Uric acid nephropathy, acute

Acute uric acid nephropathy, which is characterized by the acute overproduction of uric acid and by extreme hyperuricemia, can best be prevented with which of the following ... 

The answer is c. (Hardman, pp 649—650.) Acute hyperuricemia, which often occurs in patients who are treated with cytotoxic drugs for neoplasic disorders, can lead to the deposition of urate crystals in the kidneys and their collecting ducts. This can produce partial or complete obstruction of the collecting ducts, renal pelvis, or ureter. Allopurinol and its primary metabolite, alloxanthine, are inhibitors of xanthine oxidase, an enzyme that catalyzes the oxidation of hypo xanthine and xanthine to uric acid. The use of allopurinol in patients at risk can markedly reduce the likelihood that they will develop acute uric acid nephropathy. 

In acute uric acid nephropathy, acute renal failure occurs as a result of blockage of urine flow secondary to massive precipitation of uric acid crystals in the collecting ducts and ureters. This syndrome is a well-recognized complication in patients with myeloproliferative or lymphopro-liferative disorders and results from massive malignant cell turnover, particularly after initiation of chemotherapy. Chronic urate nephropathy is caused by the long-term deposition of urate crystals in the renal parenchyma. 

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. 

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. ... 

ATLS is potentially a catastrophic complication of chemotherapy in patients with a high tumour load. It results from cytotoxic damage to large numbers of cancerous cells. The DNA and RNA released are broken down to uric acid, which precipitates in the renal tubules causing acute uric acid nephropathy. Recent evidence suggests that recombinant urate oxidase, which converts uric acid to soluble allan-toin, is successful in the treatment and prevention of ATLS in patients with haematological malignancies. 

Reactions following initial infusions of antibody are common, but these can usually be handled by a cautious rate of infusion, appropriate hydration and diuresis, and, if necessary, praned-ication. Twenty six percent of initial reactions are reported to be mild, 48 % moderate, and 26 % severe. The initial infusion reaction to some mAbs, for example, rituximab (see below), may provoke tumor lysis syndrome, cytokine release syndrome, and systemic inflammatory response syndrome. Tumor lysis syndrome, noted particularly with rituximab, can occur following cancer treatment and sometimes without treatment. It is believed to be the result of breakdown products of cancer cells leading to increased levels of some metabolites and reflected in conditions such as hypercalcemia, hyperkalemia, hyperphosphatemia, acute uric acid nephropathy, and acute renal failure. The syndrome can occur in the early stages of mAb therapy and is potentially life-threatening. Cytokine release syndrome, also called cytokine storm, is commonly seen after... 

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. 

Risk factors for ARF include advanced age, acute infection, preexisting chronic respiratory or cardiovascular disease, dehydration, and chronic kidney disease (CKD). Decreased renal perfusion secondary to abdominal or coronary bypass surgery, acute blood loss in trauma, and uric acid nephropathy also increase risk. 

Erley CM, Hirschberg RR, Hoefer W, Schaefer K (1989) Acute renal failure due to uric acid nephropathy in a patient with renal hypouricemia. Klin Wochenschr 67 308-312... 

Momose A, Kudou D, Nishimura S, Sawada Y, Kitagawa M, Funao T, Suzuki Y (1996) A case of exercise-induced acute renal failure due to uric acid nephropathy in patient with cystinuria (in Japanese). Jin-To-Tohseki (Kidney Dial) 41 853-857... 

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

A study of 55 adolescents who had been treated for lead intoxication in early childhood (11-17 years earlier) revealed no evidence of chronic nephropathy, as evidenced by endogenous creatinine clearance, BUN, serum uric acid, and routine urinalysis (Chisolm et al. 1976). PbB levels during the acute poisoning episode ranged from 100 to 650 pg/dL all patients received immediate chelation therapy. At the time of the study, their PbB levels had decreased to less than 40 pg/dL. 

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. 

In contrast to the reabsorptive defect of acute lead nephropathy, saturnine gout is characterized by renal retention of uric acid [18]. The clearance (Cp ) and maximal secretion rate (Tmp ) for p-aminohippurate (PAH) have been found to be variable in patients with occupational lead 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. 

Renal disease is a eommon complication of hyperuricaemia. Several types of renal disease have been identified. The most comnutn is urate nephropathy which is caused by the deposition of urate crystals in renal tissue or the urinary tract to form urate stones. This mtiy be associated with chronic hyperuricaemia. Acute renal failure can be cau.sed by the rapid precipitation of uric acid crystals w hich commonly occurs during treatment of patients with leukaemias and lymphomas. In the acute tumour lysis syndrome (p. 129), nucleic acids are released as a result of tumour cell breakdown and arc rapidly metabolized to uric acid. 

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