Abstract
Acid–base homeostasis is one of the most tightly regulated systems in the body. Maintaining the acid–base balance is particularly challenging for preterm infants and growing neonates. The kidney, which represents the crucial ultimate line of defense against disturbances of acid–base balance, undergoes a complex maturation process during the transition from a fetal to an extra-uterine environment. This review article summarizes the physiology of acid–base regulation by the immature human kidney and discusses disorders of acid–base balance, such as metabolic acidosis, respiratory acidosis, metabolic alkalosis, and respiratory alkalosis. In conditions of metabolic acidosis, the serum anion gap and the urinary anion gap can be useful tools to define the nature of the acidosis. Metabolic acidosis can reflect a decrease in glomerular filtration rate, or be the consequence of selective disorders of proximal or distal tubular function. Most tubulopathies associated with metabolic acidosis observed in neonates are primary, hereditary, isolated tubulopathies. Proximal renal tubular acidosis is characterized by bicarbonate wasting, while the distal types of renal tubular acidosis are secondary to distal acidification defects. All tubulopathies are associated with hypokalemia, with the exception of type 4 hyperkalemic distal renal tubular acidosis. The transporter defects in the various acid–base tubulopathies are now well defined. Treatment of the acidosis varies according to the site and mechanism of the defect. Chronic renal tubular acidosis or alkalosis severely impair growth and calcium metabolism. Early rational therapeutic intervention can prevent some of the consequences of the disorders and improves the prognosis.
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References
Henderson LJ (1908) The theory of neutrality regulation in the animal organism. Am J Phys 21:427–448. https://doi.org/10.1152/ajplegacy.1908.21.4.427
Hasselbalch KA (1916) The calculation of blood pH via the partition of carbon dioxide in plasma and oxygen binding of the blood as a function of plasma pH. Biochem Z 78:112–144
Berend K, de Vries AP, Gans RO (2014) Physiological approach to assessment of acid-base disturbances. N Engl J Med 371:1434–1445. https://doi.org/10.1056/NEJMra1003327
Iacobelli S, Lapillonne A, Guignard JP (2015) Équilibre acidobasique du nouveau-né à terme et prématuré. EMC - Pédiatrie - Maladies infectieuses 11:1–8. https://doi.org/10.1016/S1637-5017(15)51733-X
Guignard JP, John EG (1986) Renal function in the tiny, premature infant. Clin Perinatol 13:377–401
Sulyok E, Guignard JP (1990) Relationship of urinary anion gap to urinary ammonium excretion in the neonate. Biol Neonate 57:98–106. https://doi.org/10.1159/000243169
Kalhoff H, Manz F, Kiwull P, Kiwull-Schöne H (2007) Food mineral composition and acid-base balance in preterm infants. Eur J Nutr 46:188–195. https://doi.org/10.1093/jn/138.2.431S
Seri I (1995) Cardiovascular, renal, and endocrine actions of dopamine in neonates and children. J Pediatr 126:333–344
Bourchier D, Weston PJ (2015) Metabolic acidosis in the first 14 days of life in infants of gestation less than 26 weeks. Eur J Pediatr 174:49–54. https://doi.org/10.1007/s00431-014-2364-9
van der Vorst MM, Kist JE, van der Heijden AJ, Burggraaf J (2006) Diuretics in pediatrics: current knowledge and future prospects. Paediatr Drugs 8:245–264
Bonsante F, Gouyon JB, Robillard PY, Gouyon B, Iacobelli S (2017) Early optimal parenteral nutrition and metabolic acidosis in very preterm infants. PLoS One 12:e0186936. https://doi.org/10.1371/journal.pone.0186936
Kermorvant-Duchemin E, Iacobelli S, Dit-Trolli SE, Bonsante F, Kermorvant C, Sarfati G, Gouyon JB, Lapillonne A (2012) Early chloride intake does not parallel that of sodium in extremely low birth weight infants and may impair neonatal outcomes. J Pediatr Gastroenterol Nutr 54:613–619. https://doi.org/10.1097/MPG.0b013e318245b428
Iacobelli S, Kermorvant-Duchemin S, Bonsante F, Lapillonne A, Gouyon JB (2012) Chloride balance in preterm infants during the first week of life. Int J Pediatr 2012:931597. https://doi.org/10.1155/2012/931597
Oguz SS, Ergenekon E, Tümer L, Koç E, Turan O, Onal E, Türkyilmaz C, Atalay Y (2011) A rare case of severe lactic acidosis in a preterm infant: lack of thiamine during total parenteral nutrition. J Pediatr Endocrinol Metab 24:843–845
Ashurst I, O'Lone E, Kaushik T, McCafferty K, Yaqoob MM (2015) Acidosis: progression of chronic kidney disease and quality of life. Pediatr Nephrol 30:873–879. https://doi.org/10.1007/s00467-014-2873-9
KDOQI Work Group (2009) KDOQI clinical practice guideline for nutrition in children with CKD: 2008 update. Executive summary. Am J Kidney Dis 53(3 Suppl 2):S11–S104. https://doi.org/10.1053/j.ajkd.2008.11.017
Zelikovic I (2003) Hypokalaemic salt-losing tubulopathies: an evolving story. Nephrol Dial Transplant 18:1696–1700
https://www.omim.org/ last accessed September 2018
Enerbäck S, Nilsson D, Edwards N, Heglind M, Alkanderi S, Ashton E, Deeb A, Kokash FEB, Bakhsh ARA, Van't Hoff W, Walsh SB, D'Arco F, Daryadel A, Bourgeois S, Wagner CA, Kleta R, Bockenhauer D, Sayer JA (2018) Acidosis and deafness in patients with recessive mutations in FOXI1. J Am Soc Nephrol 29:1041–1048. https://doi.org/10.1681/ASN.2017080840
Rodríguez-Soriano J (2002) Renal tubular acidosis: the clinical entity. J Am Soc Nephrol 13:2160–2170
Rodríguez-Soriano J (2000) New insights into the pathogenesis of renal tubular acidosis--from functional to molecular studies. Pediatr Nephrol 14:1121–1136
Demirci FY, Chang MH, Mah TS, Romero MF, Gorin MB (2006) Proximal renal tubular acidosis and ocular pathology: a novel missense mutation in the gene (SLC4A4) for sodium bicarbonate cotransporter protein (NBCe1). Mol Vis 12:324–330
Nandagopal R, Vaidyanathan P, Kaplowitz P (2009) Transient pseudohypoaldosteronism due to urinary tract infection in infancy: a report of 4 cases. Int J Pediatr Endocrinol 195728. https://doi.org/10.1155/2009/195728
Mustaqeem R, Aggarwal S (2018) Renal tubular acidosis. Source StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Bookshelf ID: NBK519044
Plumb LA, Van't Hoff W, Kleta R, Reid C, Ashton E, Samuels M, Bockenhauer D (2016) Renal apnoea: extreme disturbance of homoeostasis in a child with Bartter syndrome type IV. Lancet 388:631–632. https://doi.org/10.1016/S0140-6736(16)00087-8
Azzi A, Chehade H, Deschênes G (2015) Neonates with Bartter syndrome have enormous fluid and sodium requirements. Acta Paediatr 104:e294–e299. https://doi.org/10.1111/apa.12981
Heinly MM, Wassner SJ (1994) The effect of isolated chloride depletion on growth and protein turnover in young rats. Pediatr Nephrol 8:555–560
Perlman JM, Moore V, Siegel MJ, Dawson J (1986) Is chloride depletion an important contributing cause of death in infants with bronchopulmonary dysplasia? Pediatrics 77:212–216
Rodríguez-Soriano J, Vallo A, Castillo G, Oliveros R, Cea JM, Balzategui MJ (1983) Biochemical features of dietary chloride deficiency syndrome: a comparative study of 30 cases. J Pediatr 103:209–214
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Iacobelli, S., Guignard, JP. Renal aspects of metabolic acid–base disorders in neonates. Pediatr Nephrol 35, 221–228 (2020). https://doi.org/10.1007/s00467-018-4142-9
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DOI: https://doi.org/10.1007/s00467-018-4142-9