The milk-alkali syndrome
- Alan S L Yu, MB, BChir
Alan S L Yu, MB, BChir
- Harry Statland and Solon Summerfield Professor of Medicine
- University of Kansas Medical Center
- Jason R Stubbs, MD
Jason R Stubbs, MD
- Associate Professor of Medicine
- Division of Nephrology & Hypertension
- University of Kansas Medical Center
The milk-alkali syndrome consists of the triad of hypercalcemia, metabolic alkalosis, and acute kidney injury associated with the ingestion of large amounts of calcium and absorbable alkali. The syndrome was originally described in association with the use of milk and sodium bicarbonate for the treatment of peptic ulcer disease . Once a classic cause of hypercalcemia, the milk-alkali syndrome virtually disappeared with the advent of new therapies of peptic ulcer disease and, by 1985, was considered the cause of less than one percent of cases of hypercalcemia .
However, there has since been a resurgence of this disorder, and it may account for up to 12 percent of cases, making it the third leading cause of hypercalcemia behind primary hyperparathyroidism and malignancy [3,4]. (See "Etiology of hypercalcemia".)
Three factors are responsible for this increase in incidence:
●The emphasis on calcium therapy for the prevention and treatment of osteoporosis.
●Readily available over-the-counter calcium carbonate preparations.
- Cope CL. Base changes in the alkalosis produced by the treatment of gastric ulcer with alkalies. Clin Sci 1936; 2:287.
- Jamieson MJ. Hypercalcaemia. Br Med J (Clin Res Ed) 1985; 290:378.
- Beall DP, Scofield RH. Milk-alkali syndrome associated with calcium carbonate consumption. Report of 7 patients with parathyroid hormone levels and an estimate of prevalence among patients hospitalized with hypercalcemia. Medicine (Baltimore) 1995; 74:89.
- Picolos MK, Lavis VR, Orlander PR. Milk-alkali syndrome is a major cause of hypercalcaemia among non-end-stage renal disease (non-ESRD) inpatients. Clin Endocrinol (Oxf) 2005; 63:566.
- Sippy BW. Gastric and duodenal ulcer: Medical cure by an efficient removal of gastric juice corrosion. JAMA 1915; 64:1625.
- Hardt LL, Rivers AB. Toxic manifestations following the alkaline treatment of peptic ulcer. Arch Intern Med 1923; 31:171.
- Kirsner JB, Palmer WL. Alkalosis complicating the Sippy treatment of peptic ulcer. Arch Intern Med 1942; 69:789.
- Kapsner P, Langsdorf L, Marcus R, et al. Milk-alkali syndrome in patients treated with calcium carbonate after cardiac transplantation. Arch Intern Med 1986; 146:1965.
- Bronner F. Mechanisms of intestinal calcium absorption. J Cell Biochem 2003; 88:387.
- Felsenfeld AJ, Levine BS. Milk alkali syndrome and the dynamics of calcium homeostasis. Clin J Am Soc Nephrol 2006; 1:641.
- McMillan DE, Freeman RB. The milk alkali syndrome: a study of the acute disorder with comments on the development of the chronic condition. Medicine (Baltimore) 1965; 44:485.
- Sutton RA, Wong NL, Dirks JH. Effects of metabolic acidosis and alkalosis on sodium and calcium transport in the dog kidney. Kidney Int 1979; 15:520.
- Patel AM, Goldfarb S. Got calcium? Welcome to the calcium-alkali syndrome. J Am Soc Nephrol 2010; 21:1440.
- Adams ND, Gray RW, Lemann J Jr. The effects of oral CaCO3 loading and dietary calcium deprivation on plasma 1,25-dihydroxyvitamin D concentrations in healthy adults. J Clin Endocrinol Metab 1979; 48:1008.
- Broadus AE, Insogna KL, Lang R, et al. Evidence for disordered control of 1,25-dihydroxyvitamin D production in absorptive hypercalciuria. N Engl J Med 1984; 311:73.
- Dorsch TR. The milk-alkali syndrome, vitamin D, and parathyroid hormone. Ann Intern Med 1986; 105:800.
- Abreo K, Adlakha A, Kilpatrick S, et al. The milk-alkali syndrome. A reversible form of acute renal failure. Arch Intern Med 1993; 153:1005.
- Picolos MK, Sims CR, Mastrobattista JM, et al. Milk-alkali syndrome in pregnancy. Obstet Gynecol 2004; 104:1201.
- Ennen CS, Magann EF. Milk-alkali syndrome presenting as acute renal insufficiency during pregnancy. Obstet Gynecol 2006; 108:785.
- Kolnick L, Harris BD, Choma DP, Choma NN. Hypercalcemia in pregnancy: a case of milk-alkali syndrome. J Gen Intern Med 2011; 26:939.
- Swanson CM, Mackey PA, Westphal SA, Argueta R. Nicotine-substitute gum-induced milk alkali syndrome: a look at unexpected sources of calcium. Endocr Pract 2013; 19:142.
- McGuinness B, Logan JI. Milk alkali syndrome. Ulster Med J 2002; 71:132.
- Lin SH, Lin YF, Cheema-Dhadli S, et al. Hypercalcaemia and metabolic alkalosis with betel nut chewing: emphasis on its integrative pathophysiology. Nephrol Dial Transplant 2002; 17:708.
- Allen SE, Singh S, Robertson WG. The increased risk of urinary stone disease in betel quid chewers. Urol Res 2006; 34:239.
- Medarov BI. Milk-alkali syndrome. Mayo Clin Proc 2009; 84:261.
- Orwoll ES. The milk-alkali syndrome: current concepts. Ann Intern Med 1982; 97:242.
- Cooke AM. Alkalosis occurring in the alkaline treatment of peptic ulcers. Quart J Med 1932; 25:527.
- BURNETT CH, COMMONS RR. Hypercalcemia without hypercalcuria or hypophosphatemia, calcinosis and renal insufficiency; a syndrome following prolonged intake of milk and alkali. N Engl J Med 1949; 240:787.
- Junor BJ, Catto GR. Renal biopsy in the milk-alkali syndrome. J Clin Pathol 1976; 29:1074.
- Kallmeyer JC, Funston MR. The milk-alkali syndrome. A case report. S Afr Med J 1983; 64:287.
- PUNSAR S, SOMER T. The milk-alkali syndrome. A report of three illustrative cases and a review of the literature. Acta Med Scand 1963; 173:435.