Oxalate nephrocalcinosis

In conclusion, the kidney protects itself against calcium oxalate nephrocalcinosis/lithiasis at different levels. Failure or saturation of these protection mechanisms, might explain why patients develop renal and/ or urinary tract calcifications. 

The same authors have shown that oxalate nephrocalcinosis and hyperoxaluria can be reproduced in animals such as rats (G6) or cats (G7) by vitamin Be deficiency. The main difference between the experimental disease and patients with oxalosis is the absence of extrarenal deposits in the former (G7). The urinary excretion of oxalate in vitamin Be-deflcient rats can be enhanced by dietary supplementation with vitamin Be antagonists, such as deoxypyridoxine or isonicotinic hydra-zide, or with glycine, which appears to be the endogenous source of the excessive oxalate production, as in patients with oxalosis (G6). 

Glycinuria results from a defect in renal tubular reabsorption. The defect in primary hyperoxaluria is the failure to catabolize glyoxylate formed by deamination of glycine. Subsequent oxidation of glyoxylate to oxalate results in urohthiasis, nephrocalcinosis, and early mortality from renal failure or hypertension. 

G7. Gershoff, S. N., and Andrus, S. B., Dietary magnesium, calcium, and vitamin Bg and experimental nephropathies in rats calcium oxalate calculi, apatite nephrocalcinosis. J. Nutr. 73, 308-316 (1961). 

In some infants receiving parenteral nntrition nephro-calcinosis occnrs. Parenteral nntrition solntions contain the oxalate precnrsors ascorbate and glycine, and in one stndy of very low birth weight infants (111) administration of parenteral nntrition protein of abont 0.5 g/kg/day was associated with an increased nrinary oxalate/creatinine ratio the effect was dose-dependent. Raised nrinary oxalate concentrations may be a factor in the pathogenesis of nephrocalcinosis in these infants. 

Since unresolved nephrocalcinosis may lead to residual abnormalities in the kidney including microscopic hematuria, hypercalcemia, and impaired tubular function [100,104,105], renal ultrasonography within a few months of initiating loop diuretics may be warranted [100 104]. If long-term diuretic therapy is needed, a thiazide diuretic alone or in combination with furosemide may reduce the risk of renal calcifications by decreasing urinary calcium and oxalate excretion [100,102,104,107,108]. However, two studies of premature infants failed to show a reduction in either urinary oxalate or calcium excretion when thiazides were added to furosemide therapy [107,109]. 

Oxalate as component and/or inducer of renal calcifications (nephrocalcinosis)... 

The acute interstititial nephritis after oxalate overload may be due to calcium oxalate crystals inducing obstructive effect, nephrocalcinosis and also by inducing apoptosis of renal epithelial cells [22, 23, 25]. 

Glyoxalate can be transaminated to glycine, reduced to glycolate, converted to a-hydroxy-/3-ketoadipate by reaction with a-ketoglutarate, or oxidized to oxalate and excreted in urine. The first three reactions require pyridoxal phosphate, NADH, and thiamine pyrophosphate, respectively. In humans, ascorbic acid (vitamin C) is a precursor of urinary oxalate (Chapter 38). Since calcium oxalate is poorly soluble in water, it can cause nephrolithiasis and nephrocalcinosis due to hyperoxaluria. 

Primary hyperoxaluria has been defined by Archer et al. (A7, A9) as a clinical entity characterized by progressive calcium oxalate urolithiasis and nephrocalcinosis beginning in early childhood. It might be associated with disseminated extrarenal calcium oxalate deposits, a condition known as oxalosis (A7) it is not known whether oxalosis always represents a stage in the natural history of primary hyperoxaluria (S9). 

Chou, L.Y., Donohue, W.L. Oxalosis possible inborn error of metabolism with nephrolithiasis and nephrocalcinosis due to calcium oxalate as predominating features. Pediatrics 10, 660-666 (1952)... 

Urinary oxalate plays a crucial role in urolithiasis, primarily due to the extremely low solubility of its calcium salt. This may lead to crystalluria, urolithiasis and nephrocalcinosis. The pathology of oxalate in humans can be divided into three principal groups ... 

Neuhaus TJ, Belzer T, Blau N, Hoppe B, Sidhu H, Leumann E Urinary oxalate excretion in urolithiasis and nephrocalcinosis. Arch Dis Child 2000 82 322-326. 

Davies M (1989) High-dose vitamin D therapy indications, benefits and hazards. Int J Vit Nutr Res 30 81-86 De Santo NG, lorio BD, Capasso G, Paduano C, Stamler R, Langman CB, Stamler J (1992) Population based data on urinary excretion of calcium, magnesium, oxalate, phosphate and uric acid in children from Cimitile (southern Italy). Pediatr Nephrol 6 149-157 Dick PT, Shuckett BM, Tang B, Daneman A, Kooh SW (1999) Observer reliability in grading nephrocalcinosis on ultrasound examinations in children. Pediatr Radiol 29 68-72... 

High oxalate concentrations in human urine and blood cause primary and secondary hyperoxaluria, chronic renal failure and formation of nephrocalcinosis. Therefore, precise and sensitive methods are required to detect oxalate in urine or blood, and in food for quality analysis. Measurement of oxalate in biological matrices requires separation methods due to the presence of other interfering species. Direct electrochemical detection methods have been proven to be simple and economical for the detection of... 

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