Hyperoxaluric calcium nephrolithiasis

Oxalate is a metabolic waste product excreted by the kidney. Hyperoxaluria is a common cause of kidney stones due to the low solubility of calcium oxalate salts. Severe hyperoxaluria may lead to loss of renal function and systemic oxalosis. Hyperoxaluria can be caused by genetic defects that lead to endogenous overproduction or by absorption of excessive amounts of oxalate from the diet. This article reviews oxalate metabolism and the clinical syndromes leading to hyperoxaluria. Nephrolithiasis is the most common chronic disorder of the urinary tract in the United States. Calcium oxalate is the predominant component in 70% to 80% of kidney stones. Oxalate is an end product of human metabolism produced in the liver and excreted primarily by the kidney. Oxalate is also absorbed from the diet so that renal excretion reflects the combined endogenous and exogcnous oxalate loads. The clinical significance of oxalate is related to the low solubility of its calcium salt. High urine oxalate excretion increases urine calcium oxalate supersaturation and, therefore, the risk of kidney stone formation. In human urine, calcium concentration is about ten fold greater than oxalate on a molar basis. Relatively modest increases in urine oxalate excretion will have significant effects on urine supersaturation [1], especially in patients with hypercalciuria where calcium is in even greater excess of oxalate. Hyperoxaluria can be caused by defects in oxalate metabolism, overabsorption of dietary oxalate secondary to bowel disease, or from consumption of diets rich in oxalate or oxalate precursors. Oxalate excretion tends to be higher in kidney stone formers than control subjects, though there is considerable overlap between the groups [2-4]. Hyperoxaluria has been estimated to occur in 8% to 50% of stone formers [5-7]. The wide range of prevalence estimates for hyperoxaluria is likely due to differences in laboratory methods, definition of upper limit of normal for urine oxalate excretion, and dietary differences in the populations studied. Most laboratories define hyperoxaluria as oxalate excretion greater than 0.5 mmole per day (45 mg/day). The importance of oxalate in kidney stone disease cannot be questioned. However, less emphasis has been placed on oxalate than other stone risk factors over the years. The reasons for this are myriad. Laboratory measurement of oxalate is complex and has become widely available only in recent years. Measuring oxalate content of foodstuffs is difficult so that complete and reliable catalogues of food oxalate content are lacking. Without adequate knowledge of food oxalate content dietary manipulations of oxalate are difficult in both research and clinical settings. Finally, interventions aimed at reducing urine oxalate have not received the same rigorous controlled trials that have been used in evaluating thiazide diuretics for hypercalciuria, potassium citrate for hypocitraturia, and allopurinol for hyperuricosuria. However, in the last 10 to 15 years there have been many significant advances that have focused attention on oxalate. New insights into oxalate metabolism from studies of patients with primary hyperoxaluria, improved understanding of intestinal absorption and secretion, and the potential role of oxalate degrading bacteria in controlling intestinal absorption of oxalate have enhanced our understanding and treatment of calcium oxalate nephrolithiasis.