Seminars in nephrology
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The discovery of aquaporin-1 (AQP1) by Agre and associates answered the longstanding biophysical question of how water specifically crosses biological membranes. In the kidney at least 7 aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. ⋯ Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting is seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy and SIADH both AQP2 expression levels and apical plasma membrane targetting is increased suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders.
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Pancreas transplantation is being performed with increasing frequency and increasing technical success. The availability of new immunosuppressant agents has been associated with a reduction in the previously high rates of allograft rejection in recipients of simultaneous pancreas-kidney transplants. These lower rejection rates have, in turn, led to changes in surgical techniques and a resurgence of interest in isolated pancreas transplantation--either in nonuremic patients or, more commonly, in patients who have already received a prior kidney transplant. Pancreas transplantation has emerged as an important option for the management of patients with type I diabetes mellitus and diabetic nephropathy.
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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.