Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 7783706

Uric acid nephrolithiasis.

A Halabe·O Sperling
View original source ↗Export metadata ↓

Abstract

Uric acid is the end-product of purine nucleotide metabolism in man. The renal handling of urate is a complicated process, resulting in a fractional clearance of 8.2-10.3%. The anhydrous form is thermodynamically the most stable uric acid crystal. Uric acid is a weak acid that ionizes with a Pka at pH 5.75. At the normal acidic region, uric acid solubility is strongly increased by urinary pH. The prevalence of uric acid stones varies between countries, reflecting climatic, dietary, and ethnical differences, ranging from 2.1% (in Texas) to 37.7% (in Iran). The risk for uric acid stone formation correlates with the degree of uric acid supersaturation in the urine, depending on uric acid concentration and urinary pH. Hyperuricosuria is the major risk factor, the most common cause being increased purine intake in the diet. Acquired and hereditary diseases accompanied by hyperuricosuria and stone disease include: gout, in strong correlation with the amount of uric acid excreted, myelo- and lymphoproliferative disorders, multiple myeloma, secondary polycythemia, pernicious anemia and hemolytic disorders, hemoglobinopathies and thalassemia, the complete or partial deficiency of HGPRT, superactivity of PRPP synthetase, and hereditary renal hypouricemia. A common denominator in patients with idiopathic and gouty stone formers is a low urinary pH. Uric acid nephrolithiasis is indicated in the presence of a radiolucent stone, a persistent undue urine acidity and uric acid crystals in fresh urine samples. A radiolucent stone in combination with normal or acidic pH should raise the possibility of urate stones.(ABSTRACT TRUNCATED AT 250 WORDS)

Explore related subjects

AllopurinolDietHumansKidneyKidney CalculiModels, BiologicalPurinesUric AcidUrinary CalculiWater-Electrolyte BalanceJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

A Halabe, O Sperling. 1994. Uric acid nephrolithiasis.. https://pubmed.ncbi.nlm.nih.gov/7783706/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2002

In vivo assessment of free radical activity during shock wave lithotripsy using a microdialysis system: the renoprotective action of allopurinol.

PURPOSE: Shock wave lithotripsy is believed to cause renal damage directly through cellular injury from high energy shock waves and indirectly through vascular injury and resultant ischemia, which gives rise to oxygen free radical compounds. The transient and volatile nature of free radicals and derived products makes their detection difficult. Moreover, certain medications may provide a protective effect against shock wave lithotripsy induced renal parenchymal injury. We introduced an innovative microdialysis system for in vivo sampling of interstitial fluids that can be analyzed for free radical mediated lipid peroxidation products after shock wave lithotripsy treatment in the swine model. In addition, this system was used to test the antioxidant or renoprotective action of allopurinol. MATERIALS AND METHODS: Ten juvenile swine were assigned to a nonmedicated control group that underwent shock wave lithotripsy or to a group that was premedicated with allopurinol before shock wave lithotripsy. Each group of animals underwent shock wave lithotripsy to the lower pole of the right kidney and received a total of 10,000 shock waves. Dialysate fluid was collected at 1,000-shock wave increments via probes surgically implanted into the lower pole of the right and left kidneys before lithotripsy. Samples were immediately preserved in liquid nitrogen and subsequently analyzed for the presence and concentration of conjugated diene levels, a measure of lipid peroxidation. Five additional juvenile swine were assigned to a sham treated group that did not undergo shock wave lithotripsy. Dialysate fluid was collected from the lower pole of the right and left kidneys to establish baseline or pre-lithotripsy levels of conjugated dienes. RESULTS: After shock wave lithotripsy conjugated diene levels increased almost 100-fold over that in the right kidneys of the nonmedicated control group. The difference was statistically significant compared to levels in the contralateral untreated kidneys (p <0.01). Right kidneys in the group premedicated with allopurinol did not demonstrate an increase in conjugated diene levels during shock wave lithotripsy. CONCLUSIONS: The results of this study confirm shock wave lithotripsy induced free radical activity as well the antioxidant and protective nature of allopurinol. The newly described microdialysis system enables real-time sampling of interstitial fluids during shock wave lithotripsy. It represents a unique method for assessing free radical formation and evaluating the protective effects of additional antioxidant medications.

Allopurinol↗
PubMed2001

Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy is characterized by an imbalance between left ventricular performance and myocardial energy consumption. Experimental models suggest that oxidative stress resulting from increased xanthine oxidase (XO) activity contributes to this imbalance. Accordingly, we hypothesized that XO inhibition with intracoronary allopurinol improves left ventricular efficiency in patients with idiopathic dilated cardiomyopathy. METHODS AND RESULTS: Patients (n=9; ejection fraction, 29+/-3%) were instrumented to assess myocardial oxygen consumption (MVO(2)), peak rate of rise of left ventricular pressure (dP/dt(max)), stroke work (SW), and efficiency (dP/dt(max)/MV O(2) and SW/MVO(2)) at baseline and after sequential infusions of intracoronary allopurinol (0.5, 1.0, and 1.5 mg/min, each for 15 minutes). Allopurinol caused a significant decrease in MVO(2) (peak effect, -16+/-5%; P<0.01; n=9) with no parallel decrease in dP/dt(max) or SW and no change in ventricular load. The net result was a substantial improvement in myocardial efficiency (peak effects: dP/dt(max)/MVO(2), 22+/-9%, n=9; SW/MVO(2), 40+/-17%, n=6; both P<0.05). These effects were apparent despite concomitant treatment with standard heart failure therapy, including ACE inhibitors and beta-blockers. XO and its parent enzyme xanthine dehydrogenase were more abundant in failing explanted human myocardium on immunoblot. CONCLUSIONS: These findings indicate that XO activity may contribute to abnormal energy metabolism in human cardiomyopathy. By reversing the energetic inefficiency of the failing heart, pharmacological XO inhibition represents a potential novel therapeutic strategy for the treatment of human heart failure.

Allopurinol↗
PubMed2001

A novel parasite-derived suicide gene for cancer gene therapy with specificity for lung cancer cells.

The enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) expressed by the parasite Trypanosoma brucei (Tb) can convert allopurinol, a purine analogue, to corresponding nucleotides with greater efficiency than its human homologue. We have developed a retroviral system that expresses the parasitic enzyme and tested its capacity to activate the prodrug allopurinol to a cytotoxic metabolite. Cytotoxicity assays demonstrated that five non-small cell lung carcinoma cell lines transduced with the construct were sensitized to the prodrug by 2.1- to 7.6-fold compared with control values. This selectivity was not observed in seven other cell lines also expressing the construct, such as breast carcinoma. Assays indicated that enhanced cytotoxicity to allopurinol correlated with induction of apoptosis in lung cancer cells. The selectivity of this suicide gene was not explained either by the TbHGPRT expression or by the allopurinol accumulation. Our study shows that this novel system may represent a therapeutic tool for gene prodrug targeting of lung cancer, considering the fact that allopurinol is well tolerated in humans.

Allopurinol↗