Renal hypouricemia

In this text, we emphasize that ALPE should always be considered in patients who complain of severe loin pain and nausea after sprinting in an athletics meeting, and while ALPE frequently develops in patients with renal hypouricemia, it also develops in those without it. 

This patient was the first case in which ALPE developed in the presence of renal hypouricemia [3]. On September 26,1984, he participated in a 400-m race in a school athletics meeting. On September 27, nausea and vomiting occurred about 12 h later at 0100 hours, and then bilateral loin pain and abdominal pain developed. Because... 

This patient developed ALPE in the presence of renal hypouricemia [3]. He caught a cold, and took aspirin at 400 mg, ethenzamide at 150 mg, and acetaminophen at 300 mg on October 8 and 9, 1987. On October 10, he participated in two 100-m races... 

Fig. 29. The clinical course of ALPE complicated by renal hypouricemia...

This patient (Case 1 in Fig. 57) and his son developed ALPE in the presence of renal hypouricemia [36]. After two 150-m sprints and rope skipping (40 skips) in a town athletics meeting, he developed ALPE. Gene analysis was performed to check for renal hypouricemia. The patient s son also developed ALPE (Case 2 in Fig. 57). The details are given in Chap. 10, Sect. 1. 

This patient and his father (Patient 18) developed ALPE in the presence of renal hypouricemia [36] (Case 2 in Fig. 57). The son developed ALPE after participating in two 400-m races, a mock cavalry battle, and a tug of war in an athletics meeting. At a local clinic, a nonsteroidal anti-inflammatory drug (NSAID) was administered orally under a diagnosis of muscular pain, and the condition was exacerbated. Gene... 

Renal hypouricemia was observed in 76 (57%) of the 133 patients in whom the serum levels of uric acid were recorded. Patients with a serum uric acid level of 2.0mg/dl or less at baseline were regarded as having hypouricemia. 

Risk factors for exercise-induced acute renal failure (ALPE) include anaerobic exercise, renal hypouricemia, administration of antipyretic analgesics for cold, and dehydration. We review renal hypouricemia here and in Chap.10. 

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. 

Previously, the disordered renal transport of uric acid in patients with renal hypouricemia had been explained by a 4-component model. In our review, 59% of the patients with ALPE and renal hypouricemia were classified as the presecretory reabsorption defect type, followed by the total defect in uric acid transport (no secretion and no reabsorption) and total reabsorption defect types (Table 8). 

Comparison of Patients With and Without Renal Hypouricemia... 

Of the 155 cases of patients with ALPE collected from the literature, we examined the presence or absence of renal hypouricemia in 133 for whom the serum levels of uric acid were reported (Table 9). The mean ages in the renal hypouricemia and non-renal hypouricemia groups were 20.2 7.4 years and 23.3 8.4 years, respectively. In the... 

Fig. 56. Serum creatinine, uric acid, and FEUA values at the onset (peak) and recovery of ALPE in patients with and without renal hypouricemia...

Table 8. Types of disordered renal uric acid transport in 76 patients with renal hypouricemia and ALPE...

Table 9. Comparison of ALPE patients with and without renal hypouricemia...

We performed delayed CT after the administration of contrast medium in 11 patients with both ALPE and renal hypouricemia. In 10 of the 11 patients, patchy renal ischemia was noted [4], suggesting that renal ischemic conditions after anaerobic exercise were similar regardless of the presence or absence of renal hypouricemia. 

Reason why Patients with Renal Hypouricemia Frequently Develop ALPE, and its Mechanism... 

It remains to be clarified why patients with renal hypouricemia frequently develop acute renal failure. The following hypothesis has been proposed. Oxidative stress is essential for the onset of ischemic acute renal failure. In the kidney, uric acid acts as a protective mechanism against oxidative stress. However, in patients with renal hypouricemia, a decrease in uric acid may allow exposure of the kidney to oxidative stress, causing ALPE [152,153]. 

The mechanism by which these patients develop ALPE also remains to be clarified. However, two hypotheses have been put forward, and active oxygen/renovascular spasm or tubular obstruction may be involved. One hypothesis is that patients with renal hypouricemia are exposed to active oxygen because the level of an active oxygen... 

In conclusion, intrarenal topical circulatory disorder or vascular spasm may develop in patients with renal hypouricemia, leading to acute renal failure. 

URAT1 Gene Analysis in Patients with Renal Hypouricemia who Developed ALPE... 

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. 

Table 10. URAT1 (SLC22A12) mutation in patients with renal hypouricemia who developed ALPE...

Fig. 60. Analysis of R90H (G269A) and W258X (G774A) by direct DNA sequencing in a family with renal hypouricemia...

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