Endothelin in hypertension and proatherogenic states

The role of renal endothelin receptors in diseases associated with hypertension appears to be critical. Hirata and colleagues 184 utilized the IPRK to demonstrate that ETB receptor stimulation induced release of nitric oxide. They found that ET-1 and ET-3 released nitric oxide via ETB receptors in renal vessels. ETB receptors were downregulated in deoxycorticosterone acetate (DOCA-salt) rat kidneys explaining why ETB-mediated NO release was reduced in DOCA-salt rats, an event which may modulate...

Coexisting chronic diseases

Conventional wisdom dictates that pre-existing renal insufficiency is a well-established significant risk factor in the ARF of contrast-associated nephropathy 101 . However, a study by Levy et al. 102 questions this wisdom. These authors performed a cohort analytical study involving over 16,000 patients undergoing radiocontrast procedures. One hundred and seventy-four patients diagnosed with contrast-associated nephropathy were paired to a like number of nephr-opathy-free patients matched for...

Mechanisms by which xenobiotics may induce an immune response

As summarized in Table 1, xenobiotics may induce an immune reaction by at least four mechanisms 1 by inducing an abnormal immune response due to activation of antigen presenting cells, 2 by promoting an immune response directed against an autoantigen modified by the toxin or its metabolite, 3 by activating a limited set of autoreactive T cells and 4 by inducing global immune disregulation. M.E. De Broe, G.A. Porter, W.M. Bennett amp G.A. Verpooten Editors . Clinical Nephrotoxins, 2nd Ed., 51-64...

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...

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...

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...

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

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,...