Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease

Jérôme Harambat, Kevin Kunzmann, Karolis Azukaitis, Aysun K Bayazit, Nur Canpolat, Anke Doyon, Ali Duzova, Anna Niemirska, Betul Sözeri, Daniela Thurn-Valsassina, Ali Anarat, Lucie Bessenay, Cengiz Candan, Amira Peco-Antic, Alev Yilmaz, Sibylle Tschumi, Sara Testa, Augustina Jankauskiene, Hakan Erdogan, Alejandra Rosales & 11 others Harika Alpay, Francesca Lugani, Klaus Arbeiter, Francesca Mencarelli, Aysel Kiyak, Osman Dönmez, Dorota Drozdz, Anette Melk, Uwe Querfeld, Franz Schaefer, 4C Study Consortium

Research output: Contribution to journalArticle

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Abstract

Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m2 and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression.

Original languageEnglish
Pages (from-to)1507-1514
Number of pages8
JournalKidney International
Volume92
Issue number6
DOIs
Publication statusPublished - Dec 2017

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Acidosis
Chronic Renal Insufficiency
Bicarbonates
Disease Progression
Serum
Glomerular Filtration Rate
Kidney Diseases
Pediatrics
Secondary Hyperparathyroidism
Alkalies
Parathyroid Hormone
Proportional Hazards Models
Chronic Kidney Failure
Comorbidity
Prospective Studies
Confidence Intervals
Growth

Keywords

  • Journal Article

Cite this

Harambat, J., Kunzmann, K., Azukaitis, K., Bayazit, A. K., Canpolat, N., Doyon, A., ... 4C Study Consortium (2017). Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease. Kidney International, 92(6), 1507-1514. https://doi.org/10.1016/j.kint.2017.05.006

Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease. / Harambat, Jérôme; Kunzmann, Kevin; Azukaitis, Karolis; Bayazit, Aysun K; Canpolat, Nur; Doyon, Anke; Duzova, Ali; Niemirska, Anna; Sözeri, Betul; Thurn-Valsassina, Daniela; Anarat, Ali; Bessenay, Lucie; Candan, Cengiz; Peco-Antic, Amira; Yilmaz, Alev; Tschumi, Sibylle; Testa, Sara; Jankauskiene, Augustina; Erdogan, Hakan; Rosales, Alejandra; Alpay, Harika; Lugani, Francesca; Arbeiter, Klaus; Mencarelli, Francesca; Kiyak, Aysel; Dönmez, Osman; Drozdz, Dorota; Melk, Anette; Querfeld, Uwe; Schaefer, Franz; 4C Study Consortium.

In: Kidney International, Vol. 92, No. 6, 12.2017, p. 1507-1514.

Research output: Contribution to journalArticle

Harambat, J, Kunzmann, K, Azukaitis, K, Bayazit, AK, Canpolat, N, Doyon, A, Duzova, A, Niemirska, A, Sözeri, B, Thurn-Valsassina, D, Anarat, A, Bessenay, L, Candan, C, Peco-Antic, A, Yilmaz, A, Tschumi, S, Testa, S, Jankauskiene, A, Erdogan, H, Rosales, A, Alpay, H, Lugani, F, Arbeiter, K, Mencarelli, F, Kiyak, A, Dönmez, O, Drozdz, D, Melk, A, Querfeld, U, Schaefer, F & 4C Study Consortium 2017, 'Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease', Kidney International, vol. 92, no. 6, pp. 1507-1514. https://doi.org/10.1016/j.kint.2017.05.006
Harambat, Jérôme ; Kunzmann, Kevin ; Azukaitis, Karolis ; Bayazit, Aysun K ; Canpolat, Nur ; Doyon, Anke ; Duzova, Ali ; Niemirska, Anna ; Sözeri, Betul ; Thurn-Valsassina, Daniela ; Anarat, Ali ; Bessenay, Lucie ; Candan, Cengiz ; Peco-Antic, Amira ; Yilmaz, Alev ; Tschumi, Sibylle ; Testa, Sara ; Jankauskiene, Augustina ; Erdogan, Hakan ; Rosales, Alejandra ; Alpay, Harika ; Lugani, Francesca ; Arbeiter, Klaus ; Mencarelli, Francesca ; Kiyak, Aysel ; Dönmez, Osman ; Drozdz, Dorota ; Melk, Anette ; Querfeld, Uwe ; Schaefer, Franz ; 4C Study Consortium. / Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease. In: Kidney International. 2017 ; Vol. 92, No. 6. pp. 1507-1514.
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T1 - Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease

AU - Harambat, Jérôme

AU - Kunzmann, Kevin

AU - Azukaitis, Karolis

AU - Bayazit, Aysun K

AU - Canpolat, Nur

AU - Doyon, Anke

AU - Duzova, Ali

AU - Niemirska, Anna

AU - Sözeri, Betul

AU - Thurn-Valsassina, Daniela

AU - Anarat, Ali

AU - Bessenay, Lucie

AU - Candan, Cengiz

AU - Peco-Antic, Amira

AU - Yilmaz, Alev

AU - Tschumi, Sibylle

AU - Testa, Sara

AU - Jankauskiene, Augustina

AU - Erdogan, Hakan

AU - Rosales, Alejandra

AU - Alpay, Harika

AU - Lugani, Francesca

AU - Arbeiter, Klaus

AU - Mencarelli, Francesca

AU - Kiyak, Aysel

AU - Dönmez, Osman

AU - Drozdz, Dorota

AU - Melk, Anette

AU - Querfeld, Uwe

AU - Schaefer, Franz

AU - 4C Study Consortium

N1 - Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

PY - 2017/12

Y1 - 2017/12

N2 - Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m2 and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression.

AB - Recent studies in adult chronic kidney disease (CKD) suggest that metabolic acidosis is associated with faster decline in estimated glomerular filtration rate (eGFR). Alkali therapies improve the course of kidney disease. Here we investigated the prevalence and determinants of abnormal serum bicarbonate values and whether metabolic acidosis may be deleterious to children with CKD. Associations between follow-up serum bicarbonate levels categorized as under 18, 18 to under 22, and 22 or more mmol/l and CKD outcomes in 704 children in the Cardiovascular Comorbidity in Children with CKD Study, a prospective cohort of pediatric patients with CKD stages 3-5, were studied. The eGFR and serum bicarbonate were measured every six months. At baseline, the median eGFR was 27 ml/min/1.73m2 and median serum bicarbonate level 21 mmol/l. During a median follow-up of 3.3 years, the prevalence of metabolic acidosis (serum bicarbonate under 22 mmol/l) was 43%, 60%, and 45% in CKD stages 3, 4, and 5, respectively. In multivariable analysis, the presence of metabolic acidosis as a time-varying covariate was significantly associated with log serum parathyroid hormone through the entire follow-up, but no association with longitudinal growth was found. A total of 211 patients reached the composite endpoint (ESRD or 50% decline in eGFR). In a multivariable Cox model, children with time-varying serum bicarbonate under 18 mmol/l had a significantly higher risk of CKD progression compared to those with a serum bicarbonate of 22 or more mmol/l (adjusted hazard ratio 2.44; 95% confidence interval 1.43-4.15). Thus, metabolic acidosis is a common complication in pediatric patients with CKD and may be a risk factor for secondary hyperparathyroidism and kidney disease progression.

KW - Journal Article

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DO - 10.1016/j.kint.2017.05.006

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SP - 1507

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JO - Kidney International

JF - Kidney International

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