Leukemia (Blood Cancer)

 Calcium oxalate crystals which look like grains of sand come together to form kidney stones, these stones can inflict severe pain now imagine having to deal with recurrent kidney stones which could be a sign of multiple genetic disorders that go undetected for years, one of these genetic conditions is called primary hyperoxaluria or ph primary hyperoxaluria is a family of rare autosomal recessive disorders in which the liver overproduces oxalate an end product of metabolism in humans that has no known benefit oxalate is normally excreted by the kidneys.

Then what happens? Differently in people with ph well the genetic mutations lead to certain enzyme deficiencies in the hepatocytes causing overproduction of oxalate there are three known types of ph; ph1, ph2, and ph3 which are caused by one of three different mutations as a result the breakdown of glyoxylate are disrupted glyoxylate then starts to build up in the cell's cytoplasm regardless of the ph type excess glyoxylate is broken down into oxalate by the hepatic enzyme LDH, A therapy that targets LDH can inhibit oxalate overproduction in all ph types the overproduced oxalate then travels to the kidneys where it is normally filtered along with other waste and harmful products when excess oxalate accumulates it starts to bind with calcium forming calcium oxalate crystals.

These crystals may clump together to form kidney stones also known as nephrolithiasis the stones can cause obstructions in the kidneys the urinary tract and the bladder, multiple surgical interventions which can cause damage to the kidneys may be required to remove stones, and calcium oxalate crystals can also cause nephrocalcinosis or calcification of the kidney, calcification causes kidney damage infection and inflammation and reduces the kidneys filtering ability leading to a decline in renal function. If untreated this can lead to chronic kidney disease and eventually end-stage renal disease which may require dialysis and a dual liver-kidney transplant. Systemic oxalosis will begin when the glomerular filtration rate drops below 35 to 40m/m, in systemic oxalosis the excess calcium oxalate that cannot be filtered by the kidneys escapes and starts to deposit in the tissues of the skin, heart, eyes, and skeleton.

Early diagnosis along with aggressive supportive treatment can reduce the formation of new kidney stones and slow the progression to end-stage renal disease and systemic oxalosis there are ongoing efforts to develop treatments that if approved will address the overproduction of oxalate by hepatic LDH which drives the progression of PH.