Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial Mediterranean fever (FMF) is an autosomal recessive disease clinically characterized by recurrent short self-limited attacks of fever accompanied by peritonitis, pleurisy, and arthritis and can lead to amyloidosis and renal failure in the longer term. It is prevalent mainly in non-Ashkenazi Jews, Armenians, Turks, and Arabs. Due to the lack of an accurate diagnostic test, patients often experience years of attacks and invasive diagnostic procedures before the correct diagnosis is made and adequate treatment is begun. Recently, the gene responsible for FMF, denoted pyrin, has been cloned, and three disease mutations have been described (French FMF Consortium, 1997; International FMF Consortium, 1997). In the current study we assessed the spectrum of mutations in this gene in 16 unrelated families of Turkish origin. The three previously reported missense mutations (Met-Ile at codon 680, Met-Val at codon 694, and Val-Ala at codon 726) accounted for 29 of the 34 disease alleles. In one patient in whom no disease mutation was identified, the clinical picture was atypical enough to raise questions regarding the diagnosis. These results imply that the origin of FMF in Turkey is heterogeneous, that molecular diagnosis of FMF is possible in the majority of cases and clinically helpful, and that delineation of the undiscovered disease mutation(s) in the remaining cases remains a high priority.
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PMID:Assessment of pyrin gene mutations in Turks with familial Mediterranean fever (FMF). 960 38

Concentrations of sulfate can increase eightfold in the blood of patients with severe reductions in glomerular filtration rate. Sulfate enters the body almost exclusively as the amino acids cysteine and methionine, and leaves in the urine predominantly as inorganic sulfate. Concentrations in plasma may exceed 2.5 mol/L in renal failure, and raise the anion gap by 5 mEq/L. In studies by the author and colleagues, hemodialysis using large dialyzers and brisk blood flow rates effectively lowered the concentrations of sulfate in plasma to normal in the immediate post dialysis period; the sulfate reduction ratio actually exceeded the urea reduction ratio. Significant correlation was observed between the two ratios. Concentrations of sulfate, in conjunction with other data, may prove useful for estimating dietary intake of protein and monitoring control of acid-base balance.
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PMID:Effect of hemodialysis on the hypersulfatemia of chronic renal failure. 968 59

Loss of heterozygosity (LOH) is a molecular phenomenon that denotes the loss of one of the two alleles at a specific locus. It is frequently associated with tumour suppressor genes in various cancers and also with hyperproliferative disorders, although not exclusively. Interestingly, in conditions where there is an inherited germline mutation, the lost allele is always the functional one, thereby rendering a phenotypically dominant disease of recessive character at the cellular level. A disease more recently shown to be associated with LOH is polycystic kidney disease type 1, a systemic disorder characterized by significant pleiotropy. The main pathology is from renal cyst formation that eventually leads to end-stage renal failure during adult life. We describe the identification of a missense mutation in the repeated part of the PKD1 gene, exon 31, that substitutes valine for methionine. The mutation, M3375V, cosegregates with the disease phenotype in a large Cypriot family. During transplantation of one patient, one of the polycystic kidneys was removed and DNA was isolated from cystic epithelial cells. In 3 of 17 cysts examined with intragenic and flanking polymorphic markers on chromosome 16 we detected LOH, since the wild-type allele was lost, thereby rendering the affected kidneys of mosaic character. The degree of LOH was extensive and varied among the three cysts, supporting the multiplicity of expression of the phenomenon on different occasions. No LOH was detected for other selected loci examined. Our work further supports the hypothesis that the rate-limiting step in cyst formation may be the occurrence of a second somatic hit, although other factors may be also involved. The high frequency of mutations at this locus may, to a great extent, explain the variability in phenotype observed among patients in the same families, and the relatively high frequency of the disease worldwide.
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PMID:Loss of heterozygosity in polycystic kidney disease with a missense mutation in the repeated region of PKD1. 992 8

In this investigation, sulfur amino acids (sAA) and sulfhydryls were determined in the plasma and erythrocytes (RBC) of 10 uremic patients on regular hemodialysis (HD) treatment and 10 healthy subjects, before and after supplementation with 15 mg/d of folic acid and 200 mg/d of pyridoxine for 4 wk. The basal total plasma concentrations of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly), gamma-glutamylcysteine (gamma-Glu-Cys), glutathione (GSH), and free cysteinesulfinic acid (CSA) were significantly higher in HD patients when compared to healthy subjects, whereas methionine (Met) and taurine (Tau) concentrations were the same in the two groups. HD patients showed significantly higher RBC levels of Hcy and Cys-Gly, whereas the RBC concentrations of Met, Cys, Tau, and GSH were not different from those in the healthy subjects. The plasma concentrations of sAA and sulfhydryls differed compared with RBC levels in the healthy subjects and HD patients. In both groups, supplementation with high doses of folic acid and pyridoxine reduced the plasma Hcy concentration. In addition, increased plasma concentrations of Cys-Gly and GSH were found in the HD patients and of CSA in the healthy subjects. After vitamin supplementation, the RBC concentrations of Hcy, Cys, and GSH increased and that of Tau decreased in healthy subjects. The only significant finding in RBC of HD patients was an increase in GSH levels after supplementation. This study shows several RBC and plasma sAA and sulfhydryl abnormalities in HD patients, which confirms earlier findings that RBC and plasma pools play independent roles in interorgan amino acid transport and metabolism. Moreover, high-dose supplementation with folic acid and pyridoxine significantly reduced Hcy levels, but did not restore the sAA and sulfhydryl abnormalities to normal levels. The increase that was observed in GSH after vitamin supplementation may have a beneficial effect in improving blood antioxidant status in uremic patients. Finally, the findings of elevated plasma Cys levels correlating to the elevated plasma Hcy levels in the presence of elevated plasma CSA levels, both before and after vitamin supplementation, led to the hypothesis that a block in decarboxylation of CSA is linked to hyperhomocysteinemia in end-stage renal failure.
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PMID:Effects of high-dose folic acid and pyridoxine on plasma and erythrocyte sulfur amino acids in hemodialysis patients. 1036 67

Hyperplasia of the parathyroid glands and high levels of parathyroid hormone (PTH) are among the most consistent findings in patients with chronic renal failure. In early renal failure, alterations in vitamin D metabolism play a key role in the development of secondary hyperparathyroidism. Low levels of calcitriol and decreased expression of the vitamin D responsive element may allow greater synthesis and secretion of PTH. Phosphorus independent of serum calcium and calcitriol increases PTH synthesis and secretion by a post-transcriptional mechanism. Studies in vivo in uremic rats demonstrated that an increase in dietary phosphorus induces parathyroid gland hyperplasia. If the rats are then fed a low-phosphorus diet, the levels of serum PTH return to normal; however, the size of the parathyroid glands remains enlarged. No apoptosis was observed in the glands. To further characterize the effects of phosphorus on PTH synthesis and secretion, intact rat parathyroid glands were metabolically labeled during a 4-hour incubation in methionine-free medium containing 1.25 mM Ca2+, [35S]methionine, and either 2.8 mM or 0.2 mM phosphorus. Total PTH secretion, as measured in the medium, was increased more than 6-fold in glands incubated in high-phosphorus medium compared with glands incubated in the low-phosphorus medium. Thus, in the past 20 years, numerous investigators have provided strong evidence for the action of phosphorus on PTH secretion. Unfortunately, the absence of a parathyroid cell line is slowing the progress in understanding the molecular mechanism(s) involved in phosphorus regulation of PTH.
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PMID:The role of phosphorus in the development of secondary hyperparathyroidism and parathyroid cell proliferation in chronic renal failure. 1037 36

An 18-month-old girl presented with macrocytic megaloblastic anaemia followed by haemolytic uraemic syndrome. Metabolic investigations led to the identification of an inborn error of cobalamin metabolism consisting of defective methylcobalamin biosynthesis, probably cobalamin G, since methionine synthase activity was decreased under standard reducing conditions. Despite treatment, pulmonary hypertension progressively developed and responded to oxygen therapy. Renal involvement evolved to terminal failure and haemodialysis, while pulmonary hypertension was controlled by oxygen therapy. Such clinical manifestations have never been reported in association with a defect of methylcobalamin and thus of methionine biosynthesis. A congenital abnormality of cobalamin metabolism was suspected then confirmed in the presence of typical haematological features associated with unusual clinical manifestations such as progressive renal failure and pulmonary hypertension.
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PMID:Haemolytic uraemic syndrome and pulmonary hypertension in a patient with methionine synthase deficiency. 1048 6

Methylenetetrahydrofolate reductase (MTHFR) plays a central role in the folate cycle and contributes to the metabolism of the amino acid homocysteine. It catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, thus generating the active form of folate required for remethylation of homocysteine to methionine. Deficiency of MTHFR may be associated with an increase in plasma homocysteine, which in turn is associated with an increased risk of vascular disease. This article summarizes the biochemistry, the function in the folate cycle, and the molecular genetics of this enzyme. Particular emphasis has been given to the role of two common polymorphisms (MTHFR 677C-->T, 1298A-->C) in cardiovascular disease, cerebrovascular disease, venous thrombosis, longevity, neural tube defects, pregnancy/preeclampsia, diabetes, cancer, psychiatry, renal failure and renal replacement therapy. Finally, the rare genetic defects underlying severe MTHFR deficiency are also considered.
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PMID:Molecular biology of 5,10-methylenetetrahydrofolate reductase. 1072 Feb 11

There is overwhelming epidemiological evidence that hyperhomocysteinaemia is an independent and graded cardiovascular risk factor, although a cause-and-effect relationship is still unproven. Acquired causes of hyperhomocysteinaemia include B-vitamin deficiencies and renal insufficiency. The most important inherited cause is a point mutation in methylenetetrahydrofolate reductase gene, which is, remarkably, not associated with an increased cardiovascular risk. A methionine loading test identifies substantially more subjects with hyperhomocysteinaemia compared with a fasting homocysteine determination alone. Repeated blood sampling is necessary due to an intra-individual variability in homocysteine concentrations up to 25%. A conservative reference value for fasting homocysteine is 15 micromol/l, although there seems to be no definite threshold in the presumed linear relation between homocysteine concentration and cardiovascular risk. The pathophysiological mechanism of homocysteine-induced cardiovascular disease is still not elucidated. The concept of endothelial dysfunction, demonstrated by impaired endothelium-dependent vasodilation, by oxidant damage has been confirmed in hyperhomocysteinaemic healthy adults. Folic acid supplementation (0.5 mg daily) can be considered the optimum homocysteine lowering therapy, with the exception of renal failure patients. Ongoing large prospective, randomised controlled clinical trials are investigating the potential beneficial effect of homocysteine lowering therapy on cardiovascular morbidity and mortality in subjects with hyperhomocysteinaemia.
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PMID:Hyperhomocysteinaemia as a cardiovascular risk factor: an update. 1140 72

An elevated total homocysteine plasma concentration is associated with an increased morbidity and mortality due to cardiovascular disease in the general population, in patients with renal failure and in recipients of kidney or heart transplants. The fasting or post-methionine loading plasma concentration of total homocysteine is elevated in 50-60% of renal transplant recipients with stable graft function and in the majority of heart transplant recipients. Fasting and post-methionine loading hyperhomocysteinemia can be normalized in virtually all renal transplant patients by a combination of folic acid (5 mg/d), vitamin B6 (50 mg/d) and vitamin B12 (0.4 mg/d). In individuals without renal failure much lower doses of folate and vitamin B12 are able to correct hyperhomocysteinemia. Currently, prospective studies are under way to clarify whether folate and vitamin therapy improves cardiovascular disease morbidity and mortality in the general population and in organ transplant recipients. While population wide screening for and treatment of hyperhomocysteinemia is generally not recommended, treatment of high risk patients, including renal failure patients and kidney and heart transplant recipients, can be considered but still represents an experimental therapy.
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PMID:Hyperhomocysteinemia in organ transplantation. 1078 48

Bacteria or their antigens persisting in the kidneys may induce the classical type of chronic pyelonephritis (CP), which progresses slowly, and may finally result in end-stage renal failure requiring dialysis. Pyelonephrogenic strains enter uro-epithelial and renal epithelial cells--where they accumulate--or may invade the renal interstitium. Promoting factors are obstruction, reflux, urolithiasis, nephrolithiasis, pregnancy, diabetes mellitus, humoral and cellular immunodeficiencies, immunosuppression treatment (e.g. following transplants), autoimmune phenomena (antigenic mimicry). Therapy comprises the treatment of underlying disease, antibiotics as indicated by the resistogram, acidification of urine (L-methionine), i.v. immunoglobulins (IgM, IgG) and oral vaccination with lyophilized uropathogens.
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PMID:[Chronic pyelonephritis. Synopsis of laboratory values and ultrasound lead to diagnosis]. 1090 12


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