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)

Severity of urinary tract morbidity increases with intensity and duration of Schistosoma haematobium infection. We assessed the ability of yearly drug therapy to control infection intensity and reduce S. haematobium-associated disease in children 5-21 years old in an endemic area of Kenya. In year 1, therapy resulted in reduced prevalence (66% to 22%, P < 0.001) and intensity of S. haematobium infection (20 to 2 eggs/10 mL urine), with corresponding reductions in the prevalence of hematuria (52% to 19%, P < 0.001). There was not, however, a significant first-year effect on prevalence of urinary tract abnormalities detected by ultrasound. Repeat therapy in years 2 and 3 resulted in significant regression of hydronephrosis and bladder abnormalities (41% to 6% prevalence, P < 0.01), and further reductions in proteinuria. Repeat age-targeted therapy was associated with decreased prevalence of infection among young children (< 5 yr) entering into the targeted age group. Two years after discontinuation of therapy, intensity of S. haematobium infection and ultrasound abnormalities remained suppressed, but hematuria prevalence began to increase (to 33% in 1989). Reinstitution of annual therapy in 1989 and 1990 reversed this trend. We conclude that annual oral therapy provides an effective strategy for control of morbidity due to S. haematobium on a population basis, both through regression of disease in treated individuals, and prevention of infection in untreated subjects.
Mem Inst Oswaldo Cruz 1992
PMID:Age-targeted chemotherapy for control of urinary schistosomiasis in endemic populations. 134 96

Dent's disease, a renal tubular disorder characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, and nephrolithiasis, is due to inactivating mutations in the x-linked renal specific chloride channel CLC-5. CLC-5 belongs to the family of voltage-gated chloride channels, which function as homodimeric proteins with each subunit consisting of 18 helices and a chloride selectivity filter, i.e. pore. None of the 15 CLC-5 missense mutations reported in patients with dent's disease involves the chloride selectivity filter, but 12 of these are clustered around the interface of the two subunits, thereby emphasising the important role for the interaction between the two subunits at the interface of the homodimeric CLC-5. In the kidney, CLC-5 forms part of the receptor-mediated endocytic pathway, and defects in this pathway due to a loss of CLC-5 function, may help to account for the LMWP, hyperphosphaturia, hypercalciuria and nephrolithiasis. The molecular studies and the generation of mouse models of the disease have increased our understanding of the renal tubular mechanisms that regulate mineral homeostasis.
Bull Mem Acad R Med Belg 2004
PMID:Dent's disease--a nephrolithiasis disorder associated with defective receptor-mediated endocytosis. 1561 94

Dent's disease is an hereditary renal tubular disorder characterized by low-molecular-weight (LMW) proteinuria, hypercalciuria and nephrolithiasis. The disease is due to mutations of CLC-5, a member of the family of voltage-gated CLC chloride channels. CLC-5 is distributed in cells lining the proximal tubule (PT) of the kidney, where it co-localizes with albumin-containing endocytic vesicles that form part of the receptor-mediated endocytic pathway that mediates the reabsorption of low-molecular-weight (LMW) proteins filtered at the glomerular level. Since progression along the endocytic apparatus requires endosomal acidification, it has been suggested that dysfunction of CLC-5 in endosomes may lead to inefficient reabsorption of LMW proteins and dysfunction of PT cells. Investigations conducted in a CLC-5 knockout (KO) mouse model harbouring all the characteristic renal tubular defects of Dent's disease showed a severe impairment of endocytosis by PT cells, such that the endocytic tracer peroxidase was poorly transferred into early endocytic vesicles. These data demonstrated that an impairment of receptor-mediated endocytosis in PT cells is the basis for the defective uptake of LMW proteins in patients with Dent's disease. The endocytosis and processing of LMW proteins involves the multiligand tandem receptors, megalin and cubilin, that are abundantly expressed at the brush border of PT cells. The characterization of the endocytic defect in CLC-5 KO mice revealed that ligands of both megalin and cubilin were affected, whereas a decrease in total kidney content of megalin and cubilin at the protein level was detected. Using analytical subcellular fractionation and quantitative immunogold labelling, we demonstrated a selective disappearance of megalin and cubilin at the brush border of PT cells. These observations allowed us to conclude that defective protein endocytosis linked to CLC-5 inactivation is due to a major and selective loss of megalin and cubilin at the brush border, reflecting a trafficking defect in renal PT cells. These results improve our understanding of Dent's disease, taken as a paradigm for renal Fanconi syndrome and nephrolithiasis, and demonstrate multiple roles for CLC-5 in the kidney. These studies also provided insights in important functions such as apical endocytosis, handling of proteins by renal tubular cells, calcium metabolism, and urinary acidification.
Bull Mem Acad R Med Belg 2004
PMID:Chloride channels and endocytosis: new insights from Dent's disease and CLC-5 knockout mice. 1561 95

Endocytosis is a distinctive property of all eukaryotic cells. Polarized cells face two different worlds by membranes of distinct composition: the basolateral membrane is exposed to the constant internal medium, whereas the apical membrane is exposed to variable environments. Endocytosis on both aspects also depends on different machineries. This short review illustrates the molecular basis and physiopathological implications of apical endocytosis. In a cultured epithelial cell line, Src selectively triggers apical macropinocytosis by activating the actin cytocortex via signalling membrane lipids generated by an amplification cascade involving phosphoinositide 3-kinase, phospholipase C and phospholipase D. Several actors of Src response are also activated by enteroinvasive bacteria, to trigger their entry into enterocytes. In the thyroid gland, the rates of thyroglobulin apical micropinocytosis and transfer to lysosomes determine the level of thyroid hormone production, by controlling the encounter of the prohormone with converting hydrolases. TSH selectively promotes the encounter, by inducing the expression of rate-limiting catalysts, the small GTPases Rab5 and Rab7, and of their exchange factor(s). This induction is constitutive in autonomous adenomas. In kidney proximal tubular cells, apical receptor-mediated endocytosis ensures full recapture of ultrafiltrated proteins. Inactivating mutations of the endosomal chloride channel, ClC-5, that are responsible for Dent's disease, cause a loss of surface receptors leading to proteinuria. These examples illustrate how three levels of regulation of apical endocytosis, namely the mode of entry, the rate of vesicular trafficking and the subcellular addressing account for a variety of human diseases.
Bull Mem Acad R Med Belg 2005
PMID:[Apical endocytosis: molecular controls and physiopathologic implications]. 1639 73

Membranous nephropathy (MN) is one of the most common glomerulopathies. Current treatments are entirely empirical, and concept-driven therapies are dramatically lacking. In the rat experimental model established by Heymann in 1959, the target antigen is expressed at the surface of podocytes where immune complexes are formed, inducing complement activation results in heavy proteinuria. However, megalin is not detected on human podocytes and in immune deposits in patients with MN. We recently identified neutral endopeptidase (NEP), a podocyte antigen that can digest biologically active peptides, as the target antigen of antibodies deposited in the subepithelial space of glomeruli in a subset of patients with antenatal MN. The mothers became immunized because they are deficient in NEP due to truncating mutations in the gene. MN could be transferred to the rabbit by injection of mothers' Ig. We discuss new pathophysiological aspects of the disease with special emphasis on allo-immunization, novel potential antigenic targets, and therapeutic prospects.
Bull Mem Acad R Med Belg 2008
PMID:[Extra-membranous glomerulonephritis: from the experimental model to the human pathology of new-born and adult]. 1902 6

In Nigeria, schistosomiasis, caused predominantly by the species Schistosoma haematobium, is highly endemic in resource-poor communities. We performed a school-based survey in two rural communities in Osun State (Southwestern Nigeria) and assessed macrohaematuria, microhaematuria and proteinuria as indirect indicators for the presence of disease. Urine samples were inspected macroscopically for haematuria and screened for microhaematuria and proteinuria using urine reagent strips. The microscopic examination of schistosome eggs was used as the gold standard for diagnosis. In total, 447 schoolchildren were included in this study and had a 51% prevalence of urinary schistosomiasis. The sensitivity of microhaematuria (68%) and proteinuria (53%) for infection with S. haematobium was relatively low. In patients with a heavy infection (>or= 500 eggs/10 mL), the sensitivity of microhaematuria was high (95%). When the presence of macrohaematuria and the concomitant presence of microhaematuria and proteinuria were combined, it revealed a sensitivity of 63%, a specificity of 93% and a positive predictive value of 91%. Macrohaematuria also showed high specificity (96%) and a positive predictive value of 92%, while sensitivity was < 50%. These data show that combining urine reagent strip tests (presence of proteinuria and microhaematuria) and information on macrohaematuria increased the accuracy of the rapid diagnosis of urinary schistosomiasis in an endemic rural West African setting. This simple approach can be used to increase the quality of monitoring of schistosomiasis in schoolchildren.
Mem Inst Oswaldo Cruz 2009 May
PMID:A simple approach improving the performance of urine reagent strips for rapid diagnosis of urinary schistosomiasis in Nigerian schoolchildren. 1954 72