Assessment of the effectiveness, safety, and biocompatibility of icodextrin in automated peritoneal dialysis. The Dextrin in APD in Amsterdam (DIANA) Group.

OBJECTIVE: Our study assessed the efficacy, safety, and biocompatibility of icodextrin (I) solution compared to glucose (G) solution as the daytime dwell in continuous cycling peritoneal dialysis (CCPD). DESIGN: In a randomized, open, prospective, parallel group study of two year's duration, either I or G was used for the long daytime dwell in CCPD patients. METHOD: The study was carried out in a university hospital and teaching hospital. Established CCPD patients and patients new to the modality were both included. Clinic visits were made at three-month intervals. In all patients, clinical data were gathered; ultrafiltration (UF) was recorded; and serum, urine, and dialysate samples and effluents were collected. Peritoneal defense characteristics and mesothelial markers were determined. Every six months, peritoneal kinetics studies were performed, and serum samples for icodextrin metabolites were taken. RESULTS: Thirty-eight patients (19 G, 19 I) started the study. The median follow-up was 16 months and 17 months respectively (range: 0.5 - 26 months and 3 - 26 months, respectively). Daytime UF volumes increased significantly (p < 0.001), and 24-hour UF tended to increase from baseline in the I group. Dialysate creatinine clearance increased non significantly in both groups over time. In I patients, serum disaccharides (maltose) concentration increased from 0.05+/-0.01 mg/mL [mean+/- standard error of mean (SEM)] at baseline, to an average concentration in the follow-up visits of 1.15+/- 0.04 mg/mL (p <0.001). At the same time, serum sodium levels decreased from 138.1 +/- 0.7 mmol/L to an average concentration in the follow-up visits of 135.9 +/- 0.8 mmol/L (p < 0.050). At 12 months, the serum sodium concentration increased to a non significant difference from baseline. Serum osmolality increased, but did not differ significantly from G users at any visit. During peritonitis (P), daytime dwell UF decreased significantly compared to non peritonitis (NP) episodes in G patients (p < 0.0 01), but remained stable in I patients. Total 24-hour UF also decreased in G patients (p < 0.001), but not in I patients. In these I patients, serum disaccharides increased from 0.05 +/- 0.01 mg/mL to 1.26 +/- 0.2 mg/mL during follow-up. During peritonitis, serum disaccharides concentration did not increase further (1.47 +/- 0.2 mg/mL, p= 0.56). Thirty P episodes occurred during follow-up: 16 in G patients and 14 in I patients (1 per 17.6 months and 1 per 21.9 months, respectively.) After one year, absolute number and percentage of effluent peritoneal macrophages (PM phi s) were significantly higher in I patients than in G patients. The difference in percentage persisted after two years. The phagocytic capacity of PM phi s decreased over time, resulting in a borderline significant difference for coagulase-negative staphylococci phagocytosis (p=0.005) and a significant difference for E. coli phagocytosis (p <0.05) in favor of I patients. PM phi oxidative metabolism, PM phi cytokine production, and effluent opsonic capacity remained stable over time with no difference between the groups. Mass transfer area coefficients (MTACs) and clearances were stable and appeared unaffected by G or I treatment. Effluent cancer antigen 125 (CA125) was stable in G users and tended to decrease in I users. Effluent interleukin-8 (IL-8), carboxy-terminal propeptide of type I procollagen (PICP ), and amino-terminal propeptide of type III procollagen (PIIINP) did not change over time and did not differ between the groups. CONCLUSION: The use of I for the long daytime dwell in CCPD led to an increase in total UF of at least 261 mL per day, which was maintained over at least 24 months. During I treatment, serum I metabolites increased significantly and serum sodium concentrations decreased initially. As a result, serum osmolality increased slightly. Clinical adverse effects did not accompany these findings. The UF gain in the I patients was even higher during P, without a

Peritoneal kinetics and mesothelial markers in CCPD using icodextrin for daytime dwell for two years.

OBJECTIVE: To evaluate the safety, efficacy, and biocompatibility of icodextrin (Ico), continuous cycling peritoneal dialysis (CCPD) patients were treated for 2 years with either Ico- or glucose (Glu)-containing dialysis fluid for their daytime dwell (14 - 15 hours). Prior to entry into the study, all patients used standard Glu solutions (Dianeal, Baxter BV, Utrecht,The Netherlands). DESIGN: Open, randomized, prospective two-center study. SETTING: University hospital and teaching hospital. PATIENTS: Both established patients and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18 years or with peritonitis in the previous month, and women of childbearing potential unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients entered the study (19 Glu, 19 Ico). MAIN OUTCOME MEASURES: Daytime dwell peritoneal effluents were collected every 3 months in combination with other study variables (clinical data, laboratory measurements, dialysis-related data, and urine collection). Peritoneal transport studies were carried out every 6 months. RESULTS: In Glu- and Ico-treated patients, peritoneal transport of low molecular weight solutes and protein clearances neither changed during follow-up nor differed between the two groups. Peritoneal membrane markers (CA125, interleukin-8, carboxyterminal propeptide of type I procollagen, and aminoterminal propeptide of type III procollagen) measured in effluents did not differ between the groups and did not change over time. All these markers showed a dialysate/plasma ratio of more than 1, suggesting local production. Residual renal function remained stable during follow-up and adverse clinical effects were not observed. CONCLUSIONS: Peritoneal membrane transport kinetics and markers remained stable in both groups over a 2-year follow-up period. Membrane markers were higher in effluents than in serum, suggesting local production. No clinical side effects were demonstrated. Icodextrin was a well-tolerated effective treatment.

Peritoneal defense using icodextrin or glucose for daytime dwell in CCPD patients.

OBJECTIVE: To investigate peritoneal defense during icodextrin use in continuous cyclic peritoneal dialysis (CCPD). DESIGN: In an open, prospective, 2-year follow-up study, CCPD patients were randomized to either glucose (Glu) or icodextrin (Ico) for their long daytime dwell. SETTING: University hospital and teaching hospital. PATIENTS: Both established and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18 years, those who had peritonitis in the previous month, and women of childbearing potential, unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients (19 Glu, 19 Ico) started the study. The median follow-up was 16 and 17 months for Glu and Ico respectively (range 0.5-25 months and 5-25 months, respectively). OUTCOME MEASURES: Peritoneal defense characteristics and peritoneal dialysis-related infections were recorded every 3 months. RESULTS: Total peritoneal white cell count tended to decrease over time in both groups. After 1 year, absolute numbers and percentages of effluent peritoneal macrophages (PMphis) were significantly higher in Ico than in Glu patients; this difference in the percentage persisted after 2 years. Percentage of mesothelial cells increased overtime in Ico patients. The phagocytic capacity of PMphis decreased over time, resulting in a borderline significant difference for coagulase-negative staphylococci (p = 0.05) and a significant difference for Escherichia coli (p < 0.05) phagocytosis in favor of Ico patients. PMphi oxidative metabolism remained stable over time without a difference between the groups. PMphi cytokine production and effluent opsonic capacity also remained stable over time. Finally, 16 peritonitis episodes in Glu and 14 in Ico patients occurred. Glucose patients had 37 and Ico patients 32 exit-site infections during the study. CONCLUSION: CCPD patients using Ico did equally as well as Glu-treated patients with respect to clinical infections and most peritoneal defense characteristics. However, in a few peritoneal defense tests, Ico-treated patients did better.

Icodextrin use in CCPD patients during peritonitis: ultrafiltration and serum disaccharide concentrations.

BACKGROUND AND METHODS: In a randomized study on the biocompatibility of icodextrin (I) versus glucose (G) in CCPD we used icodextrin or glucose for the long daytime dwell. During the night-time dwells glucose was used in all patients. In case of peritonitis icodextrin was continued. In all patients ultrafiltration (UF) was recorded and serum icodextrin metabolites were determined every 3 months and during peritonitis in I-users when available. RESULTS: Thirty-eight patients ( 19 G, 19 I) entered the study and suffered 30 peritonitis episodes (16 G, 14 I). During peritonitis (P), daytime dwell UF decreased significantly in G (P=0.001), but remained stable in I patients compared to non-peritonitis (NP) episodes. Total 24-h UF decreased in G (P=0.001) and in I patients (P=0.04), as the result of a decreased daytime UF and night-time UF, respectively. There was no difference in the used glucose concentrations during the P versus NP episodes. In five I-patients serum disaccharides increased from 0.05+/-0.01 to 1.26+/-0.23mg/ml during follow up. During peritonitis serum disaccharide concentrations did not increase further (1.47+/-0.24 mg/ml, P= 0.56). In I patients total carbohydrate minus glucose rose to 5.72 +/- 1.2 mg/ml during follow up, and to 6.63 +/- 1.04 mg/ml during peritonitis (P=0.7). These concentrations are comparable to CAPD patients despite the longer dwelltime in CCPD (8-10 versus 14-16 h, respectively). Adverse reactions attributable to icodextrin were not encountered. CONCLUSIONS: In contrast to glucose, icodextrin preserved the daytime dwell ultrafiltration during peritonitis. Serum icodextrin metabolites increased during icodextrin use, but remained stable during peritonitis. Adverse effects were not observed.

Diameter of inferior caval vein (VCD) and bioelectrical impedance analysis (BIA) for the analysis of hydration status in patients on hemodialysis.

BACKGROUND: Vena cava diameter (VCD) measurement is an accepted method to evaluate hydration status in patients on hemodialysis. Bioelectrical impedance analysis (BIA) is a less laborious method to assess hydration variables and more suitable for routine patient care. However, BIA has not yet been validated in dialysis patients. We investigated whether BIA can replace VCD in patients on hemodialysis. METHODS: In 20 stable hemodialysis patients [age (+/-SD): 47+/-17 yrs, dialysis duration (+/-SD): 76+/-59 months] hydration status was evaluated by VCD. Impedance variables such as resistance, reactance and phase angle were provided by BIA. They were used to calculate intracellular water (ICW), extracellular water (ECW) and total body water (TBW). RESULTS: VCD did not correlate with TBW-BIA, but correlated with ECW/TBW (r = 0.46; p<0.025), ECW/m2 (r = 0.42; p<0.005) and ICW/ECW (r = -0.49; p<0.005). Hemodialysis decreased TBW with 2.7+/-1.91. The difference in ECW before and after dialysis (8.9+/-1.3 and 7.4+/-1.41, respectively) was significant (p = 0.001). The same did not hold true for ICW (13.3+/-1.4 and 13.1+/-1.41). Major underhydration (n = 9; VCD <6.5 mm/m2) revealed sharp limits for ICW/ECW (>1.80) and ECW/TBW (<0.35), whereas these BIA-variables were significantly (p<0.005) different from those in minor underhydration (n = 8; 6.6 < VCD <8.0 mm/m2), normohydration (n = 15; 8 11.5 mm/m2). CONCLUSION: BIA can replace VCD only in major underhydration (VCD < 6.5 mm/m2). Fluid loss during hemodialysis is caused by a decrease of ECW, compatible with the postulation that excess fluid volume is carried by the extracellular compartment.

Four-site skinfold anthropometry (FSA) versus body impedance analysis (BIA) in assessing nutritional status of patients on maintenance hemodialysis: which method is to be preferred in routine patient care?

BACKGROUND: Both four-site skinfold anthropometry (FSA) and bioelectrical impedance analysis (BIA) claim to be useful in routine clinical practice of maintenance dialysis as easy methods to assess nutritional status. The purpose of this study was to investigate which of these two methods is to be preferred. METHODS: Both before and after dialysis nutritional and hydration status were evaluated by BIA in 20 stable hemodialysis patients. Variables of nutritional status as lean body mass (LBM) and body fat (BF) were assessed by four-site skinfold anthropometry (LBM-FSA and BF-FSA) and BIA (LBM-BIA and BF-BIA). Variables of hydration status were total body water (TBW), its distribution into intracellular and extracellular compartments (ICW and ECW, respectively) and ICW/ECW. RESULTS: Weight loss during dialysis correlated with a change of LBM-FSA (r = 0.75, p <0.005) and also with that of LBM-BIA (r = 0.69, p < 0.005). To promote reliability of follow-up measurements in intervention studies it is warranted to evaluate nutritional status in an unchanged hydration status. The highly significant correlation (r = 0.93, p < 0.005) between the two techniques and the comparability between means and SD indicate that both techniques were almost equivalent to each other, although, compared to LBM-BIA, LBM-FSA was less affected by changes in fluid status. The sam held true for BF-BIA and BF-FSA. BF-FSA correlated significantly with BF-BIA (r = 0.65, p <0.005), whereas no difference of mean +/- SD was found between BF-FSA and BF-BIA. CONCLUSION: FSA and BIA are almost comparable techniques to assess both LBM and BF, although FSA is less affected by changes in fluid status. However, assessing LBM in normohydration is mandatory. Compared with FSA, BIA is able to establish hydration status and lacks depency on operator interpretation. Therefore, in routine patient care the BIA technique is the one to be preferred.

Detection of hydration status by total body bioelectrical impedance analysis (BIA) in patients on hemodialysis.

The purpose of the present study was to investigate whether total body bioelectrical impedance analysis (BIA) could be appropriate to assess normohydration (i.e. dry weight) in hemodialysis patients. This study is warranted, because the simultaneous assessment of both hydration and nutritional status by BIA requires the presence of a situation of normohydration in order to guarantee valid conclusions about the nutritional analysis. Segmental bioelectrical impedance was performed to classify patients according to their hydration status. BIA measurements revealed significant differences in TBW, ECW and ICW/ECW between three hydration subgroups (under-, normo-, and overhydration), whereas ICW was similar. Therefore, TBW, ECW and ICW/ECW appear appropriate variables to assess hydration status in patients on hemodialysis. Hemodialysis diminished ECW significantly, whereas ICW did not change, suggesting that a decrease of ECW explains the fluid loss during hemodialysis.

Icodextrin instead of glucose during the daytime dwell in CCPD increases ultrafiltration and 24-h dialysate creatinine clearance.

BACKGROUND AND METHODS: Icodextrin 7.5% is an iso-osmolar, glucose polymer-containing peritoneal dialysis solution with an ultrafiltration potential similar to glucose 3.86%. We compared in an open, randomized, prospective study the ultrafiltration potential of icodextrin with that of glucose during the daytime dwell of 23 patients treated with automated peritoneal dialysis (CCPD). RESULTS: Daytime ultrafiltration volume and 24-h ultrafiltration volume increased significantly in icodextrin-treated patients (n = 11) at 3 and 6 months, allowing patients a less rigid fluid restriction or an adapted treatment schedule. This improved the patients' subjective well-being. Although ultrafiltration at 9 and 12 months also increased it did not reach statistical significance. Similar to the gain in ultrafiltration volume, 24-h dialysate creatinine clearance per 1.73 m2 (DCl/1.73 m2) and DCl/1.73 m2 per litre used dialysate (DCl/1.73 m2/l) increased in icodextrin-treated patients. DCl/1.73 m2/l per litre ultrafiltrate (DCl/1.73 m2/l/UF) did not increase. No side-effects of icodextrin were encountered, although serum disaccharide levels increased. CONCLUSION: Icodextrin enhances ultrafiltration during the daytime dwell in CCPD patients. As a result of an increased 24-h ultrafiltration volume, DCl/1.73 m2 and DCl/1.73 m2/l improve. DCl/1.73 m2/l/UF does not rise, which suggests that the increase in DCl/1.73 m2 and DCl/1.73 m2/l is caused by convective transport.

Assessment of total body water and lean body mass from anthropometry, Watson formula, creatinine kinetics, and body electrical impedance compared with antipyrine kinetics in peritoneal dialysis patients.

BACKGROUND: Indirect methods such as anthropometry (A), Watson formula (W), creatinine kinetics (CK), and body electrical impedance (BEI) are increasingly applied to determine total body water (TBW) and lean body mass (LBM) in dialysis patients. These methods share the disadvantage that they have been validated for healthy men only. We studied which of these four commonly applied methods can best be used routinely in CAPD patients. METHODS: TBW estimates obtained from A, W, CK, and BEI were compared with those obtained by a gold standard (antypirine distribution volume, ADV) in eight CAPD patients. In addition, several BEI equations to derive lean body mass (LBM) were compared with LBM estimated by ADV in order to determine which equation is the most valuable for the assessment of LBM by BEI in CAPD patients. RESULTS: TBW as ADV was 41.4 +/- 6.6 (mean +/- SD) L. TBW estimated by W, A and CK underestimated ADV by a mean +/- SD of 2.3 +/- 13, 5 +/- 8.4 and 12.3 +/- 10.9% respectively. TBW as measured by BEI overestimated ADV by 2.5 +/- 8.8%. The correlation coefficients between ADV-TBW and TBW estimated by the indirect methods were r = 0.88 (A), r = 0.87 (BEI), r = 0.82 (CK), and 0.68 (W). LBM estimated by ADV was 56.7 +/- 8.9 (mean +/- SD) kg; LBM by different BEI equations ranged from 49.9 +/- 7 to 58.1 +/- 10.7 kg. The correlation coefficient between LBM by ADV and LBM according to the various BEI equations ranged from 0.81 to 0.93. CONCLUSION: A and BEI can be used to estimate TBW, but the considerable SD (or inaccuracy) makes individual predictions hazardous. Considering the correlation coefficients and difference between LBM by ADV and LBM according to different BEI equations, Deurenberg's formula can be advocated for use in the estimation of LBM by BEI.

Serum disaccharides and osmolality in CCPD patients using icodextrin or glucose as daytime dwell.

OBJECTIVE: To evaluate the safety, efficacy, and biocompatibility of icodextrin- and glucose-containing dialysis fluid during continuous cycling peritoneal dialysis (CCPD), patients were treated for 2 years with either icodextrin- or glucose-containing dialysis fluid for their daytime dwell (14-15 hours). Prior to entry into the study, all patients used a standard glucose solution (Dianeal 1.36%, 2.27%, or 3.86%, Baxter, Utrecht, The Netherlands). DESIGN: Open, randomized, prospective, two-center study. SETTING: University hospital and teaching hospital. PATIENTS: Both established and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18, those with peritonitis in the previous month, and women of childbearing potential, unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients entered the study, and 25 (13 glucose, 12 icodextrin) had a follow-up period of 12 months or longer in December 1996. MAIN OUTCOME MEASURES: Serum icodextrin metabolites: one to five glucose units (G1-G5), a high molecular weight fraction (G > 10), and total carbohydrate level, as well as a biochemical profile were determined every 3 months in combination with all other study variables. RESULTS: In icodextrin-treated patients, serum disaccharide (maltose) concentrations increased from 0.05 +/- 0.01 (mean +/- SEM) at baseline, to an average concentration in the follow-up visits of 1.14 +/- 0.13 mg/mL (p < 0.001). All icodextrin metabolites increased significantly from baseline, as illustrated by the serum total carbohydrate minus glucose levels: from 0.42 +/- 0.05 mg/mL to an average concentration in the follow-up visits of 5.04 +/- 0.49 mg/mL (p < 0.001). At the same time, serum sodium levels decreased from 138.1 +/- 0.7 mmol/L to an average concentration in the follow-up visits of 135.4 +/- 0.8 mmol/L (p < 0.05). However, after 12 months the serum sodium concentration increased nonsignificantly (NS) from baseline to 136.6 +/- 0.9 mmol/L, after an initial decrease. Serum osmolality increased significantly from baseline in icodextrin users at 9 and 12 months, but did not differ significantly from glucose users in any visit. In icodextrin-treated patients, the calculated serum osmolal gap increased significantly from 4.1 +/- 1.4 mOsm/kg to an average of 11.8 +/- 1.7 mOsm/kg (p < 0.01). The sum of the serum icodextrin metabolites in millimoles/liter equaled the increase in osmolal gap. Body weight increased in icodextrin users (71.9 +/- 2.8 kg to 77.8 +/- 3.0 kg; NS). Clinical adverse effects did not accompany these findings. Residual renal function remained stable during follow-up. CONCLUSIONS: The serum icodextrin metabolite levels in the present study increased markedly and were the same as those found previously in continuous ambulatory peritoneal dialysis patients treated with icodextrin, despite the longer dwell time for CCPD patients (14-16 hr versus 8-12 hr). The initial decrease in serum sodium concentration was followed by an increase to a concentration not different from baseline at 12 months. The pathophysiology of this finding is speculated. Calculated osmolal gap in icodextrin patients increased significantly (p < 0.01) at every follow-up visit, and could be explained by the serum icodextrin metabolite increase. We encountered no clinical side effects of the observed levels of icodextrin metabolites.

Chronic renal failure and sexual functioning: clinical status versus objectively assessed sexual response.

BACKGROUND: Sexual dysfunctions are common among patients with chronic renal failure. The prevalence was assessed in a population of 281 patients (20-60 years), and it was attempted to determine whether their mode of treatment (haemodialysis, peritoneal dialysis, or kidney transplantation), or biochemical and endocrine variables and neuropathy affect sexual functioning. Patients with rheumatoid arthritis served as a comparison group. METHODS: Assessment included clinical history, physical and laboratory examinations, questionnaires measuring erotosexual dysfunctions, and a psychophysiological test procedure. The latter is a laboratory method which measures, in a waking state, subjective and physiological sexual arousal. RESULTS: Men on haemodialysis or peritoneal dialysis suffered significantly more often from 'Hypoactive Sexual Desire Disorder', 'Sexual Aversion Disorder' and 'Inhibited Male Orgasm' than men with kidney transplantation or rheumatoid arthritis. Interestingly, the prevalence of 'Male Erectile Disorder' did not differ significantly between the four groups and ranged between 17 and 43%. Of the women, transplanted patients suffered significantly less from 'Hypoactive Sexual Desire Disorder' than the other three groups; the prevalence of other sexual dysfunctions did not differ between the groups. Although 'Male Erectile Disorder' and 'Female Sexual Arousal Disorder' had a relatively high prevalence there were no differences in the four groups of patients in genital responses during psychophysiological testing. Genital responses during psychophysiological assessment had no relationship to the duration of renal replacement treatment, biochemical/endocrine variables, or the presence/ absence of neuropathy. CONCLUSION: The prevalence of sexual dysfunction was high. Sexual dysfunction in men on haemodialysis or peritoneal dialysis was not so much due to erectile failure but largely to loss of sexual interest, subjectively ascribed to fatigue. The latter was also found in women on haemodialysis or peritoneal dialysis.

Biocompatibility of a 1.1% amino acid-containing peritoneal dialysis fluid compared to a 2.27% glucose-based peritoneal dialysis fluid.

The biocompatibility of a 1.1% amino acid-containing peritoneal dialysis fluid (AA-PDF) was compared to that of a 2.27% glucose-based peritoneal dialysis fluid (G-PDF). Peritoneal macrophages (PMO), isolated from the peritoneal dialysis (PD) effluents of 10 chronic ambulatory PD patients, were tested for their phagocytosis capacity and peak chemiluminescence response. A subset of PMO was cultured for 24 h with and without lipopolysaccharide (LPS) to study the release of interleukin-1 beta (IL-1 beta) and 8 (IL-8). As control, the interleukin release by blood monocytes of healthy donors was tested. The opsonic activity of the PD effluent was tested as well. Compared to PMO isolated from G-PDF, PMO from AA-PDF showed a significantly better phagocytosis capacity. There was no difference in the peak chemiluminescence response between PMO from AA-PDF and G-PDF. The release of IL-1 beta by unstimulated PMO isolated from the two fluids did not differ. Compared to control monocytes, however, PMO from both fluids showed a considerable spontaneous release of IL-1 beta. When stimulated with LPS, IL-1 beta production by PMO from G-PDF exceeded that of PMO from AA-PDF (p < 0.002). The release of IL-8 by PMO from G-PDF was significantly higher in comparison with PMO from AA-PDF, both spontaneously and after stimulation with LPS (p < 0.02). The opsonic activity of undiluted and to 75% diluted effluents was significantly higher for G-PDF than for AA-PDF (p < 0.01). Thus, compared to the regularly used G-PDF, the phagocytosis capacity as measure for PMO function seems to be better preserved after in vivo exposure to AA-PDF. In addition, the higher release of IL-1 beta and IL-8 by PMO isolated from G-PDF suggests a stronger intra-abdominal activation of PMO, with G-PDF acting as a chemical inflammatory agent. Whether the lower opsonic activity of the AA-PDF is more important for biocompatibility than the other parameters is not clear. Therefore, it is concluded that, although macrophage function is better preserved, it is not proven that the 1.1% AA-PDF studied has an improved biocompatibility compared to 2.27% G-PDF.

Acute renal failure in patients with severe civilian trauma.

We reviewed our experience with patients suffering from civilian trauma to identify risk factors for the development of acute renal failure (ARF) and ARF outcome. Of the 437 patients consecutively admitted to a surgical intensive care unit (SICU), 206 had a SICU stay of at least 1 day and ARF developed in 30 of these patients. All ARF patients had additional organ system failure (OSF). Pre-existing chronic disease (including chronic renal failure), malnutrition, injury severity score (ISS), number of organs injured, sepsis, and all OSFs before the onset of ARF were factors predisposing to ARF. Mortality was 40%. Chronic disease, malnutrition, ISS, failure of cardiovascular, pulmonary, hepatic, and neurological systems (either before and after ARF) were significantly associated with mortality. When OSFs were considered in their temporal relationships to ARF, only cardiovascular and pulmonary failure before, and gastrointestinal failure after, the onset of ARF were related to mortality. An increasing number of OSFs increased mortality, both before and after the development of ARF. However, the number of OSFs before was significantly greater than after ARF. Sepsis was not associated with increased mortality. Thus, the outcome of ARF patients with critical trauma seems to be dependent on factors predisposing to ARF. Our results suggest that more attention must be paid to prevention of these precipitating conditions.

Citrate anticoagulation and divalent cations in hemodialysis.

Anticoagulation with citrate in combination with a calcium-free, magnesium-containing dialysate (Ca-Mg+) and intravenous supplementation of calcium is a safe procedure in renal failure patients at high risk of bleeding. Since magnesium may antagonize the anticoagulant effect of citrate by forming complexes with citrate, we studied the in vitro and in vivo interactions of calcium and magnesium on citrate anticoagulation. In the in vitro studies the activated partial thromboplastin time (APTT) was 88 s, both after addition of 3.0 mumol magnesium and after addition of 1.0 mumol calcium. The combination of 2.4 mumol magnesium and 1.0 mumol calcium achieved similar APTT values of about 35 s as 3.5 mumol calcium alone. Moreover, in a Lee-White blood clotting time, the anticoagulant effect of 7 mumol citrate was neutralized by either 10.5 mumol of a mixture of the two cations or 10.5 mumol calcium chloride alone. In 6 chronic hemodialysis patients the in vivo interactions of calcium and magnesium on citrate were measured. At the dialyzer outlet, the whole blood activated clotting time (ACT) was significantly (p < 0.05) shorter during dialysis with a Ca-Mg+ dialysate than during dialysis with a calcium- and magnesium-free dialysate (Ca-Mg-). With the Ca-Mg- dialysate the ACT at the dialyzer outlet was still significantly longer than the ACT in the arterial line before citrate infusion. We also compared the serum concentrations of calcium and magnesium during the Ca-Mg- dialysate which was used in combination with intravenous calcium and magnesium supplementation - 0.18 and 0.08 mmol/min respectively--and during a conventional calcium- and magnesium-containing dialysate (Ca+Mg+).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibacterial peritoneal defence in automated peritoneal dialysis: advantages of tidal over continuous cyclic peritoneal dialysis?

In tidal peritoneal dialysis (TPD) only a part of the infused dialysate is drained with each exchange, leaving a residual volume on top of which fresh fluid is cycled. As the persistent presence of a buffered intraperitoneal reserve volume might favour peritoneal macrophage (PMO) function, PMO obtained from eight patients during a 3-h continuous cyclic peritoneal dialysis (CCPD) or TPD session were studied in a randomized cross-over trial. PMO were studied for uptake of E. coli (complement-dependent) and S. epidermidis (antibody-dependent), as well as for their killing capacity and peak chemiluminescence response. In addition, dialysate was sampled during both treatment sessions and studied for pH, osmolality, and effect on the viability of donor phagocytes and mesothelial cells. TPD-derived PMO were significantly better able to phagocytose E. coli than CCPD-PMO (48 +/- 8 versus 33 +/- 6% uptake, P < 0.05), whereas the other tested functional capacities revealed no significant difference between TPD- and CCPD-PMO. During TPD dialysate pH ranged from 6 to 7 as compared to a pH range from 5 to 7 in CCPD. The presence of a residual dialysate volume resulted in less wash-out of cells and opsonins early in the treatment, and to some extent blunted the noxious effects of fresh dialysis solutions. Overall, however, tidal PD appeared to have no advantage over CCPD regarding preservation of peritoneal defences.

In vivo exposure to the currently available peritoneal dialysis fluids decreases the function of peritoneal macrophages in CAPD.

Previous in vitro studies have revealed that the currently available peritoneal dialysis fluids (PDF) inhibit several functions of phagocytic cells. To investigate the clinical relevance of those in vitro findings, we compared the in vivo effect of PDF pH on peritoneal macrophage (PMO) function in chronic peritoneal dialysis patients. In a randomized crossover setting, each of eight patients used exclusively PDF at pH five (D5) or pH seven (D7) on day one. The next day the patients who used D5 were switched to D7 and vice versa. Likewise the effect of glucose-mediated hypertonicity was studied in eight other patients, using PDF with 1.36% glucose (D136) or 3.86% glucose (D386). PMO were isolated from the effluents and studied for their phagocytic and killing capacity, and their ability to mount a respiratory burst (chemiluminescence response). PMO obtained after the intraperitoneal instillation of D7 were significantly better able to phagocytize both S. epidermidis (65 +/- 9 vs 37 +/- 8% uptake, p < 0.005) and E. coli (43 +/- 8 vs 25 +/- 4% uptake, p < 0.005). In addition, PMO harvested from D7 effluents revealed a significantly higher killing capacity than PMO derived from D5 effluents for S. epidermidis (60 +/- 5 vs 38 +/- 6%, p < 0.005) as well as for E. coli (51 +/- 10 vs 25 +/- 9%, p < 0.025). Moreover, PMO derived from D7 effluents mounted a significantly higher respiratory burst as compared to PMO in vivo exposed to D5 for the same time.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute renal failure in patients with acute pancreatitis: prevalence, risk factors, and outcome.

A total of 267 consecutive patients presenting with acute pancreatitis were studied retrospectively. We analysed the collected data to determine the prevalence of acute renal failure (ARF), and factors significantly predisposing to its occurrence and outcome. The prevalence of ARF in our patients was 16%. Only 2% had isolated ARF. Seventy-three percent of patients with additional organ system failure suffered ARF after the onset of other organ failure. The number of organ system failure was significantly greater before, compared to after, the development of ARF. Using multiple logistic regression we found that pre-existing chronic disease and cardiovascular and haematological failure were independent risk factors positively related to the development of ARF, whereas systemic infection was not. Overall mortality from ARF was 81%. Chronic disease, local complications and the presence of additional organ system failure and their number significantly increased mortality in ARF patients. No patients requiring renal replacement therapy survived. ARF is a common complication of severe acute pancreatitis, but occurs late in the disease course, and mostly preceded by other organ system failure. The prognosis of patients with ARF is extremely poor, indicating that more emphasis should be placed on prevention of ARF.

Effect of changes in daily protein intake on renal function in chronic renal insufficiency: differences in reaction according to disease entity.

Protein restriction is advocated in patients with chronic renal insufficiency (CRI) in an attempt to slow down further renal function deterioration, with the most obvious effect in patients with chronic glomerulonephritis (GN) and diabetic nephropathy, and much less in other disease entities, such as adult polycystic kidney disease (APKD), tubulointerstitial nephritis (TIN) and nephrosclerosis (NS). The mechanism by which protein restriction slows down the progression of renal failure remains unclear. Decline of hyperfiltration has been implicated. Whether long-term protein restriction in patients with CRI is associated with a decrease in hyperfiltration is not clear. We studied the effects of prolonged protein intake variation (isocaloric diets in 4-week periods of low (goal: 30-40 g protein daily) and high protein intake (goal: 80-90 g daily) on renal function in 51 patients with CRI. Patients were divided into subgroups according to the underlying renal disease (GN, n = 17; APKD, n = 9; TIN, n = 12; NS, n = 13). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured at the end of each study period. Overall, GFR rose from 39 (9-90) to 46 (9-100) ml/min/1.73 m2 (median and ranges, p < 0.01), and ERPF from 158 (39-558) to 171 (32-676) ml/min/1.73 m2 (p < 0.01). GFR rose significantly in GN (15%, range -23 to 51%), APKD (5%, range -10 to 33%), and NS (8%, range -8 to 25%). ERPF only rose significantly in GN (14%, range -45 to 47%) and APKD (9%, range -9 to 25%).(ABSTRACT TRUNCATED AT 250 WORDS)

Non-invasive conductivity method for detection of dynamic body fluid changes: in vitro and in vivo validation.

Since intracellular and extracellular fluid volume (ICV, ECV) cannot be measured under dynamic circumstances, a non-invasive conductivity technique was developed for this purpose. To validate the technique, experiments in vitro and in vivo were performed. In vitro, dilution of blood led to a variation in haematocrit, which could be calculated accurately by means of the low-frequency conductivity value combined with the plasma conductivity value. Combination of high- and low-frequency conductivity values made calculation of haematocrit possible without measuring plasma conductivity. Changes in mean cellular volume, caused by addition of osmotically active substances, were detectable in the same way. Haemolysis of blood cells was performed to validate the intracellular conductivity. For in vivo validation the effects of position change (erect to supine) and of 40 mg frusemide i.v. were investigated. Position change caused a significant decrease in ECV and tended to increase blood volume (BV). Frusemide caused a mean iso-osmotic urine production of 1.8 +/- 0.2 litres. ECV decreased 12.3 +/- 2.0% (P < 0.05), while ICV increased 5.0 +/- 3.0% (P < 0.05). BV decreased by 7.0 +/- 5.4% (P < 0.05), while mean blood pressure increased (P < 0.05). Changes in both ECV and in ICV were correlated with diuresis (r = 0.88 and r = 0.85 respectively; P < 0.01). The ICV increase was unexpected and might be caused by an aldosterone-induced transcellular sodium influx. From both studies it can be concluded that non-invasive conductivity measurements are reliable for detecting changes in ECV and ICV under dynamic circumstances.