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)

Primary renal tubulointerstitial disease resulting from proximal tubule antigen-specific antibodies and immune complex formation has not been well characterized in humans. We report a cohort of patients with a distinct, underappreciated kidney disease characterized by kidney antibrush border antibodies and renal failure (ABBA disease). We identified ten patients with ABBA disease who had a combination of proximal tubule damage, IgG-positive immune deposits in the tubular basement membrane, and circulating antibodies reactive with normal human kidney proximal tubular brush border. All but one of the patients also had segmental glomerular deposits on renal biopsy specimen. Patients with ABBA disease were elderly and presented with AKI and subnephrotic proteinuria. Serum from all patients but not controls recognized a high molecular weight protein in renal tubular protein extracts that we identified as LDL receptor-related protein 2 (LRP2), also known as megalin, by immunoprecipitation and mass spectrometry. Immunostaining revealed that LRP2 specifically colocalized with IgG in the tubular immune deposits on the ABBA biopsy specimen but not the control specimen analyzed. Finally, ABBA serum samples but not control samples showed reactivity against recombinantly expressed N-terminal LRP2 fragments on Western blots and immunoprecipitated the recombinantly expressed N-terminal region of LRP2. This case series details the clinicopathologic findings of patients with ABBA disease and shows that the antigenic target of these autoantibodies is LRP2. Future studies are needed to determine the disease prevalence, stimulus for ABBA, and optimal treatment.
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PMID:LDL Receptor-Related Protein 2 (Megalin) as a Target Antigen in Human Kidney Anti-Brush Border Antibody Disease. 2912 26

Renal diseases have been recognized as a major cause of secondary dyslipidemia since the late 1950's. Two main pathological conditions of renal diseases, impaired renal function and severe proteinuria (nephrotic syndrome), are individually or conjointly associated with altered lipid metabolism depending on the primary diseases. An impaired renal function causes reductions in lipoprotein and hepatic TG lipase activity, the VLDL recep- tor abundance, and ApoC-II to apoC-III ratio, as well as in ApoA-I and LCAT activities. These alterations result in reduced VLDL clearance and the disturbance of HDL synthesis and maturation, leading to uremic dyslipidemia: increased levels of TG, IDL-C, and small-dense LDL-C and decreased levels of HDL-C. Lipid disorders in nephrotic syndrome (NS) are characterized by increased levels of LDL-C and/or TG. NS-induced hypoalbuminemia enhances the synthesis of cholesterol, cholesterol ester, and ApoB, leading to the increased production of LDL and VLDL. Recently, two intriguing molecules were newly identified as inhibitors of lipoprotein clearance. Pro-protein Convertase Subtilisin/Kexin type 9 (PCSK9) is upregulated in NS, and decreases LDL clearance via prompting degradation of the LDL receptor, while angiopoietin-like 4 (Angptl4) is also induced in NS and restricts VLDL clearance via inhibiting lipoprotein lipase. NS impairs HDL maturation from HDL3 to HDL2 due to a reduction of LCAT, with HDL-C levels preserved. Finally, considering that diabetic nephropathy is representative of progressive renal disease and that gluco- corticoids are an anchor drug for the treatment of NS, diabetes- or drug-associated dyslipidemia is occasional- ly superimposed on the original renal dyslipidemia. [Review].
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PMID:[Renal Dyslipidemia]. 3069 62


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