Kidney failure from oxalate nephropathy is a devastating complication of disorders of oxalate metabolism (e.g., primary hyperoxaluria), oxalate absorption (e.g., enteric hyperoxaluria), and toxic ingestion (e.g., ethylene glycol). In these disorders, high concentration of oxalate in proximal tubular fluid leads to supersaturation, calcium oxalate crystal formation, obstruction, and direct injury to tubular epithelial cells leading ultimately to decreased glomerular filtration rate (GFR). Oxalate may be toxic even in the absence of supersaturation and calcium oxalate crystal formation. Oxalate has been shown to cause endothelial dysfunction as well as mitochondrial damage and oxidative stress to kidney tubular cells. Substantial epidemiologic evidence also links kidney stones—of which calcium oxalate is the predominant type—to the development of both CKD and CVD.
In CKD of any cause, systemic oxalate levels rise because the primary route of oxalate excretion is through the kidneys. Lower GFR leads to higher concentrations of oxalate in plasma and glomerular ultrafiltrate, resulting in increased exposure of remaining tubular cells to oxalate. Low GFR may initiate a progressive cycle of oxalate retention, kidney damage, lower GFR, and further oxalate retention. Indeed, calcium oxalate crystals have been identified in the renal parenchyma, myocardium, and blood vessels of patients with CKD from any cause. In CKD, plasma oxalate levels (POx) increase with falling GFR whereas 24h urinary oxalate excretion (UOx24) remains relatively unchanged even in advanced CKD. However, POx and UOx24 are not simply GFR markers. We are testing whether hyperoxaluria may be an under-appreciated risk factor for CKD progression by measuring 24h urine oxalate excretion in the CRIC cohort study.