A link between proximal and distal tubular injury and recovery
The studies in the IPRK and in vivo outlined in the previous section highlighted that both proximal straight tubules S3 and MTAL were potential targets for hypoxic injury. The anatomical proximity of these tubular segments emphasizes the location of both segments in a region under constant threat of hypoxia. Outer medullary hyperaemia is a consistent phenomenon following renal artery clamping to induce acute renal failure first described by Mason and others 158, 159 . It was hypothesized that...
Characterization of Th1 and Th2 cells
CD4 T-lymphocytes are heterogeneous in terms of production of cytokines, and have different functions 19, 20 . Th1 cells secrete IL-2, IFN-y and lym-photoxin which explains their role in activating macrophages and cytotoxic cells and therefore in cell-mediated immune responses. Th1 cells also help B-cells in the production of some isotypes IgG2a in mice and IgG2b in rats. Th2 cells produce IL-4, IL-5, IL-6, IL-10 and IL-13, promote IgE and IgG1 switch in rats and mice , and activate eosinophils...
Introduction
Pharmacology and clinical pharmacology define the desirable and undesirable effects of drugs and xenobiotics whereas pharmacokinetics defines the various processes that are involved in absorption - distribution - elimination of these agents. Needless to say that the former may strongly influence the latter. The kidney and the liver have complementary functions in the elimination of drugs and xenobiotics. Li-pophilic non-ionic substances of molecular weight higher than 300-500 dalton and highly...
Endocytosis
One of the mechanisms of active reabsorption is endocytosis. Fluid phase endocytosis consists of the incorporation of fluid and solutes in vesicles formed at the base of the brush border membrane of the proximal tubular cells Figure 1 . A more efficient absorptive endocytosis involves first binding of a drug, such as the cationic aminoglycoside and or may be cadmium 30, 31 , to a carrier phosphatidylinositol located in the luminal membrane of the wall of the pi-nocytotic vesicle occurs followed...
Glomerulopathies
Non-steroidal anti-inflammatory drugs are known to induce a nephrotic syndrome in addition to acute tubulointerstitial nephritis discussed in 43 . Glom-erulopathies include minimal change disease, focal glomerulosclerosis that could represent a continuum with the former entity and membranous glomerulo-pathy. A recent review of 97 patients with non-steroi-dal anti-inflammatory drugs-induced nephropathy reported the following incidence minimal change disease 39.2 , acute tubulointerstitial...
Advantages of the IPRK model
The IPRK is an intact model of the kidney function, which is well suited to examining critical functions, which require an intact renal architecture to mimic the in vivo situation. Such critical functions modified by the renal architecture encompass substrate delivery, including oxygen, and the links between vascular and tubular function. The model has the advantages of eliminating systemic hormonal and sympathetic nervous system influences, while still allowing tight control of pressure and...
Disadvantages of the IPRK model
In common with most isolated organs, the disadvantages of the IPRK include some physiological limitations. There are also the unique anatomical artifacts arising from cell-free perfusion and there is a requirement for significant technical surgical skill. While the cell-free IPRK model exhibits much higher flow than in vivo kidney, it now appears that this vasodilated state arises from relative nitric oxide excess rather than simply low perfusate viscosity. Defining this more clearly will...
Abnormal immune response due to activation of antigen presenting cells
The recognition of peptides MHC complexes at the cell surface of an antigen presenting cell by a specific T lymphocyte is not sufficient for triggering an immune response. Dendritic cells, that are the professional antigen presenting cells, need to be activated for initiating the immune response 1 . Signals delivered by pathogens through the toll receptors at the dendritic cell surface and signals generated in injured tissues activate dendritic cells. For example, platelets that con-stitutively...
Usa Ifa
Faculty of Health Sciences and Tygerberg Hospital University Hospital Ibn Rochd Intensive Care Unit H pital RHMS Baudour Service de N phrologie Rue Louis Caty 118 B-7331 Baudour Belgium Northwestern University Feinberg School of Medicine Department of Medicine Division of Nephrology 303 East Chicago Avenue Chicago, Illinois 60611-3008 USA University of the Witwatersrand Division of Nephrology Johannesburg Hospital 7 York Road Parktown Department of Occupational and Environmental H pital Erasme...
Mechanisms of drug induced acute renal failure
Because of the rich blood flow to the kidney 25 of the resting cardiac output , plus the enormous oxygen supply required to support active ion and solute transport, the kidneys are vulnerable to any change in blood flow and or oxygen deprivation. In particular, acute tubular necrosis involving the thick ascending limb TAL is a prominent manifestation of a sudden reduction in renal blood flow with accompanying hy-poxia. This anatomic site is especially vulnerable to oxygen deprivation due to the...
Reabsorption by simple diffusion
Passive reabsorption is driven by the progressive reabsorption of tubular fluid along the nephron. To penetrate the membranes of the tubular epithelium, whose main constituents are lipids, compounds should be liposoluble. As ionized compounds are in general hydrophilic, only the undissociated molecules of weak bases and acids will be rapidly reabsorbed by simple diffusion 15 . Consequently determinants for the rate of reabsorption are the pKa of the organic acid or base, the urinary pH, and the...
Role of Th1 and Th2 cells in the development of nephropathies
Th1 cells very probably play an important role in nephropathies associated with pauci immune deposits and with interstitial infiltrates of T-cells and macrophages 25 . Neutrophils and platelets are also found. The role of Th1 cells has been clearly demonstrated in experimental murine models of crescentic glomerulonephritis induced by immunization with glomerular basement membrane antigens or by immunization with heterologous sheep or goat immunoglo-bulin prior to injection of heterologous...
Effect of HgCl gold salts and Dpenicillamine in rats
Brown-Norway BN rats injected thrice a week with HgCl2 1 mg kg bw, sc HAUCI4 1 mg kg bw, sc aurothioropanolsulfonate sodium salt, the gold salt used in France for rheumatoid arthritis allochrysine , 20 mg kg bw, sc treatment, or D-penicillamine, develop an autoimmune disease while LEW rats are resistant. The disease is characterized by the production of numerous autoantibodies anti-laminin, a component of the glomerular basement membrane, anti-dsDNA, anti-thyroglobulin antibodies and an...
Jennings Paul
University of Innsbruck Institute of Physiology Fritz-Pregl Strasse 3 A-6020 Innsbruck Austria University Hospital Antwerp Department of Intensive Care Wilrijkstraat 10 B-2650 Edegem Antwerpen Belgium Chris Hani Baragwanath Hospital Department of Renal Medicine P.O. Box 92188 Norwood 2117 South Africa University of Arkansas for Medical Sciences Department of Medicine 4301 W. Markham Mail Slot 501 Little Rock, Arkansas 72205-7199 USA Kanazawa University Faculty of Medicine School of Health...
Usa Drq
Universidad Autonoma de Madrid Departemento de Biologia Cellular y Molecular L115 Medizinische Hochschule Hannover Department of Nephrology Carl-Neuberg-Strasse 1 D-30625 Hannover Germany Department of Drug Information and Communication Graduate School of Pharmaceutical Sciences H pital Erasme Universit Libre de Bruxelles Service de N phrologie 808 Route de Lennik B-1070 Bruxelles Belgium University Hospital of Antwerp Department of Nephrology Wilrijkstraat 10 B-2650 Edegem Antwerpen Belgium...
Chemicalinduced disregulation of the immune system
Chemicals may also cause an autoimmune kidney disease in the context of B- and or T-cell activation, independent of antigen-specific recognition. This will lead to B-cell polyclonal activation with production of autoantibodies since, normally, autoreactive B-cells exist but are not activated due to a lack of T-cell help. Autoreactive T-cells with a high affinity for auto-pep-tides are eliminated in the thymus or at the periphery while those with a low affinity for auto-peptides escape deletion...
References
1. Nolan CR, Anderson RJ. Hospital -acquired acute renal failure. JASN 1998 9 710-718. 2. Vijayan A, Miller SB. Acute renal failure prevention and non-dialytic therapy. Sem. Nephrol 1998 18 523-532. 3. Turney JH, Marshall DH, Brownjohn AM, Ellis CM and Parsons FM. The evolution of acute renal failure 1956-1988. Q J Med 1990 73 83-104. 4. Rasmussen HH, Ibels LS. Acute renal failure multi variant analysis of causes and risk factors. Am J Med 1982 73 211-218. 5. Hou SH, Bushunsky DA. Wish BB,...
Usa 1
Karolinska Institute amp Huddinge University Hospital University of Antwerp Department of Microbiology Universiteitsplein 1 B-2610 Wilrijk Antwerpen Belgium University of Queensland Princess Alexandra Hospital Brisbane, Queensland 4102 Australia University of Queensland Renal Research Centre Royal Brisbane Hospital Clinical Sciences Building Brisbane, Queensland 4029 Australia University of T bingen Medical Section III Section of Nephrology and Hypertension Ottfried-M ller-Str. 10 D-72076 T...