Researchers gaining a better understanding of the genetic basis for oxalate absorption.
Nephrolithiasis results from an interaction between diet and genetic predisposition. Most renal stones contain calcium oxalate, which is why controlling urinary calcium concentration is viewed as prophylactic.
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Sometimes, however, patients with a calcium oxalate stone don’t have elevated urinary calcium. In these cases, the cause may be hyperoxaluria. Because urinary oxalate is not measured routinely, typically a urine sample must be sent out for analysis. If oxalate is elevated, even mildly, moderate dietary oxalate restriction may be the best course to follow. In fact, eliminating the 10 foods highest in oxalate per serving may be all that is needed to decrease oxalate enough to reduce the risk of recurrent stones.
Most patients are already advised to cut out the three foods highest in oxalate: rhubarb, spinach, and beets (both roots and leaves).
The other oxalate-rich foods that should be eliminated are peanuts, bran, tree nuts, legumes (including soy), chocolate, brans, and regular tea (not herbal). An 11th food, parsley, is actually highest of all in oxalate concentration, and I have encountered several kidney stone patients who regularly ate substantial amounts of the decorative parsley on catered and restaurant food plates. For most of my hyperoxaluric patients, eliminating these foods has brought oxalate down substantially, even if not to “normal” levels.
If a patient is an oxalate hyperabsorber, greater restriction may be needed. Some Web sites provide oxalate values of foods. The Oxalosis and Hyperoxaluria Foundation Web site, for example, classifies foods as low, moderate and high in oxalate content, so no counting of oxalate mg is needed (www.ohf.org/docs/Oxalate2004.htm). My colleague Susan A. Kynast-Gales, PhD, RD, and I have compiled a database of all 1,203 published food oxalate values in the English literature since 1980 at http://www.spokane.wsu.edu/research%26service/HREC
/FoodOxalateOverview.asp. Note that the actual oxalate content of a food varies with its cultivation conditions, the variety and sometimes its cooking process, so if the exact value is needed, a direct analysis of that food must be done. For dietary counseling, however, avoidance of a relatively few foods is often sufficient, even for those with a genetic predisposition to hyperoxaluria.
Researchers are making headway in understanding the genetic basis for oxalate absorption. Oxalate enters and leaves cells, including epithelia, via an oxalate-chloride exchanger, driven by the balance of the concentration gradients of the anions across the cell membrane. In the kidney and intestine, it is expressed on the apical membrane, where it mediates oxalate secretion. The mouse gene for this transfer is designated as SLC26A6. Two recent reports on mice lacking this active gene (knock-out or KO) have given us fresh insights into oxalate kinetics and a gene potentially causing human hyperoxaluria.
First, Robert W. Freel, MD, at the University of Florida, and his colleagues (Am J Physiol Gastrointest Liver Physiol. 2006;290:G719-728) reported that both ileal oxalate absorption and urinary oxalate excretion are enhanced in SLC26A6-null (KO) mice. Gut lumen-to-blood oxalate flux (i.e., absorption) was three times greater, and blood-to-gut lumen flux (i.e., secretion) was one half in KO mice compared to wild-type (WT) mice, so net absorption was much greater in the KO mice. This enhanced oxalate absorption in KO mice raised their plasma oxalate levels by 28% and their urinary oxalate fourfold.
This same transporter protein is found in renal epithelia. Shortly after publication of the paper by Dr. Freel’s group, a team led by Zhirong Jiang, MD, of the Yale University School of Medicine in New Haven, reported that nephrolithiasis developed in KO mice as a result of impaired reabsorption of oxalate in the kidney as well as increased intestinal absorption (Nat Genet. 2006;38:474-478). Consequently, the relative urinary supersaturation of calcium oxalate was 62.5 in KO mice, compared with 16.7 in WT mice. The investigators confirmed the finding of Freel et al that KO mice have a defect in intestinal oxalate secretion that results in an enhanced absorption. Interestingly, male KO mice had a higher incidence of stones than females, probably due to their higher urinary calcium, which Dr. Jiang’s team could not explain. When KO mice were fed an oxalate-free diet, their urinary oxalate fell from 3.5 to 1 mM, similar to urinary oxalate in WT mice fed a commercial mouse diet with oxalate. This confirmed that overabsorption of dietary oxalate was the source of the increase in urinary oxalate.
The human SLC26A6 transport protein has the same metabolic properties as the mice protein, so a genetic defect in this gene may be responsible for human oxalate hyperabsorption that leads to
calcium oxalate nephrolithiasis. Susanne Voss, MD, and her colleagues at the University of Bonn in Germany showed that average intestinal oxalate absorption is 25% higher in idiopathic calcium oxalate stoneformers than healthy controls, although there is considerable overlap (J Urol. 2006;175:1711-1715). Only in the stoneformers did absorption values greater than 20% appear (the normal value is 6%-10%).
