Metabolic Acidosis
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Zhabiz SolhjouRenal Division, Brigham and Women’s Hospital, Boston, Massachusetts

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Martina M. McGrathRenal Division, Brigham and Women’s Hospital, Boston, Massachusetts
Renal Division, Veterans Affairs Boston Healthcare System, Boston, Massachusetts

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  • 1

    Seifter JL, Chang H-Y: Extracellular acid-base balance and ion transport between body fluid compartments. Physiology (Bethesda) 32: 367379, 2017 PubMed

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    Matyukhin I, Patschan S, Ritter O, Patschan D: Etiology and management of acute metabolic acidosis: An update. Kidney Blood Press Res 45: 523531, 2020 PubMed

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    Sun S, Li H, Chen J, Qian Q: Lactic acid: No longer an inert and end-product of glycolysis. Physiology (Bethesda) 32: 453463, 2017 PubMed

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  • 9

    Kraut JA, Madias NE: Lactic acidosis. N Engl J Med 371: 23092319, 2014 PubMed

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    Rudkin SE, Grogan TR, Treger RM: The Δ anion gap/Δ bicarbonate ratio in early lactic acidosis: Time for another delta? https://kidney360.asnjournals.org/content/2/1/20. Kidney360 2: 2025, 2020

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  • 11

    Kraut JA, Madias NE: Lactic acidosis: Current treatments and future directions. Am J Kidney Dis 68: 473482, 2016 PubMed

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    Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, et al.; SMART Investigators and the Pragmatic Critical Care Research Group: Balanced crystalloids versus saline in critically ill adults. N Engl J Med 378: 829839, 2018 PubMed

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    Palevsky PM: Intravenous fluids: Finding the right balance. Clin J Am Soc Nephrol 13: 19121914, 2018

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    Self WH, Evans CS, Jenkins CA, Brown RM, Casey JD, Collins SP, et al.; Pragmatic Critical Care Research Group: Clinical effects of balanced crystalloids vs saline in adults with diabetic ketoacidosis: A subgroup analysis of cluster randomized clinical trials. JAMA Netw Open 3: e2024596, 2020 PubMed

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    Group KDIGO; Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group: KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int 98[4S]: S1S115, 2020 PubMed

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    Ferrannini E, Baldi S, Frascerra S, Astiarraga B, Heise T, Bizzotto R, et al.: Shift to fatty substrate utilization in response to sodium-glucose cotransporter 2 inhibition in subjects without diabetes and patients with type 2 diabetes. Diabetes 65: 11901195, 2016 PubMed

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  • 20

    Palmer BF, Clegg DJ: Euglycemic ketoacidosis as a complication of SGLT2 inhibitor therapy. Clin J Am Soc Nephrol 16: 12841291, 2021 PubMed

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    Erondu N, Desai M, Ways K, Meininger G: Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care 38: 16801686, 2015 PubMed

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    Rosenstock J, Ferrannini E: Euglycemic diabetic ketoacidosis: A predictable, detectable, and preventable safety concern with SGLT2 inhibitors. Diabetes Care 38: 16381642, 2015 PubMed

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  • 23

    Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB: Euglycemic diabetic ketoacidosis: A potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care 38: 16871693, 2015 PubMed

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    Kum-Nji JS, Gosmanov AR, Steinberg H, Dagogo-Jack S: Hyperglycemic, high anion-gap metabolic acidosis in patients receiving SGLT-2 inhibitors for diabetes management. J Diabetes Complications 31: 611614, 2017 PubMed

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  • 25

    Vitale RJ, Valtis YK, McDonnell ME, Palermo NE, Fisher NDL: euglycemic diabetic ketoacidosis with COVID-19 infection in patients with type 2 diabetes taking SGLT2 inhibitors. AACE Clin Case Rep 7: 1013, 2021 PubMed

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  • 26

    Donnan K, Segar L: SGLT2 inhibitors and metformin: Dual antihyperglycemic therapy and the risk of metabolic acidosis in type 2 diabetes. Eur J Pharmacol 846: 2329, 2019 PubMed

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  • 27

    Ting S, Chua H-R, Cove ME: Euglycemic ketosis during continuous kidney replacement therapy with glucose-free solution: A report of 8 cases. Am J Kidney Dis 78: 305308, 2021 PubMed

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  • 28

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  • 30

    Hundemer GL, Fenves AZ, Phillips KM, Emmett M: Sodium thiosulfate and the anion gap in patients treated by hemodialysis. Am J Kidney Dis 68: 499500, 2016 PubMed

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  • 31

    Rein JL, Miyata KN, Dadzie KA, Gruber SJ, Sulica R, Winchester JF: Successfully treated calcific uremic arteriolopathy: Two cases of a high anion gap metabolic acidosis with intravenous sodium thiosulfate. Case Rep Nephrol 2014: 765134, 2014 PubMed

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  • 32

    Mao M, Lee S, Kashani K, Albright R, Qian Q: Severe anion gap acidosis associated with intravenous sodium thiosulfate administration. J Med Toxicol 9: 274277, 2013 PubMed

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  • 33

    Mariano F, Biancone L: Metformin, chronic nephropathy and lactic acidosis: A multi-faceted issue for the nephrologist. J Nephrol 34: 11271135, 2021 PubMed

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    DeFronzo R, Fleming GA, Chen K, Bicsak TA: Metformin-associated lactic acidosis: Current perspectives on causes and risk. Metabolism 65: 2029, 2016 PubMed

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    Alvarez CA, Halm EA, Pugh MJV, McGuire DK, Hennessy S, Miller RT, et al.: Lactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: A retrospective nested case-control study. Endocrinol Diabetes Metab 4: e00170, 2020 PubMed

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  • 38

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  • 39

    Pham AQT, Xu LHR, Moe OW: Drug-induced metabolic acidosis. F1000Res 4: F1000, 2015 PubMed

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    Calello DP, Liu KD, Wiegand TJ, Roberts DM, Lavergne V, Gosselin S, et al.; Extracorporeal Treatments in Poisoning Workgroup: Extracorporeal treatment for metformin poisoning: Systematic review and recommendations from the Extracorporeal Treatments in Poisoning Workgroup. Crit Care Med 43: 17161730, 2015 PubMed

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  • 41

    Madias NE: Metabolic acidosis and CKD progression. Clin J Am Soc Nephrol 16: 310312, 2021

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    Raphael KL: Metabolic acidosis and subclinical metabolic acidosis in CKD. J Am Soc Nephrol 29: 376382, 2018 PubMed

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    Gennari FJ, Hood VL, Greene T, Wang X, Levey AS: Effect of dietary protein intake on serum total CO2 concentration in chronic kidney disease: Modification of Diet in Renal Disease study findings. Clin J Am Soc Nephrol 1: 5257, 2006 PubMed

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    Chen W, Levy DS, Abramowitz MK: Acid base balance and progression of kidney disease. Semin Nephrol 39: 406417, 2019 PubMed

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    Goraya N, Simoni J, Sager LN, Mamun A, Madias NE, Wesson DE: Urine citrate excretion identifies changes in acid retention as eGFR declines in patients with chronic kidney disease. Am J Physiol Renal Physiol 317: F502F511, 2019 PubMed

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    Phisitkul S, Khanna A, Simoni J, Broglio K, Sheather S, Rajab MH, et al.: Amelioration of metabolic acidosis in patients with low GFR reduced kidney endothelin production and kidney injury, and better preserved GFR. Kidney Int 77: 617623, 2010 PubMed

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    Driver TH, Shlipak MG, Katz R, Goldenstein L, Sarnak MJ, Hoofnagle AN, et al.: Low serum bicarbonate and kidney function decline: The Multi-Ethnic Study of Atherosclerosis (MESA). Am J Kidney Dis 64: 534541, 2014 PubMed

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    Gardner J, Tuttle K, Raphael KL: Influence of medications containing acid salts on serum bicarbonate in CKD. Kidney360 1: 330336, 2020

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    Goraya N, Simoni J, Sager LN, Madias NE, Wesson DE: Urine citrate excretion as a marker of acid retention in patients with chronic kidney disease without overt metabolic acidosis. Kidney Int 95: 11901196, 2019 PubMed

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    Wesson DE, Buysse JM, Bushinsky DA: Mechanisms of metabolic acidosis–induced kidney injury in chronic kidney disease. J Am Soc Nephrol 31: 469482, 2020

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    Di Iorio BR, Bellasi A, Raphael KL, Santoro D, Aucella F, Garofano L, et al.; UBI Study Group: Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: The UBI Study. J Nephrol 32: 9891001, 2019 PubMed

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    Raphael KL, Isakova T, Ix JH, Raj DS, Wolf M, Fried LF, et al.: A randomized trial comparing the safety, adherence, and pharmacodynamics profiles of two doses of sodium bicarbonate in CKD: The BASE Pilot Trial. J Am Soc Nephrol 31: 161174, 2020 PubMed

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    Navaneethan SD, Shao J, Buysse J, Bushinsky DA: Effects of treatment of metabolic acidosis in CKD: A systematic review and meta-analysis. Clin J Am Soc Nephrol 14: 10111020, 2019

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    Witham MD, et al.; BiCARB study group: 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: 91, 2020 PubMed

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    Kendrick J, Shah P, Andrews E, You Z, Nowak K, Pasch A, et al.: Effect of treatment of metabolic acidosis on vascular endothelial function in patients with CKD: A pilot randomized cross-over study. Clin J Am Soc Nephrol 13: 14631470, 2018 PubMed

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    Clegg DJ, Gallant KMH: Plant-based diets in CKD. Clin J Am Soc Nephrol 14: 141143, 2019

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    Brady C, Chemaly ER, Lohr JW, Parker MD: Veverimer: An advance in base therapy for metabolic acidosis. Ann Transl Med 8: 1331, 2020 PubMed

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    Bushinsky DA, Hostetter T, Klaerner G, Stasiv Y, Lockey C, McNulty S, et al.: Randomized, controlled trial of TRC101 to increase serum bicarbonate in patients with CKD. Clin J Am Soc Nephrol 13: 2635, 2018 PubMed

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    Wesson DE, Mathur V, Tangri N, Stasiv Y, Parsell D, Li E, et al.: Veverimer versus placebo in patients with metabolic acidosis associated with chronic kidney disease: A multicentre, randomised, double-blind, controlled, phase 3 trial. Lancet 393: 14171427, 2019 PubMed

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    Wesson DE, Mathur V, Tangri N, Stasiv Y, Parsell D, Li E, et al.: Long-term safety and efficacy of veverimer in patients with metabolic acidosis in chronic kidney disease: A multicentre, randomised, blinded, placebo-controlled, 40-week extension. Lancet 394: 396406, 2019 PubMed

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    Messa PG, Alfieri C, Vettoretti S: Metabolic acidosis in renal transplantation: Neglected but of potential clinical relevance. Nephrol Dial Transplant 31: 730736, 2016 PubMed

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    Ritter A, Mohebbi N: Causes and consequences of metabolic acidosis in patients after kidney transplantation. Kidney Blood Press Res 45: 792801, 2020 PubMed

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    Park S, Kang E, Park S, Kim YC, Han SS, Ha J, et al.: Metabolic acidosis and long-term clinical outcomes in kidney transplant recipients. J Am Soc Nephrol 28: 18861897, 2017 PubMed

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    Gojowy D, Skiba K, Bartmanska M, Kolonko A, Wiecek A, Adamczak M: Is metabolic acidosis a novel risk factor for a long-term graft survival in patients after kidney transplantation? Kidney Blood Press Res 45: 702712, 2020 PubMed

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    Djamali A, Singh T, Melamed ML, Stein JH, Aziz F, Parajuli S, et al.: Metabolic acidosis 1 year following kidney transplantation and subsequent cardiovascular events and mortality: An observational cohort study. Am J Kidney Dis 73: 476485, 2019 PubMed

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    Cervantes CE, Menez S, Monroy Trujillo JM, Hanouneh M: Clinical approach to a patient with an acid-base disturbance. Am J Kidney Dis 77: A9A11, 2021 PubMed

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    Morales A, Danziger J: Management consideration in drug-induced lactic acidosis. Clin J Am Soc Nephrol 15: 15111512, 2020 PubMed

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    Zand Irani A, Almuwais A, Gibbons H: Acquired pyroglutamic acidosis due to long-term dicloxacillin and paracetamol use. BMJ Case Rep 13: e233306, 2020 PubMed

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    Poirier-Blanchette L, Simard C, Schwartz BC: Spurious point-of-care lactate elevation in ethylene glycol intoxication: Rediscovering a clinical pearl. BMJ Case Rep 14: e239936, 2021 PubMed

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