Kidney international. Supplement最新文献

Experimental studies have provided in vivo and in vitro data to support the notion that dyslipidemia contributes to glomerular and interstitial injury of the renal parenchyma. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are a new class of lipid-lowering agents that have been extensively studied during the past decade. These agents have significant effects on circulating lipids and both renal and vascular injury. New insights into the mechanisms of action of these agents have revealed an important effect on a variety of inflammatory and fibrogenic processes that appear to have major implications for human renal and cardiovascular diseases.

Background: Growth factors have been suggested to play a role in the development and progression of diabetic nephropathy. Vascular endothelial growth factor (VEGF) is a potent cytokine family that induces angiogenesis and markedly increases endothelial permeability. The aim of the present study was to investigate plasma levels of VEGF in a large cohort of type 1 diabetic patients with diabetic nephropathy and in long-standing type 1 diabetic patients with persistent normoalbuminuria, and to evaluate VEGF as a predictor of nephropathy progression.

Methods: We measured VEGF with an enzyme-linked immunosorbent assay (ELISA) technique in 199 type 1 diabetic patients with diabetic nephropathy (122 males, age 41 +/- 10 years, diabetes duration 28 +/- 8 years), glomerular filtration rate (GFR) (median [range]) 75 [10-143] mL/min/1.73 m2, and in 188 long-standing type 1 diabetic patients with persistent normoalbuminuria (115 males, age 43 +/- 10 years, diabetes duration 27 +/- 9 years). One hundred fifty-five of the proteinuric patients were followed for at least 3 years after baseline examination with yearly GFR measurements.

Results: Plasma levels of VEGF were significantly increased in patients with nephropathy as compared to the normoalbuminuric group; (median [range]): 45.7 [22.0-410] versus 27.1 [22.0-355] ng/L, respectively, P < 0.001. This difference was ascribed to elevated VEGF levels in nephropathic men: 51.8 [22.0-410] versus 22.0 [22.0-308] ng/L, P < 0. 001. No differences were found between women with and without nephropathy: 37.8 [22.0-325] versus 36.6 [22.0-335] ng/L, NS. In proteinuric patients with GFR above and below the median value, there was no difference in the level of VEGF, NS. Plasma VEGF was below the detection limit (22.0 ng/L) in 60 patients with nephropathy and 93 patients with normoalbuminuria, P < 0.001. The mean rate of GFR decline was 3.5 (SE: 0.4) mL/min/year, and the following baseline variables acted as predictors of progression: albuminuria, mean arterial blood pressure and male gender. Hemoglobin A1c and plasma VEGF did not act as predictors. No significant differences between patients with and without proliferative retinopathy were detected.

Conclusions: Our data suggest that VEGF is elevated early in the course of diabetic nephropathy in men with type 1 diabetes mellitus. Baseline albuminuria, arterial blood pressure and male gender was predictors of diabetic nephropathy progression, while plasma VEGF and Hemoglobin A1c did not contribute. The importance of VEGF in the initiation of diabetic nephropathy remains to be established.

A significant complication in renal transplantation is the progressive decline of allograft function, commonly called chronic rejection. This complication has been regarded as a result of continuous immunological activity against the allograft. However, the role of nonimmunological factors has become increasingly apparent in triggering or exacerbating immunological mechanisms. Although the role of immunological factors is predominant, the correction of nonimmunological factors may contribute in improving the probability of long-term graft function. However, immunosuppressive therapy remains the cornerstone for reducing the risk of chronic rejection and late graft failure.

Background: In rats with experimental chronic renal failure (CRF), low-protein diets protect against histologic damage and improve mortality. In CRF patients, low-protein diets ameliorate uremic symptoms and certain CRF complications. Fortunately, low-protein diets are nutritionally sound in CRF patients because they activate compensatory mechanisms that conserve protein with a low-protein diet. These results do not determine if dietary protein restriction can slow the rate of progression of CRF or the time to dialysis.

Methods: Reports evaluating low-protein diets and changes in nutritional status and/or progression of CRF are analyzed for efficacy. The MDRD Study is reviewed in depth.

Results: When dietary compliance was achieved, the nutritional status was unimpaired and progression was slowed. Studies with limited dietary compliance failed to find any beneficial effect on progression. Problems in study design suggest caution before accepting the initial MDRD Study conclusion that dietary restriction does not slow progression. Subsequent analyses of MDRD results indicate that protein restriction can slow progression of CRF.

Conclusion: Evidence that dietary protein spontaneously decreases in progressively uremic patients should not be construed as an argument against the use of dietary therapy. Rather, it is a persuasive argument to restrict dietary protein intake in order to minimize CRF complications while preserving nutritional status. In patients with uremia or progression despite other measures, dietary therapy should be started along with monitoring for dietary compliance and nutritional adequacy.

Background: Acute renal failure (ARF) in critically ill patients is mostly part of a multi-organ failure. Therefore, the effects of renal replacement therapy on the liver are clinically important. We investigated the effects of ultrafiltrates of patients treated with continuous venovenous hemofiltration (CVVH) on liver cells in vitro.

Methods: Patients with ARF were consecutively treated with CVVH using Multiflow60 (group I) or FH66 filters (group II). They were comparable with respect to diagnosis, age, sex, laboratory parameters, and renal replacement treatment, but were different in daily diuresis, serum levels, and blood flow. Ultrafiltrates were collected within the first 10 minutes after change of hemofilter. Proliferation (bromodeoxyuridine), vitality (lactate dehydrogenase), and acute-phase protein secretion of HepG2 cells were measured.

Results: Ultrafiltrates changed liver cell function significantly compared with medium control. Proliferation (group I 29.8+/-5.2% vs. group II 48.4+/-6.6%, P < 0.05) and vitality (group I 78.7+/-2.0% vs. group II 87.6+/-1.7%, P < 0.01) of HepG2 cells were significantly different. On the one hand, the secretion of the negative acute-phase protein transferrin [group 13.1+/-0.2 (ng/microg protein) vs. group II 5.1+/-0.5 (ng/microg protein), P < 0.01] was significantly reduced by Multiflow60 ultrafiltrates. On the other hand, positive acute-phase protein alpha1-acid glycoprotein was significantly stimulated by Multiflow60 ultrafiltrates [group I 2.6+/-0.1 (ng/microg protein) vs. group II 1.7+/-0.1 (ng/microg protein), P < 0.001].

Conclusion: This study demonstrates hepatoactive mediators in the ultrafiltrates. They are hepatotoxic and influence acute-phase protein metabolism. Further studies have to elucidate the different effects in both groups and the analysis of the putative mediator(s). It remains a challenging task to consider therapeutic measures to optimize renal replacement therapy in critically ill patients.

Background: Hematocrit plays a major role in primary hemostasis by influencing blood viscosity and platelet adhesion. During continuous venovenous hemofiltration (CVVH), it is suspected that an increased hematocrit is accompanied by an activation of hemostasis and frequently leads to thromboses in the extracorporeal system. In order to examine this hypothesis, we studied the influence of hematocrit on hemostasis during CVVH.

Methods: Fourteen patients (8 men and 6 women, mean age 65+/-10 years) with acute renal failure undergoing CVVH were prospectively enrolled. Polysulfone hemofilters (AV 600; Fresenius, Oberursel, Germany) were used in all of the patients; blood flow rates were adjusted to 120 ml/min. No blood products and coagulation-related medication, except unfractionated heparin, were applied. Study exclusion criteria included a history of thromboembolism and artificial heart valves. Hemostasis activation markers (fibrinopeptide A, thrombin-antithrombin III complex, beta-thromboglobulin, platelet retention) and hematocrit values were determined before and at three-day intervals during the course of CVVH treatment.

Results: The mean hematocrit value (mean +/- SEM) was 29+/-1% (range, 22 to 35%). Patients with hematocrit values of less than 30% (N = 7) were compared with patients with higher hematocrit values (>30%, N = 7). The patients with a lower hematocrit (<30%) showed a stronger activation of hemostasis during CVVH when compared with those with a higher hematocrit (>30%), as indicated by a tendency toward higher values for fibrinopeptide A (25+/-8 vs. 14+/-5 ng/ml, P = 0.35), thrombin-antithrombin III complex (15+/-4 vs. 10+/-2 ng/ml, P = 0.66), and a higher beta-thromboglobulin/creatinine ratio (0.62+/-0.17 vs. 0.48+/-0.12, P = 0.8).

Conclusion: Contrary to our hypothesis, hematocrit values of more than 30% are not accompanied by an increased hemostasis activation during CVVH. Concerning hemostasis activation, hematocrit values between 30 and 35% may be suitable for patients on CVVH.

While the use of hemofiltration to treat septic shock has potential benefits, the existing studies are difficult to compare because of their variety of inclusion criteria. The concept is to remove the various mediators of severe sepsis and septic shock, such as cytokines and eicosanoids, so that acute renal failure and the resultant multi-organ failure and possible death can be delayed or prevented. The dilemmas include: (a) hemofiltration cannot distinguish between these pro-inflammatory mediators as they are of similar molecular weights, and thus it is difficult to determine which one or combination should be eliminated for the best hemodynamics; (b) timing of the hemofiltration to remove a particular cytokine may make a difference in patient outcome; (c) the most efficacious convection rate of ultrafiltration has not been determined yet; (d) since these mediators quickly saturate the membrane, it should be frequently changed, and thus biocompatibility, availability and costs are added issues; (e) the choice of buffer is different according to the diagnosis of these critically ill patients. Before designing clinical trials, further experimentation is necessary to explore these problems.

Continuous renal replacement therapy (CRRT) has now been in use for more than a decade in the management of patients with combined renal and hepatic failure. CRRT remains the treatment of choice in this group of critically ill patients because of improved cardiovascular and intracranial stability when compared with conventional intermittent hemofiltration and/or dialysis and effective solute clearances when compared with forms of peritoneal dialysis. Over the last decade, the technique has evolved with the introduction of pumped CRRT circuits. using machines that can accurately regulate fluid balance, and the commercial introduction of bicarbonate-based or "lactate-free" substitution fluids and/or dialysates. Whether continuous dialysis or hemofiltration is the mode of treatment choice remains unanswered, with greater amino acid and ammonia losses during dialysis, whereas hemofiltration leads to increased middle molecule and cytokine removal when compared with dialysis, the latter mainly caused by membrane adsorption. Whether the improved cardiovascular stability observed during these techniques is due to the removal of inflammatory mediators or is related to cooling as a consequence of the technique remains to be determined.

There are many controversial results about the influence of acute renal failure (ARF) and renal replacement therapy (RRT) on patient outcome in intensive care units. This retrospective study compared demographics. severity, course, and prognosis of ARF during 36 months (period 1, 1991 through 1993; 128 cases) and 18 months (period 2, 1994 through 1995; 141 cases). Compared with period 1, during period 2 there was a markedly increased incidence of ARF. There were no significant differences in patient demographics or etiology of renal failure, but the therapeutic approach to ARF was quite different. During period 2, RRT was started at earlier stages of renal insufficiency (that is, less elevated creatinine serum concentrations or reduced diuresis). Additionally, there was a significant increase in the numbers of continuous RRT (CRRT) replacing the discontinuous mode of dialysis treatment. Compared with period 1, mortality was reduced from 78.9 to 59.6% during period 2 (P < 0.001). There were no differences in mortality between the patients from internal and surgical wards. Mortality in patients treated with CRRT was in period 1 and in period 2 higher than mortality in patients treated with intermittent RRT, but these results are biased by a preferred use of CRRT in severely ill patients with an unstable circulatory system. These data suggest that the early onset of RRT reduces the mortality of intensive care unit patients with ARF independent of underlying diseases. An influence of the method of RRT, sex, and age on outcome of patients with ARF could not be proven.