[BENEFIT Kidney--significance of a nephrology screening at intervention outset and therapy success]. / BENEFIT Niere -- Bedeutung eines Nephrologie-Screenings für Interventionsbeginn und Therapieerfolg.

BACKGROUND AND OBJECTIVE: Early specialist care of patients with renal disease, including timely and planned onset of dialysis, determine the course of the disease, quality of life, hospitalization and life expectancy. A multi-centre enquiry by standardized questionnaire was undertaken to define and analyse medical care of newly dialysis-requiring patients. PATIENTS AND METHODS: Data on 551 patients in five different regions of Germany who for the first time required renal replacement treatment were prospectively collected between July 2002 and March 2003. Documentation of history, clinical findings and biochemical tests was done on consecutive patients with a standardized questionnaire, until the desired number of cases was reached. RESULTS: The mean age of the patients (55.4% males) was 64.8 years. 30.7% had diabetes mellitus, 22.3% arterial hypertension/nephrosclerosis and 16.9% glomerulonephritis/vasculitis. Early predominantly nephrological care had been undertaken in 38.7% of patients. 59.0% were cared for almost exclusively by their general practitioner until the time when dialysis was started. 229 patients (41.6%) were referred to specialist (nephrologists) only when dialysis had become necessary. The onset of dialysis was at the right time in only 50.5% of this group. Comparing the care given by nephrologists with that by general practitioners, elective (i.e. planned) dialysis was begun in 81.0% vs. 48.0% (p<0.05). Hospitalization in the two groups was 54.5% vs. 83.7% (p<0.05), the duration of hospital stay 11.4 vs. 17.4 days (p<0.05). CONCLUSION: Fewer than 40% of patients with chronic renal disease in preterminal renal failure (stage IV) were under the care of nephrologists. The lower the degree of nephrological care the more frequent was there a delay in the onset of dialysis treatment. The incidence and the duration of hospital stay was longer. Structured treatment pathways and incentives need to be formulated to reduce the incidence of wrong or substandard treatment of patients with impaired renal function.

Proteinuria and plasma total homocysteine levels in chronic renal disease patients with a normal range serum creatinine: critical impact of true glomerular filtration rate.

Conflicting data have been reported concerning the independent association between proteinuria and plasma total homocysteine (tHcy) levels, particularly among chronic renal disease (CRD) patients with a normal range serum creatinine. Studies of this potential relationship have been limited by failure to assess true GFR, failure to assess proteinuria in a quantitative manner, or arbitrary restriction of the range of proteinuria examined. We examined the potential independent relationship between plasma tHcy levels and a wide range of quantitatively determined proteinuria (i.e., 0.000-8.340 g/day), among 109 CRD patients with a normal range serum creatinine (range; 0.8-1.5 mg/dl; median=1.2 mg/dl). Glomerular filtration rate (GFR) was directly assessed by iohexol clearance, and plasma status of folate, pyridoxal 5'-phosphate, and B12, along with serum albumin, were also determined. Linear modeling with ANCOVA revealed that proteinuria was not independently associated with tHcy levels (partial R=0.127; P=0.201), after adjustment for potential confounding by GFR (partial R=0.408; P<0.001), age, sex, plasma B-vitamin status, and serum albumin. Moreover, descending across quartiles (Q) [from Q4 to Q1] of GFR, ANCOVA-adjusted (i.e., for age, sex, and folate status) geometric mean tHcy levels (micromol/l) were significantly increased: tHcy Q4 GFR=9.6; tHcy Q3 GFR=10.5; tHcy Q2 GFR=11.9; tHcy Q4 GFR=14.5; P<0.001 for overall Q difference. We conclude that across a broad spectrum of quantitatively determined proteinuria, after adjustment for true GFR, in particular, there is no independent relationship between proteinuria and tHcy levels among CRD patients with a normal range serum creatinine.

Homocysteine, cystathionine, methylmalonic acid and B-vitamins in patients with renal disease.

Moderate hyperhomocysteinemia is very frequent in renal patients. Aside from homocysteine (HCY) itself, the metabolites methylmalonic acid (MMA) and cystathionine (CYS) supply further information about disturbances in HCY metabolism. In two groups of renal patients, transplant and hemodialysis patients, we measured HCY, MMA and CYS and evaluated their diagnostic value for impaired HCY metabolism due to vitamin deficiency and renal insufficiency. We investigated serum samples from 63 transplant patients and 38 patients undergoing hemodialysis. HCY, MMA and CYS were assayed by gas chromatography-mass spectrometry, vitamin B6 by HPLC, B12 and folate by chemiluminescence immunoassay. The determination of HCY, MMA, and CYS in renal patients provides specific information about intracellular disturbances of HCY metabolism. The frequency of increased metabolite levels in renal patients was much higher than the frequency of lowered vitamin concentrations in serum. Furthermore, the metabolite levels in transplant patients were only moderately increased, whereas they were strongly increased in patients on hemodialysis (HCY 19.2 vs. 28.8 micromol/l, MMA 292 vs. 1025 nmol/l, CYS 733 vs. 2711 nmol/l). Our findings may support the use of MMA determination in the diagnosis of vitamin B12 deficiency in renal patients. Compared to vitamin B12 deficiency, renal dysfunction itself appears to cause only a modest elevation in serum MMA. Regression analysis revealed that the moderate elevation of HCY and CYS in transplant patients is mainly a consequence of impaired remethylation of HCY to methionine with activated transsulfuration, whereas the mildly elevated MMA level is attributable to renal dysfunction. In patients on hemodialysis, all three metabolites were markedly elevated, indicating a strongly disturbed HCY metabolism. Based on a backward regression, we discovered that the HCY metabolism was strongly disturbed by renal insufficiency and vitamin deficiency. The markedly elevated HCY level was mainly attributable to functional vitamin B12 deficiency indicated by high MMA, and the strong CYS elevation was due to renal dysfunction and inhibition of this pathway by low levels of vitamin B6. In conclusion, besides HCY, the determination of MMA and CYS levels supports an early diagnosis of B-vitamin deficiency in renal patients. MMA is a more sensitive indicator of intracellular vitamin B12 deficiency than vitamin B12 in serum.

Evaluation of renal Kt/V as a marker of renal function in predialysis patients.

BACKGROUND: The use of renal Kt/V (r-Kt/V) as an indicator for the need of dialysis initiation has been recommended in the NKF-DOQI guidelines. In analogy to clinical practice in peritoneal dialysis, a fall of r-Kt/V below a threshold of 2.0 per week may indicate inadequate renal toxin elimination. However, there are no studies linking r-Kt/V with other parameters of glomerular filtration rate (GFR) in predialysis patients, and the validity of r-Kt/V as parameter for timing of dialysis initiation is unknown. METHODS: Renal function was assessed repeatedly in 125 patients (N = 465 measurements). In predialysis patients (r-Kt/V <2.5 per week) r-Kt/V was compared with creatinine [CCr], urea [CUr], averaged creatinine/urea clearance [CCr/Ur], Cockcroft-Gault formula [CCG], and MDRD prediction equation 6 (MDRD6-GFR). The diagnostic performance of r-Kt/V as a parameter for timing the initiation of dialysis was evaluated. RESULTS: Renal Kt/V <2.5 was prevalent in 24.9% of cases (N = 116, mean 1.92 +/- 0.34). In this group mean CCr was 13.8 +/- 4.9, mean CUr 6.7 +/- 1.3, and CCr/Ur 10.2 +/- 2.9 mL/min/1.73 m2. There was no correlation of r-Kt/V with serum creatinine and MDRD6-GFR, but a significantly positive correlation with CCr/Ur (r2 = 0.3382, P < 0.001). Sensitivity of r-Kt/V to detect CCr/Ur < 10.5 mL/min/1.73 m2, defined as the threshold for dialysis initiation, was 73.6% with a specificity of 91.9%. CONCLUSIONS: These results suggest that r-Kt/V is a parameter of acceptable specificity but poor sensitivity for the timing of dialysis initiation. Additional measures of renal function, such as the average of measured creatinine and urea clearance, also should be taken into consideration when deciding on the timing of dialysis initiation prior to the development of clinical signs of uremia and malnutrition.

Prophylactic hemofiltration in severely traumatized patients: effects on post-traumatic organ dysfunction syndrome.

OBJECTIVE: To evaluate the effects of prophylactic veno-venous hemofiltration (CVVH) in the absence of renal failure on multiple organ dysfunction syndrome after severe multiple trauma. DESIGN: Prospective, randomized study. SETTING: Intensive care unit (ICU) in a university hospital. PATIENTS: Twenty-four patients with severe multiple trauma (injury severity score > or = 27), no renal failure on admission and no contraindication for moderate heparinization. INTERVENTIONS: Twelve patients received conventional treatment while 12 patients were treated additionally with isovolemic CVVH for 5 days starting within 24 h following trauma. Signs of organ dysfunction were assessed daily including monitoring of systemic hemodynamic by means of pulmonary artery catheterization during the first 5 days after trauma. MEASUREMENTS AND MAIN RESULTS: Prophylactic CVVH did not affect the overall severity of organ dysfunction as assessed by MOF or APACHE II scores. However, the pattern of impaired organ systems was influenced by CVVH: while the post-traumatic decrease in platelet count in patients subjected to CVVH was more pronounced than in controls (e.g. day 4: control: 115,080 +/- 15,087, CVVH: 57,383 +/- 4,201 microliters-1; p < 0.05) the development of hyperdynamic circulatory failure was simultaneously attenuated, as reflected by a limited increased in cardiac output and an attenuated decrease in systemic vascular resistance and oxygen extraction ratio (e.g. systemic vascular resistance on day 4: control: 624.3 +/- 46.17, CVVH: 842.7 +/- 79.24 dyn.s.cm-5; p < 0.005). CONCLUSION: CVVH blunts the cardiovascular response to multiple trauma and increases tissue oxygen extraction. However, the concomitant decrease in platelet counts represents a limitation for the use of prophylactic CVVH in surgical patients.

Chronic renal transplantation: a model for the hyperhomocysteinemia of renal insufficiency.

Renal transplant recipients (RTR) are considered representative of patients with chronic renal insufficiency (CRI) in general with respect to both reduced, progressively declining renal function, and increased risk for cardiovascular disease (CVD). In accord with this argument, we hypothesized that total (t) plasma concentrations of the putatively atherothrombotic amino acid homocysteine (Hcy) would be equivalent in RTR and CRI patients with comparable renal function. We determined plasma tHcy, folate, pyridoxal 5'-phosphate, and B12 concentrations, in addition to serum creatinine and albumin concentrations, in 86 chronic, stable RTR, and 238 patients with CRI. Within comparable ranges of serum creatinine (i.e. RTR=0.6-4.2 mg/dl; CRI=0.7-4.1 mg/dl), tHcy concentrations did not differ between the two groups (RTR=15.0 micromol/l; CRI=14.9 micromol/l, P=0.899). ANCOVA revealed that renal function, gauged as a simple creatinine measurement, was the major independent determinant of plasma tHcy concentrations, accounting for approximately 80-90% of the total variability in tHcy predicted by the full model (i.e. full model R(2)) containing, in addition to creatinine, the seven other potential explanatory variables. If controlled trials confirm that tHcy-lowering treatment reduces CVD events rates in RTR, these results should be applicable to CRI patients in general.

Pollen assemblages as paleoenvironmental proxies in the Florida Everglades.

Analysis of 170 pollen assemblages from surface samples in eight vegetation types in the Florida Everglades indicates that these wetland sub-environments are distinguishable from the pollen record and that they are useful proxies for hydrologic and edaphic parameters. Vegetation types sampled include sawgrass marshes, cattail marshes, sloughs with floating aquatics, wet prairies, brackish marshes, tree islands, cypress swamps, and mangrove forests. The distribution of these vegetation types is controlled by specific environmental parameters, such as hydrologic regime, nutrient availability, disturbance level, substrate type, and salinity; ecotones between vegetation types may be sharp. Using R-mode cluster analysis of pollen data, we identified diagnostic species groupings; Q-mode cluster analysis was used to differentiate pollen signatures of each vegetation type. Cluster analysis and the modern analog technique were applied to interpret vegetational and environmental trends over the last two millennia at a site in Water Conservation Area 3A. The results show that close modern analogs exist for assemblages in the core and indicate past hydrologic changes at the site, correlated with both climatic and land-use changes. The ability to differentiate marshes with different hydrologic and edaphic requirements using the pollen record facilitates assessment of relative impacts of climatic and anthropogenic changes on this wetland ecosystem on smaller spatial and temporal scales than previously were possible.

Hepatotoxic substance(s) removed by high-flux membranes enhances the positive acute phase response.

BACKGROUND: Acute phase proteins (APPs) are enhanced in end-stage renal disease patients (ESRD) requiring dialysis treatment. They are involved in a variety of pathologic processes like muscle proteolysis, cachexia, regulation of appetite, and atherosclerosis. They are predictive for mortality. APPs are not only makers but also active substances. They are mainly produced in liver cells and are primarily, but not exclusively, regulated by proinflammatory cytokines. To what extent hepatic APPs are influenced by uremic toxins is still unclear. Therefore, we investigated the effects of different ultrafiltrates (UFs) on the synthesis of alpha1-acid glycoprotein (AGP) in HepG2 cells. METHODS: A cross-sectional as well as a crossover study with high-/low-flux membranes was conducted to investigate the impact of UFs on bioactivity of liver cell cultures. Metabolic activity (MTT test), cytotoxicity (lactate dehydrogenase release), and the positive APP AGP were measured in HepG2 cells. RESULTS: Cultured hepatocytes treated with UFs from high-flux membranes exhibited a higher cytotoxicity (18.6 +/- 0.3% high-flux vs. 13.9 +/- 0.2% low-flux, P < 0.001) and a lower metabolic activity (29.3% high-flux vs. 50.3% low-flux, P < 0.001) in comparison with low-flux UFs. In addition, enhanced APP secretion could be observed under costimulatory conditions (high-flux 5.0 +/- 0.7 vs. low-flux 3.1 +/- 0.6 ng/microg protein, P < 0.05). The effects of high- and low-flux UFs were strongly expressed at the beginning and were still significantly different after 120 minutes of hemodialysis (HD) treatment. The crossover experiments confirmed that UFs collected during high-flux HD had a higher capacity to stimulate AGP synthesis in liver cells. CONCLUSION: The effects of UFs from dialysis patients demonstrate that hepatotoxic substances can be removed by dialysis. Stimulating the acute phase response UF collected during high-flux HD had a higher impact on liver cells in comparison with low-flux UF. These substances are putative cofactors involved in cytokine regulation.

An increased serum level of free Apo(a) in renal patients is more striking than that of Lp(a) and is influenced by homocysteine.

Lipoprotein(a) [Lp(a)] excess combined with hyperhomocysteinaemia and hyperfibrinogenaemia may contribute to the high incidence of vascular diseases in dialysis patients. This study is aimed at investigating the role of free apolipoprotein(a) [fapo(a)] in renal patients. We have been able to show that, as compared with controls (0.53 mg/l), the median serum concentrations of fapo(a) in patients with nephrotic syndrome (2.58 mg/l) and with peritoneal dialysis (3. 40 mg/l) were strongly elevated (5- to 7-fold), while the fapo(a) levels in patients undergoing haemodialyis (1.02 mg/l) and after renal transplantation (0.90 mg/l) were about doubled. The observed differences in fapo(a) levels indicate that several mechanisms may increase the level of fapo(a), i.e., reduced renal clearance, enhanced hepatic synthesis, or homocysteine releasing apolipoprotein(a) from Lp(a). In the study collective, the median total homocysteine levels were significantly elevated in all patient groups, stronger in patients on haemodialysis (31.4 micromol/l) and peritoneal dialysis (31.2 micromol/l) than in patients with nephrotic syndrome (19.7 micromol/l) and after renal transplantation (19.5 micromol/l). In transplant patients with adequate renal function and without other apolipoprotein(a)-increasing factors, fapo(a) was significantly increased when total homocysteine exceeded 22 micromol/l. In conclusion, our findings let us presume that an increased fapo(a) level in renal patients possibly could be one of the reasons contributing to the high incidence of vascular diseases in these patients, because fapo(a) not covalently linked with Lp(a) is even more easily able to inhibit the fibrinolytic system than the complete Lp(a). These preliminary results have to be confirmed by further investigations.

In vivo effects of dialysate flow rate on Kt/V in maintenance hemodialysis patients.

It is generally assumed that hemodialysis adequacy is only minimally affected by increasing the dialysate flow rate (Qd). Recent in vitro studies showed that dialyzer urea clearance (Kd(urea)) may increase substantially more than expected in response to an increase in Qd. Because these studies implied that dialysis efficacy may benefit from greater Qds, we studied in vivo the effects of various Qds on the delivered dose of dialysis in 23 maintenance hemodialysis (MHD) patients. Hemodialysis was performed at Qds of 300, 500, and 800 mL/min for at least 3 weeks each, whereas specific dialysis prescriptions (treatment time, blood flow rate [Qb], ultrafiltration volume, and type and size of dialyzer) were kept constant. Delivered dose of dialysis, assessed by single-pool Kt/V (Kt/V(sp)) and double-pool Kt/V (Kt/ V(dp)), was measured at least three times for each Qd (218 measurements). Mean +/- SEM Kt/V(sp) was 1.19 +/- 0.03 at Qd of 300 mL/min, 1.32 +/- 0.04 at 500 mL/min, and 1.45 +/- 0.04 at 800 mL/min. The relative gains in Kt/V(sp) for increasing Qd from 300 to 500 mL/min and 500 to 800 mL/min were 11.7% +/- 8.7% and 9.9% +/- 5.1%, respectively. Kt/V(dp) increased at a similar percentage (11.2% +/- 8.9% and 10.3% +/- 5.1%, respectively). The observed gain in urea clearance by increasing Qd from 500 to 800 mL/min was significantly greater than the increase in Kd(urea) predicted from mathematical modeling (5.7% +/- 0.4%; P = 0.0008). Removal ratios for creatinine and the high-molecular-weight marker, beta(2)-microglobulin, were not affected by increasing Qd from 500 to 800 mL/min. The proportion of patients not achieving adequacy (Kt/V(sp) >/= 1.2) was reduced from 56% at Qd of 300 mL/min to 30% at 500 mL/min and further to 13% at 800 mL/min. It is concluded that increasing Qd from 500 to 800 mL/min is associated with a significant increase in Kt/V. Hemodialysis with Qd of 800 mL/min should be considered in selected patients not achieving adequacy despite extended treatment times and optimized Qbs.

Hepatoactive substances eliminated by continuous venovenous hemofiltration in acute renal failure patients.

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.

Gender-specific differences in dialysis quality (Kt/V): 'big men' are at risk of inadequate haemodialysis treatment.

BACKGROUND: Inadequate dialysis dose is closely related to mortality and morbidity of maintenance haemodialysis (MHD) patients. According to the DOQI guidelines a minimum prescribed dialysis dose of single-pool Kt/V (Kt/Vsp)=1.3, equivalent to equilibrated double pool Kt/V (e-Kt/Vdp)=1.1, is recommended. Knowledge of patient-related risk factors for inadequate delivery of hacmodialysis would be helpful to select patient subgroups for intensive control ofdialysis adequacy. METHODS: A retrospective survey was conducted to assess the prevalence of inadequate dialysis dose according to DOQI criteria during a 7-month period. A total of 320 e-Kt/Vdp measurements in 62 MHD patients were evaluated (mean effective dialysis time 222+/-32 min). Residual renal function (RRF) was expressed as renal weekly Kt/V (r-Kt/Vweek) and included into assessment of total weekly renal and dialytic Kt/V (t-Kt/Vweek). RESULTS: Inadequacy (e-Kt/Vdp<1.10) was prevalent in 37.2% of all measurements and in 22/62 patients (35.5%). In 54% of underdialysed patients r-Kt/Vweek compensated for insufficient dialytic urea removal. Mean weekly Kt/V was inadequate (t-Kt/Vweek<3.30) in 12/62 patients (19.4%) of whom 91.7% (11/12) were male. Body-weight, urea distribution volume (UDV). and body-surface area (BSA) were significantly higher in inadequately is adequately dialysed males. UDV>42.0 litres or BSA>2.0 m2 and a lack of RRF (r-Kt/Vweek<0.3) put 'big men' at increased risk to receive an inadequate dose of dialysis. CONCLUSION: Our data identify patients at risk for inadequate haemodialysis treatment. Special attention should be focused on 'big men' with UDV>42.0 litres or BSA>2.0 m2. In this subset of patients frequent measurements of t-Kt/Vweek and assessment of RRF should be mandatory.

Effects of acidosis on acute phase protein metabolism in liver cells.

Metabolic acidosis has been shown to act as a causative factor in muscle protein breakdown and negative nitrogen balance, as well as in decreased albumin synthesis. Albumin and other acute phase proteins (APP) are mainly synthesized in the liver following induction by interleukins, hormones and other mediators. Acute phase proteins have been shown to be predictors of cardiovascular mortality in the general population and in patients with end stage renal disease (ESRD). Clinical investigation gives evidence that albumin is reduced by acidosis in ESRD patients. The aim of our study was to investigate the role of the liver in acidosis, i.e. the influence of acidosis on metabolic activity and secretion of APP by liver cells (HepG2). Cells were cultured in a medium containing different amounts of bicarbonate. Metabolic activity was significantly diminished when the bicarbonate concentration of the extracellular medium was reduced (86.13+/-1.90% (pH 7.0) vs. 99. 53+/-90% (pH 7.4); p<0.01). While cellular release of negative APP was significantly decreased (albumin: 4.6+/-0.41 (pH 7.0) vs. 7.54+/-0.62 (pH 7.4) [ng/microg protein], p<0.001, transferrin: (0. 78+/-0.08 (pH 7.0) vs. 1.07+/-0.07 (pH 7.4) [ng/microg protein], p<0. 05), no significant influence of acidosis (pH 7.0) on the positive APP, alpha(1)-acid glycoprotein (AGP) (1.69+/-0.25) (pH 7.0) vs. 1.62+/-0.23 (pH 7.4) [ng/microg protein]), could be shown. Our data indicate that acidosis results in inhibition of liver cell metabolic activity and in reduced secretion of the negative acute phase proteins albumin and transferrin. In contrast, secretion of the positive acute phase protein AGP seems to be unchanged at pH 7.0 as compared to pH 7.4. We conclude that negative and positive APP in liver cells (HepG2) appear to be differently regulated by acidosis.

Liver cell reactive components in peritoneal dialysis fluids.

Metabolic changes in peritoneal dialysis (PD) patients are an important aspect concerning long-term outcome. Liver plays the main role in regulating metabolism. The effects of peritoneal dialysis fluids (PDF) on liver cell function are scarcely investigated. Therefore, we investigated the effects of PDF, different in some components, on liver cell metabolism in vitro. Metabolic activity (MTT), cell integrity (LDH release), proliferation (BrdU incorporation) and synthesis of albumin and transferrin are measured by incubating HepG2 cells for 3 h and 24 h with six different PDFs: (a) lactate-buffered, pH5.5: PDF I (1.5% gluc.); PDF II (4.5% gluc. ); (b) bicarbonate-buffered, pH7.4: PDF III (1.5% gluc.), PDF IV (4. 5% gluc.); (c) amino acid-based solutions, pH 7.4: PDF V (low AA level) and PDF VI (high AA level). Metabolic activity of bicarbonate-treated cells is greatly enhanced in comparison to lactate-buffered PDFs. These findings are confirmed by proliferation data. Synthesis of albumin and transferrin is significantly enhanced by amino acid-based solutions. Our data demonstrate, that lactate-buffered PDF impair liver cells much stronger than bicarbonate-buffered PDF. pH is the parameter which contributes to cytotoxicity and impaired metabolism to a major extent. In contrast to glucose-containing solutions, amino acid-based PDF stimulate protein synthesis in liver cells.