Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case is described of an infant who suffered from progressive, severe dystrophy, hemolytic and megaloblastic anemia, hematuria, proteinuria and slight uremia. He died at 4 months of age following two acute episodes of heart failure. Abnormally increased excretion of methylmalonate and homocystine was detected by our screening program for metabolic disorders. Amino acid analyses showed that the plasma and urine levels of methionine were very low whereas those of cystathionine were raised. Vitamin B12 deficiency, malabsorption or abnormal cobalamin transport were excluded by a normal serum total cobalamin and normal transcobalamins. These findings suggested a congenital error of cobalamin metabolism. Treatment with vitamin B12 resulted in a biochemical though not a clinical response. Postmortem examination revealed severe vascular lesions with changes in the kidney characteristic of thrombotic microangiopathy supporting a diagnosis of hemolytic-uremic syndrome. It is assumed that the elevated plasma homocysteine induced the vascular lesions by causing detachment of endothelium.
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PMID:Congenital defect in intracellular cobalamin metabolism resulting in homocysteinuria and methylmalonic aciduria. I. Case report and histopathology. 52 29

The reactive vascular-injuring amino acid homocysteine was previously shown to be increased in plasma in diabetic patients with clinical signs of nephropathy. In this study, plasma homocysteine was measured in type 1 diabetic patients with normoalbuminuria (n = 22), microalbuminuria (n = 40) and proteinuria (n = 14) in order to investigate whether plasma homocysteine levels are increased already at the stage of incipient nephropathy, i.e. microalbuminuria. Furthermore, patients were characterized according to the degree of retinopathy. Plasma homocysteine in the whole population (n = 76) was related to B-Folate (r = 0.38, p < 0.01), S-Creatinine (r = 0.55, p < 0.001), S-Urea (r = 0.37, p < 0.01), U-Albumin (r = 0.46, p < 0.001), urinary N-acetyl-beta- glucosaminidase (r = 0.40, p < 0.001), systolic blood pressure (r = 0.36, p < 0.01) and diabetes duration (r = 0.44, p < 0.001). There were no differences in plasma homocysteine levels between patients with normoalbuminuria (8.0 +/- 1.7 mumol l-1; mean +/- SD) and those with microalbuminuria (9.1 +/- 3.4 mumol l-1). However, patients with clinical signs of nephropathy had higher plasma homocysteine levels (12.9 +/- 5.7 mumol l-1, p < 0.01) compared to the other two groups. There was no association between plasma homocysteine levels and different degrees of retinopathy. Thus, the present study does not show any relation between plasma homocysteine levels and early stages of diabetic nephropathy or retinopathy indicating that elevated concentrations of plasma homocysteine does not explain the increased risk for atherosclerosis observed in patients with microalbuminuria.
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PMID:Lack of association between plasma homocysteine levels and microangiopathy in type 1 diabetes mellitus. 770 67

The onset of preeclampsia at or near to term is associated with low maternal and neonatal morbidity and mortality. In contrast, those patients (1%) who suffer early onset preeclampsia engender significant maternal and perinatal morbidity and mortality. Therefore, because of the lack of proven prophylaxis for preeclampsia, prediction of risk or identification of subclinical disease is desirable to identify patients for more intensive observation. There are certain at-risk groups of patients such as those with chronic hypertension, pregestational diabetes, multifetal gestation, and previous preeclampsia. These patients account for the majority of cases of preeclampsia in multiparas, yet only account for 14% of preeclampsia in nulliparous women. Thus, the majority of cases of preeclampsia arises from nulliparous women without medical complications at low risk. Differences in the time of onset, severity, and organ system involvement suggest there may be different underlying etiologies that ultimately lead to preeclampsia manifested as the triad of maternal hypertension, proteinuria, and edema. Distinct markers therefore may identify subgroups of at-risk patients with separate underlying causes. These markers ultimately could be used for diagnosis of disease before the clinical appearance of maternal disease (hypertension, proteinuria, and edema). Based on data from patients with established disease, with the involvement of various organ systems, potential candidate markers would include renal function (kallikrein-creatinine); coagulation and fibrinolytic systems and platelet activation (platelet volume); markers of vascular function (fibronectin, prostacyclin, thromboxane) and oxidant stress (lipid peroxides, 8-isoprostane, antioxidants, anticardiolipin antibodies, hemoglobin, iron, transferrin, homocysteine, hypertriglyceridemia, albumin isoforms); placental peptide hormones (CRH, CRHbp, activin, inhibin, hCG); vascular resistance (uteroplacental flow velocity waveforms); genetic markers; insulin resistance; and glucose intolerance. Although cross-sectional studies have identified these potential markers, they need to be evaluated in prospective longitudinal studies with rigorous definition of outcome to determine if they are useful in predicting preeclampsia and whether they can identify different subgroups of patients.
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PMID:Prediction of preeclampsia. 1010 70

A decrease of plasma homocysteine (Hcy) may represent a therapeutic promise for reducing the impact of atherosclerosis. N -Acetyl-cysteine (NAC) is a thiol-containing compound interfering with endogenous thiols, cysteine (Cys) and Hcy, by forming with them mixed disulphides with a possibly more efficient renal clearance. The aim of this work was to assess the effect of NAC intravenous infusion on plasma levels of different forms of Hcy and particularly to verify the effect on Hcy renal excretion. We collected basal blood samples at 0.5, 1, 2, 5, 8 and 24 h after the beginning of NAC infusion (50 mg kg(-1)body wt.) and also 24-h urine samples of the day of NAC infusion and of the day before and of the day after the infusion in ten healthy subjects (mean age 73+/-15). Urinary and plasma thiols (Hcy, Cys and NAC) were assayed by HPLC. Both total plasma Hcy (approx. 69%vs basal values) and Cys (approx. 40%vs basal values) fell progressively, reaching a minimum 5 h after infusion start; total free (i.e. not bound to proteins) Hcy (2.2+/-1.8 down from 4.4+/-4.2 nmol ml(-1)) and Cys (70.4+/-39.8 down from 113. 3+/-61.2 nmol ml(-1)) decreased as well. Reduced (thiolic-free form) Hcy and Cys decreased during infusion, though not as pronounced as for the other forms. Percentagewise, out of the total plasma levels, Hcy and Cys total free form and reduced form tended to increase over infusion as well as their difference (i.e. the plasma mixed disulphide moiety), thus supporting the idea that excess NAC displaces thiols from their plasma binding sites forming mixed disulphides. Urinary total Cys and Hcy excretion significantly increased at the end of the day of NAC infusion (tenfold for Cys and fivefold for Hcy) and reduced appreciably on the following day. Also urinary excretion of the free form of Cys and Hcy increased at the end of the day of NAC infusion, although in a lower amount with respect of total amounts, meaning a reduction of percentage Cys and Hcy excreted as the free form; for none of the patients had proteinuria, the 'free' form of urine thiols has to be identified in the 'reduced' form, the difference between the total and free form reflecting the 'mixed disulphide' moiety. NAC intravenous administration induces an efficient and rapid reduction of plasma thiols, particularly of Hcy; our data support the hypothesis that NAC displaces thiols from their binding protein sites and forms, in excess of plasma NAC, mixed disulphides (NAC-Hcy) with an high renal clearance. This effect may represent the start of an alternative approach in the treatment of hyperhomocysteinaemic conditions.
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PMID:N -Acetyl-cysteine reduces homocysteine plasma levels after single intravenous administration by increasing thiols urinary excretion. 1052 47

The homocysteine plasma level is determined by non-genetic and genetic factors. In recent years evidence has accumulated that the total homocysteine plasma level of patients under different forms of renal replacement therapy is influenced by a common mutation at nucleotide position 677 of the gene coding for 5,10-methylenetetrahydrofolate reductase (MTHFR 677C-->T). Furthermore, compound heterozygosity for the 677T allele and a novel A-->C polymorphism at nucleotide position 1298 of MTHFR is suggested to correlate with a decrease of folate plasma concentrations. Because polymorphisms of genes coding for proteins involved in the metabolism of homocysteine may contribute to elevated total homocysteine plasma concentrations, molecular genetic analyses of the homocysteine pathways experienced a drift towards screening for candidate genes with a putative relationship to total homocysteine plasma levels. One example is the cloning of the FOLR1 gene coding for the folate-binding protein (Folbp1), which has recently been inactivated in mice, thus representing an elegant model to investigate the consequence on the homocysteine metabolism. Furthermore, the recent characterization of the CUBN gene encoding the intrinsic factor-vitamin B12 receptor (cubilin) provides a basis to identify the causative mutations in patients suffering from a hereditary syndrome of hyperhomocysteinemia that presents with megaloblastic anemia and proteinuria. This review focuses on recent insights into the molecular genetics of MTHFR, FOLR1, and CUBN, and their relationships to the metabolism of the amino acid homocysteine.
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PMID:Recent insights into the molecular genetics of the homocysteine metabolism. 1116 18

Conflicting data have been reported concerning the independent association between proteinuria and plasma total homocysteine (tHcy) levels, particularly among chronic renal disease (CRD) patients with a normal range serum creatinine. Studies of this potential relationship have been limited by failure to assess true GFR, failure to assess proteinuria in a quantitative manner, or arbitrary restriction of the range of proteinuria examined. We examined the potential independent relationship between plasma tHcy levels and a wide range of quantitatively determined proteinuria (i.e., 0.000-8.340 g/day), among 109 CRD patients with a normal range serum creatinine (range; 0.8-1.5 mg/dl; median=1.2 mg/dl). Glomerular filtration rate (GFR) was directly assessed by iohexol clearance, and plasma status of folate, pyridoxal 5'-phosphate, and B12, along with serum albumin, were also determined. Linear modeling with ANCOVA revealed that proteinuria was not independently associated with tHcy levels (partial R=0.127; P=0.201), after adjustment for potential confounding by GFR (partial R=0.408; P<0.001), age, sex, plasma B-vitamin status, and serum albumin. Moreover, descending across quartiles (Q) [from Q4 to Q1] of GFR, ANCOVA-adjusted (i.e., for age, sex, and folate status) geometric mean tHcy levels (micromol/l) were significantly increased: tHcy Q4 GFR=9.6; tHcy Q3 GFR=10.5; tHcy Q2 GFR=11.9; tHcy Q4 GFR=14.5; P<0.001 for overall Q difference. We conclude that across a broad spectrum of quantitatively determined proteinuria, after adjustment for true GFR, in particular, there is no independent relationship between proteinuria and tHcy levels among CRD patients with a normal range serum creatinine.
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PMID:Proteinuria and plasma total homocysteine levels in chronic renal disease patients with a normal range serum creatinine: critical impact of true glomerular filtration rate. 1168 24

Two siblings, a boy age 12 and his sister age 4 years, presented with proteinuria and hematuria, hypertension, and chronic hemolytic anemia. At age 13 years, the boy developed an episode of severe hypertensive encephalopathy and transient renal failure. Both children are attending normal school, have no neurologic symptoms, and only minimal pigmentary retinal abnormalities. Renal biopsy showed a chronic thrombotic microangiopathic nephropathy. Both patients had hyperhomocysteinemia and mild methylmalonic aciduria. Fibroblasts showed decreased cobalamin uptake, reduced methyl- and adenosyl-cobalamin formation, and deficient incorporation of formate and propionate, compatible with the Cbl-C complementation group, but milder than that found in cells from most patients. Both patients and their father carry a balanced reciprocal translocation. Parenteral hydroxycobalamin treatment reduced the homocysteine levels, and methylmalonic acid disappeared. Increasing the dosage of hydroxycobalamin from 1 to 2.5, then 5 mg daily together with betaine, further reduced homocysteine levels (boy from 118 to 23 microM and girl from 59 to 14 microM). With this treatment, hemolysis has stopped, hematuria has disappeared, proteinuria has almost normalized, and creatinine clearance has been stable. Investigations for chronic thrombotic microangiopathy should include testing for this unusual but treatable disorder, regardless of age of presentation.
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PMID:Cobalamin disorder Cbl-C presenting with late-onset thrombotic microangiopathy. 1221 Mar 50

Cobalamin C (cbl C) deficiency, an inherited disorder of vitamin B12 metabolism, causes elevated levels of methylmalonic acid and homocysteine and decreased methionine in all body fluids. Renal complications of cbl C disease are thrombotic microangiopathy (TMA), chronic renal failure, tubulointerstitial nephritis and proximal renal tubular acidosis. There is, however, only one case report of primary glomerular pathology, focal segmental glomerulosclerosis, in a cbl C deficient patient. We report a case of an atypical glomerulopathy in a 16-year-old male patient with cbl C deficiency. The glomerulopathy manifested with proteinuria and progressive renal insufficiency. The renal histologic, immunofluorescent and ultrastructural findings were similar, but not identical, to idiopathic membranoproliferative glomerulonephritis (MPGN) but also overlapped with those of a TMA. The serum complement profile was normal; there were scanty glomerular deposits of C3, no deposits of IgG and ultrastructural findings that were similar to those seen in either MPGN type III or a TMA. On the basis of these findings we have designated the renal disease as an atypical glomerulopathy.
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PMID:Cobalamin C deficiency complicated by an atypical glomerulopathy. 1237 6

The mortality rate among dialysis patients is high. Although guidelines have been in place to improve outcomes in dialysis patients, new emphasis is being placed on better management of patients who are pre-end-stage renal disease (pre-ESRD)-patients with chronic kidney disease (CKD). Spearheaded by the National Kidney Foundation, the National Institute of Health, and the nephrology community at large, an effort is underway to improve the care of patients with kidney disease. We hope that improvement in health and outcomes of patients with kidney disease will be optimized through attention to care before the development of advanced renal disease. Cardiovascular disease (CVD) is an important comorbidity of chronic kidney disease, and reducing cardiovascular events in this population is an important goal for the people who care for chronic kidney disease patients. In this article, we review the available literature regarding certain risk factors for cardiovascular disease: proteinuria, hyperglycemia, hypertension, homocysteine, hyperlipidemia, and inflammation. When possible, recommendations for treatment are provided based on the information reviewed.
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PMID:Comorbidity and cardiovascular risk factors in patients with chronic kidney disease. 1243 94

Enhanced oxidative stress is involved in the progression of renal disease. Since angiotensin converting enzyme inhibitors (ACEI) have been shown to improve the antioxidative defence, we investigated, in patients with nondiabetic nephropathy, the short-term effect of the ACEI ramipril on parameters of oxidative stress, such as advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), homocysteine (Hcy), and lipid peroxidation products. Ramipril (2.5-5.0 mg/day) was administered to 12 newly diagnosed patients for 2 months and data compared with a patient group under conventional therapy (diuretic/beta-blockers) and with age- and sex-matched healthy subjects (CTRL). Patients had mild to moderate renal insufficiency and showed, in the plasma, higher fluorescent AGE and carboxymethyllysine (CML) levels, as well as elevated concentrations of AOPPs, lipofuscin and Hcy when compared with CTRL. Basal data of the patients on conventional therapy did not differ significantly from the ramipril group, except for higher Hcy levels in the latter. Administration of ramipril resulted in a drop in blood pressure and proteinuria, while creatinine clearance remained the same. The fluorescent AGEs exhibited a mild but significant decline, yet CML concentration was unchanged. The AOPP and malondialdehyde concentrations decreased, while a small rise in neopterin levels was evident after treatment. The mentioned parameters were not affected significantly in the conventionally treated patients. Evidence that ramipril administration results in a mild decline of fluorescent AGEs is herein presented for the first time. The underlying mechanism may be decreased oxidative stress, as indicated by a decline in AOPPs and malondialdehyde.
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PMID:Effects of ramipril in nondiabetic nephropathy: improved parameters of oxidatives stress and potential modulation of advanced glycation end products. 1269 71


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