Seminars in nephrology
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Seminars in nephrology · Jan 2000
ReviewTransplantation for the millennium: attaining tolerance in our time--the Holy Grail.
Despite tremendous advances in organ transplantation over the past 40 years, life-long immunosuppression is still required to maintain the transplanted organ. The induction of human tolerance to defined foreign antigens while maintaining completely intact all the rest of the immune repertoire, in the absence of maintenance immunosuppression, continues to be the dream of the transplant scientist and clinician, the "Holy Grail," the quest which energizes much recent research. This article presents an overview on recent developments on transplantation tolerance.
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Studies performed over the last 10 years have evaluated the role of nitric oxide (NO) in the control of renal hemodynamics. This article reviews the effects of administration of nitric oxide synthase (NOS) blockers on renal function in experimental animals and human volunteers. ⋯ These experimental studies also support the presence of an important interaction between NO, angiotensin II, and renal nerves in the control of renal function. The use of acute and chronic administration of NOS blockers has generated a great deal of new and exciting information regarding the role of NO in the regulation of normal renal function.
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Seminars in nephrology · Jan 1999
ReviewThe role of apoptosis in autoimmunity: immunogen, antigen, and accelerant.
The immunologic basis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE) is complex and multifaceted. Recent advances in the field of apoptosis have suggested new paradigms for the development of autoimmunity. ⋯ In addition, we will describe some of the features that distinguish nonpathogenic anti-DNA autoantibodies from those which deposit in the kidney and lead to lupus nephritis. Finally, we will attempt to synthesize the vast body of data connecting apoptosis and SLE into a single hypothesis in which we suggest that apoptotic cells are a primary source of immunogen, and that abnormalities in the handling of apoptotic cells can lead to a breakdown in self-tolerance.
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Extensive skeletal muscle injury, whether caused by mechanical crush or by extreme physical exertion, is incompatible with life, unless treated early and vigorously. The immediate cause of morbidity is leakiness of the sarcolemmal membrane to cardiotoxic or nephrotoxic cations and metabolites (K, PO4, myoglobin and urate) of the sarcoplasma, and rapid massive uptake by the muscles of extracellular fluid, sodium and calcium, leading to profound hypovolemic and hyocalcemic shock. Casualties who survive the early steep of hyperkalemia and arterial hypotension are susceptible to myoglubinuric acute renal failure owing mainly to the combination of renal vasoconstriction, nephrotoxicity, and tubular obstruction by myoglobin plugs and urate. ⋯ The alkali regimen ameliorates the acidosis associated with shock and the hyperkalemia, and protects against the nephrotoxicity of myoglobin and urate by alkalinization of the urine. Mannitol, through its impermeant hyperoncotic properties, decompresses and mobilizes muscle edema and promotes renal tubular flow, thus flushing myoglobin plugs and enhancing urinary elimination of nephrotoxic metabolites. With this regimen and when necessary also with the use of dialysis, a substantial salvage of lives, limbs, and kidney function has been achieved recently compared with invariable mortality for casualties who were buried for 3 to 4 hours or more in the early 1940s (World War 2).
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Electrolyte abnormalities, hypertension and acute renal failure commonly occur in children admitted to the intensive care unit. Perturbations in sodium, potassium, and calcium or hypertensive crisis require prompt therapy to avoid major cardiac or neurological events. Hemodialysis, peritoneal dialysis, or hemofiltration can effectively and safely be performed, even in small and hemodynamically unstable children. Although suitable equipment is available for all renal replacement options, attention to precise details such as fluid administration and flow rates are essential.