Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0451641 (urolithiasis)
 3,973 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male Wistar rats were fed a basal diet, Purina Laboratory Chow, and an oxalate calculi-producing diet (CPD). The CPD was the basal diet containing 3 per cent glycolic acid. Sodium pyruvate, DL-alanine, alpha-keto glutaric acid, thiamine pyrophosphate, and L-glutamic acid were added to the CPD to determine their effectiveness in preventing calculi formation. The effectiveness of methyl glyoxal was determined by adding it to the drinking water. Rats fed CPD for 4 weeks developed calculi in the ureters, bladder, renal tubules, and/or renal pelvis and papilla. Rats in groups fed alanine and/or pyruvate had no calculi in their renal tubules or ureters; additionally, these rats had a significant reduction in incidence and amount of deposits in the renal pelvis and bladder. Rats in groups fed alpha-keto glutaric acid, thiamine pyrophosphate, L-glutamic acid, and methyl glyoxal developed equally or more severe oxalate urolithiasis than those on CPD alone. Results of this study show that either pyruvate or alanine at appropriate levels may be beneficial in preventing oxalate urolith formation.
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PMID:Prevention of oxalate urolithiasis by some compounds. 64

Oxalate urolithiasis in male rats was experimentally induced by feeding a basal diet composed of Purina laboratory chow and 3 per cent glycolic acid. When this basal oxalate calculus-producing diet containing 10 per cent alanine was fed to rats, the incidence of oxalate urolithiasis was markedly reduced. Moreover, when Purina laboratory chow containing 10 per cent alanine was fed to rats which had been on the calculi-producing basal diet for 4 weeks, it appeared that most uroliths were dissolved. Excess intake of alanine increased the concentration of alanine in urine and this apparently aided in the prevention and treatment of urolithiasis.
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PMID:Control of oxalate urolithiasis by DL-alanine. 118 33

Two patients with atypical manifestations of aberrant peroxisomal biogenesis are described. Contrary to previous studies, which had shown that Zellweger syndrome patients usually have normal levels of urinary oxalate excretion, the patients in the present study had evidence of abnormal oxalate metabolism in the form of hyperoxaluria and, in one of the patients, calcium oxalate urolithiasis. Activity of the liver-specific peroxisomal enzyme alanine:-glyoxylate aminotransferase (AGT), which is a major determinant of the level of endogenous oxalate synthesis in humans, was normal in one patient and markedly supranormal in the other. Using the technique of post-embedding protein A-colloidal gold immunoelectron microscopy, AGT was found to be mainly cytosolic in the livers of both patients, with significant amounts also localized in the nuclei. In a small minority of the hepatocytes of one patient, who was homozygous for the more common (major) AGT allele, large numbers of unidentified fibrillar arrays were found in the cytosol, which labelled heavily for immunoreactive AGT. The background cytosolic AGT labelling was markedly reduced in such cells when compared to the majority of cells that did not contain fibrils. In the other patient, who was heterozygous for the major and minor AGT alleles, there appeared to be low levels of mitochondrial AGT labelling. In the light of these data, the possible metabolic function of cytosolic AGT in the livers of panperoxisomal disease patients is discussed.
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PMID:Cytosolic compartmentalization of hepatic alanine:glyoxylate aminotransferase in patients with aberrant peroxisomal biogenesis and its effect on oxalate metabolism. 805 36

Diets supplemented with up to .6% DL-Met (DLM) or .68% 2-hydroxy-4-(methylthio)butanoic acid (HMB, Alimet) acidify the urine and reduce the incidence of urolithiasis in pullets and laying hens. Excessive acidification potentially may reduce eggshell quality and bone mineralization by interfering with Ca metabolism and may severely challenge the liver and kidneys, which are the primary organs responsible for attenuating metabolic acidosis. To evaluate these possibilities, 30-wk-old Single Comb White Leghorn hens in full production (five hens per replicate, six replicates per diet treatment) were fed for 30 d a 15.7% CP corn and soybean meal-based control layer ration alone or supplemented with DLM (.5, 1, 1.5, or 2%) or equimolar HMB (.56, 1.13, 1.69, or 2.25%). None of the diets caused mortality or gross hepatic or renal damage. Hens fed diets supplemented with the highest levels of DLM and HMB exhibited significant reductions in feed intake, hen-day egg production, and liver mass and had lower plasma concentrations of alanine amino-transferase and isocitrate dehydrogenase when compared with hens fed the control diet. Kidney mass was not significantly affected by high levels of DLM or HMB, but plasma uric acid was significantly higher in hens fed 2% DLM compared with hens fed the control diet. The highest levels of DLM and HMB did not significantly alter total plasma Ca or inorganic phosphate concentrations, nor were percentage eggshell or femur mineralization (femur ash mass:defatted bone mass, femur ash mass:bone volume) significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Responses of laying hens to diets containing up to 2% DL-methionine or equimolar (2.25%) 2-hydroxy-4-(methylthio)butanoic acid. 814 73

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder characterised by an increased urinary excretion of calcium oxalate, leading to recurrent urolithiasis, nephrocalcinosis and accumulation of insoluble oxalate throughout the body (oxalosis) when the glomerular filtration rate falls to below 40-20 mL/min per 1.73 m(2). The disease is due to a functional defect of the liver-specific peroxisomal enzyme alanine: glyoxylate aminotransferase (AGT), the gene of which is located on chromosome 2q37.3. The diagnosis is based on increased urinary oxalate and glycollate, increased plasma oxalate and AGT measurement in a liver biopsy. AGT mistargeting may be investigated by immuno-electron microscopy and DNA analysis. End-stage renal failure is reached by the age of 15 years in 50% of PH1 patients and the overall death rate approximates 30%. The conservative treatment includes high fluid intake, pyridoxine and crystallisation inhibitors. Since the kidney is the main target of the disease, isolated kidney transplantation (Tx) has been proposed in association with vigorous peri-operative haemodialysis in an attempt to clear plasma oxalate at the time of Tx. However, because of a 100% recurrence rate, the average 3-year graft survival is 15%-25% in Europe, with a 5-10-year patient survival rate ranging from 10% to 50%. Since the liver is the only organ responsible for the detoxification of glyoxylate by AGT, deficient host liver removal is the first rationale for enzyme replacement therapy. Subsequent orthotopic liver Tx aims to supply the missing enzyme in its normal cellular and subcellular location and thus can be regarded as a form of gene therapy. Because of the usual spectrum of the disease, isolated liver Tx is limited to selected patients prior to having reached an advanced stage of chronic renal failure. Combined liver-kidney Tx has therefore become a conventional treatment for most PH1 patients: according to the European experience, patient survival approximates 80% at 5 years and 70% at 10 years. In addition, the renal function of survivors remains stable over time, between 40 and 60 mL/min per 1.73 m(2) after 5 to 10 years. In addition, liver Tx may allow the reversal of systemic storage disease (i.e. bone, heart, vessels, nerves) and provide valuable quality of life. Whatever the transplant strategy, the outcome is improved when patients are transplanted early in order to limit systemic oxalosis. According to the European experience, it appears that combined liver-kidney Tx is performed in PH1 patients with encouraging results, renal Tx alone has little role in the treatment of this disease, and liver Tx reverses the underlying metabolic defect and its clinical consequences.
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PMID:Combined liver-kidney transplantation in primary hyperoxaluria type 1. 1060 4

From the age of 31 a patient began to suffer from recurrent calcium oxalate urolithiasis. Liver biopsy showed a decrease in catalytic activity of the hepatic peroxisomal enzyme alanine: glyoxilate aminotransferase (AGT), which was mistargeted from peroxisomes to mitochondria. The genetic analysis revealed a mutation of the AGT gene. At age 47 he developed end-stage renal failure and underwent hemodialysis. After 12 months of hemodialysis he presented a rapidly declining clinical condition, a decrease of the residual renal function, a livedo reticularis with painful of extremities, and shortly thereafter a general weakness, which predominated on lower limbs. Apart from renal failure, routine biological examination and CSF were normal. Nerve conduction studies and electromyography supported the diagnosis of polyradiculoneuropathy. Pathological studies revealed mixed demyelinating-axonal lesions and deposits of calcium oxalate crystals within the media and the intima of epineural arterioles. A combined liver-kidney transplant was rapidly performed. The patient's condition improved in a few months and motor signs completely disappeared.
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PMID:[Polyradiculoneuropathy in an adult with primitive hyperoxaluria]. 1069 61

We previously reported the importance of osteopontin (OPN) in the formation of urinary calculus. Since OPN protein is present in normal kidneys, we investigated the difference in OPN at the DNA level between normal subjects and urolithiasis patients. There has not been any genetic investigation of OPN in familial urolithiasis previously reported worldwide. To confirm hereditary predisposing factors for urolithiasis, changes in OPN DNA within a family were investigated in relation to the presence or absence of urinary calculus. Leukocyte OPN DNA from two normal subjects and five patients with urinary calculus was investigated by SSCP analysis: OPN DNA nucleotide sequence was determined, based on the result of SSCP analysis. As a result, a mutation of GCC to GCT, encoding amino acid position 250 (Ala-250) was found. To confirm the frequency of mutation at this site, OPN DNA was extracted from peripheral blood in 36 normal subjects (Con group), 25 patients with familial urolithiasis (FSF), and 40 patients with recurrent urinary calculus and who had had two or more previous episodes (RSF). The degree of mutation at Ala-250 was then examined by restriction fragment length polymorphism (RFLP) method. As described above, the nucleotide codon encoding the amino acid sequence position 250, Ala-250, was GCC in two normal subjects. This is the original codon. In five patients with urolithiasis it was GCT, showing a substitution of C with T. On examining the frequency of this mutation, the ratio of normal homozygous GCC was 11/36 in the Con group, 1/25 in FSF and 1/40 in RSF. The ratio of heterozygous GCC/GCT was 16/36 in the Con group, 15/25 in FSF and 26/40 in RSF, and the ratio of homozygous GCT was 9/36 in the Con group, 9/25 in FSF and 13/40 in RSF. Furthermore, the gene frequency of the normal codon GCC was 0.528 in the Con group, 0.3 in FSF and 0.35 in RSF, showing a significantly higher incidence in the Con group (P < 0.05). The gene frequency of mutated GCT was 0.472 in Con group, 0.7 in FSF and 0.65 in RSF, showing a significantly higher incidence in urolithiasis patients (P < 0.05). On investigating the inheritance of Ala-250 in five families in which both parent and offspring demonstrated urolithiasis, the nucleotide substitution in Ala-250 in parents with urolithiasis was inherited by their offspring. In all five families the offspring developed urinary calculus. This study showed that there is no difference in OPN structure between the Con group and urolithiasis patients. However, it was predicted that due to the frequency of normally coded GCC being high in the Con group a difference in the amount of OPN might be caused by a difference in transcription velocity between the two groups. Furthermore, it was suggested that examining the inheritance of Ala-250 within a family is a diagnostic method for identifying the predisposing hereditary factors for urolithiasis patients.
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PMID:Analysis of osteopontin DNA in patients with urolithiasis. 1092 24

Primary hyperoxaluria type 1, the most common form of primary hyperoxaluria, is an autosomal recessive disorder caused by a deficiency of the liver-specific enzyme alanine: glyoxylate aminotransferase (AGT). This results in increased synthesis and subsequent urinary excretion of the metabolic end product oxalate and the deposition of insoluble calcium oxalate in the kidney and urinary tract. As glomerular filtration rate (GFR) decreases due to progressive renal involvement, oxalate accumulates and results in systemic oxalosis. Diagnosis is still often delayed. It may be established on the basis of clinical and sonographic findings, urinary oxalate +/- glycolate assessment, DNA analysis and, sometimes, direct AGT activity measurement in liver biopsy tissue. The initiation of conservative measures, based on hydration, citrate and/or phosphate, and pyridoxine, in responsive cases at an early stage to minimize oxalate crystal formation will help to maintain renal function in compliant subjects. Patients with established urolithiasis may benefit from extracorporeal shock-wave lithotripsy and/or JJ stent insertion. Correction of the enzyme defect by liver transplantation should be planned, before systemic oxalosis develops, to optimize outcomes and may be either sequential (biochemical benefit) or simultaneous (immunological benefit) liver-kidney transplantation, depending on facilities and access to cadaveric or living donors. Aggressive dialysis therapies are required to avoid progressive oxalate deposition in established end-stage renal disease (ESRD), and minimization of the time on dialysis will improve both the patient's quality of life and survival.
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PMID:Primary hyperoxaluria type 1: still challenging! 1681 May 17

Polymorphism in manganese superoxide dismutase gene (Mn-SOD) is a new approach to identify its probable association with urolithiasis. Oxidative stress may be involved in the development of stone formation in the renal system. MnSOD is one of the primary enzymes that directly scavenges potential harmful oxidizing species. A valine (Val) to alanine (Ala) substitution at amino acid 16, occurring in the mitochondrial targeting sequence of the MnSOD gene, has been associated with an increase in urolithiasis risk. This study was conducted to investigate the association of MnSOD gene polymorphism with the risk of urolithiasis. We investigated the MnSOD in 66 stone-forming adults and 72 healthy volunteers. DNA was isolated from peripheral blood and genotyping was performed with PCR-based methods. Then PCR products were cut by BsaW1. Products were run on 3% agarose gel, 246 bp regions were 1-Ala-9, 164 and 82 bp products were determined as 2 Val-9. Chi-square test was used for comparison between patients and controls. In the control group the homozygote Ala allele was significantly higher than in the patient group (P < 0.01). The distribution of Ala/Val and homozygote Val alleles in the patient group was significantly higher than in the control group (P < 0.05). MnSOD genotype determination may provide a tool to identify individuals who are at risk of urolithiasis. This experiment also provides data about antioxidant status and stone formation.
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PMID:Manganese superoxide dismutase (Mn-SOD) gene polymorphisms in urolithiasis. 1762 94

Primary renal hypouricemia (PRH) refers to a rare condition of increased renal urate clearance, caused by an isolated inborn error of membrane transport of urate in the renal proximal tubule. Several cases of exercise-induced acute renal failure and urolithiasis have been reported. This is the first study that assessed tubular function in PRH using NMR-based metabonomic urine analysis. The study groups consisted of 36 unrelated asymptomatic subjects with PRH, defined as serum uric acid levels (sUA) <2.5 mg/dL and fractional excretion of uric acid (FEUA) >10%, after exclusion of diseases and drugs that may affect urate homeostasis, and 39 sex and age-matched healthy individuals with normal sUA levels (>4.0 mmol/L) and FEUA<10%. Individuals with primary hypouricemia presented similar biochemical profiles to the controls without significant differences with regard to FE of electrolytes and renal threshold for phosphate excretion. Individuals with primary hypouricemia were differentiated from healthy individuals in the orthogonal signal correction/partial least-squares-discriminant analysis models of the NMR data with a statistically significant separation. The components that contributed to this separation were the lower levels of hippurate, creatinine, and trimethylaminoxide, and the higher levels of phenylalanine, alanine, glycine, glutamate, acetate, and of an unidentified metabolite (3.3 ppm) observed in hypouricemic subjects compared with controls. Primary hypouricemia, though considered an isolated renal tubular defect, is often associated with a more generalized proximal tubular disorder that mimics a partial Fanconi syndrome.
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PMID:Evaluation of the proximal tubular function in individuals with primary renal hypouricemia: an NMR-based metabonomic study. 1959 59


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