky IB (2009) Hepcidin—a potential novel biomarker for iron status in chronic kidney disease. Clin J Am Soc Nephrol 4:1051–1056PubMedCrossRefPubMedCentral Zaritsky J, Young B, Wang HJ, Westerman M, Olbina G, Nemeth E, Ganz T, Rivera S, Nissenson AR, Salusky IB (2009) Hepcidin—a potential novel biomarker for iron status in chronic kidney disease. Clin J Am Soc Nephrol 4:1051–1056PubMedCrossRefPubMedCentral
30.
Zurück zum Zitat Bamgbola OF, Kaskel FJ, Coco M (2009) Analyses of age, gender and other risk factors of erythropoietin resistance in pediatric and adult dialysis cohorts. Pediatr Nephrol 24:571–579PubMedCrossRef Bamgbola OF, Kaskel FJ, Coco M (2009) Analyses of age, gender and other risk factors of erythropoietin resistance in pediatric and adult dialysis cohorts. Pediatr Nephrol 24:571–579PubMedCrossRef
Metadaten
Titel
Association of higher erythropoiesis stimulating agent dose and mortality in children on dialysis
verfasst von
Rachel M. Lestz
Barbara A. Fivush
Meredith A. Atkinson
Publikationsdatum
01.10.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 10/2014
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-014-2820-9

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