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Relevant bibliographies by topics / Hypouricemia

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Academic literature on the topic 'Hypouricemia'

Author: Grafiati

Published: 4 June 2021

Last updated: 8 February 2022

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Journal articles on the topic "Hypouricemia"

1

Kawasoe, Shin, Kazuki Ide, Tomoko Usui, Takuro Kubozono, Shiro Yoshifuku, Hironori Miyahara, Shigeho Maenohara, Mitsuru Ohishi, and Koji Kawakami. "Distribution and Characteristics of Hypouricemia within the Japanese General Population: A Cross-Sectional Study." Medicina 55, no. 3 (March 4, 2019): 61. http://dx.doi.org/10.3390/medicina55030061.

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Background and objectives: There is insufficient epidemiological knowledge of hypouricemia. In this study, we aimed to describe the distribution and characteristics of Japanese subjects with hypouricemia. Materials and Methods: Data from subjects who underwent routine health checkups from January 2001 to December 2015 were analyzed in this cross-sectional study. A total of 246,923 individuals, which included 111,117 men and 135,806 women, met the study criteria. The participants were divided into quartiles according to their serum uric acid (SUA) levels. We subdivided the subjects with hypouricemia, which was defined as SUA level ≤ 2.0 mg/dL, into two groups and compared their characteristics, including their cardiovascular risks. Results: The hypouricemia rates were 0.46% overall, 0.21% for the men and 0.66% for the women (P < 0.001). The number of the subjects with hypouricemia showed two distributions at SUA levels of 0.4–1.1 mg/dL (lower hypouricemia group), which included a peak at 0.7–0.8 mg/dL, and at SUA levels of 1.4–2.0 mg/dL (higher hypouricemia group). The men in the higher hypouricemia group had lower body mass indexes (BMI) and triglyceride (TG) levels and had higher fasting blood glucose levels than those in the lower hypouricemia group. The women in the higher hypouricemia group were younger; had lower BMI, total protein, TG, total cholesterol and low-density lipoprotein cholesterol levels; and had higher estimated glomerular filtration rates levels compared to those in the lower hypouricemia group. Conclusions: The characteristics of the individuals in the lower and higher hypouricemia groups differed significantly, indicating different pathophysiologies within each group.

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Wakasugi, Minako, Junichiro James Kazama, Ichiei Narita, Tsuneo Konta, Shouichi Fujimoto, Kunitoshi Iseki, Toshiki Moriyama, et al. "Association between Hypouricemia and Reduced Kidney Function: A Cross-Sectional Population-Based Study in Japan." American Journal of Nephrology 41, no. 2 (2015): 138–46. http://dx.doi.org/10.1159/000381106.

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Background: Hypouricemia, conventionally defined as a serum uric acid level of ≤2 mg/dl, is considered a biochemical disorder with no clinical significance. However, individuals with renal hypouricemia have a high risk of urolithiasis and exercise-induced acute kidney injury, both of which are risk factors for reduced kidney function. Methods: To test the hypothesis that individuals with hypouricemia would be at a higher risk of reduced kidney function, we conducted a population-based cross-sectional study using data from the Specific Health Checkups and Guidance System in Japan. Logistic analysis was used to examine the relationship between hypouricemia and reduced kidney function, defined as estimated glomerular filtration rate <60 ml/min/1.73 m2. Results: Among 90,710 men (mean age, 63.8 years) and 136,935 women (63.7 years), 193 (0.2%) and 540 (0.4%) were identified as having hypouricemia, respectively. The prevalence of hypouricemia decreased with age in women (p for trend <0.001), but not in men (p for trend = 0.24). Hypouricemia was associated with reduced kidney function in men (odds ratio, 1.83; 95% confidence interval, 1.23-2.74), but not in women (0.61; 0.43-0.86), relative to the reference category (i.e., serum uric acid levels of 4.1-5.0 mg/dl) after adjusting for age, drinking, smoking, diabetes, hypertension, hypercholesterolemia, obesity, and history of renal failure. Sensitivity analyses stratified by diabetic status yielded similar results. Conclusions: This study is the first to provide evidence that hypouricemia is associated with reduced kidney function in men. Further research will be needed to determine the long-term prognosis of individuals with hypouricemia.

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Shimizu, Yoshio, Keiichi Wakabayashi, Ayako Totsuka, Yoko Hayashi, Shusaku Nitta, Kazuaki Hara, Maiko Akira, Yasuhiko Tomino, and Yusuke Suzuki. "Exercise-Induced Acute Kidney Injury in a Police Officer with Hereditary Renal Hypouricemia." Case Reports in Nephrology and Dialysis 9, no. 2 (July 29, 2019): 92–101. http://dx.doi.org/10.1159/000501877.

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Hereditary renal hypouricemia is characterized by hypouricemia with hyper-uric acid clearance due to a defect in renal tubular transport. Patients with hereditary renal hypouricemia have a higher risk of exercise-induced acute kidney injury (EAKI) and reduced kidney function. Although the best preventive measure is avoiding exercise, there are many kinds of jobs that require occupational exercise. A 27-year-old male police officer suffered from stage 3 AKI after performing a 20-m multistage shuttle run test. His mother had previously been diagnosed as having renal hypouricemia at another facility. The patient had reported having hypouricemia during a health check at a previous police station, but his serum uric acid concentration was within the normal range at our hospital. After treatment, he recovered from EAKI and exhibited low serum uric acid and hyper-uric acid clearance. Since the patient desired to continue his career requiring strenuous exercise, it was difficult to establish a preventive plan against the recurrence of EAKI. Patients with hereditary renal hypouricemia who must undergo strenuous occupational anaerobic exercise are at higher risk of developing EAKI than other workers. The risks of EAKI among patients with hypouricemia should be considered when undergoing physical occupational training.

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Kawamura, Yusuke, Akiyoshi Nakayama, Seiko Shimizu, Yu Toyoda, Yuichiro Nishida, Asahi Hishida, Sakurako Katsuura-Kamano, et al. "A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals." Biomedicines 9, no. 8 (August 13, 2021): 1012. http://dx.doi.org/10.3390/biomedicines9081012.

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Background: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FEUA). Further studies on FEUA in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. Methods: In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of URAT1 (NFV-URAT1), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FEUA data. The effects of NFV-URAT1 on FEUA and SUA were also investigated using linear and multiple regression analyses. Results: Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV-URAT1 were observed in 1040 hypouricemic individuals. Furthermore, NFV-URAT1 significantly increased FEUA and decreased SUA, enabling FEUA and SUA levels to be estimated. Conversely, FEUA and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-URAT1. Conclusions: Our findings reveal that specific patterns of FEUA and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests.

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Morales, Manuel, and Victor Garcia-Nieto. "Hypouricemia and Cancer." Oncology 53, no. 4 (1996): 345–48. http://dx.doi.org/10.1159/000227585.

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SPERLING, O. "Hereditary renal hypouricemia." Molecular Genetics and Metabolism 89, no. 1-2 (September 2006): 14–18. http://dx.doi.org/10.1016/j.ymgme.2006.03.015.

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Shichiri, Masayoshi. "Diabetic Renal Hypouricemia." Archives of Internal Medicine 147, no. 2 (February 1, 1987): 225. http://dx.doi.org/10.1001/archinte.1987.00370020045033.

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Shichiri, M. "Diabetic renal hypouricemia." Archives of Internal Medicine 147, no. 2 (February 1, 1987): 225–28. http://dx.doi.org/10.1001/archinte.147.2.225.

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Stiburkova, Blanka, Jana Bohata, Iveta Minarikova, Andrea Mancikova, Jiri Vavra, Vladimír Krylov, and Zdenek Doležel. "Clinical and Functional Characterization of a Novel URAT1 Dysfunctional Variant in a Pediatric Patient with Renal Hypouricemia." Applied Sciences 9, no. 17 (August 23, 2019): 3479. http://dx.doi.org/10.3390/app9173479.

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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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Yoon, Jaeho, Raul Cachau, Victor A. David, Mary Thompson, Wooram Jung, Sun-Ha Jee, Ira O. Daar, Cheryl A. Winkler, and Sung-Kweon Cho. "Characterization of a Compound Heterozygous SLC2A9 Mutation That Causes Hypouricemia." Biomedicines 9, no. 9 (September 6, 2021): 1172. http://dx.doi.org/10.3390/biomedicines9091172.

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Renal hypouricemia is a rare genetic disorder. Hypouricemia can present as renal stones or exercise-induced acute renal failure, but most cases are asymptomatic. Our previous study showed that two recessive variants of SLC22A12 (p.Trp258*, pArg90His) were identified in 90% of the hypouricemia patients from two independent cohorts: the Korean genome and epidemiology study (KoGES) and the Korean Cancer Prevention Study (KCPS-II). In this work, we investigate the genetic causes of hypouricemia in the rest of the 10% of unsolved cases. We found a novel non-synonymous mutation of SLC2A9 (voltage-sensitive uric acid transporter) in the whole-exome sequencing (WES) results. Molecular dynamics prediction suggests that the novel mutation p.Met126Val in SLCA9b (p.Met155Val in SLC2A9a) hinders uric acid transport through a defect of the outward open geometry. Molecular analysis using Xenopus oocytes confirmed that the p.Met126Val mutation significantly reduced uric acid transport but does not affect the SLC2A9 protein expression level. Our results will shed light on a better understanding of SLC2A9-mediated uric acid transport and the development of a uric acid-lowering agent.

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Dissertations / Theses on the topic "Hypouricemia"

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HAMAJIMA, NOBUYUKI, MARIKO NAITO, EMI MORITA, YOSHINORI ITO, KOJI SUZUKI, RIEKO OKADA, and SAYAKA KURIKI. "SLC22A12 W258X FREQUENCY ACCORDING TO SERUM URIC ACID LEVEL AMONG JAPANESE HEALTH CHECKUP EXAMINEES." Nagoya University School of Medicine, 2011. http://hdl.handle.net/2237/14914.

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Lahmi, Nathalie. "La goutte : clinique et thérapeutique." Paris 5, 1994. http://www.theses.fr/1994PA05P157.

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Mančíková, Andrea. "Vliv polymorfismu urátových transportérů na exkreci kyseliny močové." Doctoral thesis, 2020. http://www.nusl.cz/ntk/nusl-435532.

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Uric acid excretion disorders are the most common cause of primary dysuricemia. The kidneys eliminate two-thirds of uric acid production and the other third is eliminated in the gastrointestinal tract. Renal reabsorption and secretion occur through the polarised epithelial cells in the proximal tubules. Uric acid transporters are expressed on these cell membranes. Reabsorption deficiency leads to hypouricemia and elevated fraction excretion associated with urolithiasis, nephrolithiasis or acute renal injury. Decreased uric acid secretion in the kidneys and small intestine leads to hyperuricemia, which develops into gout in 10% of individuals. Genome wide association studies detected a strong effect of SLC22A12 (URAT1), SLC2A9 (GLUT9) reabsorbing transporters and ABCG2 (ABCG2) secreting transporter on uric acid serum concentration variability. This thesis aimed to map out urate transporter allelic variants in a cohort of primary dysuricemia patients and identification of the variants causing defective uric acid excretion. Six non-synonymous variants were described in SLC22A12 (URAT1) and SLC2A9 (GLUT9) genes in hypouricemic individuals, which had not been identified previously in any population studies. Significant decreases in uric acid transport have been demonstrated experimentally in vitro,...

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ZHANG, JIAN-GUO, and 張健國. "Hypouricemic effect of Gynura formosana extract using long-time water boiling." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/83918016125192401280.

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碩士
嘉南藥理大學
保健營養系
104
Background and Purpose: Hyperuricemia has become a risk foctor of kidney disease, hypertension and other chronic diseases. Therefore the control of plasma uric acid levels is important. The purpose of our study, is to investigate whether the hot water extract of Gynura formosana as shows the hypouricemic effect in mice. Methods: 35 three-week-old ICR male mice, after a one week adaptation, were divided into the following 5 groups: C group (normal control group), P group (hyperuricemic modle), A group (Allopurinol treatment group), GL and GH group was tube fed with Gynura formosana extract 100 mg/kg BW, 500 mg/kg BW respectively, group C was injected with 0.5% CMC solution, the other groups are intraperitoneal injectied with PO 250 mg/kg, daily for continous 7 days.Group C and P were tube fed with saline, group A was tube fed with Allopurinol (10 mg/kg) daily once, group GL and GH were tube fed with the test sample. After animal sacrifice, plasma uric acid concentration, urea nitrogen (BUN), creatinine were assayed, The enzyme activtites of xanthine oxidase (XO) and xanthine dehydrogenase (XDH), catalase, Glutathione Peroxidase, superoxide dismutase in liver were also measered. We also measured the levels of lipid peroxidation index (TBARS) in liver. Results: Plasma uric acid levels in P group were significantly higher than other groups, Allopurinol medication and GF exteact feeding were significantly decreased the plasma uric acid levels. Gynura formosana water extact also significantly decreased, the XDH enzyme activity. Liver GSH contents in GL, GH group were significantly lower than that in P group. The activities of CAT, SOD, GPx in GH group were significantly lower than that in P group. Conclusion: The results indicate that Gynura formosana extract shows the hypouricemic effect which could be due to th inhibition of liver XDH activity.

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Chen, Tzu-Yu, and 陳姿妤. "Evaluation of hypouricemic effect of submerged culture of Ganoderma lucidum in hyperuricemic rats." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/543pzz.

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碩士
國立臺灣海洋大學
食品科學系
105
Hyperuricemia is a disease caused by high uric acid in the blood. It has been considered as an important factor for gout and may be linked to hypotension, hyperlipidemia, diabetes, metabolic syndrome and cardiovascular diseases. The aims of this study are to evaluate of the hypouricemic effects of submerged culture of Ganoderma lucidum in hyperuricemic rats. The dried weight yields for the mycelium and extracellular polysaccharides in the submerged culture of G. lucidum were 3.84 ± 0.37 g/L and 0.21 ± 0.04 g/L, respectively. The contents of phenolics in the lyophilized powder of submerged culture of G. lucidum (GS)、mycelium (GM) and extracellular polysaccharides (GP) were 24.57、34.33、20.52 mg GAE/g dry weight, respectively. The contents of flavonoids in the lyophilized powder of mycelium was 0.32 mg QE/g dry weight. Sprague-Dawley rats were induced to hyperuricemic rats by intraperitoneal injection potassium oxonate (PO) (250 mg/kg b.w.), and randomly divided into seven groups of 8 animals: (1) Normal control, NC (2) Hyperuuricemic control, HC (3) HC + allopurinol (10mg/kg b.w.), HA (4) HC + GM (200 mg/kg b.w.), HM2 (5) HC + GM (400 mg/kg b.w.), HM4 (6) HC + GP (200 mg/kg b.w.), HP2 (7) HC + GP (400 mg/kg b.w.), HP4. The average daily body weights of all induced hyperuricemic rats were significantly higher than that of N group. The serum uric acid levels for HC group was significantly higher than the N group (p < 0.001). The serum uric acid levels for HA and HM2 groups was significantly decrease (p < 0.001). The liver xanthine oxidase activity for HM2 and HM4 group were significantly lower than that of HC group (p < 0.001). The plasma BUN levels for HM4、HP4 and HP4 groups were significantly decrease. The ALT levels for HP2 and HP4 groups were significantly lower than that of N group. These results demonstrated that feeding the hyperuricemic rats with G. lucidum mycelium at the dosage of 200 mg/kg b.w. could significantly decrease the serum uric acid level.

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Hung, Shuo-Chun, and 洪碩駿. "The hypouricemic effects of the water extracts of Gynura formosana and Ocimum gratissimum in oxonate-treated mice." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/97716946073963127136.

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碩士
嘉南藥理科技大學
保健營養系
101
Background and Purpose: Hyperuricemia and metabolic syndroms, including obesity, heart disease, hypertension and kidney disease, have been reported to be highly prevalent in many countries. The purpose of this study was to investigate the antioxidant ability and the hypouricemic effect of the water extracts of Gynura formosana and Ocimum gratissimum in mice treated with potassium-oxonate. Methods: The in vitro antioxidant ability of the water extracts of the vegetables were measured, including Trolox equivalent antioxidant capacity, (TEAC), DPPH scavenging effect, reducing power, the ferrous iron-chelating effect. The hypouricemic effect was conducted with animals. 42 three-week-old ICR male mice were divided into 7 groups, all animals except the Vehicle group (normal control group) were treated with potassium oxonate (PO, 250mg/kg BW, i.p.) to induce hyperuricemia for 7 days. The animals were tube fed with the following test samples: saline (vehicle and PO groups), Allopurinol drug (AL group, as the curring group) , water extract of Gynura formosana 100mg/kg BW or 500mg/kg BW (GF1 or GF5 group) , water extract of Ocimum gratissimum 100mg/kg BW or 500mg/kg BW (OG1 or OG5 group) for seven consecutive days. The concentration of plasma uric acid, BUN and creatinine, the enzyme activities of xanthine oxidase(XO) and xanthine dehydrogenase (XDH) in liver, thiobarbituric acid-reactive substances (TBARS) levels in tissues were measured. The renal uric acid salt transporter protein(URAT1) and organic anion transporter (OAT) were aslo measured with Western blot. Result: The PO group showed significantly the highest levels of plasma uric acid, the AL group reduced the plasma uric acid levels significantly. The plasma uric acid concentrations in all the test groups, (GF1, GF5 or OG1, OG5) were significantly lower than the PO group (p <0.05). There is no significant difference among the 7 groups in liver XO activity. However, the XDH activity showed significantly higher in PO group than that in the remaining groups (GF1, GF5, OG1, OG5 and vehicle groups). Liver TBARS content showed no significantly difference among the 7 groups. The protein levels of URAT1 and OAT1 also showed no significant differences among the 7 groups. Conclusion: The water extracts of Gynura formosana and Ocimum gratissimum showed the in vitro antioxidant ability and also showed the hypouricemic effect in mice treated with potassium-oxonate. The hypoucricemic mechanism of the water extracts of Gynura formosana and Ocimum gratissimum could be due to their inhibition effect of liver XDH activity.

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Book chapters on the topic "Hypouricemia"

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Bien, Christian G., Christian E. Elger, Ali R. Afzal, Sirajedin Natah, Ritva Häyrinen-Immonen, Yrjö Konttinen, George S. Zubenko, et al. "Renal Hypouricemia, Hereditary." In Encyclopedia of Molecular Mechanisms of Disease, 1828–30. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-29676-8_914.

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Metze, Dieter, Vanessa F. Cury, Ricardo S. Gomez, Luiz Marco, Dror Robinson, Eitan Melamed, Alexander K. C. Leung, et al. "Hereditary Renal Hypouricemia." In Encyclopedia of Molecular Mechanisms of Disease, 832–33. Berlin, Heidelberg: Springer Berlin Heidelberg, 2009. http://dx.doi.org/10.1007/978-3-540-29676-8_9221.

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Sforza, G. Riario, C. Di Cosmo, A. L. Di Mele, E. Morelli, C. Romano, C. P. Quaratino, and A. Giacomello. "Significance of Hypouricemia." In Advances in Experimental Medicine and Biology, 243–45. Boston, MA: Springer US, 1991. http://dx.doi.org/10.1007/978-1-4899-2638-8_55.

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Sperling, O. "Urolithiasis in Hereditary Renal Hypouricemia." In Urolithiasis and Related Clinical Research, 13–16. Boston, MA: Springer US, 1985. http://dx.doi.org/10.1007/978-1-4684-7272-1_3.

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Sperling, O. "Urate Deposition and Stone Formation in the Kidney in Renal Hypouricemia." In Urate Deposition in Man and its Clinical Consequences, 65–77. Berlin, Heidelberg: Springer Berlin Heidelberg, 1991. http://dx.doi.org/10.1007/978-3-642-84491-1_7.

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Gaspar, Gabriel A.-V., Juan G. Puig, Felicitas A. Mateos, Carlos R. Oria, Maria E. M. Gomez, and Antonio A. Gil. "Hypouricemia due to Renal Urate Wasting: Different Types of Tubular Transport Defects." In Purine and Pyrimidine Metabolism in Man V, 357–63. Boston, MA: Springer US, 1986. http://dx.doi.org/10.1007/978-1-4684-5104-7_61.

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Pelatti, A., C. P. Quaratino, C. D’ Amario, R. Tentarelli, G. Riario Sforza, and A. Giacomello. "Hypouricemia and an Increased Clearance of Uric Acid are Observed in Liver Diseases?" In Purine and Pyrimidine Metabolism in Man VIII, 57–60. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-2584-4_14.

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Kaneko, Kiyoko, Shin Fujimori, Takaaki Kanbayashi, and Ieo Akaoka. "Renal Handling of Hypoxanthine and Xanthine in Normal Subjects and in Cases of Idiopathic Renal Hypouricemia." In Advances in Experimental Medicine and Biology, 309–15. Boston, MA: Springer US, 1989. http://dx.doi.org/10.1007/978-1-4684-5673-8_51.

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Kawachi, Masanori, Norio Kono, Ikuo Mineo, Hiroaki Kiyokawa, Hiromu Nakajima, Takao Shimizu, Akira Ono, et al. "Renal Hypouricemia Associated with Hyperoxypurinemia due to Decreased Renal Excretion of Oxypurines: a New Defect in Renal Purine Transport." In Advances in Experimental Medicine and Biology, 239–42. Boston, MA: Springer US, 1991. http://dx.doi.org/10.1007/978-1-4899-2638-8_54.

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Kaneko, Kiyoko, Shin Fujimori, Hisashi Yamanaka, and Ieo Akaoka. "Effect of Hypouricemic Agents on Serum Carbohydrate-Deficient Transferrin in Gouty Patients." In Purine and Pyrimidine Metabolism in Man VIII, 27–30. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-2584-4_7.

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Conference papers on the topic "Hypouricemia"

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Pavelcova, K., J. Bohata, K. Pavelka, and B. Stiburkova. "P107 Polymorphisms in SLC2A9 and SLC22A12 genes are related to hyperuricemia, gout and also to hypouricemia." In 39th European Workshop for Rheumatology Research, 28 February–2 March 2019, Lyon, France. BMJ Publishing Group Ltd and European League Against Rheumatism, 2019. http://dx.doi.org/10.1136/annrheumdis-2018-ewrr2019.95.

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