However, in severe cases that are chronic, permanent kidney failure or death may result. Long term consumption of large amounts of calcium supplementation associated with milk-alkali syndrome has also been linked to adverse cardiovascular outcomes. It was found that over supplementation of calcium can lead to an increased risk for myocardial infarction and vascular calcification. Epidemiology
In the early years after the discovery of milk-alkali syndrome, the prevalence of the disease among people treated with Sippys treatment varied from 2% to 18%. The wide range was attributed to the differing amounts of alkali absorbed among people. In the 1900s, the mortality rate of people with milk-alkali syndrome was found to be 4.4%.The use of milk and alkali to treat gastric ulcers greatly contributed to the development of milk-alkali syndrome in people but the incidence of milk-alkali syndrome greatly diminished when the true cause of most gastric ulcers was identified and drugs other than antacids were developed to treat heartburn, such as acid-reducing drugs like H2-receptor antagonists or proton pump inhibitors. These new drugs replaced Sippys diet treatment for peptic ulcers. However, the incidence of milk-alkali syndrome has increased again since the 1990s due to increased osteoporosis awareness and the preventative routine use of calcium supplements. The consumption of calcium supplementation in todays society, mostly to prevent osteoporosis, has aided in the resurgence of milk-alkali syndrome and has sparked conversation about changing the name of milk-alkali syndrome to calcium alkali syndrome as it more accurately reflects the cause of this syndrome.
However, it is well known that MAS is usually associated with a triad of symptoms that include hypercalcemia, alkalosis, and acute kidney injury. In general, milk-alkali syndrome starts with excess calcium levels in the body (hypercalcemia), which causes the bodys pH to increase (become more alkaline) resulting in metabolic alkalosis and ultimately contributes to a decrease in renal function.Factors involved in the development of hypercalcemia include excess intestinal absorption of calcium, saturation of the bones buffering capacity for calcium, decreased renal excretion, and abnormal vitamin D metabolism. Underlying kidney disease is a risk factor for MAS, but even people with healthy kidneys can develop the syndrome.For a healthy individual, if calcium levels are high, the kidneys will decrease its production of calcitriol (active vitamin D) by reducing the hydroxylation of calcidiol (inactive vitamin D); lower calcitriol levels means a lower rate of calcium absorption in the small intestine, which eventually offsets the elevated calcium levels. However, excessive ingestion of calcium of more than 10-15 g per day has been reported to cause calcium levels too high for renal calcitriol suppression to control, resulting in net calcium absorption that ultimately causes hypercalcemia.Hypercalcemia affects the kidneys in multiple ways that altogether contributes to hypovolemia. Prolonged hypercalcemia can decrease glomerular filtration rate (GFR) via vasoconstriction, reduce creatinine clearance, and eventually cause renal insufficiency. Hypercalcemia also causes natriuresis by blocking the Na-K-Cl cotransporter (NKCC) in the medullary thick ascending limb of the loop of Henle, leading increased sodium excretion followed by water excretion that leads to hypovolemia.