Uric acid nephrolithiasis

Patients with recurrent attacks, evidence of tophi or joint destruction, or uric acid nephrolithiasis are candidates for maintenance therapy with allopurinol or probenecid to lower serum uric add levels. 

Uric acid excretion is reduced in patients with chronic kidney disease, putting them at risk for hyperuricemia. In patients with persistently acidic urine and hyperuricemia, uric acid nephrolithiasis can occur in up to 25% of patients in severe cases, uric acid stones can cause nephropathy and renal failure. Extreme hyperuricemia can occur because of rapid tumor cell destruction in patients undergoing chemotherapy for certain types of cancer (see Chap. 85). 

Some drugs can cause hyperuricemia and gout, such as thiazide diuretics, niacin, pyrazinamide, cyclosporine, and occasionally, low-dose aspirin. In most cases, these drugs block uric acid secretion in the kidney. Long-term consequences of gout and hyperuricemia include joint destruction, tophi, and nephrolithiasis. 

The term gout describes a disease spectrum including hyperuricemia, recurrent attacks of acute arthritis associated with monosodium urate crystals in leukocytes found in synovial fluid, deposits of monosodium urate crystals in tissues (tophi), interstitial renal disease, and uric acid nephrolithiasis. 

Uric acid nephrolithiasis occurs in 10% to 25% of patients with gout. Predisposing factors include excessive urinary excretion of uric acid, acidic urine, and highly concentrated urine. 

Prostatic hypertrophy, infection, cancer Improperly placed bladder catheter Anticholinergic medication Cancer with abdominal mass Retroperitoneal fibrosis Nephrolithiasis Nephrolithiasis Oxalate Indinavir Sulfonamides Acyclovir Uric acid... 

Since allopurinol blocks xanthine conversion to uric acid, urinary xanthine excretion is increased, creating a risk of xanthine crystal formation in the urinary system or even in muscles this can result in nephrolithiasis (12). It is still an open question whether a predisposition to renal disease or renal disease itself is required to precipitate these adverse effects. It is also not known whether increased excretion of orotic acid, due to an interaction of allopurinol with pyrimidine formation, has any consequences for these adverse effects or for its role in reducing glucose tolerance. 

Hricik DE, Goldsmith GH. Uric acid nephrolithiasis and acute renal failure secondary to streptozotocin nephrotoxicity. Am J Med 1988 84(l) 153-6. 

Triamterene has been reported to cause photosensitivity reactions, increase in uric acid concentration, and blood dyscrasias.91 Nephrolithiasis may occur in susceptible patients. Megaloblastic anemia has been reported in patients with depleted folic acid stores such as those with hepatic cirrhosis. In a study conducted on rats, daily treatment of the animals with doses of 1.5, 3 and 4.5 mg/lOOg over the period of three weeks caused severe degenerative changes of renal cortical and medullary tubules resembling osmotic nephrosis.93 Reversible acute renal failure from combined triamterene and indomethacin in healthy subjects is reported.94 It is recommended that this potentially nephrotoxic association be avoided. 

Cameron, M.A., N.M. Maalouf, B. Adams-Huet, O.W. Moe, and K. Sakhaee. Urine Composition in Type 2 Diabetes Predisposition to Uric Acid Nephrolithiasis. Journal of the American Society of Nephrology 17, no. 5 (May 2006) 1422-28. 

Uric acid nephrolithiasis should be treated with adequate hydration (2 to 3 L/day), a daytime urine-alkalinizing agent, and a 250-mg bedtime dose of acetazolamide. 

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. 

The medical management of uric acid nephrolithiasis includes hydration sufficient to maintain a urine volume of... 

The mainstay of drug therapy for recurrent uric acid lithiasis is allopurinol. It is effective in reducing both serum and urinary uric acid levels, thus preventing the formation of calculi. Allopurinol is also recommended as prophylactic treatment in patients who wfll receive cytotoxic agents for the treatment of lymphoma or leukemia. The marked increase in uric acid production associated with cytolysis of a neoplasm predisposes a patient to the development of uric acid nephrolithiasis. 

Uric acid nephrolithiasis calcium renal stones Malignant mesothelioma Status epilepticus Herpes simplex encephalitis Neurosyphilis Status epilepticus Cognitive dysfunction Malignant non-Hodgkin s lymphomas Treatment of PCP associated with AIDS Acanthamoeba keratitis Peripheral arterial occlusive disease Congenital or acquired protein C deficiency Respiratory distress syndrome associated with prematurity... 

Candidates for teriparatide treatment include women who have a history of osteoporotic fracture, who have multiple risk factors for fracture, or who failed or are intolerant of previous osteoporosis therapy. Teriparatide should not be used in patients who are at increased baseline risk for osteosarcoma (including those with Paget s disease of bone, unexplained elevations of alkaline phosphatase, open epiphyses, or prior radiation therapy involving the skeleton). Full-length PTH(l-84), which is in clinical trials, has not been associated with osteosarcomas. Other adverse effects have included exacerbation of nephrolithiasis and elevation of serum uric acid levels. 

Thiazide diuretic prototype acts in distal convoluted tubule (DCT) to block Na+/Cl transporter used in HTN, CHF, nephrolithiasis. Tox a sulfonamide increased serum lipids, uric acid, glucose K wasting. 

Increased uric acid in serum as a result of animal protein overconsumption and alcohol abuse is frequent nowadays. Concentrations above 6,5 mg uric acid/100 ml serum can lead to the deposition of uric acid or its salts in tissues, which in turn can lead to gout. Up to 40% of the patients suffering from gout also have uric acid nephrolithiasis. Without showing the symptoms of gout, however, uric acid stones as well as urate stones can form when the solubility product is exceeded either because of extreme uricosuria and/or because of an unfavorable urinary pH. About 20% of all urinary stones are totally or partially composed of uric acid or urate. 

Out of 529 inpatients with nephrolithiasis, in 30.4% these stones consisted of pure uric acid (Table 4). In 133 of 161 patients with uric acid stones, which means in almost 83%, the concrement had led to a congestion of the descending urinary tract this occurred on both sides in 15 cases. As can also be seen from Table 4, in more than 20% of the cases a treatment with a uricosuricum — generally Benzbromaron — had been started. 

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. 

Yii, F. Uric and Nephrolithiasis. In Uric acid. Handbook of Experimental Pharmakology. Vol. 51, Kelley, W.N., Weiner, J.M. (eds.) Berlin-Heidelberg-New York, Springer (1978), p. 397. 

Hyperuricosuria with increased urinary concentration of uric acid and undue low pH of urine are probably the main but not the only factors in the pathogenesis of nephrolithiasis in gouty patients (1). 

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. 

Urinary excretion of cAMP, uric acid and phosphate in gouty patients without (A) and with nephrolithiasis (B). 

---