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Biomedical subjects

D G Struijk

Publications and source records attributed to D G Struijk.

At least 55 records · Page 3Linked to original sources

Effect of amino acid based dialysate on peritoneal blood flow and permeability in stable CAPD patients: a potential role for nitric oxide?

Amino acid dialysis solution 1.1% (Nutrineal) contains L-arginine, a substrate for nitric oxide (NO) synthesis. NO causes vasodilation in many organs. To investigate effects of the amino acid dialysis solution on peritoneal permeability and perfusion, standard peritoneal permeability analyses were performed in 10 stable CAPD patients; one with Nutrineal and another with glucose dialysate (Dianeal 1.36%). The mass transfer area coefficient (MTAC) of nitrate and cGMP were calculated to study a possible role of NO. The MTAC of CO2 was measured to estimate peritoneal blood flow. The MTAC of CO2 was higher during the 4-hour dwell with the amino acid solution: median 93 ml/min (amino acid solution) vs. 60 ml/min (glucose solution); p < 0.01. This suggests an increased peritoneal blood flow during the administration of amino acids. Also the MTACs of low molecular weight solutes were greater with amino acids compared to glucose: creatinine 11.6 ml/min vs. 10.0, urea 19.0 vs. 16.6, urate 9.5 vs. 8.0; p < or = 0.01 for all. This points to an increased effective peritoneal surface area during amino acids. The clearances of the macromolecules beta 2-microglobulin and alpha 2-macroglobulin were also greater with the amino acid dialysis solution (p < 0.05), but there was only a small increase in the clearances of albumin and IgG. The increase in albumin loss during the 4-hour dwell with amino acids was only marginal. The MTACs of nitrate and cGMP were similar with the 2 solutions, without evidence of local production of these solutes. No difference was found between the 2 solutions in the dialysate concentrations of the prostaglandins PGE2, 6-keto-PGF1 alpha, PGF2 alpha and TxB2. The transcapillary ultrafiltration rate was higher during the amino acid dwell (p < 0.01), but no significant difference in net ultrafiltration was found, because the lymphatic absorption tended to be slightly greater with amino acids. The difference in transcapillary ultrafiltration with the 2 solutions was probably blood flow dependent, as the peritoneal filtration fraction was essentially the same in the 2 experiments. It is concluded that amino acid dialysis solution had a vasoactive effect. It mainly influenced the peritoneal blood flow and the effective peritoneal surface area. These effects could not be attributed to NO, as judged from nitrate or cGMP MTACs.

Adult↗

Renal function influences interleukin-8 background production by cultured human mesothelial cells.

Previous studies have demonstrated that mesothelial cells (MC) are important in the local host defense system of the peritoneal cavity. Most studies on the function of MC are performed on MC derived from material of patients with normal renal function (NRF). The aim of the present study was to examine differences in interleukin (IL)-8 expression by MC from patients with NRF and from patients with end-stage renal disease (ESRD). Therefore, MC were isolated from the omentum and pleural exudate of patients with NRF, from spent effluent of stable peritoneal dialysis (PD) patients, and from omentum obtained during catheter implantation prior to PD treatment. MC were stimulated with increasing doses of IL-1 beta or tumor necrosis factor-alpha for 24 hours, after which the supernatant was analyzed for IL-8 content. The IL-8 background level of MC isolated from patients with NRF was significantly lower than the IL-8 background level of MC derived from patients with ESRD. Although IL-8 production appeared to be higher in the ESRD MC, this difference was not significant after stimulation. While the overall immunity is depressed in uremia, MC are activated. The relatively high background of IL-8 might lead to an insensitivity of neutrophils by blocking the receptors and explain their impaired chemotaxis in uremia.

Adult↗

Similarities in functional state of the kidney in patients treated with CAPD and hemodialysis.

Differences have been reported in the decline of residual renal function in patients on continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD), but it is unknown whether the urinary handling of water and solutes is similar in these patient groups. Ten CAPD patients with residual renal function were investigated during a clearance period (CP) of 24 hours, and 11 HD patients were investigated during one interdialytic interval of three days. In CAPD patients the urinary volume excretion was 0.65 +/- 0.31 mL/min (mean +/- SD), and the inulin clearance was 3.85 +/- 2.82 mL/min. A negative correlation was found between the peritoneal net ultrafiltration rate and both the urinary volume excretion rate (r = -0.80, p < 0.01) and the fractional sodium clearance (r = -0.69, p < 0.05). In HD patients the urinary volume excretion increased from 0.36 +/- 0.36 mL/min during the initial eight hours of CP (HD-A) to 0.64 +/- 0.29 mL/min during the last ten hours of CP (HD-D, p < 0.05), and the inulin clearance increased from 1.9 +/- 1.3 (HD-A) to 2.9 +/- 1.1 (HD-D, p < 0.005). The fractional sodium clearance increased from 8.5 +/- 5.7% (HD-A) to 14.4 +/- 9.0% (HD-D, p < 0.05). It can be concluded that the fractional excretion of volume and fractional clearance of solutes were similar in patients treated with CAPD and hemodialysis. The most important regulating factor seems to be the volume status influenced by volume removal by peritoneal net ultrafiltration in CAPD patients, and volume expansion during the interdialytic interval in hemodialysis patients.

Adult↗

The standard peritoneal permeability analysis: a tool for the assessment of peritoneal permeability characteristics in CAPD patients.

Peritoneal transport characteristics in CAPD patients are often assessed by the peritoneal equilibration test (PET), which uses a four hour dwell with glucose 2.27% dialysate. From the test, the dialysate/plasma ratio of creatinine (D/PCr), the dialysate/initial dialysate ratio of glucose (D/Do) and net ultrafiltration (NUF, drained minus instilled volume) are calculated. The standard peritoneal permeability analysis (SPA) is a modification and extension of the PET: glucose 1.36% dialysate is used, to which dextran 70 (1 g/liter) is added for the calculation of fluid kinetics. Mass transfer area coefficients (MTAC's) of low molecular weight solutes, clearances of proteins and the change in intraperitoneal volume (delta IPV) can be assessed. In this study the SPA was analyzed, and a comparison with the PET was made. A total number of 138 SPA's was analyzed in 86 different clinically stable patients. Normal values were calculated for both SPA and PET parameters in the same tests. Median (ranges) of comparable transport parameters from SPA and PET were: MTACCr, 10.4 ml/min (5.7 to 19.3); glucose absorption, 61% (35 to 87); delta IPV, 9.5 ml (-761 to 310); D/PCr, 0.76 (0.53 to 1.14); D/D0, 0.37 (0.13 to 0.56); NUF, -75 ml (-675 to 450). The agreement between SPA and PET was analyzed using the method of Bland and Altman. A fairly good agreement was present between NUF and delta IPV. Systematic errors were found when D/PCr and MTACCr were compared: D/P overestimated MTAC mainly in the low range, whereas in the high range values were underestimated. A similar pattern was seen for the transport parameters of glucose. In 40 patients negative net ultrafiltration was present, and possible reasons for this were assessed. In 9 patients no reason could be identified. It can be concluded that the SPA provides useful and extensive information on peritoneal transport parameters. Compared to the PET, the SPA has better discriminative power for the transport of glucose and creatinine.

Adult↗

Analysis of inflammatory mediators and peritoneal permeability to macromolecules shortly before the onset of overt peritonitis in patients treated with CAPD.

OBJECTIVE: To investigate whether changes in peritoneal membrane characteristics and inflammatory mediators in dialysate precede the onset of overt infection during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. DESIGN: CAPD patients with a high peritonitis incidence stored every night bag at 4 degrees C. Routinely, each bag was thrown away after two days. Only if patients developed peritonitis, all bags were delivered for study. Thus, two night bags immediately prior to the first peritonitis bag were available for analysis. A control study was done 14 days after recovery. Dialysate samples were measured for TNF alpha, IL-6, PGE2, 6-keto-PGF1 alpha, TxB2, and serum proteins. The clearance of beta 2-microglobulin was used as an indicator of the effective peritoneal surface area. The intrinsic peritoneal permeability was characterized by the restriction coefficient. RESULTS: Eight episodes occurred in 5 patients. The night dwells available prior to the first peritonitis effluent were drained maximally nine dwells and minimally one dwell before the first peritonitis bag. Dialysate leukocyte counts exceeded 100 x 10(6)/L only on the day of manifest infection. However, bacterial cultures were already positive at least one day before overt infection in four episodes and in three of these cases two days before. No changes were observed prior to peritonitis for the clearance of beta 2-microglobulin or the restriction coefficient. In contrast to these permeability characteristics, the cytokines, TNF alpha and, though less significant, also IL-6, were increased in dialysate one day prior to overt infection, when compared to the values obtained at the control investigation. This was especially evident in effluents drained no longer than two dwells before the first peritonitis bag. Prostaglandin concentrations in dialysate were not different before the onset of manifest peritonitis from the values measured after recovery. CONCLUSION: In this study, the increased effective peritoneal surface area and intrinsic peritoneal permeability during acute infection appeared to be preceded by elevations in the cytokines TNF alpha and, to a lesser extent, IL-6. These increments occurred only very shortly before the onset of clinical symptoms.

6-Ketoprostaglandin F1 alpha↗

Effects of intraperitoneal cyclooxygenase inhibition on inflammatory mediators in dialysate and peritoneal membrane characteristics during peritonitis in continuous ambulatory peritoneal dialysis.

Peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD) can be used as an in vivo model to study the contribution of mediators in dialysate to the regulation of peritoneal permeability. Previously we reported that changes in the peritoneal appearance rates of the cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF alpha) were related to alterations in the effective peritoneal surface area. Changes in the intrinsic peritoneal permeability were mainly related to those in the peritoneal appearance rate of the prostanoid prostaglandin E2 (PGE2) and partly also to that of IL-6. In this intervention study the role of these mediators was further analyzed. Eleven peritonitis episodes were followed on 8 consecutive days from the start of the infection and once after recovery. Indomethacin was given intraperitoneally during the first 3 days. beta 2-Microglobulin clearance was used as indicator of the effective peritoneal surface area. The intrinsic peritoneal permeability was characterized functionally by the restriction coefficient. The 15 peritonitis episodes studied previously served as the control group. This study supports the formerly obtained relationships in two ways. First, significant reductions were observed for peritoneal PGE2, 6-keto-PGF1 alpha, and TxB2 during cyclooxygenase inhibition to 6%, 0.6%, and 9% of the values on day 1, whereas simultaneously the intrinsic permeability was less increased. This indomethacin effect on intrinsic permeability was not entirely significant, probably because of the additional role of IL-6, which was not influenced by indomethacin. Also, the appearance rate of TNF alpha in the effluent was not affected by cyclooxygenase inhibition. Accordingly, the changes in the effective surface area were similar to those in the control group. Second, in 8 of the 11 cases, new rises both in peritoneal PGE2 and in intrinsic permeability occurred after discontinuation of indomethacin. Rebounds were not seen for TNF alpha or IL-6, and, consistently, not for the effective surface area. In conclusion, local cyclooxygenase inhibition results in a less-increased intrinsic permeability during peritonitis but has no effect on the effective surface area. These data support our previous finding that IL-6 and TNF alpha contribute to alterations in surface area, whereas PGE2 is more involved in intrinsic peritoneal permeability changes.

Adult↗

Does impaired transcellular water transport contribute to net ultrafiltration failure during CAPD?

OBJECTIVES: To assess the contribution of transcellular water transport in net ultrafiltration failure during continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Retrospective. SETTING: Renal Unit, Academic Medical Center, Amsterdam. PATIENTS: One group of 6 patients with clinical severe ultrafiltration loss and a group of 10 stable CAPD patients without ultrafiltration problems. INTERVENTION: In all patients, two peritoneal permeability tests were done within one week, using glucose 1.36% dialysate on one day and glucose 3.86% on the other day. Dextran 70 was used as a volume marker. RESULTS: The difference in net ultrafiltration between 3.86% glucose and 1.36% glucose dialysate was 569 +/- 51 mL (control) and 153 +/- 103 mL (poor ultrafiltration group; p < 0.005). The dialysate/plasma (D/P) concentration ratios increased in both groups with glucose 1.36%. When using 3.86% glucose, the D/P ratio decreased in the control group with a median minimum value one hour after completion of inflow. It is possible that sieving of sodium was due to transcellular water transport by crystalloid osmosis during the hypertonic dwell, as a dissociation between the transport of water and sodium is unlikely to occur in transport through the much larger intercellular pores. The D/P sodium ratio after one hour was related to the mass transfer area coefficient (MTC) of creatinine and the percentage of glucose absorption in the control group. No decrease in D/P ratio was found in the poor ultrafiltration group. This suggests impairment of transcellular water transport. No significant differences were present between both groups with regard to MTC creatinine (10.2 and 14.0 mL/min), glucose absorption (71% and 71%), effective lymphatic absorption rate (1.34 and 1.01 mL/min), and residual volume (248 and 178 mL). Only 1 patient in the ultrafiltration loss group continued with CAPD. The others had to be transferred to hemodialysis; 1 of them developed sclerosing peritonitis. CONCLUSION: The sieving of sodium during CAPD may be caused by transcellular water transport. Deficient sieving as assessed by the absence of a decreased D/P ratio after one hour of a hypertonic dwell suggests impairment of transcellular water transport. This is associated with severe ultrafiltration failure. It indicates that failure of transcellular water transport, possibly by glycosylation of specific proteins on the cell membrane, may be considered one of the causes of ultrafiltration failure during CAPD.

Biological Transport↗

Nitrate in stable CAPD patients and during peritonitis.

During continuous ambulatory peritoneal dialysis (CAPD) peritoneal vessels are dilated. Nitric oxide (NO) causes vasodilation in many organs. Nitrate, a stable metabolite of NO, was measured in plasma and dialysate. In 6 stable CAPD patients standard peritoneal analyses were performed. The mass transfer area coefficient (MTAC) of nitrate was 11.5 mL/min (10.0-17.0 mL/min) (median and range). The MTAC of creatinine was of the same order of magnitude: 10.7 mL/min (8.0-14.2 mL/min), although the molecular weight of nitrate is lower (62 vs 113 dalton). The correlation between the MTAC of nitrate and the MTAC of creatinine indicated diffusion from the circulation and not local production of NO (r = 0.71; p = 0.11). Peritoneal permeability is increased in the acute phase of peritonitis, partly caused by extensive vasodilation. The potential role of NO during peritonitis was investigated in 8 CAPD patients with 11 peritonitis episodes in the acute phase and after recovery. The median dialysate/plasma (D/P) ratio of nitrate in the acute phase was 1.47 (range 0.96-2.55), which was higher than after recovery: 1.07 (0.99-1.75), p < 0.05. No relation was found between the D/P ratio of nitrate and the D/P ratio of TNF alpha (tumor necrosis factor). In conclusion, dialysate nitrate levels in stable CAPD patients are likely to be determined by diffusion from the circulation. D/P ratios exceeding 1.0 during the acute phase of peritonitis are probably the result of local NO production. This may contribute to the marked vasodilation during peritonitis.

Acute Disease↗

Dialysate CA125 in stable CAPD patients: no relation with transport parameters.

We investigated dialysate CA125 concentrations (dCA125) and its possible relation to transport parameters in 67 stable CAPD patients. dCA125 can be regarded as a reflection of mesothelial cell mass or mesothelial cell turn-over. In every patient a standard peritoneal permeability analysis (SPA) was done. dCA125 was determined in the effluent of all SPA's. The examinations were done during a 4 h dwell with glucose 1.36%. In 29 tests dextran 70(milligrams) was added for fluid kinetics. dCA125 was positively related to age (p = 0.03) and negatively to the duration of CAPD (p = 0.0003). No correlation existed with peritonitis incidence (p = 0.21). Also, no relationship was present with the mass transfer area coefficient of creatinine, or with net ultrafiltration. The intrinsic permeability to macromolecules, expressed as the restriction coefficient (rc) was also not related to dCA125 (p = 0.14). Data on fluid kinetics showed that neither transcapillary ultrafiltration rate, effective lymphatic absorption rate, the change in intraperitoneal volume (delta IPV) nor glucose absorption were related to dCA125. A subgroup of patients (n = 20) had low CA125 values (< 11 U/ml). They were treated with CAPD for a longer period of time (23 vs 16 months, p = 0.02), and had a higher rc (2.59 vs 2.23, p < 0.0001). The relationship between low dCA125 and duration of CAPD can possibly be explained by vanishing of the mesothelial layer, as has been reported in patients on long-term CAPD. The higher rc of the low dCA125 group is probably also related to duration of CAPD, and not directly to the mesothelial cell mass, as the mesothelium is no osmotic barrier and because no pathophysiological mechanism can explain the relationship between a low mesothelial cell mass and a low permeability to macromolecules. It can be concluded that mesothelial cell mass is negatively related to the duration of CAPD treatment, but mesothelial cells are unlikely to play an important role in transport kinetics.

Adult↗

A prospective study of peritoneal transport in CAPD patients.

A prospective two year follow-up study of the functional characteristics of the peritoneal membrane was conducted in 61 CAPD patients. Peritoneal transport of solutes, calculated by mass transfer area coefficients for urea and creatinine, peritoneal clearances for proteins, percentage of absorption of glucose, as well as net ultrafiltration were measured every four months. After five months on CAPD a decrease was found for the transport of most solutes (P < 0.05, mean values, ml/min/1.73 m2): urea 18.1 to 16.2, creatinine 9.5 to 8.4, IgG 0.049 to 0.040 and alpha 2-macroglobulin 0.020 to 0.015, as well as for the absorption of glucose (57.9 to 53.2%, P < 0.05). Net ultrafiltration increased simultaneously from 44.6 to 100.5 ml/4 hr/1.73 m2, P < 0.05. From five months to two years on CAPD a significant increase in the transport of all solutes except alpha 2-macroglobulin was found, as well as a decrease in net ultrafiltration. Peritoneal transport at the end of the study was not significantly different from the starting values. Our findings indicate an initial effect of CAPD itself on peritoneal transport, probably due to the recent start of the treatment. Baseline values were reached after five months on CAPD. Thereafter a gradual increase in peritoneal solute transport occurred during two years of treatment. This can be explained by an increase in the effective peritoneal surface area.

Adult↗

Fluid and solute transport in CAPD patients using ultralow sodium dialysate.

Transcapillary ultrafiltration during CAPD is determined by the ultrafiltration coefficient of the peritoneal membrane and by Starling forces, the latter being mainly determined by the osmolality of the dialysate. Dialysate sodium concentration decreases during a dwell, implying that: (1) sodium passes the peritoneal membrane to a lesser extent than H2O, and (2) more H2O than sodium is removed in overhydrated patients. We therefore compared two dialysate solutions with similar osmolality, but different sodium concentration (Na+ 129 mmol/liter and 102 mmol/liter). Two peritoneal permeability tests (2 x 6 hrs, dextran 70 as volume marker) with an interval of two days were performed in 10 CAPD patients. Transcapillary ultrafiltration rate was higher with ultralow sodium dialysate (USD) than normal sodium dialysate (NSD): 1.80 +/- 0.16 ml/min versus 1.58 +/- 0.18 (P < 0.01). It was especially higher during the last two hours of the dwell: 0.49 +/- 0.12 ml/min (USD) versus 0.27 +/- 0.13 (NSD). The effective lymphatic absorption rate was not different: 1.01 +/- 0.12 ml/min (USD) versus 1.05 +/- 0.09 (NSD). Using two different kinetic models, the reflection coefficients for glucose, sodium and chloride were 0.032, 0.029 and 0.027 (for the convection model) and 0.033, 0.030 and 0.027 (for the diffusion model). As a consequence the decline in osmotic pressure was more gradual during the exchange with USD. The peritoneal membrane characteristics, that is the effective peritoneal surface area and the peritoneal restriction coefficient, were not altered by the composition of the dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Appearance of tumor necrosis factor-alpha and soluble TNF-receptors I and II in peritoneal effluent of CAPD.

Dialysate and serum concentrations of tumor necrosis factor-alpha (TNF-alpha), soluble TNF-receptor I (sTNFRI) and soluble TNF-receptor II (sTNFRII) were measured during stable and infectious CAPD to determine whether these mediators are released intraperitoneally or derived from the circulation. Dialysate/serum ratios were compared to those of various marker proteins for peritoneal transport and to interleukin-6 (IL-6), which is locally produced. Peritoneal immunoreactive TNF-alpha could be detected in 19 of 20 stable CAPD patients after a night dwell, but only occasionally and in lower concentrations during and after a standard four-hour peritoneal permeability test. Both sTNFRs highly exceeded TNF-alpha dialysate concentrations. In case of peritonitis a median 16-fold increase in dialysate TNF-alpha occurred on the first day, which declined towards control values during a longitudinal follow-up of eight consecutive days. sTNFRI and sTNFRII in dialysate increased three- to fourfold. Their peaks, however, appeared on the second peritonitis day. Bioactive TNF-alpha was only detected when immunoreactive levels exceeded 1000 pg/ml. Serum values of all variables were not altered during infection; sTNFRs exceeded TNF-alpha 300- to 400-fold. During stable CAPD indirect evidence was obtained for transperitoneal transport from plasma to dialysate of TNF-alpha (molecular wt 17 kD), sTNFRI (55 kD) and sTNFRII (75 kD). Dialysate/serum (D/S) ratios were higher, the lower the molecular weight; they were related to D/S ratios of those marker proteins with the nearest molecular weight; D/S ratios were unrelated to the intraperitoneally produced IL-6. Furthermore, the observed D/S ratios were as expected theoretically for their molecular weights.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Clinical significance and detection of individual differences and changes in transperitoneal transport.

A review is given on the pathophysiology of the transport of solutes and fluid during continuous ambulatory peritoneal dialysis. Special attention is paid to the assessment of peritoneal permeability in individual patients, its inter- and intraindividual variability, the effect of systemic disease, some regulatory mechanisms, and alterations observed during long-term continuous ambulatory peritoneal dialysis.

Adult↗

Diurnal blood-pressure variations in haemodialysis and CAPD patients.

The influence of variations in fluid state on diurnal blood pressure was studied by measuring day-time and night-time blood pressure during a 3-day interdialytic period in 10 normotensive and 10 hypertensive haemodialysis patients using Spacelab 90207 Monitors. Ambulatory blood pressure was also measured during 24 h in 11 normotensive and nine hypertensive CAPD patients, and in nine normotensive and 11 hypertensive control patients with a normal renal function. Antihypertensive drugs had been discontinued for at least 3 weeks before the study period. Optimal dry weight in the haemodialysis patients was estimated by echography of the inferior vena cava and in the CAPD patients on clinical grounds. Although in the dialysis patients and controls a significant nocturnal blood pressure reduction was found, day-night blood pressure difference in the dialysis patients was blunted when compared with the control patients. No significant differences in diurnal blood pressure variation was found between the normotensive and the hypertensive patients. Day-night blood pressure differences in the haemodialysis patients did not change during the 3-day interdialytic period. Also the more stable fluid state of the CAPD patients was not associated with significant different diurnal blood pressure variation compared to the haemodialysis patients. We conclude that factors other than changes in extracellular fluid volume are responsible for a blunted day-night difference in blood pressure in dialysis patients.

Adult↗