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     

Exercise-induced acute renal failure associated with renal vasoconstriction]

Exercise-induced acute renal failure without rhabdomyolysis is not a rare condition. We experienced 6 cases (5 men and a woman) during last the 8 years. All cases complained of severe loin pain and nausea after mild to moderate exercises (for example, a track race in an athletic meeting). The elevation of serum and urinary myoglobin was undetected. In 4 of 5 patients with abdominal CT, renal patchy vasoconstriction (wedge-shaped low-density lesion) was observed. This was diagnosed as exercise-induced acute renal failure with loin pain (serum creatinine levels: 1.7-8.6 mg/dl). The renal function in 5 of the 6 cases normalized in about three weeks by fluid replacement therapy and hemodialysis support, which one patient received for 3 days. One patient required a long time for improvement of renal function and renal insufficiency persisted (serum creatinine 1.8 mg/dl). In 2 patients, the concentration of serum uric acid became very low after the recovery of renal function. These two patients were diagnosed as an isolated hyperuricosuric hypouricemia. More than half of the 6 patients had previously experienced the same episodes (loin pain and nausea) after exercise. Exercise-induced acute renal failure, probably due to renal patchy vasoconstriction, seems to be not a rare disease. The etiology of renal patchy vasoconstriction after exercises remains to be elucidated. The occurrence of acute renal failure must be taken into consideration when the youngster, especially with renal hypouricemia, complains of severe loin pain and nausea after exercise such as a track race.     

Oxidative imbalance in idiopathic renal hypouricemia

An important complication of idiopathic renal hypouricemia is exercise-induced acute renal failure (ARF). The most plausible explanation for this complication is that decreased antioxidant potential leads to kidney injury by reactive oxygen species (ROS). We demonstrated this oxidative imbalance by a concomitant assessment of ROS production and antioxidant system capability in a 15- year-old girl with idiopathic renal hypouricemia caused by a mutation in the urate transporter (URAT1) gene. Her serum level of ROS increased with decreasing antioxidant potential capacity soon after the initiation of anaerobic stress due to treadmill exercise. Thereafter, serum levels of ROS and antioxidant potential showed a parallel course, returning to the baseline values at 240 min after exercise. Some patients with idiopathic renal hypouricemia demonstrate oxidative imbalance soon after exercise with a predisposition to exercise-induced acute renal failure. Antioxidant properties may alter this imbalance by augmenting the antioxidant activity.     

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     

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.     

Two cases of nephrotic syndrome (NS)-induced acute kidney injury (AKI) associated with renal hypouricemia

Renal hypouricemia is a clinical disorder attributed to an increased renal urate excretion rate and is well known to involve a high risk of urolithiasis and exercise-induced acute kidney injury (AKI). This report concerns two interesting cases of nephrotic syndrome (NS)-induced AKI associated with renal hypouricemia. A 64-year-old female (Case 1) and a 37-year-old male (Case 2) were hospitalized because of AKI (serum creatinine: 2.07 mg/dl and 3.3 mg/dl, respectively), oliguria and NS. They were treated with prednisolone and temporary hemodialysis. Renal function improved, but hypouricemia persisted during hospitalization. Histological findings in both cases led to a diagnosis of minimal change nephrotic syndrome and identification of the diuretic phase of tubulointerstitial damage because of findings such as acute tubular necrosis. Furthermore, distal tubules of Case 2 showed an amorphous mass, possibly a uric acid crystal. Analysis of the two cases with the URAT1 gene, encoded by SLC22A12, found a homozygous mutation in exon 4 (W258stop) of each one. Our cases show that patients with renal hypouricemia may be susceptible to AKI without involvement of exercise if they possess some facilitators. Renal hypouricemic patients should therefore be carefully examined for all complications from renal hypouricemia because of high risk of AKI.     

Magnetic resonance imaging in renal infarction and ischemia

Two cases of renal segmental infarction and 1 case of renal patchy ischemia demonstrated by magnetic resonance imaging (MRI) are reported. MRI of renal infarction in two renal grafts following surgical ligation revealed an area of noncorticomedullary differentiation and an area with a low signal intensity. Renal ischemia in 1 patient with acute renal dysfunction with severe loin pain and patchy renal vasoconstriction was visualized as an ill-defined focus of low signal intensity in the renal cortex, indicating a long T1 relaxation time. Delayed wedge-shaped contrast enhancement was demonstrated on CT scan in the same area. The common finding in renal infarction and ischemia in our cases was the area of low signal intensity on MRI.     

Regulation of cell survival during renal development

Apoptosis occurs in an orchestrated fashion during kidney development. In contrast, it is a relatively rare event in normal developed (adult) kidney. However, a predictable pattern of apoptosis is observed in adult kidney in two settings, during which parts of the developmental pattern are recapitulated. These are regeneration following acute ischemic injury and the process of cystogenesis in polycystic kidney disease. Apoptosis in kidney is regulated by agents both intrinsic and extrinsic to the renal cell. The protooncogene b-cell lymphoma/leukemia gene product-2 (bcl-2) is an important intrinsic factor. The growth factor epidermal growth factor is an important extrinsic regulator. A thorough understanding of the control of renal apoptosis during development and recovery from ischemic injury and in cystogenesis may lead to new therapies to prevent or ameliorate abnormalities of kidney formation, to enhance regeneration following acute ischemic injury, and to slow the progression of renal failure in polycystic kidney disease. Received October 14, 1997; received in revised form December 10, 1997; accepted January 28, 1998     

Patients with renal hypouricemia with exercise-induced acute renal failure and chronic renal dysfunction

We here report the case of a 38-year-old male with back pain and vomiting occurring after exercise. Serum creatinine level was elevated, and he was admitted to our hospital with diagnosis of acute renal failure (ARF). He had experienced similar attacks at least 4 times, including the present episode, from the age of 22 years. After admission, the patient was managed only by resting, and remission was nearly attained in about 1 month. The renal biopsy specimen performed on day 15 showed findings of acute tubular necrosis, thickening of the tubular basement membrane, and interstitial fibrosis. After remission, the serum uric acid level was 0.7-0.8 mg/dl, fractional excretion of uric acid was 0.63, and the possibility of other diseases facilitating the excretion of uric acid was denied. Therefore, ARF associated with idiopathic renal hypouricemia was diagnosed. Since only mild responses were observed in a pyradinamide loading test and a benzbromarone loading test, the case was considered to be a presecretary reabsorption disorder type. Renal function tests showed the almost complete recovery of the glomerular filtration rate (GFR: 114 ml/min/1.73 m2), but the urine concentrating ability was markedly decreased (specific gravity 1.019 and osmolarity 516 mOsm/kgxH2O in Fishberg test). Past data from this patient indicated that this renal dysfunction had been persisting for ten years. We examined 9 patients with renal hypouricemia and focused on the differences between the two groups (with or without complications). Four patients had a history of exercise-induced ARF or calculus. The urine concentrating ability was significantly lower in these patients (group A) than in the other patients without complications (group B). The glomerular filtration rate in group A was within the normal range, but was lower than in group B. These results suggested the possibility that patients with renal hypouricemia with complications may have chronic renal dysfunction in the future.     

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.     

Reversible renal vasoconstriction in a patient with acute renal failure after exercise

Acute renal failure (ARF) with severe loin pain induced by anaerobic exercise is a rare condition that is accompanied by wedge-shaped contrast enhancement seen on computerized tomographic (CT) scan without evidence of rhabdomyolysis. An 18-year-old Korean male was transferred to our hospital for evaluation of mild azotemia, that developed after anaerobic exercise. The laboratory tests revealed that the serum creatinine was 2.1 mg/dl and the serum uric acid level was 1.6 mg/dl without any elevation of the serum myoglobin or creatine phosphokinase. Under the impression of exercise-induced ARF, we tried to determine the relationship between the occurrence of clinical symptoms, renal dysfunction and the characteristic CT findings by observing those changes prospectively before and after anaerobic exercise. After obtaining a written consent, the patient underwent a strenuous period of anaerobic exercise to induce the clinical symptoms. Before exercise, he was completely asymptomatic; his serum creatinine level was 0.9 mg/dl and CT scan of the kidneys showed no abnormalities. Loin pain developed 2 hours after exercise, and the serum creatinine level increased to 1.2 mg/dl 18 hours after the exercise. CT scan 18 hours after exercise showed multiple perfusion defects, and a 24-hour delayed CT scan showed multiple areas of wedge-shaped enhancement on both kidneys. These changes were completely resolved on the follow-up CT scan obtained 13 days after exercise with the return of a normal serum creatinine level. We conclude that reversible renal vasoconstriction is probably the main pathophysiologic mechanism of acute renal failure induced by anaerobic exercise.     

Bone scintigraphy in acute renal failure with severe loin pain and patchy renal vasoconstriction.

To evaluate the patterns of renal images and the diagnostic value as a screening test of the whole-body bone and renal scintigraphy with technetium-99m-methylene diphosphonate (99mTc-MDP) or -pyrophosphate (99mTc-PYP), we performed bone scintigraphy in 6 patients with acute renal failure (ARF) with severe loin pain and patchy renal vasoconstriction on postcontrast renal computed tomography (CT). All 6 patients were young and previously healthy but experienced severe loin pain after track events. Five took analgesics. Postcontrast renal CT showed patchy low-density areas or diffuse enhancement immediately after radiocontrast injection and then patchy wedge-shaped enhancement 24 or 48 h later, which subsequently disappeared 72 h later. On the whole-body bone scintigrams with 99mTc-MDP or 99mTc-PYP before obtaining renal CT, there was no increased uptake of isotope in the soft tissue, and multiple patchy increased accumulations of the isotope in the kidney were observed in 5 patients. In 2 patients, renal scintigraphies with technetium-99m-dimercaptosuccinate showed photon-deficient areas in the same areas of patchy isotope accumulation in the whole-body bone scintigraphies. Whole-body image and renal scintigraphy with bone-seeking agents may be useful as a screening test and in the search for the theoretical evidence of ARF with severe loin pain and patchy renal vasoconstriction.     

Acute renal failure after analgesic drugs including paracetamol (acetaminophen)

Seven patients with acute renal failure after ingestion of analgesic drug combinations including paracetamol were seen. They presented with oliguric renal failure and restitution of renal function was complete. Only 2 patients had severe liver damage and 2 patients had no signs of liver abnormality. Renal biopsies, studied by light and electron microscopy, in 3 patients showed focal tubular epithelial cell necrosis. Focal vascular damage, predominantly of endothelial cells, was also present in all specimens. This vascular injury was found in various locations in the kidney, including the glomerular and peritubular capillaries and small arterioles. This suggests that microvascular damage is an important mechanism for the renal injury after analgesic drugs.     

Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury.

BACKGROUND: Ischaemia/reperfusion is a major cause of acute kidney injury and can result in poor long-term graft function. Although most of the patients with acute kidney injury recover their renal function, significant portion of patients suffer from progressive deterioration of renal function. A persistent inflammatory response might be associated with long-term changes following acute ischaemia/reperfusion. Macrophages are known to infiltrate into tubulointersitium in animal models of chronic kidney disease. However, the role of macrophages in long-term changes after ischaemia/reperfusion remains unknown. We aimed to investigate the role of macrophages on the development of tubulointerstitial fibrosis and functional impairment following acute ischaemia/reperfusion injury by depleting macrophages with liposome clodronate. METHODS: Male Sprague-Dawley rats underwent right nephrectomy and clamping of left renal vascular pedicle or sham operation. Liposome clodronate or phosphate buffered saline was administered for 8 weeks. Biochemical and histological renal damage and gene expression of various cytokines were assessed at 4 and 8 weeks after ischaemia/reperfusion. RESULTS: Ischaemic/reperfusion injury resulted in persistent inflammation and tubulointerstital fibrosis with decreased creatinine clearance and increased urinary albumin excretion at 4 and 8 weeks. Macrophage depletion attenuated those changes. This beneficial effect was accompanied with a decrease in gene expression of inflammatory and profibrotic cytokines. CONCLUSIONS: These results suggest that macrophages play an important role in mediating persistent inflammation and fibrosis after ischaemia/reperfusion leading to a development of chronic kidney disease. Strategies targeting macrophage infiltration or activation can be useful in the prevention of development of chronic kidney disease following ischaemic injury.     

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.     

Dynamic renal function testing by compartmental analysis: assessment of renal functional reserve in essential hypertension.

BACKGROUND: In essential hypertension, acute haemodynamic changes due to dietary protein load cause patterns of acute changes in renal function that are fundamentally different from changes in normal controls. METHODS: Renal clearances of sinistrin, an inulin-like polyfructosan, and p-aminohippurate were determined before and after protein ingestion. These tests were performed in healthy controls and in patients with essential hypertension (mean arterial pressure of 112+/-2 mmHg, age, 52+/-2 years; mean+/-SEM) within a washout period, and after long-term treatment with carvedilol and fosinopril, respectively. RESULTS: In 15 healthy volunteers, protein ingestion increased glomerular filtration rate (GFR) from 110.3+/-3.6 to 120. 6+/-4.4 ml/min (P=0.0006; two-tailed pairwise t-test). In contrast, it led to an acute decrease in GFR in 16 hypertensive patients, from 111.8+/-2.9 to 103.6+/-3.3 ml/min (P=0.0010). The eight patients who were randomized to receive carvedilol improved in their renal response to protein (GFR increased from 101.4+/-6.4 to 107.1+/-5.4 ml/min; P=0.04), whereas the eight other patients randomized to receive fosinopril exhibited no change in GFR (final value 105+/-4.9 ml/min). In the patients, the acute shifts in renal plasma flows were not significant. Mean arterial blood pressure of the patients decreased from 112+/-2 to 100+/-3 mmHg (P=0.0015). CONCLUSIONS: In essential hypertension an acute protein load induces a decrease in GFR that may normalize under antihypertensive treatment. The acute changes in GFR can be reliably monitored by the here-described compartmental analysis method of renal functional reserve.     

Reversible acute renal allograft dysfunction due to gabapentin

BACKGROUND: The use of gabapentin as an effective analgesic agent for neuropathic pain has expanded considerably. Its lack of both anticholinergic side effects and interference with the metabolism of drugs via the cytochrome P450 pathway make it especially useful for transplant recipients. METHODS AND RESULTS: We describe the case of a renal transplant recipient with a long-term stable functioning allograft who developed reversible acute renal dysfunction after beginning gabapentin therapy for chronic pain due to diabetic neuropathy. CONCLUSIONS: We suggest that gabapentin may cause acute renal dysfunction by a mechanism involving renal afferent vasoconstriction. Caution should be employed when considering the use of gabapentin in transplant recipients, especially when combined with other agents that may potentiate renal vasoconstriction.     

Renal hypouricemia in school-aged children: screening of serum uric acid level before physical training

We present two cases of a 12-year-old Japanese boy and a 14-year-old Japanese girl who had exercise-induced acute renal failure (ARF). They experienced general fatigue, nausea/vomiting, and vague discomfort in the abdomen after physical exercise at school. In case of the boy, abdominal pain subsided, but renal dysfunction lasted 17 days, with peak levels of creatinine 9.4 mg/dl and uric acid 11.3 mg/dl. On the other hand, as the girl had suffered from hypouricemia before, she followed a doctor’s guidance on prevention of ARF. Consequently, she was promptly diagnosed as having exercise-induced ARF associated with hypouricemia, and rapidly recovered from ARF within a week. The difference between their clinical courses suggested a possibility that previous laboratory evaluation of serum uric acid assisted in the management of exercise-induced ARF associated with hypouricemia. School-aged children, especially Japanese and Asian, may be advised to have their serum uric acid measured before starting physical training at school.     

Increased patchy renal accumulation of 99mTc-methylene diphosphonate in a patient with severe loin pain after exercise

Radionuclide imaging in a patient who had acute renal failure with severe loin pain and patchy renal vasoconstriction is described. The patient was studied 3h after the intravenous bolus injection of 25 mCi99mTc-methylene diphosphonate (99mTc-MDP). An intense patchy renal concentration of 99mTc-MDP was observed.