What are uric acid kidney stonesUric acid kidney stones are renal calculi formed by the crystallization of uric acid in the urine.
AdvertisementsUric acid renal calculi are associated with disorders like hyperuricosuria with or without hyperuricemia. In healthy individuals diet rich in purines (explained below) can lead to increased amount of uric acid excretion (hyperuricosuria). A combination of factors like hyperuricosuria, low urinary volume and persistently low urinary pH lead to uric acid kidney stones. Certain food habits, metabolic abnormalities or hereditary factors may also play a part in the formation of these types of nephrolith. One positive fact about uric acid kidney stones is that they can be dissolved successfully.
Purines are heterocyclic aromatic organic compounds and some of them (adenine, guanine) are the building-blocks of deoxyribonucleicacid - DNA, and ribonucleicacid - RNA in the living cells. Other important purines are, hypoxanthine, xanthine, theobromine, caffeine, uric acid and isoguanine.
what causes uric acid kidney stones?As said earlier, the pathogenesis of these uric acid kidney stones involves hyperuricosuria, low urinary volume, and persistently low urinary pH. Severe hyperuricosuria occurs in patients with certain medical conditions like chronic diarrhea, myeloproliferative disorders, metabolic disorders, Lesch-Nyhan syndrome and insulin resistance.
Acidic urineThe persistent low pH urine is a greater factor than hyperuricosuria in causing the uric acid kidney stones. It is to be noted that an individual with normal uric acid excretion but a persistent low pH urine can develop the nephrolith, whereas those with a higher urine pH but excessive urate excretion may not develop the calculi. Those with hyperuricosuria but normal urine pH may develop mixed calculi composed of calcium oxalate and urate.
Acidic urine is caused by factors like renal tubular disorders, chronic diarrhea or severe dehydration. In patients with chronic acidic urine production, it is found that defects in renal tubular ammonia production and secretion is a cofactor. A gene related to uric acid kidney stones has been identified but the pathophysiology has not been totally elucidated.
Resorption and secretionNormally, uric acid exists as urate ions in the blood serum. In the human body nearly 300 to 400 mg of urate is accounted for by endogenous biosynthesis. The excess of it comes from the ingested purines. Normally almost entire urate is filtered out by the glomerulus. However only about ten percent is excreted and the balance is reabsorbed. Altogether only 70% of the excreted urate is handled by the kidneys and the rest is eliminated by the skin, hair and gut.
Tin C Ngo et al reported that nearly 99% of the filtered load of urate is reabsorbed in the S1 segment of the proximal tubule by the urate transporter URAT1. URAT1 is encoded by the gene SLC22A12. They further reported that "urate secretion occurs in the S2 segment via the organic acid transporters (OAT1 and OAT3) as well as a selective urate transporter, URAT. Post-secretory reabsorption of urate occurs in the S3 segment and is also mediated by URAT1."
Decreased urinary outputUric acid nephrolithiasis is higher in people living in tropics as well as in those working in hot conditions. Obviously these situations cause concentration of urine. The solutes in the concentrated urine tend to precipitate. In high concentrations urate precipitates as uric acid and monosodium urate. In those predisposed to uric acid calculi formation, these hot conditions induce uric acid kidney stones.
Chronic diarrheaChronic diarrhea contributes to gastrointestinal bicarbonate loss from the body and leads to acidic urine and uric acid kidney stones. Diseases like inflammatory bowel disease, Crohn's disease, ulcerative colitis, familial adenomatous polyposis, colorectal cancer and total colonic Hirschsprung's disease may require removal of colon and ileostomy or colon resection. In such conditions hypovolemia may occur leading to supersaturation of solutes in the urine and acidity of urine as well as chronic gastrointestinal loss of bicarbonate.
Hyperuricosuria and dietary purinesIn normal individuals hyperuricosuria is caused when purine and animal protein rich diet is taken. As said earlier, patients with hyperuricosuria but normal urine pH can develop kidney calculi containing urate and calcium oxalate compounds. It may be compounded by a mild protein-induced metabolic acidosis causing decrease in urine pH. Hyperuricosuria is also caused by renal diseases such as Fanconi syndrome, Hartnup disease, Wilson’s disease, and familial hypouricemic hyperuricosuria.
Diabetes, insulin resistance and obesityThere is an increase in the number of diabetes patients with uric acid kidney stones. The metabolic syndrome and type 2 diabetes cause insulin resistance. Insulin resistance lowers urine pH by impairing kidney ammoniagenesis. Daudon M et al observed that "it is suggested that patients with UA stones, especially if overweight, should be screened for the presence of type 2 diabetes or components of the metabolic syndrome."
Genetic predispositionGenetic predisposition to uric acid nephrolithiasis is well established. The ZNF365 gene on chromosome 10q21–q22 is found associated with uric acid kidney stones. The functional characteristics are yet to be totally elucidated. However this trait requires influence of certain environmental factors for its expression.
Congenital hyperuricemiaLesch–Nyhan syndrome (juvenile gout) is a rare X-linked recessive inherited disorder. It causes a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase leading to hyperuricemia and hyperuricosuria. The purines from cell break down are not salvaged causing mental retardation, gout, uric acid kidney calculi. Glycogen storage disease type I (von Gierke's disease) is an autosomal recessive glycogen storage disease. It causes hyperuricemia, hypoglycemia and hyperlactacidemia. Patients affected by these disorders have the tendency form uric acid kidney stones.
GoutMost of the patients suffering from gout also suffer from hyperuricemia. The buildup of uric acid in the blood causes its deposits in the joints causing severe pain. These patients may also develop excessive excretion of urate leading to uric acid nephrolithiasis. Gout can occur due a number of reasons, including diet, genetic predisposition, or underexcretion of urate.
Idiopathic uric acid nephrolithiasisSome uric acid nephrolithiasis patients do not have identifiable congenital or acquired cause. Their condition is described as idiopathic uric acid nephrolithiasis. They have normal uric acid excretion and also normal urine pH. They also do not have any genetic predisposition or congenital hyperuricemia.
MalignancyMyeloproliferative disorders and malignancy cause rapid cell turnover and also tumor necrosis during therapy. The tumor lysis and cell death can cause massive increase in purines leading to hyperuricemia and hyperuricosuria. Other conditions like sickle cell anemia and psoriasis also increase cell turnover leading to hyperuricemia, hyperuricosuria and uric acid kidney stone formation.
Uric acid kidney stones symptoms and diagnosisThe signs and symptoms of these calculi are similar to other nephrolith. Some of the common symptoms are back, flank and abdominal pain, nausea, renal colic, urinary tract infections, hematuria and groin pain. Persisting low urinary pH, less than 5.5 along with the above symptoms may indicate nephrolithiasis. Non-contrast-enhanced computed tomography or renal ultrasonography may help in uric acid calculus detection. Analysis of the expelled uric acid calculus can further guide in treatment modalities.
Uric acid kidney stones treatmentThe treatment must focus on hydration, increasing urinary pH and reducing purine intake if hyperuricosuria is suspected. In cases where there is severe obstruction, severe infection and unremitting pain surgical options may be considered.
Hydration and dissolve uric acid kidney stonesThe treatment is focussed on hydration to void more than 2,000 ml of urine daily. Simultaneously treatment with oral alkalies like potassium citrate or sodium bicarbonate to achieve urine pH between 6.2 to 7.0 is necessary. The treatment with potassium citrate can help in dissolving the existing uric acid calculi as well as prevent their recurrence. Urinary pH levels must be closely monitored to maintain high urine pH. However urine pH above 7.0 is conducive for calcium phosphate precipitation.
Uric acid kidney stones dietThose patients who are suffering from hyperuricosuria as well as uric acid kidney stone formers must avoid foods rich in purines like red meat and meat products, certain types of fish, poultry, shellfish, sugar-sweetened foods, high fructose corn syrup, beer and legumes. The diet also should not be high in animal protein as it may produce a transient metabolic acidosis leading to acidic urine. Taking citrus fruits helps in increasing urine pH.
AllopurinolMedicines like allopurinol block the uric acid excretion and kidney urolithiasis by inhibiting xanthine oxidase enzyme which catalyzes reactions producing urate. However as allopurinol may cause adverse reactions, its administration must be closely observed.
Surgical optionsSurgical options are available for removing uric acid kidney stones that are not dissolving. Extracorporeal shockwave lithotripsy, retrograde endoscopic lithotripsy and extraction, ureteroscopy, percutaneous nephrostolithotomy, percutaneous nephrolithotomy, combination therapy and open surgery are the surgical options available for removing the uric acid kidney stones.
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