1 First Department of Internal Medicine, Sendai Teishin Hospital, 2 Second Department of Internal Medicine and 3 Department of Blood Purification, Tohoku University School of Medicine, Sendai, Japan
Correspondence and offprint requests to: Isao Kurihara, MD, PhD, Second Department of Internal Medicine, Tohoku University School of Medicine, 1-1, Seiryo-cho, Aoba-ku, Sendai 980-8574, Japan.
Keywords: acute renal failure; exercise; medical checkups; oxygen free radicals; renal hypouricaemia
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() |
---|
![]() |
Case |
---|
![]() ![]() ![]() ![]() ![]() |
---|
On admission, his height and weight were 169 cm and 67 kg. He had no oliguria. Blood pressure was 112/60 mmHg and body temperature was 36.8°C. Physical examination did not reveal any abnormalities. Laboratory data were: haemoglobin 13.0 g/dl; haematocrit 38.9%; leukocyte count 7700/µl with normal differentiation; platelet 231000/µl; total protein 6.9 g/dl; serum sodium 143 mEq/l; serum potassium 4.5 mEq/l; serum chloride 104 mEq/l; serum calcium 10.3 mg/dl; serum phosphate 4.5 mg/dl; BUN 41.2 mg/dl; and S-Cr 2.9 mg/dl. S-UA was not measured at this time. The following parameters were within normal limits or negative: total cholesterol, triglyceride, aspartate aminotransferase, alanine aminotransferase, creatine kinase, lactate dehydrogenase, serum protein electrophoresis, C-reactive protein, antinuclear antibody, rheumatoid factor, antistreptolysin O, total serum haemolytic complement activity, hepatitis B surface antigen, hepatitis C antibody, electrocardiogram and X-ray of the chest and the abdomen. Repeated urinalyses also revealed no abnormalities. An abdominal CT scan did not reveal hydronephrosis, renal atrophy or renal calcifications.
After admission he was free of medication. On August 25, BUN was 34.0 mg/dl, S-Cr 2.3 mg/dl and S-UA 2.3 mg/dl. With the improvement of renal function, marked hypouricaemia became apparent: S-Cr decreased to 1.8, 1.3 and 1.0 mg/dl, and S-UA decreased to 1.8, 1.5 and 1.0 mg/dl on August 26, 28 and 31 respectively. Increased excretion of uric acid into the urine (740 mg/day, normal 600700 mg/day) and increased clearance ratio of uric acid against Cr (CUA/CCr) (48.7%, normal 5.511.1%) were also observed. No tubular dysfunction except for uric acid was detected in this patient. Therefore, a diagnosis of exercise-induced ARF associated with renal hypouricaemia was considered.
Table 1 shows the results of pyrazinamide suppression and benzbromarone tests, which were performed to evaluate the disturbances in the renal handling of uric acid [9]. Neither pyrazinamide nor benzbromarone had any significant effects on CUA or CUA/CCr.
|
|
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() |
---|
In our patient, neither pyrazinamide nor benzbromarone produced any significant effects on CUA or CUA/CCr. In general, unresponsiveness to pyrazinamide strongly suggests a defect in uric acid secretion or a total defect at the pyrazinamide-sensitive uric acid transport site. Unresponsiveness to benzbromarone suggests a marked defect in the uric acid reabsorptive site or a lack of action of benzbromarone due to its tubular-sensitive failure [9]. Considering that these drugs normally produce large changes in CUA/CCr [1], our results suggest that the present case has an extensive defect in uric acid transport, including secretory function. Baseline levels of CUA less than the glomerular filtration rate indicate that the uric acid reabsorptive function is partly preserved. Shichiri et al. reported that a subtotal defect in uric acid transport might explain the above results [9], and we considered that our patient had features similar to those of renal hypouricaemia.
The pathogenesis of exercise-induced ARF in patients with renal hypouricaemia is still uncertain. Acute uric acid nephropathy due to an increase in the excretion of urinary uric acid has been proposed in this condition [4,8]. However, the observation of renal tubular obstruction by uric acid crystals at renal biopsy has been reported only by Erley et al. [4]. Ishikawa et al. reported that contrast-enhanced CT scan in patients with this disease showed wedge-shaped contrast enhancement, indicative of the patchy renal vasoconstriction responsible for ARF [5].
It is thought that the reabsorption and secretion of uric acid occurs simultaneously along the proximal tubules [11]. This complex renal handling of uric acid appears to be inefficient in terms of excretion.
Uric acid is a powerful antioxidant, and is a scavenger of oxygen free radicals [12] which it has been suggested injure nephron segments, especially proximal tubules. In patients with renal hypouricaemia, the uric acid pool is very small, the static intracellular concentration of uric acid is low, and the total amount of uric acid mobilized into proximal tubular cells is also very small, although the daily urinary excretion of uric acid is usually normal [7]. During exercise, the production of oxygen free radicals increases, and an increase in muscular blood flow results in a decrease in renal blood flow [5,9]. This phenomenon may lead to severe vasoconstriction in patients with hypouricaemia, which is likely to occur when the intracellular concentration of uric acid is low [7]. In addition, oxygen free radicals may be overproduced after the recovery of renal blood flow in patients with severe vasoconstriction compared to those in healthy people, as shown in ischaemia-reperfusion models [13,14]. For these reasons, patients with renal hypouricaemia may be prone to develop ARF.
Yeun and Hasbargen demonstrated that allopurinol prevented ARF as well as exercise-induced increases in the excretion of uric acid into the urine and CUA/CCr in patients with renal hypouricaemia [8]. These results suggest that acute uric acid nephropathy may cause ARF in this disease. On the other hand, allopurinol is known to be a strong antioxidant that reduces the production of oxygen free radicals by inhibiting xanthine oxidase [14,15]. These facts also emphasize the importance of oxygen free radicals in ARF in patients with renal hypouricaemia. As our patient wished to remain active he was treated with vitamin C (ascorbic acid, 200 mg/day) and vitamin E (-tocopherol, 200 mg/day) as antioxidants to help preventing the recurrence of exercise-induced ARF. To date, he has not experienced a similar attack.
In summary, we report a typical case of exercise-induced ARF associated with renal hypouricaemia. Although hypouricaemia was only mild before the onset of ARF, marked hypouricaemia has continued after ARF. We think that the patient had latent abnormalities in the renal handling of uric acid, and showed overt hypouricaemia concomitant with exercise-induced ARF.
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() |
---|