Pathophysiology and Treatment of Enteric Hyperoxaluria

Abstract

Enteric hyperoxaluria is a distinct entity that can occur as a result of a diverse set of gastrointestinal disorders that promote fat malabsorption. This, in turn, leads to excess absorption of dietary oxalate and increased urinary oxalate excretion. Hyperoxaluria increases the risk of kidney stones and, in more severe cases, CKD and even kidney failure. The prevalence of enteric hyperoxaluria has increased over recent decades, largely because of the increased use of malabsorptive bariatric surgical procedures for medically complicated obesity. This systematic review of enteric hyperoxaluria was completed as part of a Kidney Health Initiative-sponsored project to describe enteric hyperoxaluria pathophysiology, causes, outcomes, and therapies. Current therapeutic options are limited to correcting the underlying gastrointestinal disorder, intensive dietary modifications, and use of calcium salts to bind oxalate in the gut. Evidence for the effect of these treatments on clinically significant outcomes, including kidney stone events or CKD, is currently lacking. Thus, further research is needed to better define the precise factors that influence risk of adverse outcomes, the long-term efficacy of available treatment strategies, and to develop new therapeutic approaches.

Keywords: chronic kidney disease; fat malabsorption; hyperoxaluria; nephrolithiasis.

Figure 1.

Urinary oxalate is derived from a combinaiton of hepatic metabolism and gastrointestinal absorption in enteric hyperoxaluria. (A) Oxalate is an end product of glyoxalate metabolism in the liver. The remainder of systemic oxalate comes from ingestion of certain fruits and vegetables. The oxalate in these plants is in the form of relatively insoluble calcium oxalate crystals. Hence, under normal conditions, only 5%–10% of ingested oxalate is absorbed and the remainder passes into the stool. However, in patients with fat malabsorption of any cause (enteric hyperoxaluria), undigested fatty acids reach the large intestine where they can combine with calcium; (B) the net effect is to release more free oxalate into the intestinal lumen. It is thought that this free oxalate is largely absorbed paracellularly in the large intestine. Due to the fat malabsorption, among patients with enteric hyperoxaluria, the net percentage of ingested oxalate that ends up being absorbed can increase to ≥30%. Any oxalate that comes from the liver or is absorbed from the diet is delivered by (C) the blood to (D) the kidneys, where it is excreted via a combination of glomerular filtration and proximal tubular secretion. The increased delivery of oxalate to the kidneys leads to (E) increased urinary oxalate excretion, which in turn places these patients at risk of calcium oxalate kidney stones, corticomedullary nephrocalcinosis, and oxalate nephropathy.