Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Uric acid, a weak organic acid, has very low pH-dependent solubility in aqueous solutions. About 70% of urate elimination occurs in urine, the kidney standing as a major determinant of plasma levels. The complex renal handling results in a fractional clearance of less than 10%. Recently identified urate-specific transporter/channels are involved in tubular handling and extracellular transport. Extracellular fluid, rather than urine output, is the main regulator of urate excretion. A number of interfering agents, including widely used drugs such as aspirin, losartan, diuretics, may decrease or increase urate elimination. Hyperuricemia induced by hypouricosuria often accompanies the metabolic syndrome, and insulin resistance has been hypothesized as the common underlying defect. Hyperuricosuria, associated with dehydration or exercise, results in acute uric acid nephropathy, and causes an obstructive acute renal failure (ARF). This reversible ARF can be prevented by forced hydration with bicarbonate or saline solutions. Renal hypouricemia, due to mutations of urate transporter, is a rare cause of exercise-induced ARF. The existence of chronic urate nephropathy, gouty nephropathy, is still under discussion. Uric acid nephrolithiasis results from supersaturation, strongly influenced by low urine pH, rather than altered urate turnover. Alkali and fluid intake prove successful in managing uric acid stones.
 ...
PMID:Uric acid elimination in the urine. Pathophysiological implications. 1560 13

Uric acid nephrolithiasis is typically found in individuals with a low urine pH and a normal concentration of urinary uric acid. Patients with a history of gout are at greater risk of forming uric acid stones, as are patients with obesity, diabetes, or the complete metabolic syndrome. The unifying renal tubular abnormality of these disorders appears to be the excretion of abnormally acidic urine. This article focuses on the relationship of these disorders to the development of uric acid stones. The diagnosis of uric acid stones can be elusive, because pure uric acid stones are radiolucent on plain radiographs. Ultrasound, or preferably noncontrast helical CT scanning, is required for their detection. The treatment of uric acid stones should focus on alkalinization of the urine with citrate or bicarbonate salts. Additional interventions such as increase in fluid intake and decrease in animal protein ingestion are often beneficial. Patients with documented hyperuricemia often require specific therapy to lower serum uric acid concentration and subsequent excretion.
 ...
PMID:Uric acid nephrolithiasis. 1753 Nov 80

Uric acid nephrolithiasis is characteristically a manifestation of a systemic metabolic disorder. It has a prevalence of about 10% among all stone formers, the third most common type of kidney stone in the industrialized world. Uric acid stones form primarily due to an unduly acid urine; less deciding factors are hyperuricosuria and a low urine volume. The vast majority of uric acid stone formers have the metabolic syndrome, and not infrequently, clinical gout is present as well. A universal finding is a low baseline urine pH plus insufficient production of urinary ammonium buffer. Persons with gastrointestinal disorders, in particular chronic diarrhea or ostomies, and patients with malignancies with a large tumor mass and high cell turnover comprise a less common but nevertheless important subset. Pure uric acid stones are radiolucent but well visualized on renal ultrasound. A 24 h urine collection for stone risk analysis provides essential insight into the pathophysiology of stone formation and may guide therapy. Management includes a liberal fluid intake and dietary modification. Potassium citrate to alkalinize the urine to a goal pH between 6 and 6.5 is essential, as undissociated uric acid deprotonates into its much more soluble urate form.
 ...
PMID:Uric Acid Nephrolithiasis: A Systemic Metabolic Disorder. 2504 26

Uric acid nephrolithiasis (UAN) is an increasingly common disease in ethnically diverse populations and constitutes about 10% of all kidney stones. Metabolic syndrome and diabetes mellitus are accounted among the major risk factors for UAN, together with environmental exposure, individual lifestyle habits and genetic predisposition. The development and overt manifestation of UAN appears to stem on the background of insulin resistance, which acts at the kidney level by reducing urinary pH, thus hampering the ability of the kidney to generate renal ammonium in response to an acid load. Unduly acidic urinary pH and overt UAN are both considered renal manifestations of insulin resistance. The mechanisms underlying increased endogenous acid production and/or defective ammonium excretion are yet to be completely understood. Although the development of UAN and, more in general, of kidney stones largely recognizes modifiable individual determining factors, the rising prevalence of diabetes, obesity and accompanying metabolic disorders calls for the identification of novel therapeutic approaches and intervention targets. This review aims at providing an updated picture of existing evidence on the relationship between insulin resistance and UAN in the context of metabolic syndrome and in light of the most recent advancements in our understanding of its genetic signature.
 ...
PMID:Metabolic syndrome and uric acid nephrolithiasis: insulin resistance in focus. 2951 Jan 80

Uric acid nephrolithiasis appears to increase in prevalence. While a relationship between uric acid stones and low urinary pH has been for long known, additional association with various metabolic conditions and pathophysiological basis has recently been elucidated. Some conditions such as diabetes and metabolic syndrome disease, excessive dietary intake, and increased endogenous uric acid production and/or defect in ammoniagenesis are associated with low urinary pH. In addition, the phenomenon of global warming could result in an increase in areas with greater climate risk for uric acid stone formation. There are three therapeutic steps to be taken for management of uric acid stones: identification of urinary pH profiles, assessment of urinary volume status, and identification of disorders leading to excessive uric acid production. However, the most important factor for uric acid stone formation is acid urinary pH, which is a prerequisite for uric acid precipitation. This article reviews recent insights into the pathophysiology of uric acid stones and their management.
 ...
PMID:Uric acid nephrolithiasis: An update. 2968 61