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)

Fabry's disease is a genetic disorder caused by the absence of alpha-galactosidase (alpha-Gal), the gene of which is carried on the long arm of the X chromosome. This enzymatic defect leads to an accumulation of glycosphingolipids in the plasma and lysosomes of endothelial, perithelial, and smooth muscle cells, especially involving those of the cardiovascular, renal and cerebrovascular systems. We report one male case of Fabry's disease with renal deterioration. A 36-year-old man who was a classic case with acroparesthesia, angiokeratoma, and hypohidrosis from 10 years of age, was diagnosed to be a hemizygote of Fabry's disease at 27 years as a result of severe decreased alpha-Gal activity of his peripheral white blood cells. This patient was found to have a point mutation of a G to A transition in exon 1. In May, 1989, he was reported to have proteinuria with normal renal function and admitted to our hospital due to renal deterioration in September, 1993. Laboratory examinations revealed a serum urea nitrogen of 65 mg/dl and creatinine value of 6.9 mg/dl. Urinary protein excretion was 3.9 g/day and urinary sugar was negative. On the renal biopsy specimens, light microscopic examinations revealed multiple sclerosing and collaptic lesions in glomeruli without severe tubulo-interstitial damage, but with stenotic change of the small arteries and arterioles. Electron microscopic examinations revealed a large number of electron dense deposits in the tubules. We diagnosed this case as Fabry's disease with chronic renal failure, however the pathogenesis of this renal progressive deterioration remained obscure. In this case, degenerative changes in the renal vessels due to Fabry's disease may be associated with rapid deterioration in renal function.
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PMID:[A case of Fabry's disease with chronic renal failure]. 1044 95

Systemic lupus erythematosus (SLE) is a systemic autoimmune syndrome defined by clinical and serologic features, including arthritis, glomerulonephritis, and certain autoantibodies such as anti-nuclear ribonucleoprotein (nRNP)/Smith antigen (Sm), DNA, and ribosomal P. Although lupus is considered primarily a genetic disorder, we recently demonstrated the induction of a syndrome strikingly similar to spontaneous lupus in many nonautoimmune strains of mice exposed to the isoprenoid alkane pristane (2,6,10,14-tetramethylpentadecane), a component of mineral oil. Intraperitoneal injection of pristane leads to the formation of lipogranulomas consisting of phagocytic cells that have engulfed the oil and collections of lymphocytes. Subsequently, pristane-treated BALB/c and SJL mice develop autoantibodies characteristic of SLE, including anti-nRNP/Sm, antiribosomal P, anti-Su, antichromatin, anti-single-stranded DNA, and anti-double-stranded DNA. This is accompanied by a severe glomerulonephritis with immune complex deposition, mesangial or mesangiocapillary proliferation, and proteinuria. All inbred mice examined appear to be susceptible to this novel form of chemically induced lupus. Pristane-induced lupus is the only inducible model of autoimmunity associated with the clinical syndrome as well as with the characteristic serologic abnormalities of SLE. Defining the immunopathogenesis of pristane-induced lupus in mice may provide insight into the causes of spontaneous (idiopathic) lupus and also may lead to information concerning possible risks associated with the ingestion or inhalation of mineral oil and exposure to hydrocarbons in the environment.
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PMID:Immunopathogenesis of environmentally induced lupus in mice. 1050 37

Sickle cell anemia and the related hemoglobinopathies are associated with a large spectrum of renal abnormalities. The patients have impaired urinary concentrating ability, defects in urinary acidification and potassium excretion, and supranormal proximal tubular function. The latter is manifest by increased secretion of creatinine and by reabsorption of phosphorus and beta(2)-microglobulin. Young patients with sickle cell disease (SCD) have supranormal renal hemodynamics with elevations in both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR). These parameters decrease with age as well as following the administration of prostaglandin inhibitors. Proteinuria, a common finding in adults with sickle cell disease, may progress to the nephrotic syndrome. Proteinuria, hypertension, and increasing anemia predict end-stage renal disease (ESRD). While ESRD can be managed by dialysis and/or renal transplantation, there may be an increased rate of complications in renal transplant recipients with SCD. Hematuria is seen in individuals with all of the SCDs as well as with sickle cell trait. In most cases the etiology of the hematuria turns out to be benign. However, there does appear to be an increased association between SCD and renal medullary carcinoma. Therefore, those SCD patients who present with hematuria should initially undergo a thorough evaluation in order to exclude this aggressive neoplasm. Papillary necrosis may occur due to medullary ischemia and infarction. Erythropoietin levels are usually lower than expected for their degree of anemia and decrease further as renal function deteriorates. An abnormal balance of renal prostaglandins may be responsible for some of the changes in sickle cell nephropathy. Acute renal failure is a component of the acute multiorgan failure syndrome (MOFS). Finally, progression of sickle cell nephropathy to ESRD may be slowed by adequate control of hypertension and proteinuria. However, the prevention of the renal complications of SCD will require a cure for this genetic disorder.
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PMID:Renal abnormalities in sickle cell disease. 1142 1

Alport syndrome (AS) is a genetic disorder of basement membranes caused by mutations in type IV collagen genes that is characterized by chronic hematuria and progressive nephropathy leading to renal failure. The main extrarenal features include sensorineural hearing loss and ocular lesions. The mode of inheritance is X-linked dominant in about 80%-85% of the affected families, whereas autosomal transmission is rarely encountered. We report a male patient originating from a healthy consanguineous Lebanese family who presented with an unusual association of obstructive uropathy and AS. Hematuria and proteinuria were initially attributed to a suspected poststreptococcal glomerulonephritis (GN) and high-grade subpelvic ureteral stenosis. Persistence of symptoms after medical treatment of poststreptococcal GN and surgical correction of obstructive uropathy finally led to renal biopsy. The observed ultrastructural changes of the glomerular basement membrane were typical for AS. Molecular genetic studies revealed a previously undescribed de novo mutation in the COL4A5 gene, excluding maternal heterozygotic carrier status. This case report emphasizes the importance of hereditary nephritis in the differential diagnosis of chronic hematuria, and demonstrates the value of molecular studies for genetic counselling in AS.
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PMID:Sporadic case of X-chromosomal Alport syndrome in a consanguineous family. 1095 21

Alport syndrome refers to a hereditary disorder characterized by progressive renal disease and a multilaminar appearance to the glomerular basement membrane (GBM). In a small group of patients with Alport syndrome, cyclosporine A was reported to decrease proteinuria and maintain stable renal function over 7 to 10 yr of follow-up. The present study examined the effect of cyclosporine A on GBM structure and the progression to renal failure in a canine model of X-linked Alport syndrome. Affected male dogs and normal male dogs treated with cyclosporine A underwent serial renal biopsies. Body weight, serum concentrations of creatinine and albumin, and GFR were sequentially determined. Controls consisted of untreated dogs that developed end-stage renal failure by 8 mo of age. Renal biopsies were assessed for glomerulosclerosis and the percent of multilaminar GBM as measured by image analysis. Significant differences were found between treated and untreated affected dogs for weight, serum creatinine, and GFR. There was a significant delay in the progression of multilaminar change to the GBM, although treated affected dogs at termination had attained approximately 100% split GBM as did untreated affected dogs. A significant difference in the number of sclerotic glomeruli was also noted; treated dogs rarely developed obsolete glomeruli during the period studied. Interstitial fibrosis was not significantly affected by cyclosporine A treatment. These findings indicate that cyclosporine A is beneficial in slowing, but not stopping, the clinical and pathologic progression of Alport syndrome. At least part of this beneficial effect comes from a delayed deterioration of GBM structure, which in turn may be related to glomerular hemodynamics altered by cyclosporine A.
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PMID:Cyclosporine a slows the progressive renal disease of alport syndrome (X-linked hereditary nephritis): results from a canine model. 1259 5

Nail-patella syndrome (NPS) is a rare, autosomal-dominant hereditary disorder characterized by nail dysplasia and multiple osseous abnormalities. Some patients may develop renal function impairment and even end-stage renal disease. We treated a 42-year-old female patient with proteinuria who presented with a web-like structure over the antecubital fossa and hypoplastic patellae. In addition, she had other characteristic findings, including bilateral iliac horn, triangular nail lunulae and hypoplastic radial head. She had impaired renal function, and renal biopsy showed mesangial proliferative glomerulonephritis. Additional cases were found in her family. Her mother had most of the signs of NPS as well as advanced renal failure. Her elder sister had knee abnormalities without the web-like elbow condition. Both daughters also had the characteristic features of NPS. During follow-up 30 months after the initial examination, the patient had stable renal function and mild proteinuria.
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PMID:Nail-patella syndrome with renal involvement and antecubital pterygia. 1264 95

Familial LCAT deficiency (FLD) is a rare genetic disorder associated with corneal opacities, anaemia and proteinuria with renal failure. Here we report detailed analyses on plasma lipids, lipoproteins, and the molecular defect in two siblings from a Polish family presenting classical symptoms of FLD and their family members with newly discovered Val309Met mutation in exon 6 of LCAT gene. Both patients displayed low total (2.19 and 2.94 mmol/l) and HDL-cholesterol concentrations (0.52 and 0.48 mmol/l), low percentage of cholesteryl esters (CE) (11.1 and 12%), and decreased apo AI and apo AII serum levels. Low LDL-cholesterol, apo B and Lp(a) levels, and increased oleate/linoleate ratios in CE could be of importance in the development of atherosclerosis in these patients with low HDL-cholesterol. LCAT activity was 10% of normal, alpha-LCAT activity was 0, and LCAT concentration was undetectable by immunoassay. Plasma CETP activity was at lower limits of normal. PCR and sequence analysis of DNA from the proband and affected brother revealed a novel G-->A mutation in exon 6 of LCAT gene, which resulted in an amino acid substitution of valine for methionine (Val309Met). The proband and affected brother were both homozygous carriers, while the mother, siblings and children of patients were heterozygous carriers of a newly discovered mutation. This is the first LCAT mutation described in the Slavic population.
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PMID:Familial lecithin-cholesterol acyltransferase deficiency: biochemical characteristics and molecular analysis of a new LCAT mutation in a Polish family. 1605 Dec 54

Genetic disorders of mineral metabolism cause urolithiasis, renal disease, and osteodystrophy. Most are rare, such that the full spectrum of clinical expression is difficult to appreciate. Diagnosis is further complicated by overlap of clinical features. Dent's disease and primary hyperoxaluria, inherited causes of calcium urolithiasis, are both associated with nephrocalcinosis and urolithiasis in early childhood and renal failure that can occur at any age but is seen more often in adulthood. Bone disease is an inconsistent feature of each. Dent's disease is caused by mutations of the CLCN-5 gene with impaired kidney-specific CLC-5 chloride channel expression in the proximal tubule, thick ascending limb of Henle, and the collecting ducts. Resulting hypercalciuria and proximal tubule dysfunction, including phosphate wasting, are primarily responsible for the clinical manifestations. Low-molecular-weight proteinuria is characteristic. Definitive diagnosis is made by DNA mutation analysis. Primary hyperoxaluria, type I, is due to mutations of the AGXT gene leading to deficient hepatic alanine-glyoxylate aminotransferase activity. Marked overproduction of oxalate by hepatic cells results in the hyperoxaluria responsible for clinical features. Definitive diagnosis is by liver biopsy with measurement of enzyme activity, with DNA mutation analysis used increasingly as mutations and their frequency are defined. These disorders of calcium urolithiasis illustrate the value of molecular medicine for diagnosis and the promise it provides for innovative and more effective future treatments.
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PMID:Stones, bones, and heredity. 1680 Nov 62

Alport syndrome (AS) is a hereditary disorder of type IV collagen characterized by the association of progressive hematuric nephritis and sensorineural hearing loss. An increase in proteinuria is linked with progressive renal failure. Preliminary data have shown that cyclosporin therapy reduces proteinuria, thereby suggesting that it may also slow the progression of AS nephropathy. We treated nine AS patients manifesting proteinuria >1 g/m(2)/day and a glomerular filtration rate (GFR) >50 ml/min/1.73 m(2) with cyclosporin for at least 6 months. At the end of this 6-month period, mean proteinuria had decreased from 2+/-1.06 to 0.65+/-0.73 g/day, and mean albuminemia had increased from 29+/-5.2 to 35+/-6.5 g/l. Mean inulin clearance had decreased from 102+/-29 to 74+/-16.3 ml/min/1.73 m(2). Cyclosporin treatment was stopped in four patients because of inefficacy or adverse effects and continued in the remaining five patients for an additional 14-42 months. At the end of this second treatment period, control renal biopsies revealed significant lesions of cyclosporin nephrotoxicity in three patients. Based on these results we conclude that while cyclosporin therapy can decrease proteinuria in most patients with AS, it may be associated with nephrotoxicity, thereby precluding its long-term use.
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PMID:Cyclosporin therapy in patients with Alport syndrome. 1702 94

Frasier syndrome is an uncommon genetic disorder featuring progressive glomerulopathy, male pseudohermaphroditism, and gonadal dysgenesis with increased risk of gonadoblastoma and malignant germ cell tumors. It is caused by mutations in the donor splice site in intron 9 of the WT1 gene. However, because of its rarity there is limited literature available on the precise spectrum and recommended treatment modalities of this syndrome. We present the clinicopathological findings in 4 patients: 3 phenotypically female adolescents presenting with proteinuria and primary amenorrhea and a 6-month-old baby girl presenting with nephrotic syndrome in whom this very unusual case of early onset was confirmed by molecular studies. The significance of early recognition of Frasier syndrome and its differentiation from Denys-Drash syndrome is reviewed and discussed. Our observation of a case presenting with early clinical manifestations, in contrast with the classical presentation in adolescence, justifies the expansion of the clinical spectrum of Frasier syndrome and contributes to the understanding and appropriate clinical management of these patients.
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PMID:Expanding the clinical spectrum of Frasier syndrome. 1737 74


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