Cause of Persistent Hypouricemia in Outpatients

Hisatome, Ichiro; Oginö, Kazuhíde; Kotake, Hiroshi; Ishiko, Riichiro; Saito, Makoto; Hasegawa, Junichi; Mashiba, Hiroto; Nakamoto, Shoji

doi:10.1159/000185233

Cited by 63 publications

(57 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, a slight but significant increase in CUA/Ccr of all the homozygotes and compound heterozygotes was observed in the probenecid loading test, suggesting that probenecid might also act on another urate transporter. It has been reported that a population of renal hypouricemic patients with a post-secretory reabsorptive defect have a pyrazinamide suppressible CUA that is not influenced by probenecid (5,7,35,36). This renal hypouricemia might be due to another urate transporter defect.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Clinical and Molecular Analysis of Patients with Renal Hypouricemia in Japan-Influence of URAT1 Gene on Urinary Urate Excretion

Ichida

Hosoyamada²,

Hisatome³

et al. 2004

Journal of the American Society of Nephrology

341

353

View full text Add to dashboard Cite

Abstract. Renal hypouricemia is an inherited and heterogeneous disorder characterized by increased urate clearance (CUA). The authors recently established that urate was reabsorbed via URAT1 on the tubular apical membrane and that mutations in SLC22A12 encoding URAT1 cause renal hypouricemia. This study was undertaken to elucidate and correlate clinical and genetic features of renal hypouricemia. The SLC22A12 gene was sequenced in 32 unrelated idiopathic renal hypouricemia patients, and the relationships of serum urate levels, and CUA/creatinine clearance (Ccr) to SLC22A12 genotype were examined. Uricosuric (probenecid and benzbromarone) and anti-uricosuric drug (pyrazinamide) loading tests were also performed in some patients. Three patients had exercise-induced acute renal failure (9.4%), and four patients had urolithiasis (12.5%). The authors identified eight new mutations and two previously reported mutations that result in loss of function. Thirty patients had SLC22A12 mutations; 24 homozygotes and compound heterozygotes, and 6 heterozygotes. Mutation G774A dominated SLC22A12 mutations (74.1% in 54 alleles). Serum urate levels were significantly lower and CUA/Ccr was significantly higher in heterozygotes compared with healthy subjects; these changes were even more significant in homozygotes and compound heterozygotes. These CUA/Ccr relations demonstrated a gene dosage effect that corresponds with the difference in serum urate levels. In contrast to healthy subjects, the CUA/Ccr of patients with homozygous and compound heterozygous SLC22A12 mutations was unaffected by pyrazinamide, benzbromarone, and probenecid. The findings indicate that SLC22A12 was responsible for most renal hypouricemia and that URAT1 is the primary reabsorptive urate transporter, targeted by pyrazinamide, benzbromarone, and probenecid in vivo.Approximately 90% of all urate that is filtered through the glomerulus is eventually reabsorbed. A four-component hypothesis has been proposed to explain the renal urate transport mechanisms; it includes glomerular filtration, presecretory reabsorption, secretion, and postsecretory reabsorption (1,2). Renal hypouricemia is a common inherited and heterogeneous disorder characterized by impaired tubular urate transport (3). The incidence of renal hypouricemia has been reported to be 0.12 to 0.72% (4,5), and exercise-induced acute renal failure and nephrolithiasis have been reported as complications (6).Renal hypouricemia has been classified into the following five types according to responses to the anti-uricosuric drug pyrazinamide, and the uricosuric drug, probenecid: (a) a presecretory reabsorptive defect with an attenuated response to both pyrazinamide and probenecid (3); (b) a post-secretory reabsorptive defect when pyrazinamide suppressible urate clearance (CUA) is not influenced by probenecid (7); (c) total inhibition of urate reabsorption when pyrazinamide induces elimination of CUA exceeding the rate of glomerular filtration (8); (d) enhanced secretion when the pyrazinamide suppressible CUA ...

show abstract

Section: Discussionmentioning

confidence: 99%

“…Renal hypouricemia is a common inherited and heterogeneous disorder characterized by impaired tubular urate transport (3). The incidence of renal hypouricemia has been reported to be 0.12 to 0.72% (4,5), and exercise-induced acute renal failure and nephrolithiasis have been reported as complications (6).…”

mentioning

confidence: 99%

Clinical and Molecular Analysis of Patients with Renal Hypouricemia in Japan-Influence of URAT1 Gene on Urinary Urate Excretion

Ichida

Hosoyamada²,

Hisatome³

et al. 2004

Journal of the American Society of Nephrology

341

353

View full text Add to dashboard Cite

show abstract

“…This condition is very rare and until now, most cases have been described in the Japanese population with a prevalence rate of 0.12%. 5 Nephrolithiasis and exercise-induced AKI have been associated with renal hypouricaemia. Patients with renal hypouricemia have a 200-fold greater predisposition to exercise-induced AKI than those without renal hypouricemia.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with renal hypouricemia have a 200-fold greater predisposition to exercise-induced AKI than those without renal hypouricemia. 5 Hereditary hypouricaemia complicated by nephrolithiasis and exercise-induced AKI has mainly been reported in Japanese patients with loss-of-function URAT1 mutations transmitted as an autosomal recessive trait. 6 When we screened the patient's brother we found that he too had severe hypouricaemia with very high urinary uric acid excretion: genetic analysis was not done.…”

Section: Discussionmentioning

confidence: 99%

A young patient of hereditary renal hypouricaemia presenting with exercise-induced rhabdomyolysis and acute kidney injury

Chakraborty¹,

Sural

2013

Ann Clin Biochem

View full text Add to dashboard Cite

Hereditary renal hypouricaemia (HRH) is a genetic disorder commonly associated with exercise-induced acute kidney injury (AKI). We report the case of a 19-year-old man who was admitted to hospital with exercise-induced AKI and who was subsequently shown to have HRH. We believe this to be the first description of a case of HRH co-presenting with rhabdomyolysis. Case reportA 19-year-old man was admitted to hospital with a history of dysuria, recurrent vomiting, severe muscle pain and weakness. Two days previously he had undertaken a session of rigorous exercise for the first time in the local gymnasium. His urine was slightly dark in colour. He had no history of illegal drug abuse, alcohol consumption, trauma, recent illness or any previous episode of a similar nature. There was no known family history of muscular or metabolic disease.On admission his vital signs were as follows: heart rate 96/min, temperature 37.18C, respiratory rate 20/min and blood pressure 130/80 mmHg. On examination there was muscular tenderness particularly in the calf muscles. There was no evidence of oedema or skin rash in the extremities. Power was 5/5 in both lower and upper limbs. The remaining physical examination was unremarkable. Laboratory investigations showed serum creatinine 736 mmol/L (reference interval 53-106 mmol/L), urea 16.7 mmol/L (reference interval 2.5 -7.5 mmol/L), sodium 138 mmol/L (reference interval 135-145 mmol/L), potassium 6.2 mmol/L (reference interval 3.5 -5.0 mmol/L), uric acid 243 mmol/L (reference interval 208 -416 mmol/L) and creatinine kinase 10,127 U/L (reference interval 10-190 U/ L). Serum C-reactive protein concentration and full blood count were within normal reference intervals. Further investigation revealed mildly increased serum alanine and aspartate aminotransferase activities. Routine urinalysis revealed protein of 1þ with 10 -12 red blood cells per high power field. Abdominal ultrasound scan was normal. A diagnosis of exercise-induced rhabdomyolysis leading to acute kidney injury (AKI) was made and the patient was treated accordingly. Following regular haemodialysis, kidney function improved gradually and he was discharged within a week of hospitalization. At this time his serum creatinine concentration was 172 mmol/L, urea 6.0 mmol/L, sodium 140 mmol/L and potassium 3.9 mmol/L.Two months later on a follow-up visit he had symptoms of myalgia with arthalgia. Laboratory investigations showed: serum creatinine 106 mmol/L, urea 5.7 mmol/L, sodium 137 mmol/L, potassium 3.9 mmol/L and uric acid 17 mmol/L. The uric acid result was rechecked and confirmed as correct on a fresh sample. He was not receiving any uric acid lowering drugs.To investigate the cause of severe hypouricaemia a fractional excretion of uric acid (FE UA ¼ urinary uric acid Â serum creatinine Â 100/serum uric acid Â urine creatinine) and 24 h urinary uric acid excretion were measured. The FE UA was 151% (reference interval 5-11%) and 24 h urinary uric acid was 2.59 mmol/24 h (reference interval 1.48-4.43 mmol/24 h). Urinary p...

show abstract

“…Blood and urinary tests to determine serum urate (Sur), urinary uric acid (Uur), Scr, and urinary creatinine (Ucr) were regularly carried out and analyzed at baseline and after 3 months of treatment. Urate clearance (Cur), creatinine clearance (Ccr), the ratio of urinary uric acid to urinary creatinine (Uur/Ucr), and the ratio of uric acid clearance to creatinine clearance (Cur/Ccr) were determined according to a previously described method 14,15) , before and after treatment with irbesartan. To assess changes in uric acid metabolism after treatment, we allocated patients into two groups, patients with Uur/Ucr <0.5 (low Uur/Ucr group, n= 20) or those with Uur/Ucr !…”

Section: Methodsmentioning

confidence: 99%

Effects of Irbesartan on Uric Acid Metabolism in Patients with Treated Essential Hypertension

Miyazaki¹,

Sakuragi

Hamada

et al. 2018

Vasc Fail

Self Cite

View full text Add to dashboard Cite

Abstract:Background: Irbesartan has been reported to inhibit renal uric acid reabsorption and thereby decrease serum uric acid (Sur) levels. However, its effect on uric acid metabolism in hypertensive patients has not been reported. Methods and Results: We conducted a retrospective observational study that included 40 hypertensive patients to clarify the effects of irbesartan (mean dose 87.5 mg) on blood pressure (BP) and uric acid metabolism [Sur, urinary uric acid (Uur), serum creatinine (Scr), urinary creatinine (Ucr), uric acid clearance (Cur), creatinine clearance (Ccr), urinary uric acid to urinary creatinine ratio (Uur/Ucr), and uric acid clearance to creatinine clearance ratio (Cur/Ccr)] at baseline and after 3 months of treatment. We allocated patients into two groups, patients with Uur/Ucr <0.5 (low Uur/Ucr group) or those with Uur/Ucr ! 0.5 (normal/ high Uur/Ucr group), into other two groups, patients with Cur/Ccr <5.5% (low Cur/Ccr group) or those with Cur/Ccr ! 5.5% (normal/ high Cur/Ccr group). The hypoexcretion group contained low Uur/Ucr group and low Cur/Ccr group, and the normal/ hyperexcretion group contained normal/high Uur/Ucr group and normal/ high Cur/Ccr group. Further, we allocated patients into another two groups, patients with Sur ! 7 mg/dl (hyperuricemic group) or those with Sur <7 mg/dl (normouricemic group). Irbesartan significantly decreased systolic BP without affecting heart rate, and decreased Sur without altering Uur/Ucr or Cur/Ccr. In the hypoexcretion group, irbesartan decreased Sur while increasing Uur/Ucr and Cur/Ccr. In contrast, in the normal/hyperexcretion and hyperuricemic groups, irbesartan decreased Sur without changing Uur/Ucr or Cur/ Ccr. In a normouricemic group, patients showed no changes in Sur after treatment with irbesartan. Conclusions: Irbesartan improved the secretion of uric acid, and reduced Sur in the hypoexcretion group, but did not influence uric acid excretion in the normal/hyperexcretion group. In hyperuricemic patients, irbesartan did not affect uric acid excretion but may have influenced uric acid production.

show abstract

Cause of Persistent Hypouricemia in Outpatients

Cited by 63 publications

References 0 publications

Clinical and Molecular Analysis of Patients with Renal Hypouricemia in Japan-Influence of URAT1 Gene on Urinary Urate Excretion

Clinical and Molecular Analysis of Patients with Renal Hypouricemia in Japan-Influence of URAT1 Gene on Urinary Urate Excretion

A young patient of hereditary renal hypouricaemia presenting with exercise-induced rhabdomyolysis and acute kidney injury

Effects of Irbesartan on Uric Acid Metabolism in Patients with Treated Essential Hypertension

Contact Info

Product

Resources

About