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Published in: Pediatric Nephrology 12/2023

08-07-2023 | Metabolic Acidosis | Original Article

Metabolic acidosis in pediatric kidney transplant recipients

Authors: Stella Kilduff, Nicole Hayde, Shankar Viswanathan, Kimberly Reidy, Matthew K. Abramowitz

Published in: Pediatric Nephrology | Issue 12/2023

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Abstract

Background

Metabolic acidosis is a risk factor for faster kidney function decline in chronic kidney disease (CKD) and in adult kidney transplant recipients (KTRs). We hypothesized that metabolic acidosis would be highly prevalent and associated with worse allograft function in pediatric KTRs.

Methods

Pediatric KTRs at Montefiore Medical Center from 2010 to 2018 were included. Metabolic acidosis was defined as serum bicarbonate < 22 mEq/L or receiving alkali therapy. Regression models were adjusted for demographic factors and donor/recipient characteristics.

Results

Sixty-three patients were identified with a median age at transplant of 10.5 (interquartile range (IQR) 4.4–15.2) years and post-transplant follow-up of 3 (IQR 1–5) years. Baseline serum bicarbonate was 21.7 ± 2.4 mEq/L, serum bicarbonate < 22 mEq/L was present in 28 (44%), and 44% of all patients were receiving alkali therapy. The prevalence of acidosis ranged from 58 to 70% during the first year of follow-up. At baseline, each 1-year higher age at transplant and every 10 ml/min/1.73 m2 higher eGFR were associated with 0.16 mEq/L (95% CI: 0.03–0.3) and 0.24 mEq/L (95% CI: 0.01–0.5) higher serum bicarbonate, respectively. Older age at transplant was associated with lower odds of acidosis (OR: 0.84; 95% CI: 0.72–0.97). During follow-up, metabolic acidosis was independently associated with 8.2 ml/min/1.73 m2 (95% CI 4.4–12) lower eGFR compared to not having acidosis; furthermore, eGFR was significantly lower among KTRs with unresolved acidosis compared with resolved acidosis.

Conclusions

Among pediatric KTRs, metabolic acidosis was highly prevalent in the first year post-transplantation and was associated with lower eGFR during follow-up.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information
Appendix
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Literature
1.
go back to reference Brown DD, Roem J, Ng DK, Reidy KJ, Kumar J, Abramowitz MK, Mak RH, Furth SL, Schwartz GJ, Warady BA, Kaskel FJ, Melamed ML (2020) Low serum bicarbonate and CKD progression in children. Clin J Am Soc Nephrol 15:755–765CrossRefPubMedPubMedCentral Brown DD, Roem J, Ng DK, Reidy KJ, Kumar J, Abramowitz MK, Mak RH, Furth SL, Schwartz GJ, Warady BA, Kaskel FJ, Melamed ML (2020) Low serum bicarbonate and CKD progression in children. Clin J Am Soc Nephrol 15:755–765CrossRefPubMedPubMedCentral
2.
go back to reference Dobre M, Rahman M, Hostetter TH (2015) Current status of bicarbonate in CKD. J Am Soc Nephrol 26:515–523CrossRefPubMed Dobre M, Rahman M, Hostetter TH (2015) Current status of bicarbonate in CKD. J Am Soc Nephrol 26:515–523CrossRefPubMed
4.
go back to reference de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM (2009) Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol 20:2075–2084CrossRefPubMedPubMedCentral de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM (2009) Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol 20:2075–2084CrossRefPubMedPubMedCentral
5.
go back to reference Ho JQ, Abramowitz MK (2022) Clinical consequences of metabolic acidosis-muscle. Adv Chronic Kidney Dis 29:395–405CrossRefPubMed Ho JQ, Abramowitz MK (2022) Clinical consequences of metabolic acidosis-muscle. Adv Chronic Kidney Dis 29:395–405CrossRefPubMed
6.
go back to reference Fernando ME, Jayanivash J, Srinivasaprasad ND, Suren S, Thirumalvalavan K (2019) Post-renal transplant metabolic acidosis: a neglected entity. Indian J Nephrol 29:116–121PubMedPubMedCentral Fernando ME, Jayanivash J, Srinivasaprasad ND, Suren S, Thirumalvalavan K (2019) Post-renal transplant metabolic acidosis: a neglected entity. Indian J Nephrol 29:116–121PubMedPubMedCentral
7.
go back to reference Djamali A, Singh T, Melamed ML, Stein JH, Aziz F, Parajuli S, Mohamed M, Garg N, Mandelbrot D, Wesson DE, Astor BC (2019) Metabolic acidosis 1 year following kidney transplantation and subsequent cardiovascular events and mortality: an observational cohort study. Am J Kidney Dis 73:476–485CrossRefPubMed Djamali A, Singh T, Melamed ML, Stein JH, Aziz F, Parajuli S, Mohamed M, Garg N, Mandelbrot D, Wesson DE, Astor BC (2019) Metabolic acidosis 1 year following kidney transplantation and subsequent cardiovascular events and mortality: an observational cohort study. Am J Kidney Dis 73:476–485CrossRefPubMed
8.
go back to reference Park S, Kang E, Park S, Kim YC, Han SS, Ha J, Kim DK, Kim S, Park SK, Han DJ, Lim CS, Kim YS, Lee JP, Kim YH (2017) Metabolic acidosis and long-term clinical outcomes in kidney transplant recipients. J Am Soc Nephrol 28:1886–1897CrossRefPubMed Park S, Kang E, Park S, Kim YC, Han SS, Ha J, Kim DK, Kim S, Park SK, Han DJ, Lim CS, Kim YS, Lee JP, Kim YH (2017) Metabolic acidosis and long-term clinical outcomes in kidney transplant recipients. J Am Soc Nephrol 28:1886–1897CrossRefPubMed
10.
go back to reference Ritter A, Mohebbi N (2020) Causes and consequences of metabolic acidosis in patients after kidney transplantation. Kidney Blood Press Res 45:792–801CrossRefPubMed Ritter A, Mohebbi N (2020) Causes and consequences of metabolic acidosis in patients after kidney transplantation. Kidney Blood Press Res 45:792–801CrossRefPubMed
11.
go back to reference Schulte K, Puchel J, Schussel K, Borzikowsky C, Kunzendorf U, Feldkamp T (2019) Effect of sodium bicarbonate in kidney transplant recipients with chronic metabolic acidosis. Transplant Direct 5:e464CrossRefPubMedPubMedCentral Schulte K, Puchel J, Schussel K, Borzikowsky C, Kunzendorf U, Feldkamp T (2019) Effect of sodium bicarbonate in kidney transplant recipients with chronic metabolic acidosis. Transplant Direct 5:e464CrossRefPubMedPubMedCentral
12.
go back to reference Skiba K, Gojowy D, Szotowska M, Bartmanska M, Kolonko A, Cierpka L, Wiecek A, Adamczak M (2018) Metabolic acidosis in kidney transplant recipients. Pol Arch Intern Med 128:587–593PubMed Skiba K, Gojowy D, Szotowska M, Bartmanska M, Kolonko A, Cierpka L, Wiecek A, Adamczak M (2018) Metabolic acidosis in kidney transplant recipients. Pol Arch Intern Med 128:587–593PubMed
13.
go back to reference Mathur V, Reaven NL, Funk SE, Tangri N (2022) Serum bicarbonate and graft and patient outcomes among kidney transplant recipients: a retrospective cohort study evaluating changes in serum bicarbonate over time. Kidney Med 5:100573CrossRefPubMedPubMedCentral Mathur V, Reaven NL, Funk SE, Tangri N (2022) Serum bicarbonate and graft and patient outcomes among kidney transplant recipients: a retrospective cohort study evaluating changes in serum bicarbonate over time. Kidney Med 5:100573CrossRefPubMedPubMedCentral
14.
go back to reference Keven K, Ozturk R, Sengul S, Kutlay S, Ergun I, Erturk S, Erbay B (2007) Renal tubular acidosis after kidney transplantation–incidence, risk factors and clinical implications. Nephrol Dial Transplant 22:906–910CrossRefPubMed Keven K, Ozturk R, Sengul S, Kutlay S, Ergun I, Erturk S, Erbay B (2007) Renal tubular acidosis after kidney transplantation–incidence, risk factors and clinical implications. Nephrol Dial Transplant 22:906–910CrossRefPubMed
15.
go back to reference Jerome Harambat KK, Azukaitis K, Bayazit AK, Canpolat N, Doyon A, Duzova A, Niemirska A (2017) Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease. Kidney Int 92:1507–1514CrossRefPubMed Jerome Harambat KK, Azukaitis K, Bayazit AK, Canpolat N, Doyon A, Duzova A, Niemirska A (2017) Metabolic acidosis is common and associates with disease progression in children with chronic kidney disease. Kidney Int 92:1507–1514CrossRefPubMed
17.
go back to reference Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefPubMedPubMedCentral Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefPubMedPubMedCentral
19.
go back to reference Furth SL, Abraham AG, Jerry-Fluker J, Schwartz GJ, Benfield M, Kaskel F, Wong C, Mak RH, Moxey-Mims M, Warady BA (2011) Metabolic abnormalities, cardiovascular disease risk factors, and GFR decline in children with chronic kidney disease. Clin J Am Soc Nephrol 6:2132–2140CrossRefPubMedPubMedCentral Furth SL, Abraham AG, Jerry-Fluker J, Schwartz GJ, Benfield M, Kaskel F, Wong C, Mak RH, Moxey-Mims M, Warady BA (2011) Metabolic abnormalities, cardiovascular disease risk factors, and GFR decline in children with chronic kidney disease. Clin J Am Soc Nephrol 6:2132–2140CrossRefPubMedPubMedCentral
20.
go back to reference Alva S, Divyashree M, Kamath J, Prakash PS, Prakash KS (2020) A study on effect of bicarbonate supplementation on the progression of chronic kidney disease. Indian J Nephrol 30:91–97CrossRefPubMedPubMedCentral Alva S, Divyashree M, Kamath J, Prakash PS, Prakash KS (2020) A study on effect of bicarbonate supplementation on the progression of chronic kidney disease. Indian J Nephrol 30:91–97CrossRefPubMedPubMedCentral
21.
go back to reference Di Iorio BR, Bellasi A, Raphael KL, Santoro D, Aucella F, Garofano L, Ceccarelli M, Di Lullo L, Capolongo G, Di Iorio M, Guastaferro P, Capasso G, UBI Study Group (2019) Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study. J Nephrol 32:989–1001CrossRefPubMedPubMedCentral Di Iorio BR, Bellasi A, Raphael KL, Santoro D, Aucella F, Garofano L, Ceccarelli M, Di Lullo L, Capolongo G, Di Iorio M, Guastaferro P, Capasso G, UBI Study Group (2019) Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: the UBI Study. J Nephrol 32:989–1001CrossRefPubMedPubMedCentral
22.
go back to reference Goraya N, Simoni J, Jo CH, Wesson DE (2014) Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate. Kidney Int 86:1031–1038CrossRefPubMed Goraya N, Simoni J, Jo CH, Wesson DE (2014) Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate. Kidney Int 86:1031–1038CrossRefPubMed
23.
go back to reference BiCARB Study Group (2020) Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis (BiCARB): a pragmatic randomised, double-blind, placebo-controlled trial. BMC Med 18:91CrossRef BiCARB Study Group (2020) Clinical and cost-effectiveness of oral sodium bicarbonate therapy for older patients with chronic kidney disease and low-grade acidosis (BiCARB): a pragmatic randomised, double-blind, placebo-controlled trial. BMC Med 18:91CrossRef
24.
go back to reference Melamed ML, Horwitz EJ, Dobre MA, Abramowitz MK, Zhang L, Lo Y, Mitch WE, Hostetter TH (2020) Effects of sodium bicarbonate in CKD stages 3 and 4: a randomized, placebo-controlled, multicenter clinical trial. Am J Kidney Dis 75:225–234CrossRefPubMed Melamed ML, Horwitz EJ, Dobre MA, Abramowitz MK, Zhang L, Lo Y, Mitch WE, Hostetter TH (2020) Effects of sodium bicarbonate in CKD stages 3 and 4: a randomized, placebo-controlled, multicenter clinical trial. Am J Kidney Dis 75:225–234CrossRefPubMed
25.
go back to reference Mariani LH, Martini S, Barisoni L, Canetta PA, Troost JP, Hodgin JB, Palmer M, Rosenberg AZ, Lemley KV, Chien HP, Zee J, Smith A, Appel GB, Trachtman H, Hewitt SM, Kretzler M, Bagnasco SM (2018) Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies. Nephrol Dial Transplant 33:310–318CrossRefPubMed Mariani LH, Martini S, Barisoni L, Canetta PA, Troost JP, Hodgin JB, Palmer M, Rosenberg AZ, Lemley KV, Chien HP, Zee J, Smith A, Appel GB, Trachtman H, Hewitt SM, Kretzler M, Bagnasco SM (2018) Interstitial fibrosis scored on whole-slide digital imaging of kidney biopsies is a predictor of outcome in proteinuric glomerulopathies. Nephrol Dial Transplant 33:310–318CrossRefPubMed
27.
go back to reference Noce A, Marrone G, Wilson Jones G, Di Lauro M, Pietroboni Zaitseva A, Ramadori L, Celotto R, Mitterhofer AP, Di Daniele N (2021) Nutritional approaches for the management of metabolic acidosis in chronic kidney disease. Nutrients 13:1–18CrossRef Noce A, Marrone G, Wilson Jones G, Di Lauro M, Pietroboni Zaitseva A, Ramadori L, Celotto R, Mitterhofer AP, Di Daniele N (2021) Nutritional approaches for the management of metabolic acidosis in chronic kidney disease. Nutrients 13:1–18CrossRef
28.
go back to reference Rodig NM, McDermott KC, Schneider MF, Hotchkiss HM, Yadin O, Seikaly MG, Furth SL, Warady BA (2014) Growth in children with chronic kidney disease: a report from the Chronic Kidney Disease in Children Study. Pediatr Nephrol 29:1987–1995CrossRefPubMedPubMedCentral Rodig NM, McDermott KC, Schneider MF, Hotchkiss HM, Yadin O, Seikaly MG, Furth SL, Warady BA (2014) Growth in children with chronic kidney disease: a report from the Chronic Kidney Disease in Children Study. Pediatr Nephrol 29:1987–1995CrossRefPubMedPubMedCentral
29.
go back to reference Franke D, Thomas L, Steffens R, Pavičić L, Gellermann J, Froede K, Querfeld U, Haffner D, Živičnjak M (2015) Patterns of growth after kidney transplantation among children with ESRD. Clin J Am Soc Nephrol 10:127–134CrossRefPubMed Franke D, Thomas L, Steffens R, Pavičić L, Gellermann J, Froede K, Querfeld U, Haffner D, Živičnjak M (2015) Patterns of growth after kidney transplantation among children with ESRD. Clin J Am Soc Nephrol 10:127–134CrossRefPubMed
30.
go back to reference Messa PG, Alfieri C, Vettoretti S (2016) Metabolic acidosis in renal transplantation: neglected but of potential clinical relevance. Nephrol Dial Transplant 31:730–736CrossRefPubMed Messa PG, Alfieri C, Vettoretti S (2016) Metabolic acidosis in renal transplantation: neglected but of potential clinical relevance. Nephrol Dial Transplant 31:730–736CrossRefPubMed
Metadata
Title
Metabolic acidosis in pediatric kidney transplant recipients
Authors
Stella Kilduff
Nicole Hayde
Shankar Viswanathan
Kimberly Reidy
Matthew K. Abramowitz
Publication date
08-07-2023
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 12/2023
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-023-06072-z

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