Two cases of exercise-induced acute renal failure with idiopathic renal hypouricemia

Acute renal failure without oliguria developed in a 25-year-old male and a 19-year-old male after exercise. Marked hypouricemia became apparent during improvement of their renal function. Increased excretion of uric acid into the urine, increased fractional excretion of uric acid(clearance ratio of uric acid against creatinine), and normal concentration of plasma xanthine and hypoxanthine were observed in both cases. Probenecid and pyrazinamide loading test suggesting decreased reabsorption of uric acid in the proximal convoluted tubules revealed that presecretory reabsorption defect of uric acid resulted in the hypouricemia in both cases. These two cases were diagnosed as having idiopathic renal hypouricemia.     

Exercise-induced acute renal failure in 3 patients with renal hypouricemia

Three cases of exercise-induced non-oliguric acute renal failure in patients with renal hypouricemia, an isolated defect of the renal urate transport system, are described. During acute renal failure, the serum uric acid levels were 5.6, 2.7 and 5.8 mg/dl, respectively, and were within normal limits. The values representing the fractional excretion of uric acid (FEUA) were 28.7, 60.0 and 12.7%, with accompanying serum creatinine levels of 8.1, 3.9 and 3.3 mg/dl, respectively. After recovery, the serum uric acid fell to 0.6, 0.7 and 1.0 mg/dl and the FEUA increased to 79.3, 52.8 and 43.2%, respectively. Two of the patients examined exhibited decreased reabsorption of filtered urate. These 3 examples of renal hypouricemia represented 23% of 13 cases of mild exercise-induced acute renal failure encountered within our experience.     

Exercise-induced acute renal failure in a patient with renal hypouricemia

We describe a case of exercise-induced acute renal failure (ARF) in a patient with hypouricemia. Following recovery from ARF, the patient’s serum urate concentration was 0.6–0.9 mg/dl, and the ratio of urate clearance to creatinine clearance (C _ua/C _Cr) was 41.9%–56.6%. There was no change in the C _ua/C _Cr following the administration of pyrazinamide or probenecid, suggesting defects of tubular urate/anion exchangers. Because the renal biopsy revealed acute tubular necrosis without uric acid crystals, the ARF of this patient might be due to oxygen free radicals resulting from exercise stress and hypouricemia. Received: 15 March 1999 / Revised: 10 September 1999 / Accepted: 14 September 1999     

A case of acute renal failure in a patient with idiopathic hypouricemia]

This report is a 17-year-old man with an acute renal failure who complained of nausea, vomiting, bilateral loin pain and abdominal pain after scuffle. Renal biopsy specimen obtained from the left kidney revealed acute tubular necrosis. After recovering renal function he showed extreme hypouricemia (serum uric acid, 0.6 mg/dl) and elevated uric acid clearance (62-78 ml/min). The fractional excretion of uric acid (CUA/Ccr) could not be influenced by either oral pyrazinamide or probenecid. As no other renal tubular or metabolic abnormalities were detected, it is suggested that presecretory reabsorption defect or subtotal defect in uric acid transportation was responsible for the hypouricemia in this patient.     

Exercise-induced acute renal failure with renal hypouricemia: a case report and a review of the literature

A previously healthy 16-year-old boy developed acute renal failure following a track race at a local athletic meeting. Several hours after the run, he expressed pain in the loins with nausea and vomiting. After 3 sessions of hemodialysis, he was referred to our hospital. On admission, serum creatinine was elevated to 2.3 mg/dl without an increase in serum uric acid level. After recovery from acute renal failure (ARF), hypouricemia (0.7 mg/dl) became evident in the patient. One year later, he suffered from ARF after a track race with the highest creatinine levels of 1.1 mg/dl. In order to clarify the cause and prognosis of ARF with renal hypouricemia, we summarized the clinical features in 18 patients previously described and our patient. Serum uric acid levels after recovery from ARF were below 1.0 mg/dl in all patients. Renal biopsy in 9 patients showed acute tubular necrosis in 8 patients and uric acid nephropathy in 1. The short-term prognosis of these patients seemed good, although 5 patients needed to undergo hemodialysis in their ARF courses. However, the recurrence of ARF episodes occurred in 6 patients (31.6%) including our patient, indicating that prevention of ARF might be necessary in these patients. More information is required to establish guidance for prevention of ARF.     

Acute renal failure after exercise in a patient with renal hypouricemia

A 22-year-old man had recurrent exercise-induced acute renal failure (ARF). He was found to have isolated renal hypouricemia: serum uric acid level was 0.7–1.0 mg/dl and fractional excretion of uric acid (FE_UA) was 37%–43%. He showed no suppression of FE_UA following the the administration of pyrazinamide, and no increase of FE_UA after benzbromarone, suggesting a subtotal defect. We investigated renal function, FE_UA, and serum nitric oxide after a treadmill exercise test in our patient and two control subjects. On the day after the exercise test, plain and enhanced abdominal computed tomography (CT) scans were performed in our patient. During the arterial phase, early equilibration phase, equilibration phase, and 2, 6, and 24 h after the injection of contrast medium, renal CT scans were performed at the same slice level. Although ARF was not induced by this level of exercise, the CT scans showed patchy contrast enhancement 2, 6, and 24 h after contrast medium administration. This finding suggests that patchy renal vasoconstriction may occur in patients with renal hypouricemia after strenuous exercise, even in the setting of normal creatinine clearance. Received: June 19, 1998 / Accepted: September 4, 1998     

Vascular erectile dysfunction in chronic renal failure

The prevalence of erectile dysfunction (ED) has increased dramatically worldwide in parallel with the aging of the population. In 1995, ED was estimated to be present in more than 150 million men. Considering population aging in Western countries, estimates predict that more than 300 million men will be affected by ED by the year 2025. ED is a common and often distressing side effect of renal failure. It is present in 30% of patients with chronic renal failure and in 50% of patients undergoing dialysis treatment. Uremic men of different ages report a high variety of sexual problems including sexual hormonal pattern alterations, reduced or loss of libido, infertility, and impotence, thereby influencing their well-being. The pathogenetic mechanisms include physiologic, psychologic, and organic causes. Since the release of sildenafil citrate, the relationship between ED and the presence of cardiovascular disease (CVD) has been evaluated in several studies. Many of the risk factors for ED are the same as those for cardiac disease. CVD and ED are closely interrelated disease processes. Indeed, ED can be considered a symptom of vascular endothelial damage. Therefore, it can be expected that impotence will appear along with CVD, and the presence of ED suggests the existence of CVD. An accurate evaluation of the sexual histories of all men who present to internists, cardiologists, and also nephrologists for early detection of ED may allow for early diagnosis and management of CVD.     

Diffusion-weighted MRI of exercise-induced acute renal failure (ALPE)

Acute renal failure with severe loin pain induced by anaerobic exercise (ALPE) is a rare condition that is accompanied by wedge-shaped contrast enhancement on computed tomography (CT) without evidence of rhabdomyolysis. In two pediatric cases with ALPE, we tried to determine the relationship between findings from CT and magnetic resonance imaging (MRI). Case 1 involved a 13-year-old Japanese girl with a diagnosis of ALPE with normo-uricemia. Contrast-enhanced CT after 24 and 48 h showed a wedge-shaped excretion delay for the contrast media. A clear wedge-shaped signal hyperintensity matching the CT images was obtained by diffusion-weighted MRI. Case 2 involved a 16-year-old boy who presented with a second attack of ALPE after diagnosis of ALPE with hypouricemia 1 year earlier. Only diffusion-weighted imaging was performed. Clear wedge-shaped signal hyperintensity was apparent, similar to Case 1. MRI is safer than contrast-enhanced CT for patients with ALPE. Diffusion-weighted MRI is a very useful examination for diagnosing ALPE, providing noninvasive detection of lesions peculiar to ALPE.     

Endothelial dysfunction and oxidative stress in chronic renal failure

Uremic patients have an increased incidence of cardiovascular disease (CVD), endothelial dysfunction and oxidative stress that can contribute to cardiovascular (CV) events. To assess the relationship between endothelial dysfunction, oxidative stress and renal failure severity, we studied 40 patients (age 57 +/- 7 yrs, 24 males) affected by chronic kidney disease (CKD) K/DOQI stage 3-5 (serum creatinine (Cr) 5.6 +/- 2.2 mg/dL) on conservative treatment, 20 uremic patients (age 57 +/- 12 yrs, 13 males) on hemodialysis (HD) and 30 healthy controls (56 +/- 12 yrs, 20 males). Before and 2 hr after oral vitamin C (2 g) administration, we measured brachial artery endothelium-dependent vasodilation (flow mediated dilation (FMD)) to reactive hyperemia following 5 min of forearm ischemia and the response to sublingual glyceril trinitrate (GTN). Measurements were made by high-resolution ultrasound and computerized analysis. FMD was lower in CKD patients than in controls (5.3 +/- 2.2 vs. 6.9 +/- 2.8%; p<0.01) and was further reduced in HD patients (3.6 +/- 2.7; p<0.01 vs. CKD patients). Response to GTN was similar in all groups. FMD was related to Cr clearance (r=0.42; p<0.01) in CKD patients, while it related inversely to Kt/V(urea) (r=-0.52; p<0.05) in HD patients. After vitamin C administration, FMD was significantly enhanced in HD (4.7 +/- 2.4%; p<0.01 vs. baseline), but not in CKD patients. Response to GTN was unaffected. However, vitamin C load reduced oxidative stress markers, and increased plasma antioxidant capability in both groups. In conclusion, the reduced endothelium-dependent dilation in the brachial artery of CKD patients is related to renal failure severity. HD patients showed a more marked alteration, which seems to be related, at least in part, to increased oxidative stress.     

A case of acute renal failure after exercise with renal hypouricemia demonstrated compound heterozygous mutations of uric acid transporter 1

Familial renal hypouricemia is a hereditary disease characterized by extraordinary high renal uric acid (UA) clearance and is associated with acute renal failure (ARF). A 17-year-old Japanese male developed ARF after anerobic exercise. Renal function improved completely after approximately 2 weeks of hydration treatment. After remission, hypouricemia became evident (1.0 mg/dL) from the initial level of UA (4.8 mg/dL) and fractional excretion of uric acid (FEUA) was >50%. His parents showed normal levels of UA and FEUA. Polymerase chain reaction of a urate anion exchanger known to regulate UA level [SLC22A12 gene: UA transporter 1 (URAT1)] demonstrated compound heterozygous mutations (Q297X and R90H). Thus, we describe a Japanese male with hypouricemia complicated by anerobic exercise-induced ARF, with definite demonstration of a genetic abnormality in the responsible gene, URAT1.     

Microvascular endothelial injury and dysfunction during ischemic acute renal failure

The pathophysiology of ischemic acute renal failure (ARF) appears to involve a complex interplay between renal hemodynamics, tubular injury, and inflammatory processes. While the current paradigm of the pathophysiology of ischemic ARF invokes both sublethal and lethal tubular injury as being of paramount importance to diminished renal function, a growing body of evidence supports the contribution of altered renal vascular function in potentially initiating and subsequently extending the initial tubular injury. We propose that the "extension phase" of ischemic ARF involves alterations in renal perfusion, continued hypoxia, and inflammatory processes that all contribute to continued tubular cell injury. Vascular endothelial cell injury and dysfunction play a vital part in this extension phase. In the constitutive state the endothelium regulates migration of inflammatory cells into tissue, vascular tone and perfusion, vasopermeability, and prevents coagulation. Upon injury, the endothelial cell loses its ability to regulate these functions. This loss of regulatory function can have a subsequent detrimental impact upon renal function. Vascular congestion, edema formation, diminished blood flow, and infiltration of inflammatory cells have been documented in the corticomedullary junction of the kidney, but linking their genesis to vascular endothelial injury and dysfunction has been difficult. However, new investigative approaches, including multiphoton microscopy and the Tie2-GFP mouse, have been developed that will further our understanding of the roles endothelial injury and dysfunction play in the pathophysiology of ischemic ARF. This knowledge should provide new diagnostic and therapeutic approaches to ischemic ARF.     

Detection of a metalloproteinase in patients with acute and chronic renal failure

The effect of different dialyzer membrane materials (cuprophan, cellulose hydrate, polyacrylonitrile, polymethylmethacrylate, ethylene-vinyl alcohol copolymer) on the ultrafiltrate proteinase activity was investigated in 26 patients with acute renal failure (ARF) and 40 patients undergoing regular hemodialysis treatment (RDT). Furthermore, the proteinase activity was characterized in vitro using azocasein and phosphorylase kinase as substrates in the absence and presence of different proteinase inhibitors. Proteinase activity of ultrafiltrates obtained from ARF patients was significantly enhanced with the dialyzer KF 101 (ethylene-vinyl alcohol copolymer). The digestion pattern of phosphorylase kinase revealed an identical type of proteinases in ultrafiltrates of ARF and RDT patients. The pH optimum of this proteinase was at alkaline pH. The proteinase activity could be inhibited in the presence of EDTA, whereas serine proteinase inhibitors were ineffective. Furthermore, the inactivated proteinase after Sephadex G-10 chromatography (in order to separate ultrafiltrate electrolytes and trace elements from protein) could be reactivated after the addition of Mg++ and/or Ca++. We conclude that a metalloproteinase can be found in ARF and RDT patients, and that KF 101 is more effectively eliminating the proteinase activity in ARF patients than other dialyzer membranes.     

Ultradian but not circadian blood pressure rhythms correlate with renal dysfunction in children with chronic renal failure

Whereas the diurnal fall of BP (dipping) is an important prognostic marker in patients with chronic renal failure (CRF), the integrity of physiologic ultradian (i.e., shorter than 24 h) cardiovascular rhythms in patients with CRF is unknown. Also, the relationship between conventional dipping analysis and Fourier spectral rhythm analysis has not been examined in renal hypertension. The prevalence and dimensions of the circadian and three ultradian (12, 8, and 6 h) cardiovascular rhythms were studied by ambulatory BP monitoring in 214 children (aged 3 to 18 yr) with CRF (stage 2 to 4 chronic kidney disease) and no antihypertensive treatment compared with 938 healthy control subjects, and the relationship of rhythm characteristics to conventional dipping parameters, renal function, proteinuria, and serum electrolytes was assessed. The CRF cohort exhibited significantly reduced amplitudes of the circadian and all ultradian cardiovascular rhythms studied (all P < 0.01). Moreover, all BP and most heart rate rhythms showed significantly delayed acrophases (time of peak; P < 0.01). Whereas conventional BP dipping parameters (day/night difference, day/night ratio) and the 24-h BP amplitude were independent of renal function, the 8-h BP amplitude was positively correlated with GFR (r = 0.3, P = 0.01) and inversely correlated with the urinary protein/creatinine ratio (r = -0.27, P < 0.05), and the 6-h BP amplitude was inversely correlated with proteinuria (r = -0.3, P < 0.02). Children who displayed 24- or 12-h cardiovascular rhythms had significantly lower serum calcium levels than children without these rhythms. In summary, children with CRF display not only blunted circadian but also blunted ultradian cardiovascular rhythms. Ultradian but not circadian rhythms or conventional dipping parameters are quantitatively associated with renal function and proteinuria.