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Ichiro Hisatome - One of the best experts on this subject based on the ideXlab platform.
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prevalence and complications of Hypouricemia in a general population a large scale cross sectional study in japan
PLOS ONE, 2017Co-Authors: Masanari Kuwabara, Kazuhide Ogino, Einosuke Mizuta, Toshihiro Hamada, Koichiro Niwa, Akira Ohtahara, Satoshi Miyazaki, Ichiro HisatomeAbstract:Backgrounds Hypouricemia was reported as a risk factor for exercise-induced acute renal injury (EIAKI) and urinary stones. However, the prevalence of kidney diseases among hypouricemic subjects has not been evaluated. This study was conducted to clarify the prevalence of Hypouricemia and the association of Hypouricemia with kidney diseases by using a large-scale Japanese population data. Methods This study is a retrospective cross-sectional study at the Center for Preventive Medicine, St. Luke’s International Hospital, Tokyo, Japan, and Sanin Rousai Hospital, Yonago, Japan. We analyzed the medical records of 90,143 Japanese subjects at the center in St. Luke’s International Hospital, Tokyo, and 4,837 subjects in Sanin Rousai Hospital, Yonago, who underwent annual regular health check-up between January 2004 and June 2010. We defined Hypouricemia as serum uric acid level of ≤2.0 mg/dL. We checked the medical history of all the study subjects and compared the rates of complications including urinary stones and kidney diseases among those with or without Hypouricemia. Results The prevalence of Hypouricemia was 0.19% in St. Luke’s International Hospital, Tokyo, and 0.58% in Sanin Rousai Hospital, Yonago. The prevalence of Hypouricemia in women was larger than that in men both in Tokyo (0.31% vs 0.068%, p<0.001) and in Yonago (1.237% vs 0.318%, p<0.001). Among 172 hypouricemic subjects (30 men), the rates of previous urinary stones and kidney diseases (including nephritis/nephrosis) were 1.2% (3.3% men, 0.7% women) and 2.3% (10% men, 0.7% women), respectively. Hypouricemic men had a 9-fold higher rate of previously having kidney diseases compared to non-hypouricemic men (p<0.001). However, the rates of other diseases including urinary stones were not significantly different between the two groups. Conclusions Hypouricemia was associated with a history of kidney disease especially in men.
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Prevalence and complications of Hypouricemia in a general population: A large-scale cross-sectional study in Japan.
PloS one, 2017Co-Authors: Masanari Kuwabara, Kazuhide Ogino, Einosuke Mizuta, Toshihiro Hamada, Koichiro Niwa, Akira Ohtahara, Satoshi Miyazaki, Ichiro HisatomeAbstract:Backgrounds Hypouricemia was reported as a risk factor for exercise-induced acute renal injury (EIAKI) and urinary stones. However, the prevalence of kidney diseases among hypouricemic subjects has not been evaluated. This study was conducted to clarify the prevalence of Hypouricemia and the association of Hypouricemia with kidney diseases by using a large-scale Japanese population data. Methods This study is a retrospective cross-sectional study at the Center for Preventive Medicine, St. Luke’s International Hospital, Tokyo, Japan, and Sanin Rousai Hospital, Yonago, Japan. We analyzed the medical records of 90,143 Japanese subjects at the center in St. Luke’s International Hospital, Tokyo, and 4,837 subjects in Sanin Rousai Hospital, Yonago, who underwent annual regular health check-up between January 2004 and June 2010. We defined Hypouricemia as serum uric acid level of ≤2.0 mg/dL. We checked the medical history of all the study subjects and compared the rates of complications including urinary stones and kidney diseases among those with or without Hypouricemia. Results The prevalence of Hypouricemia was 0.19% in St. Luke’s International Hospital, Tokyo, and 0.58% in Sanin Rousai Hospital, Yonago. The prevalence of Hypouricemia in women was larger than that in men both in Tokyo (0.31% vs 0.068%, p
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The differences of medical history between Hypouricemia and non-Hypouricemia.
2017Co-Authors: Masanari Kuwabara, Kazuhide Ogino, Einosuke Mizuta, Toshihiro Hamada, Koichiro Niwa, Akira Ohtahara, Satoshi Miyazaki, Ichiro HisatomeAbstract:The differences of medical history between Hypouricemia and non-Hypouricemia.
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depletion of uric acid due to slc22a12 urat1 loss of function mutation causes endothelial dysfunction in Hypouricemia
Circulation, 2015Co-Authors: Shinobu Sugihara, Nani Maharani, Kazuhide Ogino, Haruaki Ninomiya, Toshihiro Hamada, Masanari Kuwabara, Ichiro Hisatome, Koichiro Niwa, Masahiko Kato, Yukihito HigashiAbstract:Abstract Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes Hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with Hypouricemia. Twenty-six patients with Hypouricemia (
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depletion of uric acid due to slc22a12 urat1 loss of function mutation causes endothelial dysfunction in Hypouricemia
Circulation, 2015Co-Authors: Shinobu Sugihara, Nani Maharani, Kazuhide Ogino, Haruaki Ninomiya, Toshihiro Hamada, Masanari Kuwabara, Ichiro Hisatome, Koichiro Niwa, Masahiko Kato, Yukihito HigashiAbstract:BACKGROUND Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes Hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with Hypouricemia. METHODS AND RESULTS Twenty-six patients with Hypouricemia (<2.5 mg/dl) and 13 healthy control subjects were enrolled. Endothelial function was evaluated using flow-mediated dilation (FMD). mRNA of UA transporters expressed in cultured human umbilical endothelial cells (HUVEC) was detected on RT-PCR. There was a positive correlation between FMD and serum UA in the Hypouricemia group. URAT1 loss-of-function mutations were found in the genome of 21 of 26 patients with Hypouricemia, and not in the other 5. In the Hypouricemia groups, serum UA in homozygous and compound heterozygous patients was significantly lower than in other groups, suggesting that severity of URAT1 dysfunction may influence the severity of Hypouricemia. Thirteen of 16 Hypouricemia subjects with homozygous and compound heterozygote mutations had SUA <0.8 mg/dl and their FMD was lower than in other groups. HUVEC do not express mRNA of URAT1, suggesting the null role of URAT1 in endothelial function. CONCLUSIONS Depletion of UA due to SLC22A12/URAT1 loss-of-function mutations causes endothelial dysfunction in Hypouricemia patients.
Blanka Stiburkova - One of the best experts on this subject based on the ideXlab platform.
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Clinical and Functional Characterization of a Novel URAT1 Dysfunctional Variant in a Pediatric Patient with Renal Hypouricemia
Applied Sciences, 2019Co-Authors: Blanka Stiburkova, Jana Bohata, Andrea Mancikova, Iveta Minarikova, Jiri Vavra, Vladimir Krylov, Zdenek DoleželAbstract:Renal Hypouricemia (RHUC) is caused by an inherited defect in the main (reabsorptive) renal urate transporters, URAT1 and GLUT9. RHUC is characterized by decreased concentrations of serum uric acid and an increase in its excretion fraction. Patients suffer from Hypouricemia, hyperuricosuria, urolithiasis, and even acute kidney injury. We report the clinical, biochemical, and genetic findings of a pediatric patient with Hypouricemia. Sequencing analysis of the coding region of SLC22A12 and SLC2A9 and a functional study of a novel RHUC1 variant in the Xenopus expression system were performed. The proband showed persistent Hypouricemia (67–70 µmol/L; ref. range 120–360 µmol/L) and hyperuricosuria (24–34%; ref. range 7.3 ± 1.3%). The sequencing analysis identified common non-synonymous allelic variants c.73G > A, c.844G > A, c.1049C > T in the SLC2A9 gene and rare variants c.973C > T, c.1300C > T in the SLC22A12 gene. Functional characterization of the novel RHUC associated c.973C > T (p. R325W) variant showed significantly decreased urate uptake, an irregular URAT1 signal on the plasma membrane, and reduced cytoplasmic staining. RHUC is an underdiagnosed disorder and unexplained Hypouricemia warrants detailed metabolic and genetic investigations. A greater awareness of URAT1 and GLUT9 deficiency by primary care physicians, nephrologists, and urologists is crucial for identifying the disorder.
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a heterozygous variant in the slc22a12 gene in a sri lanka family associated with mild renal Hypouricemia
BMC Pediatrics, 2018Co-Authors: Dinesha Maduri Vidanapathirana, Eresha Jasinge, Subashinie Jayasena, Blanka StiburkovaAbstract:Renal Hypouricemia is a rare heterogeneous inherited disorder characterized by impaired tubular uric acid transport, reabsorption insufficiency and /or acceleration of secretion. The affected individuals are predisposed to nephrolithiasis and recurrent episodes of exercise-induced acute kidney injury. Type 1 is caused by dysfunctional variants in the SLC22A12 gene (URAT1), while type 2 is caused by defects in the SLC2A9 gene (GLUT9). To date, more than 150 patients with the loss-of-function mutations for the SLC22A12 gene have been found (compound heterozygotes and/or homozygotes), most of whom are Japanese and Koreans. Herein, we report a nine year old Sri Lankan boy with renal Hypouricemia (serum uric acid 97 μmol/L, fractional excretion of uric acid 33%).The sequencing analysis of SLC22A12 revealed a potentially deleterious missense variant c.1400C > T (p.T467 M, rs200104135) in heterozygous state. This variant has been previously identified in homozygous and/or compound heterozygous state with other causative SLC22A12 variant c.1245_1253del (p.L415_G417del) in Roma population. This is the first identification of a family with mild renal Hypouricemia1 associated to the p.T467 M variant. Detailed investigations of urate blood and urine concentrations in patients with unexplained Hypouricemia are needed and renal Hypouricemia should also be considered in patients other than those from Japan and/or Korea. Our finding confirms an uneven geographical and ethnic distribution of Romany prevalent SLC22A12 variant that need to be considered in Asian patients (population data Genome Aggregation Database: allele frequency in South Asia 0.007055, in East Asia 0.001330).
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A heterozygous variant in the SLC22A12 gene in a Sri Lanka family associated with mild renal Hypouricemia
BMC, 2018Co-Authors: Dinesha Maduri Vidanapathirana, Eresha Jasinge, Subashinie Jayasena, Blanka StiburkovaAbstract:Abstract Background Renal Hypouricemia is a rare heterogeneous inherited disorder characterized by impaired tubular uric acid transport, reabsorption insufficiency and /or acceleration of secretion. The affected individuals are predisposed to nephrolithiasis and recurrent episodes of exercise-induced acute kidney injury. Type 1 is caused by dysfunctional variants in the SLC22A12 gene (URAT1), while type 2 is caused by defects in the SLC2A9 gene (GLUT9). To date, more than 150 patients with the loss-of-function mutations for the SLC22A12 gene have been found (compound heterozygotes and/or homozygotes), most of whom are Japanese and Koreans. Case presentation Herein, we report a nine year old Sri Lankan boy with renal Hypouricemia (serum uric acid 97 μmol/L, fractional excretion of uric acid 33%).The sequencing analysis of SLC22A12 revealed a potentially deleterious missense variant c.1400C > T (p.T467 M, rs200104135) in heterozygous state. This variant has been previously identified in homozygous and/or compound heterozygous state with other causative SLC22A12 variant c.1245_1253del (p.L415_G417del) in Roma population. Conclusions This is the first identification of a family with mild renal Hypouricemia1 associated to the p.T467 M variant. Detailed investigations of urate blood and urine concentrations in patients with unexplained Hypouricemia are needed and renal Hypouricemia should also be considered in patients other than those from Japan and/or Korea. Our finding confirms an uneven geographical and ethnic distribution of Romany prevalent SLC22A12 variant that need to be considered in Asian patients (population data Genome Aggregation Database: allele frequency in South Asia 0.007055, in East Asia 0.001330)
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Functional analysis of novel allelic variants in URAT1 and GLUT9 causing renal Hypouricemia type 1 and 2
Clinical and Experimental Nephrology, 2016Co-Authors: Andrea Mancikova, I. Sebesta, Makiko Nakamura, Olha Hurba, Vladimir Krylov, Kimiyoshi Ichida, Blanka StiburkovaAbstract:Background Renal Hypouricemia is a rare heterogeneous inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and nephrolithiasis. Type 1 is caused by a loss-of-function mutation in the SLC22A12 gene (URAT1), while type 2 is caused by defects in the SLC2A9 gene (GLUT9). Methods and results In this article we present clinical, biochemical and molecular genetics of two Czech patients. The serum uric acid in the probands was 57 and 98 µmol/l and expressed as an increase in the fractional excretion of uric acid (40 and 18 %). The sequencing analysis of SLC22A12 and SLC2A9 revealed novel variants p.R92C and p.R203C in URAT1 and p.G72D in GLUT9. Functional studies were performed for these novel variants and for previously reported variants p.I118HfsX27, p.G216R and p.N333S in GLUT9 responsible for renal Hypouricemia in three probands from Czech Republic and United Kingdom. Functional studies showed significantly decreased urate uptake for all variants. However, urate uptake of GLUT9 variants prepared for both isoforms were not significantly different. Conclusions This is the first complex function characterization of non-synonymous allelic variants in patients with renal Hypouricemia regarding both GLUT9 isoforms. Our finding of defects in the SLC2A9 and SLC22A12 genes show the following: renal Hypouricemia is not restricted to East Asia populations; urate uptake of GLUT9 variants prepared for both isoforms were not significantly different; renal Hypouricemia type 2 has more wide clinical variability than type 1; the phenotypic severity of renal Hypouricemia is not correlated with results of functional characterizations of URAT1 and GLUT9 variants.
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Purine disorders with Hypouricemia.
Prilozi (Makedonska akademija na naukite i umetnostite. Oddelenie za medicinski nauki), 2014Co-Authors: I. Sebesta, Blanka StiburkovaAbstract:Hypouricemia is defined as a serum urate levels less than 2 mg/dL (119 μmol/L). Primary Hypouricemia is caused by disorders of purine metabolism and transport. This laboratory finding is sometimes overlooked and, following two genetic defects, should be considered in differential diagnosis of unexplained Hypouricemia. Hereditary xanthinuria is autosomal recessive and due to mutations in xanthine oxidase, leading to over-production of xanthine and minimal production of urate. Patients have very low serum urate levels and suffer from elevated levels of xanthine in the urine, leading to xanthine stones, haematuria, and sometimes occult chronic kidney failure. Hypouricemia is the key to diagnosis. Hereditary renal Hypouricemia is a new genetic defect of renal transport of uric acid. Two types were distinguished: a) renal Hypouricemia type 1, caused by the defects in the SLC22A12 gene coding the human urate transporter 1 (hURAT1) and b) renal Hypouricemia type 2, caused by the defects in the SLC2A9 gene, which encodes GLUT9 transporter. This disorder predisposes patients to exercise-induced acute renal failure and/or nephrolithiasis. Diagnosis is based on two markers: Hypouricemia ( 10%). Over one hundred cases were identified in Japan and and this number is unique worldwide. Several patients were described in Macedonia. We were able to detect four Czech families with hereditary xanthinuria and eight cases of hereditary renal Hypouricemia. In conclusion, hereditary xanthinuria and hereditary renal Hypouricemia are still unrecognized conditions. Patients with unexplained Hypouricemia need detailed purine metabolic investigations.
Toshihiro Hamada - One of the best experts on this subject based on the ideXlab platform.
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prevalence and complications of Hypouricemia in a general population a large scale cross sectional study in japan
PLOS ONE, 2017Co-Authors: Masanari Kuwabara, Kazuhide Ogino, Einosuke Mizuta, Toshihiro Hamada, Koichiro Niwa, Akira Ohtahara, Satoshi Miyazaki, Ichiro HisatomeAbstract:Backgrounds Hypouricemia was reported as a risk factor for exercise-induced acute renal injury (EIAKI) and urinary stones. However, the prevalence of kidney diseases among hypouricemic subjects has not been evaluated. This study was conducted to clarify the prevalence of Hypouricemia and the association of Hypouricemia with kidney diseases by using a large-scale Japanese population data. Methods This study is a retrospective cross-sectional study at the Center for Preventive Medicine, St. Luke’s International Hospital, Tokyo, Japan, and Sanin Rousai Hospital, Yonago, Japan. We analyzed the medical records of 90,143 Japanese subjects at the center in St. Luke’s International Hospital, Tokyo, and 4,837 subjects in Sanin Rousai Hospital, Yonago, who underwent annual regular health check-up between January 2004 and June 2010. We defined Hypouricemia as serum uric acid level of ≤2.0 mg/dL. We checked the medical history of all the study subjects and compared the rates of complications including urinary stones and kidney diseases among those with or without Hypouricemia. Results The prevalence of Hypouricemia was 0.19% in St. Luke’s International Hospital, Tokyo, and 0.58% in Sanin Rousai Hospital, Yonago. The prevalence of Hypouricemia in women was larger than that in men both in Tokyo (0.31% vs 0.068%, p<0.001) and in Yonago (1.237% vs 0.318%, p<0.001). Among 172 hypouricemic subjects (30 men), the rates of previous urinary stones and kidney diseases (including nephritis/nephrosis) were 1.2% (3.3% men, 0.7% women) and 2.3% (10% men, 0.7% women), respectively. Hypouricemic men had a 9-fold higher rate of previously having kidney diseases compared to non-hypouricemic men (p<0.001). However, the rates of other diseases including urinary stones were not significantly different between the two groups. Conclusions Hypouricemia was associated with a history of kidney disease especially in men.
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Prevalence and complications of Hypouricemia in a general population: A large-scale cross-sectional study in Japan.
PloS one, 2017Co-Authors: Masanari Kuwabara, Kazuhide Ogino, Einosuke Mizuta, Toshihiro Hamada, Koichiro Niwa, Akira Ohtahara, Satoshi Miyazaki, Ichiro HisatomeAbstract:Backgrounds Hypouricemia was reported as a risk factor for exercise-induced acute renal injury (EIAKI) and urinary stones. However, the prevalence of kidney diseases among hypouricemic subjects has not been evaluated. This study was conducted to clarify the prevalence of Hypouricemia and the association of Hypouricemia with kidney diseases by using a large-scale Japanese population data. Methods This study is a retrospective cross-sectional study at the Center for Preventive Medicine, St. Luke’s International Hospital, Tokyo, Japan, and Sanin Rousai Hospital, Yonago, Japan. We analyzed the medical records of 90,143 Japanese subjects at the center in St. Luke’s International Hospital, Tokyo, and 4,837 subjects in Sanin Rousai Hospital, Yonago, who underwent annual regular health check-up between January 2004 and June 2010. We defined Hypouricemia as serum uric acid level of ≤2.0 mg/dL. We checked the medical history of all the study subjects and compared the rates of complications including urinary stones and kidney diseases among those with or without Hypouricemia. Results The prevalence of Hypouricemia was 0.19% in St. Luke’s International Hospital, Tokyo, and 0.58% in Sanin Rousai Hospital, Yonago. The prevalence of Hypouricemia in women was larger than that in men both in Tokyo (0.31% vs 0.068%, p
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The differences of medical history between Hypouricemia and non-Hypouricemia.
2017Co-Authors: Masanari Kuwabara, Kazuhide Ogino, Einosuke Mizuta, Toshihiro Hamada, Koichiro Niwa, Akira Ohtahara, Satoshi Miyazaki, Ichiro HisatomeAbstract:The differences of medical history between Hypouricemia and non-Hypouricemia.
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depletion of uric acid due to slc22a12 urat1 loss of function mutation causes endothelial dysfunction in Hypouricemia
Circulation, 2015Co-Authors: Shinobu Sugihara, Nani Maharani, Kazuhide Ogino, Haruaki Ninomiya, Toshihiro Hamada, Masanari Kuwabara, Ichiro Hisatome, Koichiro Niwa, Masahiko Kato, Yukihito HigashiAbstract:Abstract Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes Hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with Hypouricemia. Twenty-six patients with Hypouricemia (
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depletion of uric acid due to slc22a12 urat1 loss of function mutation causes endothelial dysfunction in Hypouricemia
Circulation, 2015Co-Authors: Shinobu Sugihara, Nani Maharani, Kazuhide Ogino, Haruaki Ninomiya, Toshihiro Hamada, Masanari Kuwabara, Ichiro Hisatome, Koichiro Niwa, Masahiko Kato, Yukihito HigashiAbstract:BACKGROUND Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes Hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with Hypouricemia. METHODS AND RESULTS Twenty-six patients with Hypouricemia (<2.5 mg/dl) and 13 healthy control subjects were enrolled. Endothelial function was evaluated using flow-mediated dilation (FMD). mRNA of UA transporters expressed in cultured human umbilical endothelial cells (HUVEC) was detected on RT-PCR. There was a positive correlation between FMD and serum UA in the Hypouricemia group. URAT1 loss-of-function mutations were found in the genome of 21 of 26 patients with Hypouricemia, and not in the other 5. In the Hypouricemia groups, serum UA in homozygous and compound heterozygous patients was significantly lower than in other groups, suggesting that severity of URAT1 dysfunction may influence the severity of Hypouricemia. Thirteen of 16 Hypouricemia subjects with homozygous and compound heterozygote mutations had SUA <0.8 mg/dl and their FMD was lower than in other groups. HUVEC do not express mRNA of URAT1, suggesting the null role of URAT1 in endothelial function. CONCLUSIONS Depletion of UA due to SLC22A12/URAT1 loss-of-function mutations causes endothelial dysfunction in Hypouricemia patients.
Kimiyoshi Ichida - One of the best experts on this subject based on the ideXlab platform.
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a novel compound heterozygous mutation in the slc22a12 urat1 gene in a japanese patient associated with renal Hypouricemia
Clinica Chimica Acta, 2016Co-Authors: Kyoko Fujita, Kimiyoshi IchidaAbstract:A novel compound heterozygous mutation, including c.935_997delinsTGG, in exons 5/6 of SLC22A12 (URAT1) was identified in a patient with renal Hypouricemia. This case expands the molecular mechanisms of renal Hypouricemia, and suggests a potential relationship with exercise-induced renal failure.
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Functional analysis of novel allelic variants in URAT1 and GLUT9 causing renal Hypouricemia type 1 and 2
Clinical and Experimental Nephrology, 2016Co-Authors: Andrea Mancikova, I. Sebesta, Makiko Nakamura, Olha Hurba, Vladimir Krylov, Kimiyoshi Ichida, Blanka StiburkovaAbstract:Background Renal Hypouricemia is a rare heterogeneous inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and nephrolithiasis. Type 1 is caused by a loss-of-function mutation in the SLC22A12 gene (URAT1), while type 2 is caused by defects in the SLC2A9 gene (GLUT9). Methods and results In this article we present clinical, biochemical and molecular genetics of two Czech patients. The serum uric acid in the probands was 57 and 98 µmol/l and expressed as an increase in the fractional excretion of uric acid (40 and 18 %). The sequencing analysis of SLC22A12 and SLC2A9 revealed novel variants p.R92C and p.R203C in URAT1 and p.G72D in GLUT9. Functional studies were performed for these novel variants and for previously reported variants p.I118HfsX27, p.G216R and p.N333S in GLUT9 responsible for renal Hypouricemia in three probands from Czech Republic and United Kingdom. Functional studies showed significantly decreased urate uptake for all variants. However, urate uptake of GLUT9 variants prepared for both isoforms were not significantly different. Conclusions This is the first complex function characterization of non-synonymous allelic variants in patients with renal Hypouricemia regarding both GLUT9 isoforms. Our finding of defects in the SLC2A9 and SLC22A12 genes show the following: renal Hypouricemia is not restricted to East Asia populations; urate uptake of GLUT9 variants prepared for both isoforms were not significantly different; renal Hypouricemia type 2 has more wide clinical variability than type 1; the phenotypic severity of renal Hypouricemia is not correlated with results of functional characterizations of URAT1 and GLUT9 variants.
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Diagnostic Tests for Primary Renal Hypouricemia
Nucleosides Nucleotides & Nucleic Acids, 2011Co-Authors: I. Sebesta, Blanka Stiburkova, Josef Bartl, Kimiyoshi Ichida, Makoto Hosoyamada, J. Taylor, Anthony M. MarinakiAbstract:Primary renal Hypouricemia is a genetic disorder characterized by defective renal uric acid (UA) reabsorption with complications such as nephrolithiasis and exercise-induced acute renal failure. The known causes are: defects in the SLC22A12 gene, encoding the human urate transporter 1 (hURAT1), and also impairment of voltage urate transporter (URATv1), encoded by SLC2A9 (GLUT9) gene. Diagnosis is based on Hypouricemia ( 10%). To date, the cases with mutations in hURAT1 gene have been reported in East Asia only. More than 100 Japanese patients have been described. Hypouricemia is sometimes overlooked; therefore, we have set up the flowchart for this disorder. The patients were selected for molecular analysis from 620 Czech hypouricemic patients. Secondary causes of hyperuricosuric Hypouricemia were excluded. The estimations of (1) serum UA, (2) excretion fraction of UA, and (3) analysis of hURAT1 and URATv1 genes follow. Three transitions and one delet...
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Diagnostic Tests for Primary Renal Hypouricemia
Nucleosides Nucleotides & Nucleic Acids, 2011Co-Authors: I. Sebesta, Blanka Stiburkova, Josef Bartl, Kimiyoshi Ichida, Makoto Hosoyamada, J. Taylor, Anthony M. MarinakiAbstract:Primary renal Hypouricemia is a genetic disorder characterized by defective renal uric acid (UA) reabsorption with complications such as nephrolithiasis and exercise-induced acute renal failure. The known causes are: defects in the SLC22A12 gene, encoding the human urate transporter 1 (hURAT1), and also impairment of voltage urate transporter (URATv1), encoded by SLC2A9 (GLUT9) gene. Diagnosis is based on Hypouricemia ( 10%). To date, the cases with mutations in hURAT1 gene have been reported in East Asia only. More than 100 Japanese patients have been described. Hypouricemia is sometimes overlooked; therefore, we have set up the flowchart for this disorder. The patients were selected for molecular analysis from 620 Czech hypouricemic patients. Secondary causes of hyperuricosuric Hypouricemia were excluded. The estimations of (1) serum UA, (2) excretion fraction of UA, and (3) analysis of hURAT1 and URATv1 genes follow. Three transitions and one delet...
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Novel homozygous insertion in SLC2A9 gene caused renal Hypouricemia
Molecular Genetics and Metabolism, 2011Co-Authors: Blanka Stiburkova, Kimiyoshi Ichida, I. SebestaAbstract:Abstract Renal Hypouricemia is a heterogeneous inherited disorder characterized by impaired uric acid handling in the renal tubules. Patients are usually asymptomatic; however, some may experience urolithiasis and/or acute kidney injury. Most of the described patients (compound heterozygous and/or homozygous) are Japanese with mutations in the SLC22A12 gene (OMIM #220150). Four patients with renal Hypouricemia caused by heterozygous defects and two families with homozygous mutations in the SLC2A9 gene have been recently described (OMIM #612076). We describe the clinical history, biochemical and molecular genetics findings of a Czech family with renal Hypouricemia. The concentration of serum uric acid in the proband (16-year-old Czech girl with unrelated parents) was 0.17±0.05mg/dl and expressed as an increase in the fractional excretion of uric acid (194±99%). The sequencing analysis of the coding region of uric acid transporters SLC22A12 , SLC2A9 , SLC17A3 , ABCC4 and ABCG2 , was performed. Analysis of genomic DNA revealed novel one nucleotide homozygote insertion in exon 3 in the SLC2A9 gene in proband and her brother resulting in a truncated protein (p.Ile118HisfsX27). No sequence variants in other candidate uric acid transporter were found. Homozygous loss-of-function mutations cause massive renal Hypouricemia via total loss of uric acid absorption; however, they do not necessarily lead to nephrolithiasis and acute kidney injury. In contrast to previously reported heterozygous patients with renal Hypouricemia type 2, we did not find even slight Hypouricemia and found no decrease in the FE-UA of the heterozygous parents of the reported siblings.
Kazuhide Ogino - One of the best experts on this subject based on the ideXlab platform.
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prevalence and complications of Hypouricemia in a general population a large scale cross sectional study in japan
PLOS ONE, 2017Co-Authors: Masanari Kuwabara, Kazuhide Ogino, Einosuke Mizuta, Toshihiro Hamada, Koichiro Niwa, Akira Ohtahara, Satoshi Miyazaki, Ichiro HisatomeAbstract:Backgrounds Hypouricemia was reported as a risk factor for exercise-induced acute renal injury (EIAKI) and urinary stones. However, the prevalence of kidney diseases among hypouricemic subjects has not been evaluated. This study was conducted to clarify the prevalence of Hypouricemia and the association of Hypouricemia with kidney diseases by using a large-scale Japanese population data. Methods This study is a retrospective cross-sectional study at the Center for Preventive Medicine, St. Luke’s International Hospital, Tokyo, Japan, and Sanin Rousai Hospital, Yonago, Japan. We analyzed the medical records of 90,143 Japanese subjects at the center in St. Luke’s International Hospital, Tokyo, and 4,837 subjects in Sanin Rousai Hospital, Yonago, who underwent annual regular health check-up between January 2004 and June 2010. We defined Hypouricemia as serum uric acid level of ≤2.0 mg/dL. We checked the medical history of all the study subjects and compared the rates of complications including urinary stones and kidney diseases among those with or without Hypouricemia. Results The prevalence of Hypouricemia was 0.19% in St. Luke’s International Hospital, Tokyo, and 0.58% in Sanin Rousai Hospital, Yonago. The prevalence of Hypouricemia in women was larger than that in men both in Tokyo (0.31% vs 0.068%, p<0.001) and in Yonago (1.237% vs 0.318%, p<0.001). Among 172 hypouricemic subjects (30 men), the rates of previous urinary stones and kidney diseases (including nephritis/nephrosis) were 1.2% (3.3% men, 0.7% women) and 2.3% (10% men, 0.7% women), respectively. Hypouricemic men had a 9-fold higher rate of previously having kidney diseases compared to non-hypouricemic men (p<0.001). However, the rates of other diseases including urinary stones were not significantly different between the two groups. Conclusions Hypouricemia was associated with a history of kidney disease especially in men.
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Prevalence and complications of Hypouricemia in a general population: A large-scale cross-sectional study in Japan.
PloS one, 2017Co-Authors: Masanari Kuwabara, Kazuhide Ogino, Einosuke Mizuta, Toshihiro Hamada, Koichiro Niwa, Akira Ohtahara, Satoshi Miyazaki, Ichiro HisatomeAbstract:Backgrounds Hypouricemia was reported as a risk factor for exercise-induced acute renal injury (EIAKI) and urinary stones. However, the prevalence of kidney diseases among hypouricemic subjects has not been evaluated. This study was conducted to clarify the prevalence of Hypouricemia and the association of Hypouricemia with kidney diseases by using a large-scale Japanese population data. Methods This study is a retrospective cross-sectional study at the Center for Preventive Medicine, St. Luke’s International Hospital, Tokyo, Japan, and Sanin Rousai Hospital, Yonago, Japan. We analyzed the medical records of 90,143 Japanese subjects at the center in St. Luke’s International Hospital, Tokyo, and 4,837 subjects in Sanin Rousai Hospital, Yonago, who underwent annual regular health check-up between January 2004 and June 2010. We defined Hypouricemia as serum uric acid level of ≤2.0 mg/dL. We checked the medical history of all the study subjects and compared the rates of complications including urinary stones and kidney diseases among those with or without Hypouricemia. Results The prevalence of Hypouricemia was 0.19% in St. Luke’s International Hospital, Tokyo, and 0.58% in Sanin Rousai Hospital, Yonago. The prevalence of Hypouricemia in women was larger than that in men both in Tokyo (0.31% vs 0.068%, p
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The differences of medical history between Hypouricemia and non-Hypouricemia.
2017Co-Authors: Masanari Kuwabara, Kazuhide Ogino, Einosuke Mizuta, Toshihiro Hamada, Koichiro Niwa, Akira Ohtahara, Satoshi Miyazaki, Ichiro HisatomeAbstract:The differences of medical history between Hypouricemia and non-Hypouricemia.
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depletion of uric acid due to slc22a12 urat1 loss of function mutation causes endothelial dysfunction in Hypouricemia
Circulation, 2015Co-Authors: Shinobu Sugihara, Nani Maharani, Kazuhide Ogino, Haruaki Ninomiya, Toshihiro Hamada, Masanari Kuwabara, Ichiro Hisatome, Koichiro Niwa, Masahiko Kato, Yukihito HigashiAbstract:Abstract Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes Hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with Hypouricemia. Twenty-six patients with Hypouricemia (
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depletion of uric acid due to slc22a12 urat1 loss of function mutation causes endothelial dysfunction in Hypouricemia
Circulation, 2015Co-Authors: Shinobu Sugihara, Nani Maharani, Kazuhide Ogino, Haruaki Ninomiya, Toshihiro Hamada, Masanari Kuwabara, Ichiro Hisatome, Koichiro Niwa, Masahiko Kato, Yukihito HigashiAbstract:BACKGROUND Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes Hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with Hypouricemia. METHODS AND RESULTS Twenty-six patients with Hypouricemia (<2.5 mg/dl) and 13 healthy control subjects were enrolled. Endothelial function was evaluated using flow-mediated dilation (FMD). mRNA of UA transporters expressed in cultured human umbilical endothelial cells (HUVEC) was detected on RT-PCR. There was a positive correlation between FMD and serum UA in the Hypouricemia group. URAT1 loss-of-function mutations were found in the genome of 21 of 26 patients with Hypouricemia, and not in the other 5. In the Hypouricemia groups, serum UA in homozygous and compound heterozygous patients was significantly lower than in other groups, suggesting that severity of URAT1 dysfunction may influence the severity of Hypouricemia. Thirteen of 16 Hypouricemia subjects with homozygous and compound heterozygote mutations had SUA <0.8 mg/dl and their FMD was lower than in other groups. HUVEC do not express mRNA of URAT1, suggesting the null role of URAT1 in endothelial function. CONCLUSIONS Depletion of UA due to SLC22A12/URAT1 loss-of-function mutations causes endothelial dysfunction in Hypouricemia patients.