Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the mechanisms for a low fractional excretion of Na (FENa less than or equal to 1.0) in acute renal failure (ARF) of a sustained nature, causes were determined independent of FENa in 41 patients without volume depletion, obstruction, vasculitis or glomerulonephritis. The 16 patients (39%) with low FENa had lower incidence of preexisting azotemia, lower peak serum creatinine, but higher incidence of renal ischemia and earlier testing (by 1.7 days). Seven of ten such patients converted to high FENa on repeat, whereas FENa remained high in 15 of 17 patients with initially high values. The initial FENa was a direct function of time from the onset of ARF. Low FENa in acute but sustained renal failure is therefore best explained by milder insults; earlier determinations, and/or super-imposed renal ischemia.
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PMID:Low fractional excretion of sodium in acute renal failure: role of timing of the test and ischemia. 356 2

The elucidation of the pathogenesis of human renal disease at the molecular level has been facilitated by the growing field of gene targeting and the development of mouse strains with single-gene deletions - the 'knock-out' mice. Experimental nephrology, therefore, requires well-characterized and reliable models of human renal disease that can be induced reproducibly in mice. Today surgical procedures for the induction of renal ischemia, chronic renal failure, and ureter obstruction are feasible in mice. Models of mesangioproliferative or crescentic glomerulonephritis, glomerulosclerosis, and tubulointerstitial disease are readily available; however, these depend heavily on the mouse genetic background. Attention to the genetic background and appropriate backcrossing are, therefore, of great importance in the design and interpretation of experimental studies, especially in transgenic mice. Simple murine models displaying the clinical features of other human renal diseases such as IgA nephropathy, membranous glomerulonephritis, and renal vasculitis are still lacking. Mouse strains that spontaneously develop distinct renal pathologies similar to lupus nephritis and focal-segmental glomerulosclerosis can be intercrossed with transgenic mice to study the impact of single-gene deletions on the renal phenotype. The present review provides a survey about currently available spontaneous and inducible murine models of renal disease with special attention to problems and future perspectives for their use in transgenic animals.
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PMID:Murine models of renal disease: possibilities and problems in studies using mutant mice. 1094 Jul 15

Snakebites have the highest incidence in Asia and represent an important health problem. Clinical renal manifestations include proteinuria, hematuria, pigmenturia, and renal failure. Nephropathy usually is caused by bites by snakes with hemotoxic or myotoxic venoms. These snakes are Russell's viper, saw-scaled viper, hump-nosed pit viper, green pit viper, and sea-snake. Renal pathologic changes include tubular necrosis, cortical necrosis, interstitial nephritis, glomerulonephritis, and vasculitis. Hemodynamic alterations caused by vasoactive mediators and cytokines and direct nephrotoxicity account significantly for the development of nephropathy. Hemorrhage, hypotension, disseminated intravascular coagulation, intravascular hemolysis, and rhabdomyolysis enhance renal ischemia leading to renal failure. Enzymatic activities of snake venoms account for direct nephrotoxicity. Immunologic mechanism plays a minor role.
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PMID:Snakebite nephrotoxicity in Asia. 1862 Sep 59

The complement cascade, traditionally considered an effector arm of innate immunity required for host defense against pathogens, is now recognized as a crucial pathogenic mediator of various kidney diseases. Complement components produced by the liver and circulating in the plasma undergo activation through the classical and/or mannose-binding lectin pathways to mediate anti-HLA antibody-initiated kidney transplant rejection and autoantibody-initiated GN, the latter including membranous glomerulopathy, antiglomerular basement membrane disease, and lupus nephritis. Inherited and/or acquired abnormalities of complement regulators, which requisitely limit restraint on alternative pathway complement activation, contribute to the pathogenesis of the C3 nephropathies and atypical hemolytic uremic syndrome. Increasing evidence links complement produced by endothelial cells and/or tubular cells to the pathogenesis of kidney ischemia-reperfusion injury and progressive kidney fibrosis. Data emerging since the mid-2000s additionally show that immune cells, including T cells and antigen-presenting cells, produce alternative pathway complement components during cognate interactions. The subsequent local complement activation yields production of the anaphylatoxins C3a and C5a, which bind to their respective receptors (C3aR and C5aR) on both partners to augment effector T-cell proliferation and survival, while simultaneously inhibiting regulatory T-cell induction and function. This immune cell-derived complement enhances pathogenic alloreactive T-cell immunity that results in transplant rejection and likely contributes to the pathogenesis of other T cell-mediated kidney diseases. C5a/C5aR ligations on neutrophils have additionally been shown to contribute to vascular inflammation in models of ANCA-mediated renal vasculitis. New translational immunology efforts along with the development of pharmacologic agents that block human complement components and receptors now permit testing of the intriguing concept that targeting complement in patients with an assortment of kidney diseases has the potential to abrogate disease progression and improve patient health.
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PMID:Molecules Great and Small: The Complement System. 2556 20

Acute kidney injury (AKI) and chronic kidney disease (CKD) are associated with decreased renal function and increased mortality risk, while the therapeutic armamentarium is unsatisfactory. The availability of adequate animal models may speed up the discovery of biomarkers for disease staging and therapy individualization as well as design and testing of novel therapeutic strategies. Some longstanding animal models have failed to result in therapeutic advances in the clinical setting, such as kidney ischemia-reperfusion injury and diabetic nephropathy models. In this regard, most models for diabetic nephropathy are unsatisfactory in that they do not evolve to renal failure. Satisfactory models for additional nephropathies are needed. These include anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, IgA nephropathy, anti-phospholipase-A2-receptor (PLA2R) membranous nephropathy and Fabry nephropathy. However, recent novel models hold promise for clinical translation. Thus, the AKI to CKD translation has been modeled, in some cases with toxins of interest for human CKD such as aristolochic acid. Genetically modified mice provide models for Alport syndrome evolving to renal failure that have resulted in clinical recommendations, polycystic kidney disease models that have provided clues for the development of tolvaptan, that was recently approved for the human disease in Japan; and animal models also contributed to target C5 with eculizumab in hemolytic uremic syndrome. Some ongoing trials explore novel concepts derived from models, such TWEAK targeting as tissue protection for lupus nephritis. We now review animal models reproducing diverse, genetic and acquired, causes of AKI and CKD evolving to kidney failure and discuss the contribution to clinical translation and prospects for the future.
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PMID:Translational value of animal models of kidney failure. 2581 48

A wide spectrum of renal complications can occur with acute and chronic use of cocaine. Most cases are related to rhabdomyolysis, but other mechanisms are malignant hypertension, renal ischemia, and rapidly progressive glomerulonephritis (RPGN) associated-ANCA vasculitis. In recent years, the use of cocaine adulterated with levamisole has been associated with ANCA vasculitis and pauci-immune RPGN. RPGN is clinically manifested as a nephritic syndrome with a rapid and progressive decline in renal function, and its histopathological finding is the presence of crescents in more than 50% of the glomeruli. We report a case of a 38-year-old man chronic user of cocaine, alcohol, and cigarettes who had red urine, oliguria, swollen legs and eyelids, as well as the uremic symptoms anorexia, emesis, and mental confusion. He was admitted with acute kidney injury and performed six hemodialysis sessions during the first 16 days of hospitalization and then was transferred to a tertiary hospital for diagnostic investigation. Tests of ANF (antinuclear factor), ANCA, anti-DNA, serology for hepatitis B, C, and HIV virus were negative. A renal percutaneous biopsy revealed crescentic glomerulonephritis with mild tubular atrophy. The patient underwent pulse therapy with methylprednisolone (for 3 days) and cyclophosphamide. Then he maintained daily prednisone and monthly intravenous cyclophosphamide and evolved with progressive improvement of renal function.
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PMID:Rapidly progressive glomerulonephritis and acute kidney injury associated with cocaine use - Case report. 3257 47