Serum Creatinine and Uric Acid Levels

This patient was the first case in our series in which ALPE was detected with acute renal failure due to unknown etiology. On September 19,1976, he ran two 100-m races at an athletics meeting. On September 20, vomiting, diarrhea, and upper abdominal pain developed, and the patient attended our department. His serum creatinine and uric acid levels were 5.0 mg/dl and 17.0 mg/dl, respectively. The pain persisted for 1... 

In 1990, we reported that 3 (23%) of 13 patients with ALPE had renal hypouricemia [3]. Previously, Erley et al. [28] had reported that patients with renal hypouricemia frequently developed acute renal failure. However, we were the first to report that these patients developed exercise-induced acute renal failure (ALPE) [3]. In our 3 patients with renal hypouricemia, the mean serum creatinine and uric acid levels in acute renal failure were 5.1 2.6mg/dl and 4.7 1.7mg/dl, respectively (Fig. 56). In the remaining 10 patients without renal hypouricemia, the mean serum creatinine and uric acid levels were 3.1 1.6mg/dl and 11.4 4.2mg/dl, respectively. In the recovery phase, these levels in the hypouricemia patients were 1.1 0.3 mg/dl and 0.8 0.2 mg/dl, respectively. The mean FEUA was 58.4 18.7%. In the 10 patients without hypouricemia, the mean serum creatinine, uric acid, and FEUA values were 1.1 0.1 mg/dl, 6.1 1.2 mg/dl, and 7.8 3.0%, respectively. 

On June 6, this patient developed severe loin pain after he participated in two 150-m sprints at a town athletics meeting. After 5 days, he was referred to the outpatient clinic of our department. His serum creatinine and uric acid levels and FEUA, were 2.9mg/dl, 2.1 mg/dl, and 49.7%, respectively. His creatine phosphokinase (CPK) level was normal. When his serum creatinine level decreased to 1.58 mg/dl, a contrast medium was administered. A delayed computed tomography (CT) scan after 24 and 48 h confirmed patchy wedge-shaped contrast enhancement (Fig. 58). Under a diagnosis of ALPE, his body water balance (hydration) was controlled. In this patient, recovery was achieved 4 weeks after onset, and his serum creatinine and uric acid levels were then 1.0 mg/dl and 0.6 mg/dl, respectively. Furthermore, load tests with a uric acid reabsorption inhibitor (benzbromarone) and a uric acid excretion inhibitor (pyrazinamide) suggested presecretory reabsorption defect-related renal hypouricemia. A kidney biopsy 16 days after onset confirmed the recovery from acute tubular necrosis. 

The acute renal failure is typical for acute tubular necrosis and is characterized by a urine sediment with granular pigmented casts, and benzidine positive urine often in the absence of significant hematuria. With rhabdomyolytic acute tubular necrosis the urinary sodium concentration and fractional excretion of sodium are not always increased as in classic acute tubular necrosis [99]. One half to two-thirds of patients have ohguria, which may last from hours to many weeks. During this phase of the acute renal failure, there is a very rapid rise in the serum creatinine (often > 2.0 mg/ dl/ day), and profound increases in the serum levels of a variety of solutes normally foimd in muscle or produced from muscle derived precursors. Thus, fhe levels of potassium, phosphate, and uric acid all rise dra-... 

Twenty-five kidney transplant patients taking eielosporin were given benzbromarone 100 mg daily to treat hyperurieaemia. The plasma uric acid levels decreased from 579 to 313 micromol/L and the 24-hour urinary uric acid secretion rose from 2082 to 3233 micromol after 4 weeks of treatment. The plasma uric acid levels normalised in 21 of the patients who had creatinine clearances of over 25 mL/minute. No significant adverse effects developed and the ciclosporin serum levels remained unchanged. The authors of the report emphasise the advantages of benzbromarone over allop-urinol because of its efficacy, lack of significant adverse effects and because, unlike allopurinol, it does not interact with azathioprine, which often accompanies ciclosporin treatment. ... 

After only two days, group I, which was treated with Harolan , attained a significant decrease in uric acid (up to 50% of the initial values) and was recorded throughout the duration of the examination (Fig. 1). In comparison, the uric acid levels of the control group II remained the same. The serum values of Na, K, Ca, Mg, P, and creatinine remained within the normal range for both groups and revealed no differences over the entire period of examination. 

In patients with high serum uric acid levels we tried to rule out other causes of hyperuricemia. We assessed 24-hour uricosuria, uric acid and creatinine clearances and estimated the uric acid clearance/creati-nine clearance ratio /Cur/Ccr). 

Fig. 1 Uric acid level in blood serum and uric acid, oxypurine and creatinine excretion before and after application of benzbromarone by a patient with gout.

If renal disease is questioned, a 24 hour urine collection for creatinine clearance, protein, and electrolytes may be indicated. Elevated uric acid levels may result from lead - induced renal disease and a serum uric acid level might be performed. 

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. 

Renal Effects. The patient described by Letz et al. (1984) (see Section 2.2.3.1) who lived for 64 hours after exposure to toxic levels of 1,2-dibromoethane had acute renal failure as evidenced by severe oliguria 24 hours after exposure and abnormal clinical chemistry values (blood urea nitrogen, creatinine, and serum uric acid). Severe metabolic acidosis was present despite two hemodialysis procedures. 

Drug/Lab test interactions Methyidopa may interfere with tests for Urinary uric acid by phosphotungstate method serum creatinine by alkaline picrate method AST by colorimetric methods. Because methyidopa causes fluorescence in urine samples at the same wavelengths as catecholamines, falsely high levels of urinary catecholamines may occur and will interfere with the diagnosis of pheochromocytoma. 

In addition to an increase in serum urea and creatinine levels, uric acid and inorganic phosphate levels also increase in chronic renal failure. The increase in serum inorganic phosphate leads to deposition of calcium phosphate in bones, causing hypocalcemia. In the early stages of chronic renal failure, calcium levels are restored by the stimulation of parathyroid hormone. However, as the renal disease progresses, the ability of the kidney to hydroxylate vitamin D and thus convert it to the active form decreases, thereby affecting the uptake of calcium by the gut and thus perpetuating hypocalcemia. Serum alkaline phosphatase levels increase due to disordered bone metabolism. Loss of bicarbonate is seen in some patients with increased parathyroid hormone activity. 

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