A case of exercise-induced acute renal failure in a patient with enhanced renal hypouricaemia

Isao Kurihara1, Jun Soma2, Hiroshi Sato2, Takayuki Ikarashi1, Kazuo Tsunoda1, Ryou Miura1, Takashiro Suzuki1, Michinori Sato1, Takashi Furuyama1, Sadayoshi Ito2 and Takao Saito3

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
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 Introduction
 Case
 Discussion
 References
 
Renal hypouricaemia is a rare condition caused by an isolated defect in tubular uric acid transport, which is transmitted as an autosomal recessive trait [1]. The majority of cases have been reported in Japanese and non-Ashkenazic Jewish [2]. Two major complications in this disease are urolithiasis [3] and acute renal failure (ARF) [4,5]. In 1989, Erley et al. first described ARF in a Turkish patient with renal hypouricaemia [4]. Subsequently, exercise-induced ARF with renal hypouricaemia has been reported mainly in Japan [58]. We describe a patient with renal hypouricaemia who probably developed ARF as a result of a subtotal defect in uric acid transport. During ARF, and after recovery of renal function, the patient showed extremely low serum uric acid levels, although hypouricaemia was mild in previous medical checkups.



   Case
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 Introduction
 Case
 Discussion
 References
 
On August 24, 1998, a 24-year-old policeman was admitted to our hospital because of anorexia, low-grade fever, and bilateral loin pain 5 days after chasing and subduing a suspect. His past medical history was unremarkable. His mother was under haemodialysis (from June, 1997) because of chronic renal failure due to focal glomerulosclerosis. He had received routine group medical checkups 4 and 16 months previously, and no abnormalities were found in urinalysis, serum electrolyte, or liver function tests. The results of other laboratory tests included blood urea nitrogen (BUN) 17 and 16 mg/dl, serum creatinine (S-Cr) 0.8 and 0.8 mg/dl, and serum uric acid (S-UA) 2.6 and 2.6 mg/dl (normal 3.0–7.0 mg/dl) at 4 and 16 months respectively.

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 600–700 mg/day) and increased clearance ratio of uric acid against Cr (CUA/CCr) (48.7%, normal 5.5–11.1%) 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 1Go 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.


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Table 1. Pyrazinamide and benzbromarone tests
 
Table 2Go shows the laboratory examination results of the patient and his family members. The levels of S-UA and CUA/CCr were within normal limits in his sister and father. His mothers' data were obtained in April 1994 before the introduction of haemodialysis, when she was treated for hyperuricaemia associated with chronic renal failure. Familial occurrence was not proven based on this result.


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Table 2. Laboratory data of family members
 
After discharge from our hospital, he has taken vitamin C (200 mg/day) and vitamin E (200 mg/day) to prevent the recurrence of exercise-induced ARF. Although marked hypouricaemia (0.5–0.8 mg/dl) has persisted, a similar ARF episode has not occurred.



   Discussion
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 Introduction
 Case
 Discussion
 References
 
It has been reported that S-UA levels are not always low in patients with hypouricaemia during ARF. Sakemi et al. reported a case of exercise-induced ARF associated with renal hypouricaemia, in which an extremely high level of S-UA, 15.7 mg/dl, was found at admission [10]. However, there have been few reports in which S-UA levels were measured before the development of ARF. The present case showed typical features of exercise-induced ARF associated with renal hypouricaemia, although hypouricaemia was mild in previous routine group medical checkups before the onset of ARF. Therefore, we thought that the abnormal tubular uric acid transport was insidious before ARF, and overt hypouricaemia appeared with the development of exercise-induced ARF.

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 ({alpha}-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
 Top
 Introduction
 Case
 Discussion
 References
 

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Received for publication: 14. 5.99
Accepted in revised form: 3. 9.99





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