Gouty nephropathy

The elevated blood uric acid concentration in gout is an easily identified and readily treated abnormality. However, it is essential to identify the condition and institute therapy early to avoid the complications that result from a prolonged elevated uricemia. Complications include arthritis, tophi, urinary calculi, and gouty nephropathy. 

Recurrent gout, tophaceous gout, and gout causing renal damage (gouty nephropathy)... 

Chronic exposure to low levels of lead results in lead accumulation within the body. Workers who have been chronically exposed to lead develop interstitial fibrosis, vascular and glomerular sclerosis, and tubular atrophy and/or hypertrophy. Although acute lead nephropathy is reversible with chelator therapy and/or removal from exposure, chronic effects may be irreversible. In addition, chronic exposure to lead may result in a gouty nephropathy as lead reduces uric acid excretion and elevates blood uric acid levels. 

Gout typically involves acute attacks of arthritis, nephrolithiasis, gouty nephropathy, and aggregated deposits of sodium... 

There are two types of gouty nephropathy acute uric acid nephropathy and chronic urate nephropathy." In acnte nric acid nephropathy, acute renal failure occurs as a result of blockage of urine flow secondary to massive precipitation of nric acid crystals in the collecting ducts and ureters. This syndrome is a well-recognized complication in patients with myeloproliferative or lymphoproliferative disorders and is a result of massive malignant cell turnover, particularly after initiation of chemotherapy. 

The prevention of urate nephropathy might be a stronger indication because it is irreversible even with proper treatment. Available data indicate, however, that gouty nephropathy is extremely rare in the absence of clinical gout, and evidence that elevation of uric acid by itself may cause renal disease is weak and inconclusive. As discussed previously, renal impairment is very rare in the absence of concurrent hypertension and atherosclerosis. In addition, it is unclear whether uric acid-lowering therapy protects renal function in such individuals. Available data thus do not justify therapy for most patients with asymptomatic hyperuricemia. 

Proteinuria, hematuria, and acute tubular necrosis have been reported in severely intoxicated patients. Gouty nephropathy may occur in chronically treated patients. Azoospermia has been reported with chronic use. 

Renal Disease is a well recognized complication of gout, and the typical histologic features of chronic gouty nephropathy have been carefully studied, however, early evolution of the nephropathy and its precise relationship to hyperuricemia and uricosuria have been difficult to study in the human subject. Unfortunately, animal models of sustained hyperuricemia are difficult to produce and maintain. Recently, Stavric and colleagues described the production of hyperuricemia and urate nephropathy in rats fed orally with oxonic acid and uric acid, oxonic acid is a potent, hepatic uricase inhibitor and this chemical, combined with uric acid or RNA dietry supplements, consistently leads to hyperuricemia in this species. 

This chapter describes the acute and chronic nephrotoxic effects of lead in human populations. These effects have long been recognized in chronic adult occupational lead exposures and in nonoccupational adult exposures arising from dietary Pb intakes, producing disorders such as gouty nephropathy. In acute childhood Pb exposure, severe kidney effects in the form of Fanconi syndrome were identified in the early pediatric literature. The syndrome often co-occurred with acute encephalopathy. 

The effects of several agents on an experimental model of hyper-uricosuria and gouty nephropathy in the rat were described.xhe relationship between the ability of an agent to displace urate from protein in vitro, and uricosuric properties vivo was proven by clinical testing.85 This represents a rare and extremely valtiable validation of an experimental hypothesis and it is hoped that further such studies will appear in the future. 

In spite of the high concentration of uric acid in the blood, arthritis is rare, though not unknown. Gouty nephropathy does, however, occur. Most patients die in late childhood or adolescence with renal colic, uncontrollable vomiting or in seizures. 

Develop a pharmacotherapeutic plan for a patient with acute gouty arthritis or uric acid nephropathy that includes individualized drug selection and monitoring for efficacy and safety. 

Chronic high-dose lead exposure, usually associated with months to years of blood lead concentrations in excess of 80 g/dL, may result in renal interstitial fibrosis and nephrosclerosis. Lead nephropathy may have a latency period of years. Lead may alter uric acid excretion by the kidney, resulting in recurrent bouts of gouty arthritis ("saturnine gout"). Acute high-dose lead exposure sometimes produces transient azotemia, possibly as a consequence of intrarenal vasoconstriction. 

Treatment of chronic gouty arthritis, Half-life uric acid nephropathy. Prevents or 2-3 hours... 

Allopurinol is the antihyperuricemic drug of choice in patients with a history of urinary stones or impaired renal function, in patients who have lymphoproliferative or myeloproliferative disorders and need pretreatment with a xanthine oxidase inhibitor before initiation of cytotoxic therapy to protect against acute uric acid nephropathy, and in patients with gout who are overproducers of uric acid. The major side effects of allopurinol are skin rash, leukopenia, occasional gastrointestinal toxicity, and increased frequency of acute gouty attacks with the initiation of therapy. An allopurinol hypersensitivity syndrome characterized by fever, eosinophilia, dermatitis, vasculitis, and renal and hepatic dysfunction is a rare side effect, but is associated with a 20% mortality rate. ... 

Questions are often raised regarding the indications for drug therapy for asymptomatic hyperuricemia. The purported heneflts from treatment include prevention of acute gouty arthritis, tophi formation, nephrolithiasis, and chronic urate nephropathy. The first three complications are easily controlled shonld they develop therefore antihyperuricemic therapy is not warranted to prevent these conditions. 

Of particular interest was the fact that the cohort surviving into the 1%0 s had developed a high prevalence of gouty arthritis in comparison with patients with chronic nephritis due to causes other than lead. There was also a disproportionate hyperuricemia in these patients with chronic lead nephropathy, which was caused by a significantly lower urate clearance for any particular degree of renal insufficiency [32]. Studies of discrete tubular functions suggest that this was due to excessive reabsorption of filtered urate [33]. 

Isolated hyperuricemia is not necessarily an indication for therapy, as not all of these patients develop gout. Persistently elevated uric acid levels, complicated by recurrent gouty arthritis, nephropathy, or subcutaneous tophi, can be lowered by allopurinol, which inhibits the formation of urate, or by uricosuric agents. Some physicians recommend measuring 24-hour urinary urate levels in patients who are on a low-purine diet to distinguish underexcretors from overproducers. However, tailored and empirical therapies have similar outcomes. 

M.J. Dillon and J.S. Cameron. Uric Acid Crystal-Induced Nephropathy Evidence For A Specific Renal Lesion In A Gouty Family. J. Pathol. 

Hyperuricemia, uric acid overproduction, and hyperuricosuria are frequent clinical features of sickle cell anemia. Uric acid overproduction may result in hyperuricemia in some patients with sickle cell anemia. However, in other patients, enhanced urate excretion permits maintenance of a normal serum uric acid despite uric acid overproduction. Hyperuricosuria in normouricemic patients with sickle cell anemia may result from enhanced tTobular secretion of urate but is more likely to represent diminished urate reabsorption at a post-secretory site. Hyperuricosuria may protect the young patient with sickle cell anemia from gouty arthritis and tophi but may also increase the risk of tubular deposition of urate and nephropathy. 

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