Journal of the American Society of Nephrology : JASN
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J. Am. Soc. Nephrol. · Jan 2002
Randomized Controlled Trial Multicenter Study Clinical TrialContinuous dialysis with bicarbonate/lactate-buffered peritoneal dialysis fluids results in a long-term improvement in ex vivo peritoneal macrophage function.
To circumvent the potentially negative consequences of long-term exposure to unphysiologic acidic lactate-buffered peritoneal dialysis fluids (PDF), neutral pH solutions buffered with bicarbonate/lactate have recently been introduced in phase 2 and 3 clinical trials. This study examines the longitudinal changes in peritoneal macrophage (PMØ) function in patients dialyzed continuously with either lactate (LPD; 40 mM lactate, pH 5.2)-buffered or bicarbonate/lactate (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3)-buffered PDF. Before the study, during the run in period of a phase 3 clinical trial, all patients had been taking LPD for at least the previous 18 wk. ⋯ At 6 mo, STZ-stimulated PMØ TNF-alpha synthesis was significantly higher in patients treated with TBL compared with those treated with LPD (P = 0.0035). These data suggest that in patients continuously dialyzed with a neutral pH solution, there is a long-term improvement in PMØ function compared with patients on conventional therapy. Better PMØ function suggests improved host defense status and may affect the peritoneum's susceptibility to infection and potentially reduce the negative consequences of repeated intraperitoneal inflammation on long-term membrane function.
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J. Am. Soc. Nephrol. · Jan 2002
An epidemiologic study of early renal replacement therapy after orthotopic liver transplantation.
The preoperative impairment of renal function is associated with the need for postoperative renal replacement therapy (RRT) in patients undergoing liver transplantation. The principal goal of this investigation was to identify other factors apparent before or during transplant that were independently associated with the need for RRT in the early posttransplant period. A total of 260 consecutive adult patients who received a primary liver transplant were studied. ⋯ Patients requiring early RRT consumed more healthcare resources than patients who did not require early RRT, spending more time in intensive care (15 +/- 13 d versus 7 +/- 11 d; P < 0.001) and in the hospital (34 +/- 27 d versus 19 +/- 20 d; P < 0.001). The need for early RRT was strongly associated with death before hospital discharge (29% mortality versus 4% mortality among all others; P < 0.001). The data demonstrate that dependency on RRT in the first week after orthotopic liver transplantation stems almost entirely from preoperative renal dysfunction.
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J. Am. Soc. Nephrol. · Nov 2001
Hydration status affects nuclear distribution of transcription factor tonicity responsive enhancer binding protein in rat kidney.
Tonicity responsive enhancer binding protein (TonEBP) is the transcription factor that regulates tonicity responsive expression of proteins that catalyze cellular accumulation of compatible osmolytes. In cultured MDCK cells, hypertonicity stimulates the activity of TonEBP via a combination of increased protein abundance and increased nuclear localization. For investigating regulation of TonEBP in the kidney, rats were subjected to water loading or dehydration. ⋯ Notable exceptions were the middle to terminal portions of the inner medullary collecting ducts and blood vessels, where a change in TonEBP distribution was not evident. Immunohistochemical detection of SMIT mRNA revealed that the changes in nuclear distribution of TonEBP correlate with expression of SMIT. It is concluded that under physiologic conditions, nucleocytoplasmic distribution is the dominant mode of regulation of TonEBP in the renal medulla.
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J. Am. Soc. Nephrol. · May 2001
Effects of albumin/furosemide mixtures on responses to furosemide in hypoalbuminemic patients.
Hypoalbuminemic patients often have sufficient fluid accumulation to mandate diuretic therapy but are often resistant to diuresis. Studies have suggested that hypoalbuminemia itself impairs delivery of effective amounts of diuretic agent into the urine, the site of action. Therefore, administration of mixtures of albumin and loop diuretics may enhance responses. ⋯ Moreover, the relationship between the urinary furosemide excretion rate and the sodium excretion rate was unaffected by albumin. In conclusion, albumin failed to enhance the diuretic effects of furosemide in cirrhotic patients with ascites. Therefore, the coadministration of albumin and furosemide for the treatment of cirrhosis, and likely other hypoalbuminemic conditions, should not be used clinically.
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J. Am. Soc. Nephrol. · Feb 2001
ReviewEffects of genomic polymorphisms on the course of sepsis: is there a concept for gene therapy?
Sepsis and its sequelae are still a major cause of morbidity and mortality on today's intensive care units. The evidence that endogenous mediators actually mediate the individual's response to infection has led to various approaches to assess the individual's contribution to the course of the disease. The role of an individual's genetic background and predisposition for the extent of inflammatory responses is determined by variabilities of genes encoding endogenous mediators that constitute the pathways of inflammation. ⋯ Therefore, all genes encoding proteins involved in the transduction of inflammatory processes are candidate genes to determine the human genetic background that is responsible for interindividual differences in systemic inflammatory responses to injury. The genetically determined capacity of cytokine production and release, heat shock protein expression, nitric oxide synthase activity, gene polymorphisms of coagulation factors or factors of the innate immune system-like defensins, and other genes involved in inflammation may contribute to a wide range of clinical manifestations of an inflammatory disease. Genomic information may be used to identify groups of patients with a high risk of developing severe sepsis and multiple organ dysfunction, and determining which patients will benefit from antimediator strategies because of their genetic determination to high cytokine release in the inflammatory response will be the subject of future trials.