Evidence for net renal tubule oxalate secretion in patients with calcium kidney stones

Abstract

Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normal subjects, and 2 bariatric stone formers (BSF) during a 1-day General Clinical Research Center protocol utilizing a low-oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate-filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was >1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared with none of the controls (P < 0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normal subjects with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in calcium stone formers, potentially as a means of maintaining plasma oxalate in a tight range.

Persistence of 1,25D-induced hypercalciuria in alendronate-treated genetic hypercalciuric stone-forming rats fed a low-calcium diet

“…Although there was no significant difference in uOx between GHS and SD rats, numerically uOx was higher in GHS, consistent with the observation that patients with IH may exhibit mild hyperoxaluria (7). Compared with SD, the GHS rat has increased intestinal Ca absorption (44) leading to more free oxalate in the intestine and greater availability for Ox absorption and excretion.…”

Body Fat Content and Distribution and Urinary Risk Factors for Nephrolithiasis

“…Greater BMI was associated with higher urinary oxalate excretion among women but not among men in two studies (38,39), whereas one report noted a correlation between body weight and urinary oxalate in men but not in women (40). Potential mechanisms for the greater oxalate excretion in the obese include increased dietary intake of oxalate precursors (41), reduced oxalate degradation in the gut lumen by intestinal bacterial flora (e.g., Oxalobacter formigenes) (42), enhanced intestinal absorption (43), greater endogenous oxalate production (44), and/or differences in renal oxalate handling (45). While the association among body weight, adiposity, and urine oxalate deserves further exploration, we did not observe a significant association between various adiposity markers and SI calcium oxalate in our cohort.…”

Primary and secondary hyperoxaluria: Understanding the enigma

“…In rat kidney, tubular reabsorption has been demonstrated in the S1 and S2 segments of the proximal tubule [14] which may help decrease the tendency for calcium oxalate supersaturation in the earlier parts of the nephron [3] . Overall, the contribution of tubular secretion in addition to glomerular filtration is critical in regulating plasma oxalate levels as a strong correlation has been demonstrated between high plasma oxalate levels and oxalate secretion [20] . It has also been noted that tubular oxalate secretion is increased in PH patients possibly in an attempt to mitigate the life threatening consequences of systemic oxalosis [21] .…”