Calcium oxalate nephrolithiasis

Urinary oxalate Some patients may develop increased levels of urinary oxalate following treatment. Exercise caution in patients with a history of hyperoxaluria or calcium oxalate nephrolithiasis. 

Viscosity of THP solutions increases markedly when the sodium chloride concentration is > 60 mM. Increasing the concentration of calcium and/.or a reduction in pH also increase viscosity and may account for the involvement of THP in the pathogenesis of cast nephropathy and tubulointerstitial nephritis. THP appears to have an inhibitory effect on urinary crystal arrgegation [154] and may play a role in preventing renal stone formation [155]. In some humans with calcium oxalate nephrolithiasis, a molecular abnormality of THP has been detected [156]. Other studies showed decreased urinary levels of THP in patients with nephrolithiasis [157, 158]. A relative deficiency in THP has been associated with impaired inhibition of crystal adhesion to renal epithelial cells instone formers [159]. 

In a recent publication Sikora et al. found that increased intestinal oxalate absorption is an important risk factor for idiopathic calcium oxalate nephrolithiasis [16]. This observation may have important implications for the prevention of this disease. 

Khan SR, Johnson JM, Peck AB, Cornelius JG, Glenton PA. Expression of osteopontin in rat kidneys induction during ethylene glycol induced calcium oxalate nephrolithiasis. J.Urol. 2002 168 1173-81. 

Thamiselvan S, Hackett RE, Khan SR. Lipid peroxidaition in ethylene glycol induced hyperoxaluria and calcium oxalate nephrolithiasis. J.Urol. 1997 157 1059-63. 

Baggio B, Gambaro G, Ossi E, Favaro S, Borsatti A. Increased urinary excretion of renal enzymes in idiopathic calcium oxalate nephrolithiasis. J.Urol. 1983 129(6) 1161 -2. 

Evan AP, Lingeman JE, Coe FL, Worcester EM. Randall s plaque pathogenesis and role in calcium oxalate nephrolithiasis. Kidney Int. 2006 69 1313-8. 

Hess B, Nakagawa Y, Parks JH, Coe FL. Molecular abnormality of Tamm-Horsfall glycoprotein In calcium oxalate nephrolithiasis. Am.J.Physlol. 1991 260 569-78. 

Kok DJ, Khan SR. Calcium oxalate nephrolithiasis, a free or fixed particle diseaese. Kidney Int. 1994 46 847-54. 

Khan SR, Thamiselvan S. Nephrolithiasis a consequence of renal epithelial cell exposure to oxalate and calcium oxalate. Mol. Urol.2000 4(4) 305-11. 

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. 

Nephrolithiasis occurs in 10% to 25% of patients with gout. Factors that predispose individuals to uric acid nephrolithiasis include excessive urinary excretion of uric acid, an acidic urine, and a highly concentrated urine. The risk of renal calcuh approaches 50% in individuals whose renal excretion of uric acid exceeds 1100 mg/day. In addition to pure uric acid stones, hyperuricosuric individuals are at increased risk for mixed uric acid-calcium oxalate stones and pure calcium oxalate stones. Uric acid stones are usually small, round, and radiolucent. Uric acid stones containing calcium are radiopaque. Uric acid has a negative logarithm of the acid ioiuzation constant of 5.5. Therefore when the urine is acidic, uric acid exists primarily in the un-ionized, less soluble form. At a urine pH of 5.0, urine is saturated at a uric acid level of 15 mg/dL. When the urine pH is 7.0, the solubility of uric acid in urine is increased to 200 mg/dL. In patients with uric acid nephrolithiasis, urinary pH typically is less than 6.0 and frequently less than 5.5. When an acidic urine is saturated with uric acid, spontaneous precipitation of stones may occur. 

According to Zollner up to 40% of all gout patients aquire nephrolithiasis. There are — as found Gutman an Yu — not just uric acid stones involved, but in 12% of the gout patients calcium stones were also discovered these were mainly stones of calcium oxalate. 

Davis, J.S., Klingberg, W.G., Stowell, R.E. Nephrolithiasis and nephro-calcinosis with calcium oxalate crystals in kidneys and bones. J. Pediat. 36, 323-334(1950)... 

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)... 

A group of patients forming calcium oxalate stones are hyperuri-cosuric and it is thought that their excessive urate excretion contributes to calcium-stones formationl. The pathomechanisms invoked are dietary purine excess and endogenous uric acid overproduction, being defective tubular reabsorption of urate "unattractive because uricemia was found to be normal in patients with recurrent calcium nephrolithiasis (RCN) and hyperuricosuria. Current studies were undertaken to define the incidence, role of diet, abnormalities of the renal handling of urate, and associated metabolic disturban-c"es in patients with RCN and hyperuricosuria. 

Unfortunately nephrolithiasis is a recirrrent disease and about 75% of patients suffer the recurrence within 10 years. Therefore it is important to develop new more efficient preventative therapies, which can inhibit the formation of kidney stones or possess properties of dissolution of calciitm oxalate deposits. The possible approach constitutes modeling the potential inhibitors forming calcium oxalate crystals. On the other hand there are available compoimds directly influencing the calciiun oxalate formation (inhibitory or dissolution effect) e.g. citrate. It should be noted that compounds possessing dissolution properties of calcimn oxalate carmot interfere too much into the whole calcimn economy. 

Urinary excretion of uric acid, oxalic acid, calcium, phosphate, hydroxyproline and cAMP was higher in patients with renal stones than that observed in patients without nephrolithiasis, but the difference was not statistically significant. 

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