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)

Serial changes in glomerular capillary loop gene expression were used to uncover mechanisms contributing to primary glomerular disease in rat models of passive Heymann nephritis and puromycin nephrosis. Before the onset of proteinuria, podocyte protein-tyrosine phosphatase (GLEPP1) expression was transiently decreased in the nephrosis model, whereas the immune costimulatory molecule B7.1 was stimulated in both models. To relate these changes to the development of proteinuria, the time of onset and intensity of proteinuria were altered. When the models were induced simultaneously, proteinuria and anasarca occurred earlier with the collapse of glomerular capillary loops. Upregulation of B7.1 with the downregulation of GLEPP1, Wilms' tumor gene (WT1), megalin, and vascular endothelial growth factor started early and persisted through the course of disease. In the puromycin and the combined models, changes in GLEPP1 expression were corticosteroid-sensitive, whereas B7.1, WT1, vascular endothelial growth factor, and most slit diaphragm genes involved later in the combined model, except podocin, were corticosteroid-resistant. There was a very early increase in the nuclear expression of podocyte transcription factors ZHX2 and ZHX1 that may be linked to the changes in gene expression in the combined proteinuric model. Our studies suggest that an early and persistent change in mostly steroid-resistant glomerular gene expression is the hallmark of severe and progressive glomerular disease.
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PMID:Early changes in gene expression that influence the course of primary glomerular disease. 1745 73

Vascular endothelial growth factor (VEGF) is an important mediator in maintaining normal kidney functions. In addition, several lines of evidence suggest that upregulation of VEGF in glomeruli may be associated with or cause renal dysfunction such as diabetic nephropathy. For elucidation of the pathologic consequences of high levels of VEGF in glomeruli, transgenic (Tg) rabbits that express human VEGF(165) isoform in both kidney and liver under the control of the human alpha-1-antitrypsin promoter were generated and characterized. With the use of heterozygous Tg rabbits and their littermates aged 8 to 55 wk, renal functions and structures were investigated. Compared with control rabbits, Tg rabbits exhibited progressive proteinuria with increased GFR at the early stage and decreased GFR at the later stage. Histologic examinations revealed that Tg rabbit kidneys were characterized by considerable glomerular hypertrophy as a result of increased proliferation of both glomerular capillaries and mesangial cells accompanied by prominent podocyte hypertrophy. With increasing age starting from 20 wk, Tg rabbit kidneys showed prominent formation of microaneurysms and capillary proliferation at the vascular pole area. At a later stage (55 wk), many glomeruli showed sclerosis and tuft collapse with the formation of glomerular cysts on a background of tubular atrophy and interstitial fibrosis. This study provides the first evidence that increased expression of VEGF in glomeruli directly causes the glomerular hypertrophy that is associated with proteinuria, suggesting that VEGF exerts multiple effects on the glomerular pathophysiologic processes.
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PMID:Increased expression of vascular endothelial growth factor in kidney leads to progressive impairment of glomerular functions. 1755 51

Two women with Eisenmenger syndrome, aged 63 and 45 years, presented with different symptoms: the first patient had peripheral oedema, proteinuria, progressive fatigue and cyanosis and the other had increasing dyspnoea and blue lips. The first patient was successfully treated with diuretics but experienced a collum fracture that occurred after hypovolemic collapse caused by diuretic use. She was given sildenafil and underwent hip surgery with spinal anaesthesia 10 days later. In the following weeks, the patient was haemodynamically stable but then died suddenly; no autopsy was performed. The second patient was given oxygen therapy at home and bosentan. After 6 months the symptoms of dyspnoea resolved and her 6-minute walking distance increased from 453 to 512 m. The life expectancy of patients with congenital heart disorders such as Eisenmenger syndrome has improved dramatically, due in part to the efficacy of novel agents that inhibit endothelial-cell proliferation. With these advances, treatment of these patients is no longer restricted to tertiary-care centres. Therefore, community cardiologists, pulmonologists and internists should be aware of these congenital heart disorders and the available treatment options.
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PMID:[Two patients with Eisenmenger syndrome treated with novel agents that target vasodilation of the pulmonary capillary bed]. 1823 58

In order to determine the pattern of renal disease and risk factors for renal disease in HIV-infected Nigerians, we studied 400 consecutive HIV/AIDS patients (210 males, 190 females) aged between 18 and 65 years (mean +/- SD; 34.6 +/- 9.4 years), and examined renal disease factors attributable to the infection. Diagnosis of renal disease was based on the consistent presence of at least 1+ albuminuria and/or elevated serum creatinine (>132 micromol/l) as well as the absence of other identifiable causes of chronic kidney disease (CKD). We determined socio-demography and clinical findings, as well as full laboratory work-ups including haemogram, CD4+ cell count, serum electrolytes, urea, creatinine, protein, cholesterol and urine analysis. Renal biopsies were taken in 10 patients who had moderate to massive proteinuria and had consented to the procedure. Finally, we compared HIV/AIDS cases with and without renal disease to determine the risk factors for nephropathy. We observed a high prevalence of renal disease (proteinuria and/or elevated serum creatinine), which was present in 152 (38%) of the patients. This subgroup included 74 males and 78 females with a M:F ratio of 1:1. The mean age (+/-SD) was 35.8 (+/-10.01) years. Systolic and/or diastolic hypertension was seen in 13.2% of these patients while the mean (+/- SD) body mass index (BMI) and packed cell volume (PCV) were 18.5 (+/-3.1) kg/m(2) and 25.26 (+/-6.81)%, respectively. The mean (+/-SD) CD4+ count was 246.49 (+/-192.8) cells/microl, while the mean (+/-SD) serum creatinine and 24-h urine protein excretion rates were 210.11 (+/-337.8) micromol/l and 2.57 (+/- 2.42) g/day, respectively. In subjects with and without nephropathy, there were significant differences in age, BMI, serum cholesterol, serum albumin and CD4+ counts, suggesting that these parameters may be risk factors for nephropathy. Histology revealed mainly focal glomerulosclerosis (FGS) with glomerular collapse. We conclude that the prevalence of proteinuria in HIV-seropositive patients is high in Nigeria. Such subjects show an equal male:female distribution, and glomerular histology revealed that a majority of biopsied patients had the collapsing FSGS variant. The risk factors for renal disease included severity of the HIV infection (inferred from the generally low CD4+ count), anaemia, malnutrition and increasing age.
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PMID:Renal disease in HIV-seropositive patients in Nigeria: an assessment of prevalence, clinical features and risk factors. 1806 7

Collapsing glomerulopathy (CG) represents a morphologic pattern of disease, characterized histologically by glomerular capillary collapse, severe podocyte injury, and glomerular epithelial cell proliferation, and clinically by marked proteinuria and renal insufficiency. CG has multiple etiologies; however, many questions remain about its pathogenesis. A new set of animal models of CG, characterized by absence of the normal podocyte cytoskeletal protein alpha-actinin-4, has potential to help us gain a greater understanding of cellular events involved in producing this pattern of disease.
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PMID:Collapsing glomerulopathy: many means to a similar end. 1830 47

HIV-associated nephropathy (HIVAN) is the most well-known and aggressive kidney disease in HIV-1-infected patients. A variant of focal segmental glomerulosclerosis, it is characterized by the collapse of the glomerular tuft with podocyte hypertrophy/hyperplasia and foot process effacement, often with concurrent tubular microcystic dilation and tubulointerstitial nephritis. The disease has been intimately linked to the direct effect of HIV-1 on the kidney. It affects patients of African descent exclusively and is manifested by an acute decline in kidney function, most often in conjunction with high-grade proteinuria and uncontrolled HIV-1 infection. With the widespread use of highly active antiretroviral therapy (HAART), its prevalence is declining in Western countries. However, the epidemiology of the disease is not well defined in the poorest areas of the world, which bear a disproportionate share of the HIV-1 epidemic burden. Scientific evidence suggests that HAART can prevent the development of HIVAN. Furthermore, HAART, corticosteroids and inhibition of the renin-angiotensin axis are potentially helpful in delaying disease progression, as well as the need for renal replacement therapy.
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PMID:HIV-associated nephropathy: epidemiology, pathogenesis, diagnosis and management. 1858

Collapsing glomerulopathy (CG), characterized histologically by segmental/global glomerular capillary collapse, podocyte hypertrophy and hypercellularity and tubulo-interstitial injury; is characterized clinically by massive proteinuria and rapid progressive renal failure. CG is known to recur in renal allograft and rarely de novo. We report de novo CG 3 years post-transplant in a patient who received renal allograft from haplo-identical type donor.
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PMID:De novo collapsing glomerulopathy in a renal allograft recipient. 1871 Dec 98

We present a case report of a 59-year-old man with a history of arterial hypertension and excision of malignant melanoma. He was admitted to the hospital because of two months history of diarrhoea, weight loss and circulatory collapse. In addition, the patient suffered from marked vegetative instability with symptomatic hypotension, polyneuropathy and progression of renal insufficiency, without proteinuria. Complex examination did not reveal neoplasms, endocrine, autoimmune, infectious or neurodegenerative disorders. A serial biopsy of colon failed to provide a clue to the diagnosis. However, AA amyloidosis was found on the kidney biopsy. Neither chronic inflammation nor malignancy was revealed and, hence, no causal treatment could have been established. The patient died from multiple organ failure. The autopsy confirmed systemic AA amyloidosis. The triad consisting ofdiarrhoea, polyneuropathy and hypotension should rise the suspicion on amyloidosis.
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PMID:[Persistent diarrhoea, hypotension, polyneuropathy]. 1906 86

A case of an adolescent male with renal-coloboma syndrome (RCS) showing developmental delay is described. Birth and perinatal histories were typical. Proteinuria was initially observed at the age of 7 years during an annual mass screening program for school children. His urine was checked periodically at a local hospital. Because of an increase in proteinuria, he was referred to our hospital for further clinical evaluation. Proteinuria was moderate, ranging from 1.0 to 1.5 g/day, and was coupled with mild renal dysfunction. At that time, he was found to have myopia associated with astigmatism. He exhibited mild developmental delay, assessed by a WISC-III test. A renal biopsy sample showed marked glomerular enlargement, collapse of glomerular capillaries, mesangial matrix expansion, and tubulointerstitial change, demonstrating typical histologic features of RCS. Approximately five years after starting follow-up, the patient had severe renal dysfunction. Furthermore, optic nerve coloboma was also evident. Genetic analysis of the patient revealed a novel heterozygous mutation in exon 3 of the PAX2 gene (P130H).
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PMID:A case of renal-coloboma syndrome associated with mental developmental delay exhibiting a novel PAX2 gene mutation. 1995 29

Membranous nephropathy is a disease that affects the filtering units of the kidney, the glomeruli, and results in proteinuria accompanied by loss of kidney function. Passive Heymann nephritis is an experimental model that mimics membranous nephropathy in humans, wherein the glomerular epithelial cell (GEC) injury induced by complement C5b-9 leads to proteinuria. We examined the role of cytochrome P450 2B1 (CYP2B1) in this complement-mediated sublytic injury. Overexpression of CYP2B1 in GECs significantly increased the formation of reactive oxygen species, cytotoxicity, and collapse of the actin cytoskeleton following treatment with anti-tubular brush-border antiserum (anti-Fx1A). In contrast, silencing of CYP2B1 markedly attenuated anti-Fx1A-induced reactive oxygen species generation and cytotoxicity with preservation of the actin cytoskeleton. Gelsolin, which maintains an organized actin cytoskeleton, was significantly decreased by complement C5b-9-mediated injury but was preserved in CYP2B1-silenced cells. In rats injected with anti-Fx1A, the cytochrome P450 inhibitor cimetidine blocked an increase in catalytic iron and ROS generation, reduced the formation of malondialdehyde adducts, maintained a normal distribution of nephrin in the glomeruli, and provided significant protection at the onset of proteinuria. Thus, GEC CYP2B1 contributes to complement C5b-9-mediated injury and plays an important role in the pathogenesis of passive Heymann nephritis.
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PMID:Cytochrome P450 2B1 mediates complement-dependent sublytic injury in a model of membranous nephropathy. 2094 6


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