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)

Type I primary hyperoxaluria is an uncommon disease related to alanine glyoxylate aminotransferase (AGT) deficiency, an exclusively hepatic enzyme. AGT deficiency leads to an overproduction of oxalate in the liver and consequent hyperoxalemia and massive hyperoxaluria with renal failure. The diagnosis is confirmed by needle biopsy of the kidney showing the exact nature of the enzyme deficiency. When terminal renal failure has developed there are two therapeutic possibilities: kidney graft or a double liver-kidney graft. Kidney graft alone is often insufficient and carries the risk of recurrent disease in the graft since the liver disorder has not been corrected. Inversely, combined liver-kidney graft can not only replace the destroyed kidneys but also correct the metabolic disorder through the effect of the AGT in the donor liver. Although this approach may be successful, it is a very aggressive procedure with high mortality.
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PMID:[Mechanisms and treatment of primary type I hyperoxaluria]. 869 89

In most cases of glomerulonephritis (GN) long-term course lead to chronic renal failure. The cause of inevitably gradually progress of GN to end-stage renal disease (ESRD) is unclear. The histological abnormalities seen in patients with progressive renal failure consist of focal and segmental glomerulosclerosis and tubulointerstitial nephritis. At present it is considered that tubulointerstitial changes attends almost all forms of progressive glomerular and vascular injury. It was known that chronic tubulointerstitial nephritis is characterized morphologically by tubular atrophy, interstitial fibrosis and interstitial inflammation of variable severity. The pathomechanism of this changes is complicated. Tubular ischaemia results from obliteration of peritubular capillaries, adaptation of tubular function with increased oxygen consumption and increased glomerular capillary permeability to macromolecules are reasons of chronic tubular damage. Injured tubules release growth factors and cytokines, which induce interstitial fibroblast proliferation, chemo-attraction and proliferation of infiltrating cells, and disruption of the balance between synthesis and degradation of cellular constituents. The consequences of these processes are tubular atrophy and interstitial fibrosis. Because of many studies concurred that tubulointerstitial changes determinant the progression of GN, tubular injury markers were searched for. Although over 50 enzymes were detected in human urine, only a few have been used for diagnosis in renal disease. The most widely used are lysosomal enzyme N acetyl-beta-D-glucosaminidase (NAG) and brush border enzymes alanine-aminopeptidase (AAP) and gamma-glutamyltransferase (GGT). tubular damage in hypertension, diabetes and in diagnostics of renal disease. AAP and GGT, brush border enzymes seem to be sensitive markers of renal injury too. Pathological value of GGT was observed even in the early stage of disease. Measurement of urinary excretion of low molecular weight proteins was valuable supplement in estimation of tubulointerstitial system malfunction. These proteins are readily filtered by normal glomeruli and virtually completely reabsorbed by normal proximal tubules. Favour are alpha-1-microglobulin (alpha-1-m) and retinol-binding protein (RBP) because they are less affected than beta-2-microglobulin (beta-2-m) by low urine pH. Above presented review confirm that further research in correlation between activity of disease, histological picture, deterioration in renal function and changes in urinary excretion of markers proteins (for example alpha-1-m, AAP, NAG, GGT) is advisable, and can contribute to use in clinic diagnostics of GN.
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PMID:[The role of tubulointerstitial changes in progression of kidney function failure in patients with chronic glomerulonephritis (GN)]. 875 11

The principal physiologic roles of the kidney are to maintain normal plasma volume and composition, to regulate calcium metabolism by controlling the synthesis of 1,25-dihydroxycholycalciferol (1,25-D3), to regulate hematocrit and to metabolize low molecular weight peptides. Alterations in protein metabolism result principally from losses of these functions. Metabolic acidosis causes increased skeletal muscle protein catabolism through regulated activation of the ATP-ubiquitinproteasome proteolytic pathway. Increased proteolysis is followed by oxidation of branch chain essential amino acids. Alanine and glycine released from muscle and glutamine and glutamate released from liver serve as substrate for renal ammoniagenesis, ultimately correcting acidosis. The cycle is subverted when kidneys are absent. Secretion of a variety of proteins is also perturbed. Hepatic secretion of insulin like growth factor-1 (IGF-I) in response to growth hormone is reduced. This in turn contributes to growth retardation, adding to the effects of acidosis. Muscle is also resistant to insulin in renal failure. Renal production of 1,25-D3 is reduced contributing to hyperparathyroidism, which in turn causes increased intracellular calcium in a variety of tissues contributing to decreased synthesis of immunoglobulins, mitogen-stimulated T-cell proliferation, and decreased glucose-stimulated insulin secretion. Hepatic synthesis of some proteins, such as apolipoprotein A-I and IGF-I are decreased, but synthesis of others, such as albumin, is normal. Low molecular weight peptides such as beta 2-microglobulin, normally filtered and catabolized in the proximal tubule, accumulate in plasma and may have deleterious effects.
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PMID:Derangements of protein metabolism in chronic renal failure. 889 32

Despite careful selection of cirrhotic patients with hepatocellular carcinoma (HCC), liver resection remains associated with a greater risk than in patients without underlying liver disease. In this study we assessed by multivariate analysis parameters associated with in-hospital mortality and morbidity in a selected group of 108 Child-Pugh A cirrhotic patients undergoing liver resection of HCC. The overall incidences of in-hospital deaths and postoperative complications were 8.3% and 48.1%, respectively. By univariate analysis, the preoperative serum alanine transferase (ALT) level (p = 0.001) and intraoperative transfusions (p = 0.01) were significantly associated with in-hospital death; however, only the serum ALT concentration was an independent risk factor. In-hospital mortality rates in patients whose serum ALT was below 2N (twofold the upper limit of the normal value), between 2N and 4N, and more than 4N were 3.9%, 13.0%, and 37.5%, respectively. An ALT level greater than 2N was predominantly observed in patients with a hepatitis C virus infection and significantly associated with histologic features of superimposed active hepatitis. Patients with an ALT level greater than 2N experienced an increased incidence of postoperative ascites (58% versus 32%, p = 0.01), kidney failure (16% versus 0%, p = 0.0003), and upper gastrointestinal bleeding (6.4% versus 0%, p = 0.02). These results indicate that the preoperative ALT level is a reliable predictor of in-hospital mortality and morbidity following liver resection in Child-Pugh A cirrhotic patients. Cirrhotic patients with ALT > 2N should undergo only a limited resection; if a larger resection is required, those patients should be considered for nonsurgical therapy or liver transplantation.
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PMID:High preoperative serum alanine transferase levels: effect on the risk of liver resection in Child grade A cirrhotic patients. 914 70

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

PH1 is caused by deficiency of the liver-specific peroxisomal enzyme alanine: glycoxylate aminotransferase (AGT). Early onset with progressive renal failure and systemic oxalosis is typical. We report a case of a 42 year-old man with PH1 in whom liver biopsy and DNA-analysis showed reduced AGT-activity and homozygosity for the polymorphism C154T and the point mutation G630A. The patient seems to respond to pyridoxine treatment. We suggest that clinical suspicion of PH1 be pursued with a diagnostic liver biopsy.
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PMID:[Primary hyperoxaluria type 1 detected by liver biopsy]. 1020 44

Renal failure is a serious complication of obstructive jaundice. Early diagnosis and prevention of spontaneous evolution of the disease can improve prognosis, otherwise very poor in many cases. The Authors, on the basis of experimental researches from literature, expose their clinical experience about the validity of the determination of Alpha-Glucosidase and Alanine-Amino-Peptidase for early diagnosis and differentiation between organic or functional forms of renal failure. They conclude that determination of urinary levels of AGS and AAP is a valid aid for the evaluation of renal function in patients with obstructive jaundice.
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PMID:[Alpha-glucosidase and alanine-amino-peptidase in the early diagnosis of renal failure in obstructive jaundice]. 1039 85

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

Changes in plasma amino acid concentrations were measured in patients with hepatic failure during extracorporeal hemodiabsorption (using the Liver Dialysis Unit, "the Unit") or hemodiabsorption plus sorbent-based pheresis treatment (using the Liver Dialysis Plasmafilter Unit, "the PF-Unit") Systems. Eight patients with hepatic failure, grade 3 or 4 encephalopathy, elevated bilirubin and/or creatinine levels and respiratory or renal failure were treated for 1-3 days with the Unit alone. Three of these were also treated with the Unit containing 10 g of BCAA in the sorbent suspension. Four patients with hepatic failure treated with the PF Unit also had 10 g of branched chain amino acid (BCAA) added to the sorbents of the Unit portion of this device. Pre- and post-plasma samples were drawn and high performance liquid chromatography (HPLC) was used to separate and detect amino acids in the plasma. Both the Unit and the PF-Unit have the capability to selectively remove various amino acids, especially aromatic amino acids (AAA). The pre-treatment amino acid profiles of plasma were typical for hepatic failure, with abnormally high levels of phenylalanine, tyrosine, tryptophan, and methionine and decreased levels of valine, leucine and isbolucine. The average pre-treatment Fischer ratio (BCAA/AAA) for both Unit and PF-Unit patients was 1.43 (+/- 0.58). Treatments by both systems resulted in an increase of BCAA levels in blood and concomitant decrease of AAA levels, with an average Fischer ratio improvement of 30-38% for the Unit and PF-Unit without BCAA. The Fischer ratio improved by 90% (average) for the Unit with BCAA. Levels of many other amino acids (such as alanine, glycine, proline or lysine) increased during both Unit and PF-Unit treatments. The removal of strongly protein-bound toxin and amino acids such as tryptophan and sulphydryl amino acids was more effective by the PF-Unit. Both the Unit and the PF-Unit have the unique capability to remove toxic aromatic amino acids while increasing BCAA levels in patient. The increase in many amino acid levels may be related to the removal of toxins that interfere with normal amino acid metabolism. The addition of the PF module improves the removal of bilirubin and similarly protein-bound chemicals. Changes in amino acid profiles by the Unit and the PF-Unit contrast markedly with other extracorporeal devices.
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PMID:Effect of hemodiabsorption and sorbent-based pheresis on amino acid levels in hepatic failure. 1091 55


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