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1.
Mutational analysis of idiopathic renal hypouricemia in Korea 总被引:5,自引:0,他引:5
Cheong HI Kang JH Lee JH Ha IS Kim S Komoda F Sekine T Igarashi T Choi Y 《Pediatric nephrology (Berlin, Germany)》2005,20(7):886-890
Idiopathic renal hypouricemia is a hereditary disease characterized by abnormally high renal uric acid clearance. Most patients are clinically silent, but acute renal failure (ARF), urolithiasis, or hematuria may develop. A defect in the SLC22A12 gene, which encodes the renal uric acid transporter, URAT1, is the known major cause of this disorder. We performed a mutational analysis of the SLC22A12 gene in five Korean patients with idiopathic renal hypouricemia in this study. Two patients presented with microscopic hematuria, one with uric acid urolithiasis, and one with exercise-induced ARF. One patient was asymptomatic. Three different mutations, W258X, R90H and R477H, were detected in four of the patients. However, no mutation was found in the fifth ARF patient. This is the first study of SLC22A12 mutations in a country other than Japan. W258X was found to be the predominant SLC22A12 mutation in Korean renal hypouricemia patients, as has been reported in Japan. 相似文献
2.
Takahashi T Tsuchida S Oyamada T Ohno T Miyashita M Saito S Komatsu K Takashina K Takada G 《Pediatric nephrology (Berlin, Germany)》2005,20(5):576-578
Recent identification of the urate transporter in the kidney (URAT1, encoded by SLC22A12) led to the molecular elucidation of idiopathic renal hypouricemia, which is a predisposition toward exercise-induce acute renal failure. One Japanese patient with renal hypouricemia demonstrated compound heterozygous mutations of the URAT1 gene (Q297X and IVS2+1G>A). It was suggested that these two mutations are recurrent mutations of the URAT1 gene in a Japanese population. In addition, we expect the prevalence of renal hypouricemia, 0.23%, from the analysis of serum urate levels in 1,730 Japanese children. 相似文献
3.
Kaneko K Taniguchi N Tanabe Y Nakano T Hasui M Nozu K 《Pediatric nephrology (Berlin, Germany)》2009,24(4):869-871
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. 相似文献
4.
I Ishikawa Y Sakurai S Masuzaki N Sugishita A Shinoda N Shikura 《Nihon Jinzo Gakkai shi》1990,32(8):923-928
Three cases of exercise-induced non-oliguric acute renal failure in patients with renal hypouricemia, an isolated defect of the renal urate transport system, are described. During acute renal failure, the serum uric acid levels were 5.6, 2.7 and 5.8 mg/dl, respectively, and were within normal limits. The values representing the fractional excretion of uric acid (FEUA) were 28.7, 60.0 and 12.7%, with accompanying serum creatinine levels of 8.1, 3.9 and 3.3 mg/dl, respectively. After recovery, the serum uric acid fell to 0.6, 0.7 and 1.0 mg/dl and the FEUA increased to 79.3, 52.8 and 43.2%, respectively. Two of the patients examined exhibited decreased reabsorption of filtered urate. These 3 examples of renal hypouricemia represented 23% of 13 cases of mild exercise-induced acute renal failure encountered within our experience. 相似文献
5.
Atsushi Komatsuda Keiko Iwamoto Hideki Wakui Ken-ichi Sawada Akihiko Yamaguchi 《Renal failure》2013,35(3):223-227
Background. Renal hypouricemia is an autosomal recessive disorder resulting from inactivating mutations in the urate transporter 1 (URAT1) encoded by SLC22A12. To date, 10 mutations have been identified and W258X in the URAT1 gene is the predominant cause in middle to southwestern Japan. However, it is still unclear whether there is a regional specific distribution of mutations in northern Japan. In this study, we analyzed mutations in the URAT1 gene of five Japanese patients with renal hypouricemia in northern Japan. Methods. Peripheral blood mononuclear cells were isolated from patients with hypouricemia and healthy control subjects. A mutation analysis of the URAT1 gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. Results. We identified two mutations. These mutations [c.269G>A (R90H) and c.774G>A (W258X)] have been reported in Japanese patients. Two of five patients were homozygotes (W258X), two carried single heterozygous mutations (W258X), and the remaining one was a compound heterozygote (R90H and W258X). Conclusions. Our study suggests that there is no regional different distribution of the URAT1 genetic mutations in Japanese with renal hypouricemia. 相似文献
6.
Non-urate transporter 1-related renal hypouricemia and acute renal failure in an Israeli–Arab family
Hilla Bahat Dganit Dinour Liat Ganon Leonid Feldman Eli J. Holtzman Michael Goldman 《Pediatric nephrology (Berlin, Germany)》2009,24(5):999-1003
Idiopathic renal hypouricemia (IRHU) is a rare hereditary disease, predisposing the individual to exercise-induced acute renal
failure (EIARF) and nephrolithiasis, and it is characterized by increased clearance of renal uric acid. Most of the described
patients are Japanese, who have loss-of-function mutations in the SLC22A12 gene coding for the human urate transporter 1 (URAT1) gene. An 18-year-old youth, who was admitted for EIARF due to IRHU,
and six consanguineous Israeli–Arab family members were included in the study. The family members were tested for fractional
excretion of uric acid and molecular analysis of the URAT1 gene. Four family members, including the proband, had very low levels of blood uric acid and high rate of fractional excretion
(FE urate> 100%) of uric acid. Genetic analysis of the affected family members did not reveal a mutation in the coding regions
and intron–exon boundaries of SCL22A12. Haplotype analysis excluded SCL22A12 involvement in the pathogenesis, suggesting a different gene as a cause of the disease. We herein describe the first Israeli–Arab
family with IRHU. A non-URAT1 genetic defect that causes decreased reabsorption or, more probably, increased secretion of
uric acid, induces IRHU. Further studies are required in order to elucidate the genetic defect.
Hilla Bahat and Dganit Dinour contributed equally to the work. 相似文献
7.
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 相似文献
8.
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. 相似文献
9.
Dganit Dinour Nicola K. Gray Susan Campbell Xinhua Shu Lindsay Sawyer William Richardson Gideon Rechavi Ninette Amariglio Liat Ganon Ben-Ami Sela Hilla Bahat Michael Goldman Joshua Weissgarten Michael R. Millar Alan F. Wright Eliezer J. Holtzman 《Journal of the American Society of Nephrology : JASN》2010,21(1):64-72
Hereditary hypouricemia may result from mutations in the renal tubular uric acid transporter URAT1. Whether mutation of other uric acid transporters produces a similar phenotype is unknown. We studied two families who had severe hereditary hypouricemia and did not have a URAT1 defect. We performed a genome-wide homozygosity screen and linkage analysis and identified the candidate gene SLC2A9, which encodes the glucose transporter 9 (GLUT9). Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. In vitro, the L75R mutation dramatically impaired transport of uric acid. The mean concentration of serum uric acid of seven homozygous individuals was 0.17 ± 0.2 mg/dl, and all had a fractional excretion of uric acid >150%. Three individuals had nephrolithiasis, and three had a history of exercise-induced acute renal failure. In conclusion, homozygous loss-of-function mutations of GLUT9 cause a total defect of uric acid absorption, leading to severe renal hypouricemia complicated by nephrolithiasis and exercise-induced acute renal failure. In addition to clarifying renal handling of uric acid, our findings may provide a better understanding of the pathophysiology of acute renal failure, nephrolithiasis, hyperuricemia, and gout.In most mammals, uric acid (UA) is oxidized by the hepatic enzyme uricase to highly soluble allantoin. In humans, however, this enzyme is inactive as a result of mutational silencing,1 making UA the end product of purine metabolism. Serum UA concentration depends on both UA production and UA removal by the kidneys and intestinal tract and is high in humans compared with other mammals. Elevation of serum UA levels has been associated with various diseases, including gout, hypertension, and cardiovascular and renal disease.2 Conversely, it has been suggested that UA has a beneficial role as a natural antioxidant, and low serum UA levels have been linked to several neurologic diseases.2Studies of renal handling of UA in humans have provided evidence for a historical model of urinary UA excretion, which consists of four components: Free glomerular filtration, tubular absorption, secretion, and postsecretion reabsorption. The location and molecular physiology of the three tubular transport components, however, have not been completely clarified.3The first renal UA transporter, URAT1, was identified in 2002 by Enomoto et al.4 The significance of URAT1 in the handling of UA was demonstrated by genetic analysis of Japanese patients with hereditary renal hypouricemia.4,5 These patients were characterized by very low levels of serum UA, high fractional excretion of UA, and attenuated response of urinary urate excretion to pyrazinamide and probenecid.5 Most of these patients were asymptomatic, but some had nephrolithiasis or were predisposed to exercise-induced acute renal failure (EIARF). The Japanese patients were found to possess homozygous or compound heterozygous loss-of-function mutations in the gene SLC22A12 coding for human URAT1; most of them carry at least one allele with the truncation mutation W258X.4–6Mutations in SLC22A12 seem to be very rare outside Japan. A mutation analysis of renal hypouricemia in Korea showed that three of four patients with URAT1 mutations carried the W258X mutation.7 We previously described hereditary hypouricemia as a result of a homozygous SLC22A12 missense mutation (R496C) in three Israeli families of Iraqi origin.8 Although serum UA level and fractional excretion of UA were similar to those of the Japanese patients, none of our patients developed EIARF.A recent meta-analysis of 14 genome-wide association scans in Europe demonstrated significant association of serum UA concentration with several other genes, including SLC22A11 coding for organic anion transporter 4 (OAT4), SLC17A1 coding for NPT4, the ATP-binding cassette transporter ABCG2, and SLC2A9 coding for the glucose-facilitated transporter GLUT9.9 OAT4,10 NPT1,11 ABCG2,12 and GLUT913–16 have been shown to be expressed in renal tubular cells and to transport UA in vitro. Recently, heterozygous mutations of GLUT9 were shown to cause renal hypouricemia.16In this report, we show that homozygous mutations of GLUT9 cause severe hereditary hypouricemia complicated by nephrolithiasis and EIARF. Our findings provide further evidence for the key role played by GLUT9 in renal UA handling. 相似文献
10.
Andrea Mancikova Vladimir Krylov Olha Hurba Ivan Sebesta Makiko Nakamura Kimiyoshi Ichida Blanka Stiburkova 《Clinical and experimental nephrology》2016,20(4):578-584
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.11.
Exercise-induced acute renal failure with renal hypouricemia: a case report and a review of the literature 总被引:3,自引:0,他引:3
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. 相似文献
12.
Takeda Y Abe A Nakanishi S Umezu M Hirano K Hayakawa H Ohno I Ichida K Yamaguchi Y Hosoya T Fukagawa M 《Clinical nephrology》2011,76(1):78-82
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. 相似文献
13.
Patients with renal hypouricemia with exercise-induced acute renal failure and chronic renal dysfunction 总被引:4,自引:0,他引:4
Kikuchi Y Koga H Yasutomo Y Kawabata Y Shimizu E Naruse M Kiyama S Nonoguchi H Tomita K Sasatomi Y Takebayashi S 《Clinical nephrology》2000,53(6):467-472
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. 相似文献
14.
BACKGROUND: Renal hypouricemia is an autosomal recessive disorder resulting from inactivating mutations in the urate transporter 1 (URAT1) encoded by SLC22A12. To date, 10 mutations have been identified and W258X in the URAT1 gene is the predominant cause in middle to southwestern Japan. However, it is still unclear whether there is a regional specific distribution of mutations in northern Japan. In this study, we analyzed mutations in the URAT1 gene of five Japanese patients with renal hypouricemia in northern Japan. METHODS: Peripheral blood mononuclear cells were isolated from patients with hypouricemia and healthy control subjects. A mutation analysis of the URAT1 gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. RESULTS: We identified two mutations. These mutations [c.269G>A (R90H) and c.774G>A (W258X)] have been reported in Japanese patients. Two of five patients were homozygotes (W258X), two carried single heterozygous mutations (W258X), and the remaining one was a compound heterozygote (R90H and W258X). CONCLUSIONS: Our study suggests that there is no regional different distribution of the URAT1 genetic mutations in Japanese with renal hypouricemia. 相似文献
15.
M. Hasegawa Shirou Kawashima Takako Toba Masahiko Shikano Hiroshi Hasegawa Makoto Tomita Shigehisa Koide Shinsuke Asano Kazutaka Murakami Ryouichi Kato 《Clinical and experimental nephrology》1999,3(1):54-58
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 (FEUA) was 37%–43%. He showed no suppression of FEUA following the the administration of pyrazinamide, and no increase of FEUA after benzbromarone, suggesting a subtotal defect. We investigated renal function, FEUA, 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 相似文献
16.
Two cases of exercise-induced acute renal failure with idiopathic renal hypouricemia 总被引:1,自引:0,他引:1
Takeda Y Fujimoto T Uyama H Shiiki H Yamano S Kanauchi M Yabuta M Dohi K 《Nihon Jinzo Gakkai shi》2001,43(5):384-388
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. 相似文献
17.
Yasar Caliskan Numan Gorgulu Berna Yelken Faruk Akturk Halil Yazici Aydin Turkmen Mehmet Sukru Sever 《Clinical transplantation》2011,25(3):368-374
Caliskan Y, Gorgulu N, Yelken B, Akturk F, Yazici H, Turkmen A, Sever MS. Serum uric acid level is associated with cardiac hypertrophy in renal transplant recipients.Clin Transplant 2011: 25: 368–374. © 2010 John Wiley & Sons A/S. Abstract: Background: Serum uric acid (UA) level as a significant and independent risk factor for cardiovascular disease, and the link between this marker and left ventricular hypertrophy (LVH) in renal transplant recipients remains to be clarified. Methods: A total of 141 renal transplant recipients (83 men), between ages of 18 and 69 (mean age 37 ± 11), were included in this single center study. In addition to demographic, clinical, and laboratory parameters, serum UA concentrations were evaluated. LVH was determined by two‐dimensional and M‐mode echocardiography. Results: Serum UA levels were significantly higher (6.14 ± 1.15 mg/dL) in patients with LVH (n = 54) when compared to patients (n = 87) who did not have this abnormality (5.29 ± 1.43 mg/dL) (p = 0.006). Serum UA levels were significantly correlated with septal wall thickness, LV posterior wall thickness, LV mass index (LVMI), and pulmonary arterial pressure. Multiple linear regression analysis revealed that UA predicted LVMI (r2 = 0.150, β = 0.369, p = 0.001). However, serum creatinine (β = 0.060, p = 0.593) and age (β = 0.146, p = 0.175) were not predictors of LVMI. Conclusion: High serum UA levels are associated with LVH in renal transplant recipients, which underlines the importance of treating hyperuricemia. 相似文献
18.
The W258X mutation in SLC22A12 is the predominant cause of Japanese renal hypouricemia 总被引:4,自引:0,他引:4
Komoda F Sekine T Inatomi J Enomoto A Endou H Ota T Matsuyama T Ogata T Ikeda M Awazu M Muroya K Kamimaki I Igarashi T 《Pediatric nephrology (Berlin, Germany)》2004,19(7):728-733
Recently, a urate transporter, hURAT1 (human uric acid transporter 1) encoded by SLC22A12, was isolated from the human kidney. hURAT1 is presumed to play the central role in reabsorption of urate from glomerular filtrate. In the present study, we analyzed SLC22A12 in seven unrelated Japanese patients with renal hypouricemia whose serum level of urate was less than 1.0 mg/dl, and their family members. We performed direct DNA sequencing of the exon and exon-intron boundaries of SLC22A12 using genomic DNA. Six of the seven patients (86%) possess mutations in SLC22A12. In five patients, a homozygous G to A transition at nucleotide 774 within exon 4 of SLC22A12, which forms a stop codon (TGA) at codon 258 (TGG), was identified (W258X). In one patient, the C to T transition within exon 3, which changes threonine at codon 217 to methionine (T217 M), and the W258X mutation were found (compound heterozygote). Thus, among 12 mutational alleles in six patients, 11 were the W258X mutation (92%). Family members with the heterozygous W258X mutation (carriers) show relatively low levels of serum urate. The present study demonstrates that homozygous W258X mutation is the predominant genetic cause of idiopathic renal hypouricemia in Japanese patients. 相似文献
19.
Nishizaki N Fujinaga S Hirano D Kanai H Kaya H Ohtomo Y Shimizu T Nozu K Kaneko K 《Clinical nephrology》2012,77(2):161-163
Although renal hypouricemia is mostly asymptomatic, it is known to present a high risk of exercise-induced acute renal failure, especially in young males. However, there is little information regarding the clinical features of urolithiasis as a complication in childhood renal hypouricemia. Here we report a 4-year old female with idiopathic renal hypouricemia who presented with macroscopic hematuria due to obstructive calcium oxalate urolithiasis. She was treated successfully with percutaneous nephrolithotripsy and thereafter hematuria disappeared. Sequence analysis of the patient and her family's URAT1 gene confirmed a nonsense mutation in exon 4 (W258X). To the best of our knowledge, this is the youngest case of hereditary renal hypouricemia caused by URAT1 gene mutation, which was found by hematuria due to calcium oxalate urolithiasis. 相似文献
20.
Silverstein DM Srivaths PR Mattison P Upadhyay K Midgley L Moudgil A Goldstein SL Feig DI 《Pediatric nephrology (Berlin, Germany)》2011,26(7):1123-1128
Serum uric acid (UA) is positively associated with hypertension (HTN). HTN is common in pediatric patients receiving hemodialysis
(HD) and peritoneal dialysis (PD). We assessed the relationship between UA and BP in 63 pediatric dialysis patients by measuring
pre-treatment UA levels and BP in HD patients and in-center UA levels and blood pressure (BP) in PD patients. UA levels were
similar in both groups [6.8 ± 0.2 (HD) vs. 6.5 ± 0.3 (PD), p = 0.6]. Pre-treatment systolic BP percentile was associated with a high UA level [91.9 ± 2.3 (>6.0 mg/dL) vs. 79.3 ± 5.8 mm
Hg (≤6.0 mg/dL), p = 0.01] in HD patients only. There was a negative relationship between UA and dialysis vintage (r = −0.31, p = 0.01). In both groups, there was no relationship between UA and Kt/V. In HD patients, fluid overload was unrelated to UA
level [4.2 ± 0.6% (≤6.0 mg/dL) vs. 4.3 ± 0.3% (>6.0 mg/dL), p = 0.9]. Moreover, pre-HD treatment systolic BP percentile correlated with UA (beta 0.36, p = 0.02) independent of volume. UA levels were higher in patients receiving anti-hypertensive medications [6.3 ± 0.2 (No Meds]
vs 7.0 ± 0.2 (BP Meds) mg/dL, p= 0.01]. Finally, there was no relationship between serum UA and normalized protein catabolic rate (r = 0.14; p = 0.4). In summary, serum UA impacts BP in pediatric HD patients, independent of volume, nutritional and weight status. 相似文献