Kidney international. Supplement最新文献

Patients who are critically ill with acute renal failure and sepsis have extremely high mortality rates. While it seems reasonable that eliminating the inflammatory mediators (such as cytokines, chemokines, tumor necrosis factor-alpha, etc.) by continuous renal replacement therapy (CRRT) would be effective, studies show that only insubstantial numbers of these mediators are removed in comparison with endogenous clearance. Mass removal seems only to be effective when highly permeable membranes (sieving coefficient of approximately 1.0) are used, there is a filtrate volume greater than 2 liters/hour, and when the half-life of the substance to be eliminated is greater than 60 minutes. Removal of cytokines by membrane adsorption is another possibility. However, because the membrane surfaces are saturated after a few hours, frequent filter changes are necessary for them to generate effective adsorption of these mediators. Despite filter changes, only a brief and transient drop in the TNF plasma level has been observed. Controlled clinical trials are needed to determine whether or not CRRT actually has a beneficial effect on the systemic inflammatory response syndrome (SIRS).

The pathophysiology of sepsis is becoming a more complicated scenario. In sepsis, endotoxin or other gram-positive derived products induce a complex and dynamic cellular response giving rise to several mediators known to be relevant in the pathogenesis of septic shock, such as specific mediators. substances responsible for up- or down-regulation of cytokine receptors and cytokine antagonists, inactivators of nuclear factor-kappaB or signal transduction pathways, and precursor molecules. In this article, we delve into some new concepts stemming from the use of sorbents in continuous plasma filtration. The rationale is based on the assumption that the nonspecific removal of several mediators of the inflammatory cascade and cytokine network may improve outcome in a rabbit model of septic shock and hemodynamics in a pilot clinical study. The importance of looking for innovative treatments specifically targeted for the special needs of the critically ill patients rather than using concepts and technology applied to the treatment of chronic renal failure is underlined.

Some drugs are removed significantly by continuous renal replacement therapies (CRRTs), and a substitutional dose is required to prevent underdosing of the substance. This review outlines the basic pharmacokinetic principles that determine whether a dose adjustment is required. Only the free non-protein-bound fraction of a drug can pass through the dialyzer membrane. In postdilution hemofiltration the drug clearance equals the ultrafiltration rate, while in predilution hemofiltration, the dilution of the blood prior to filtration needs to be considered when calculating clearance. In continuous hemodialysis, drugs are eliminated by diffusion. Drugs with a higher molecular weight will diffuse more slowly and show a lower clearance than smaller drugs. The clinical relevance of a given drug clearance caused by CRRT will mainly depend on the competing drug clearance by other elimination pathways. Even a high clearance for a drug may be irrelevant for overall drug removal if nonrenal clearance pathways provide a much higher clearance rate. The ideal drug to be removed by CRRT that requires a dose adjustment has: a low protein binding, a low volume of distribution, and a low nonrenal clearance. Examples include aminoglycosides, vancomycin, fosfomycin, and flucytosine. Even if there are no studies available on the pharmacokinetics of a particular drug during CRRT, knowledge of the basic concepts of drug elimination by continuous hemodialysis allows a prediction of whether or not a dose adjustment will be required during CRRT.

Background: Continuous renal replacement therapies (CRRTs) are well accepted for critically ill patients with acute renal failure (ARF). Today, daily fluid exchange in CRRT reaches 30 to 40 liter and more. Therefore, the composition of the substitution/dialysate fluid, often primarily developed either for intermittent treatment or for peritoneal dialysis, becomes more relevant. Lactate (30 to 45 mmol/liter) is frequently used as the buffer because of the high stability of this substance. However, lactate is thought to have negative effects on metabolic and hemodynamic parameters.

Methods: Published data for different substitution fluids are presented with respect to acidosis and lactate concentration, uremia, and hemodynamic and metabolic alterations.

Results: Only a few studies compare substitution fluids with different buffers. Uremia and acidosis (pH, base excess) were sufficiently controlled during CRRT with an exchange volume of in average 30 liters using either buffer. If patients with severe liver failure and lactic acidosis were excluded, no difference in hemodynamic and metabolic parameters between the solutions occurred. The plasma lactate concentration was elevated during lactate use in some cases, but lactate levels remained within normal limits in patients without liver impairment. The bicarbonate concentration in the solutions should exceed 35 to 40 mmol/liter, as in some cases the buffer capacity of the solutions was inadequate. In patients with severe liver failure or lactic acidosis, solutions with lactate buffer were shown not to be indicated.

Conclusion: In patients with reduced lactate metabolism, for example, concomitant severe liver failure, after liver transplantation or in lactic acidosis, bicarbonate-buffered solutions should be used. In nearly all other cases of critically ill patients with ARF, lactate-buffered solutions may be used as well as bicarbonate solutions.

Critically ill patients with acute renal failure usually present with an unstable acid-base balance, often leading to cardiovascular complications and multi-organ failure. Therefore, to prevent metabolic acidosis, acid-base balance must be normalized and maintained; these patients are primarily treated with continuous hemofiltration techniques using different replacement fluids to influence the acid-base values. Dialysate solutions can be an acetate-based, lactate-based, citrate-based or bicarbonate-based buffer. This article discusses the strengths and weaknesses of each type of hemofiltration replacement fluid.

Removal of blood solutes in patients with decreased or absent glomerular filtration is the prime objective of continuous renal replacement therapies (CRRTs). However, because these blood solutes are of different molecular weights, factors such as the porosity and hydrophobicity of the filter membranes and the extracorporeal flow rates determine the CRRT that is the most effective filtration system. This article discusses both small and large solute removal, the interaction of convection and diffusion, and the potential for CRRTs to remove particular inflammatory mediators of acute renal failure.

Continuous renal replacement therapies (CRRTs) are associated with a broad pattern of additional metabolic effects beyond renal detoxification. Because of the continuous mode of therapy and the high fluid turnover usually associated with CRRTs, these side effects can become clinically relevant. With many CRRT systems currently used, heat loss is considerable, but CRRTs can also be used to modulate body temperature in hyperpyretic patients. Inappropriate glucose concentrations of some substitution fluids can result in excessive glucose intake. Most substitution and/or dialysate fluids used for CRRTs contain lactate as organic anion. In disease states with impaired lactate utilization, such as acute or chronic liver failure, and/or with increased endogenous lactate formation such as in shock states, this can result in hyperlactemia and is potentially associated with various adverse side effects. Small molecular weight substances such as amino acids or water-soluble vitamins are lost in relevant amounts. With convective clearance and the high molecular cut-off of synthetic membranes, medium-sized molecules such as hormones and cytokines are also filtered, but the pathophysiologic relevance of this observation remains to be specified. Moreover, synthetic membranes used for CRRTs have adsorptive properties for a variety of molecules, such as cytokines, complement factors, and endotoxin. Continuous blood membrane interactions cause the phenomena of bioincompatibility and a low-grade inflammatory reaction with potentially adverse consequences on protein metabolism and immunocompetence. In designing a nutritional program for a patient on CRRT, these metabolic effects--especially the loss of nutritional substrates--must be considered. Certainly, most of these side effects, such as the excessive load of lactate or the loss of nutrients, are undesirable. However, some side effects, such as the modulation of body temperature and the elimination of endotoxin and/or mediators, might be at least potentially beneficial.

Continuous venovenous hemofiltration (CVVH) is the most widely used renal replacement therapy for the treatment of critically ill patients with acute renal failure on the intensive care unit. Whether or not congestive heart failure is an indication for CVVH is controversial and needs to be discussed. Therefore, we present a patient with congestive heart failure who was treated successfully with CVVH.

Background: Acute renal failure (ARF) in critically ill patients is associated with a high mortality rate. Continuous renal replacement therapy (CRRT) is now widely used for the treatment of ARF in these critically ill patients. We retrospectively analyzed the role of CRRT as a prognostic parameter in patients receiving a cadaveric liver graft in 1998.

Methods: We reviewed the patient records of all adult recipients of a cadaveric liver graft (N = 54) in 1998 and compared those who underwent CRRT treatment (N = 19) to those without CRRT treatment (N = 35).

Results: Mortality was high in the continuous venovenous hemodialysis (CVVHD) group (58%). At the time of transplantation, creatinine (1.7+/-0.4 vs. 1.0+/-0.1 mg/dl), blood urea nitrogen (40+/-13 vs. 22+/-3 mg/dl), aspartate aminotransferase (ASAT; 585+/-420 vs. 242+/-97 U/liter), and bilirubin (11.6+/-4.1 vs. 6.5+/-1.9 mg/dl) were higher in the CVVHD group than in controls, whereas hemoglobin (10.3+/-0.6 vs. 10.8+/-0.4 g/dl), white blood cells (6.3+/-0.6 vs. 7.0+/-0.8/nl), and thrombocytes (110+/-18 vs. 90+/-10/nl) were similar. After transplantation, liver graft function was impaired in the CVVHD group as compared with controls.

Conclusions: The necessity for CRRT in patients after liver transplantation correlates with a high risk of death. Thus, more efforts have to be made to prevent renal failure in patients after liver transplantation.

Background: Recombinant hirudin (lepirudin) is a potent direct thrombin inhibitor, which has been approved for the treatment of heparin-induced thrombocytopenia type II (HIT). Because the drug is mainly eliminated by the kidneys, a single loading dose of hirudin may induce therapeutic anticoagulation for up to one week in patients with renal insufficiency. Thus, the use of hirudin in critically ill patients with renal failure could markedly increase their bleeding risk. In this study, hirudin was used in critically ill patients with suspected HIT while on continuous venovenous hemodialysis (CVVHD).

Methods: Hirudin anticoagulation was performed in seven critically ill patients with suspected HIT. Four patients were initially anuric. Three patients had residual renal function. In all 64 CVVHD treatments (mean duration 12 hr), a polysulfone high-flux hemodialyzer (0.75 m2) with a dialysate flow rate of 1.5 liter/hr and an ultrafiltration rate of up to 200 ml/hr was used. Hirudin was given either as continuous intravenous infusion or as repetitive intravenous boli. Monitoring of anticoagulation was performed by measurements of the systemic activated partial thromboplastin time (aPTT).

Results: Hirudin dosage had to be individualized according to the risk of bleeding or clotting. During CVVHD, a continuous intravenous infusion (0.006 to 0.025 mg/kg body wt/hr, N = 2) or repetitive intravenous boli (0.007 to 0.04 mg/kg, N = 5) were given. Two patients required blood transfusions prior to and during hirudin treatment. In five patients without a high bleeding risk, the hirudin dose was adjusted to achieve the target aPTT (1.5 to 2.0 x baseline) in order to prevent thrombotic complications or frequent clotting in the extracorporal circuit. Hirudin dose requirements depended on residual renal function and extracorporal clearance.

Conclusions: We conclude from these first clinical data that anticoagulation with hirudin in critically ill patients on continuous hemodialysis can be performed without excessive bleeding risk by combining close clinical and laboratory monitoring. The hirudin dose has to be reduced because of renal failure, and may require adjustment for residual or recovering renal function and extracorporal elimination.