Hyperuricemia

Anti-gout Drugs. Figure 2 Reabsorption and secretion of uric acid in the proximal renal tubulus. (a) Normal situation. Uric acid is completely reabsorbed in the proximal segment of the renal tubulus and secreted more distally. (b) Situation in untreated hyperuricemia. 

Diuretics Frequent urination, hyperuricemia, hyperglycemia, hyperlipidemia... 

Hyperuricemia is defined as serum uric acid concentration >416 p mol/L or 7.0 mg/dL. With increasing serum uric acid concentration, the risk of acute gouty arthritis increases, but asymptomatic hyperuricemia does not have to be treated pharmacologically. 

Uric acid is the endproduct of purine metabolism in man. Uric acid has a lower solubility than its progenitor metabolites, hypoxanthine and xanthine. Impaired uric acid elimination and/or increased uric acid production result in hyperuricemia and increase the risk of gouty arthritis. At physiological pH, 99% of the uric acid molecules are actually in the form of the urate salt. A decrease in pH increases the fraction of uric acid molecules relative to urate molecules. Uric acid possesses lower solubility than urate. 

Anemia, proteinuria, nausea, vomiting, fever, rash, leukopenia, neutropenia, thrombocytopenia, diarrhea, constipation, alopecia Bone marrow depression, hyperuricemia, hepatotoxicity, skin rash... 

Bone marrow depression, hepatic toxicity, nausea, vomiting, stomatitis, hyperuricemia... 

Loading of the Liver With Fructose May Potentiate Hyperlipidemia Hyperuricemia... 

While purine deficiency states are rare in human subjects, there are numerous genetic disorders of purine catabolism. Hyperuricemias may be differentiated based on whether patients excrete normal or excessive quantities of total urates. Some hyperuricemias reflect specific en2yme defects. Others are secondary to diseases such as cancer or psoriasis that enhance tissue turnover. 

Lesch-Nyhan syndrome, an overproduction hyperuricemia characterized by frequent episodes of uric acid hthiasis and a bizarre syndrome of self-mutilation, reflects a defect in hypoxanthme-guanine phosphoribo-syl transferase, an enzyme of purine salvage (Figure 34—4). The accompanying rise in intracellular PRPP results in purine overproduction. Mutations that decrease or abohsh hypoxanthine-guanine phosphoribosyltrans-ferase activity include deletions, frameshift mutations, base substitutions, and aberrant mRNA splicing. 

Purine overproduction and hyperuricemia in von Gierke s disease (glucose-6-phosphatase deficiency)... 

Harris MD> Siegel LB, Alloway JA Gout and hyperuricemia. Am Family Physician 1999 59 925. 

Niacin 50 to 750 mg tabs or caps, i m med i ate- re I ease 250 to 750 mg sustained-release 1 -5 g/day in three or more divided doses 1-2 g/day (never exceed 2 g/day due to increased risk of hepatotoxicity) hyperuricemia. 

Identify patients in whom maintenance therapy for gout and hyperuricemia is warranted. 

Some drugs can cause hyperuricemia and gout, such as thiazide diuretics, niacin, pyrazinamide, cyclosporine, and occasionally, low-dose aspirin. 

Long-term consequences of gout and hyperuricemia include joint destruction, tophi, and nephrolithiasis. 

Asymptomatic hyperuricemia usually does not require treatment. 

The risk of gout increases as the serum uric acid concentration increases, and approximately 30% of patients with levels greater than 10 mg/dL (greater than 595 pmol/L) develop symptoms of gout within 5 years. However, most patients with hyperuricemia are asymptomatic. Other risk factors for gout include obesity, ethanol use, and dyslipidemia. Gout is seen frequently in patients with type 2 diabetes mellitus and coronary artery disease, but a causal relationship has not been established. 

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. 

Although rarely performed, a 24-hour urine collection can be obtained to determine if the patient is an overproducer or an underexcretor of uric acid. Individuals who excrete more than 800 mg of uric acid in this collection are considered overproducers. Patients with hyperuricemia who excrete less than 600 mg/day are classified as underexcretors of uric acid. 

FIGURE 56-2. Treatment algorithm for gout and hyperuricemia. Renal insufficiency is defined as an estimated creatinine clearance (CrCI) of less than 30 mL/minute. IA, Intraarticular NSAID, nonsteroidal anti-inflammatory drug. 

Gout is an episodic disease, and the number of attacks varies widely from patient to patient. Thus the benefit of long-term prophylaxis against acute gout flares must be weighed against the cost and potential toxicity of therapy that may not be necessary in all patients. Asymptomatic hyperuricemia usually does not require treatment. 

Obtain a thorough medication history for prescription drug, nonprescription drug, and dietary supplement use. Determine if any of these products may be contributing to hyperuricemia. 

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