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Biomedical subjects

J Passlick-Deetjen

Publications and source records attributed to J Passlick-Deetjen.

48 records · Page 3Linked to original sources

Intraindividual comparison of ANP, cGMP and plasma catecholamines between HD and CAPD.

Patients with end stage renal failure have elevated plasma levels of atrial natriuretic peptide (ANP) which seems to be a sensitive parameter of body fluid status. A prospective study comparing patients on hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) was still missing. Six identical patients (59 +/- 10 yrs, residual diuresis 1.3 +/- 0.61, 1 data expressed as means +/- SEM) were studied in the predialysis phase and under steady state conditions on HD and on CAPD. Plasma levels of ANP, cyclic guanosine monophosphate (cGMP), adrenaline, noradrenaline and dopamine were determined. Blood and dialysate samples were repeatedly taken. Ultrafiltration-volume, dry weight and blood pressure were not different between HD and CAPD. ANP and cGMP reached the highest plasma levels in the predialysis phase with 421 +/- 180 pg/ml and 19.8 +/- 6.4 pmol/ml and decreased after the onset of dialysis treatment. On HD mean ANP levels of 279 +/- 175 pg/ml were not significantly different from those on CAPD (320 +/- 213 pg/ml). However, cGMP concentrations on CAPD (15.7 +/- 5.4 pmol/ml) surpassed the values measured on HD (10.5 +/- 3.4 pmol/ml, p less than 0.05). Plasma noradrenaline was markedly elevated in the predialysis phase (421 +/- 180 pg/ml) and decreased under dialysis treatment. Differences between HD and CAPD were not found. Adrenaline and dopamine concentrations fell within the normal range.

Atrial Natriuretic Factor↗

Changes of peritoneal membrane function during long-term CAPD.

Peritoneal equilibration tests (PETs) in patients on CAPD show wide variations. To find out whether these are correlated with time on CAPD, we investigated changes in PET in 97 tests in 86 patients. 46 PETs were performed with a 1.36% glucose solution and 40 PETs with a 3.86% glucose solution at different time intervals. Neither did the intra-individual comparison of 11 patients with 1.36% glucose solution following 1 year of treatment show any significant change nor the inter-individual comparison following a treatment time of 1 and 2 years. There was also no difference using a 3.86% glucose exchange, when the results at the beginning and after 1 year were compared. However, alterations in equilibration ratios were significant after 24 and 36 months of treatment for creatinine (36 months versus 0: p less than 0.005), glucose absorption (36 months versus 0: p less than 0.01) and UF (36 months versus 0: p less than 0.01). No correlation exists between these changes either with the number of peritonitis episodes or with the time of treatment. Though, no single factor could be identified, patients had an increase in peritoneal permeability especially after long-term treatment. Further investigations are necessary to evaluate the reasons for these changes.

Diabetic Nephropathies↗

Continuous flow peritoneal dialysis: solution formulation and biocompatibility.

When peritoneal dialysis was introduced several years ago an important alternative dialysis therapy to hemodialysis was made available for the treatment of end-stage chronic disease. However, a continuous search for new developments and technologies is necessary to find the optimal peritoneal dialysis fluid (PDF) to preserve peritoneal membrane function as long as possible. Conventional PDFs are known to compromise the functional integrity of the peritoneal membrane as a consequence of their acidic pH in combination with their high lactate content, as well as the high concentrations of glucose and glucose degradation products (GDPs) present in currently used conventional solutions. Novel solutions such as bicarbonate-buffered PDF (at neutral pH) display improved in vitro biocompatibility as compared to conventional, acidic lactate-buffered PDF. Since these novel solutions are manufactured in dual-chambered bags they also contain fewer GDPs, thus further reducing their potential toxicity and protein glycation. Clinically the novel solutions reduce inflow pain and improve peritoneal membrane transport characteristics, ultrafiltration capacity, and effluent markers of peritoneal membrane integrity. The concept of continuous flow peritoneal dialysis (CFPD) is another approach to optimize PDF. The technique of CFPD not only enables the individualization of acid-base correction by variable concentrations of HCO3- but may also help to restore peritoneal cell functions by neutral pH, reduced glucose load, diminished GDP content, and reduced advanced glycation end product (AGE) formation, thereby potentially contributing to the improved preservation of peritoneal membrane function.

Animals↗

Solutions for APD: special considerations.

Automated peritoneal dialysis (APD) has become the fastest growing dialysis modality in Europe and the United States in recent years. Freedom from daytime exchanges, flexibility of prescription, performance in recumbent position leading to enhanced treatment efficacy, and a decreased incidence of peritonitis are the main advantages of APD over CAPD. Studies on new developments of glucose-based PD fluids were performed predominantly in CAPD patients. High volumes and frequent APD cycles in patients may aggravate the adverse effects of standard CAPD fluids on the peritoneal membrane with increasing time on PD. New, glucose-based PD fluids with neutral pH, very low concentrations of glucose degradation products (GDPs), containing either lactate or bicarbonate as buffering substances have been introduced into clinical use recently. With these new fluids, various in vitro, ex vivo, and in vivo studies could demonstrate a better preservation of peritoneal cell viability and growth, less inhibited secretory cell functions, a significant reduction in the formation of advanced glycation end products (AGEs), and clinical signs for an improved preservation of peritoneal mesothelial cells indicated by an increase in effluent CA125. One has to be aware, however, that uremia per se prior to initiation of PD, as well as during PD treatment itself, directly impacts on peritoneal membrane structural changes so that new, more biocompatible PD fluids may not be completely sufficient to prevent morphologic and functional changes of the membrane. Due to a strong sodium sieving during APD, PD fluids with sodium concentrations of 125-130 mmol/L may be beneficial. Systematic calcium kinetic studies have not yet been performed in APD patients. APD fluids should offer a calcium concentration range of 1.0-1.75 mmol/L in order to enable an individualized APD prescription. For long-term APD treatment, better knowledge of peritoneal membrane physiology and PD kinetics should promote individualization of prescriptions. New, pH-neutral PD solutions with minimized amounts of GDPs may be a significant step forward to improved membrane preservation during long-term APD treatment.

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.

Amino Acids↗

An amino acid-based peritoneal dialysis fluid buffered with bicarbonate versus glucose/bicarbonate and glucose/lactate solutions: an intraindividual randomized study.

OBJECTIVE: In order to study acute metabolic changes and peritoneal transport, amino acids as osmotic agent and bicarbonate as buffer were tested as new agents in peritoneal dialysis (PD) solutions. DESIGN: In a prospective, cross-over, randomized, intraindividual study, we investigated the acute metabolic changes following the application of three different PD fluids: (1) a 1% amino acid-based PD solution buffered with bicarbonate (34 mmol/L) (Amino/Bic); (2) a 1.5% glucose anhydrous-containing bicarbonate-buffered solution (34 mmol/L) (Glu/Bic); and (3) a conventional 1.5% glucose anhydrous-based dialysis solution with lactate (35 mmol/L) (Glu/Lac). SETTING: University medical center. PATIENTS: Ten nondiabetic patients stable on continuous ambulatory peritoneal dialysis (time on dialysis, 42.5 +/- 21.5 months) were treated and monitored with the test solutions over a 6-hour dwell. Three different study days followed in a randomized order for each patient (interval of 1-3 weeks). Blood and dialysate samples were taken at 0.25, 0.5, 1, 2, 4, and 6 hours. Immediately after the 1-hr dwell (and after sampling), the patients received a standardized breakfast, thereby simulating usual food intake. RESULTS: Following the application of Amino/Bic a significant increase in plasma amino acids occurred, with peak levels (maximum 250% increase) after either the 1-hr or the 2-hr dwell. Before taking the standard meal (0.5 hr, 1 hr), the mean serum glucose level with Amino/Bic was 8% +/- 13% lower than with Glu/Bic (p = 0.06) and 14% +/- 8% lower than with Glu/Lac (p < 0.01). This difference was still significant after the standard breakfast and also for the whole dwell (average serum glucose 0.5-6 hr: Amino/Bic, 91 +/- 6 mg/dL; Glu/Bic, 100 +/- 8 mg/dL; Glu/Lac, 102 +/- 7 mg/dL; p < 0.01 MANOVA). The serum insulin profiles did not differ between the fluids. A transperitoneal protein- and amino acid-related nitrogen loss of 0.49 +/- 0.18 g and 0.48 +/- 0.12 g per dwell was measured using Glu/Bic and Glu/Lac, while a positive balance of 1.80 +/- 0.43 g was achieved with Amino/Bic. The parameters of acid-base status (pH, HCO3, pCO2) remained nearly unchanged in the blood, irrespective of the solution used, while dialysate values differed markedly. No significant differences with respect to ultrafiltration (Amino/Bic, -68 +/- 199 mL/6 hr; Glu/Bic, -51 +/- 89 mL/6 hr; Glu/ Lac, -2 +/- 134 mL/6 hr) and peritoneal creatinine clearance (Amino/Bic, 4.9 +/- 0.6 mL/min; Glu/Bic, 5.1 +/- 0.6 mL/min; Glu/ Lac, 4.8 +/- 0.5 mL/min) were measured. CONCLUSIONS: Our results demonstrate that ultrafiltration and small solute clearance over a 6-hour dwell with a 1% Amino/Bic solution were comparable to those of 1.5% Glu/Bic and 1.5% Glu/Lac. Reduced serum glucose concentrations were found with Amino/Bic and this fluid compensated the transperitoneal protein-nitrogen loss of about three glucose dwells. Bicarbonate buffering (34 mmol/L) did not change blood acid-base status combined with either glucose or amino acids.

Adult↗

Long-term dialysis with low-calcium solution (1.0 mmol/L) in CAPD: effects on bone mineral metabolism. Collaborators of the Multicenter Study Group.

OBJECTIVE: Peritoneal dialysate solutions with conventionally high-calcium (Ca) concentrations (1.75 mmol/L) are now widely replaced by solutions with a lower, more physiological calcium content to prevent hypercalcemia in patients treated with oral calcium-containing phosphate binders and/or calcitriol. While there is still debate on how far the dialysate calcium should be lowered (1.25 mmol/L or less), little information is available concerning the effects of a long-term treatment with low-calcium solutions on secondary hyperparathyroidism and bone mineral metabolism in general. DESIGN: A prospective, randomized, controlled multicenter study to compare the effects of low-calcium (LCa, dialysate calcium 1.0 mmol/L) versus standard-calcium dialysate solution (SCa, dialysate calcium 1.75 mmol/L) on bone mineral metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients over 2 years of treatment. SETTING: Nephrology and dialysis units of primary and tertiary hospitals in Germany and Switzerland. PATIENTS: All CAPD patients in the participating centers between 18 and 80 years of age, stable on CAPD for at least 1 month, free of aluminium bone disease or prior parathyroidectomy were invited to enter the study. Sixty-four patients could be randomly allotted to LCa (n = 35) or SCa (n = 29) treatment in a 2-year protocol; 34 finished the study as planned. INTERVENTIONS: Calcium carbonate (CaCO3) was given as oral phosphate binder to maintain serum phosphate < 2.0 mmol/L. If hypercalcemia supervened, CaCO3 was exchanged stepwise for aluminium hydroxide (Al(OH)3), until normocalcemia was obtained. Patients received calcitriol (0.25 microgram/day per os) if parathyroid hormone (PTH) exceeded the upper limit of normal by a factor of 2 or more. MAIN OUTCOME MEASURES: We assessed total and ionized serum calcium, phosphate, serum aluminum, alkaline phosphatase, osteocalcin, PTH (intact molecule), and phosphate binder intake at regular intervals. Measurements of bone mineral density and hand skeleton x-rays were obtained at the start and after 6 months and 2 years, respectively. RESULTS: With LCa, mean total and ionized serum calcium levels were within the normal range (total Ca: 2.0-2.6 mmol/L; ionized Ca: 1.19-1.32 mmol/L), but throughout the treatment period were significantly lower than with SCa. The incidence of hypercalcemia (> 2.8 mmol/L) was three times higher in patients on SCa, despite the significantly higher amount of Al(OH)3 and less CaCO3 given in this group. In parallel, serum aluminum increased with SCa throughout the study, whereas it was slowly decreasing with LCa. Median PTH levels remained stable at about two times the upper limit of normal over the 2 years of study with LCa. However, 23% of the patients on LCa developed severe hyperparathyroidism, with PTH levels exceeding ten times the upper limit of normal compared to only 10.3% of the patients on SCa. With SCa, median PTH decreased towards near normal levels. Alkaline phosphatase and serum osteocalcin correlated positively with PTH levels. Bone mineral density was in the lower normal range in both groups and remained unchanged at the end of the study. Skeletal x-ray films showed only minor alterations in very few patients in both groups with no correlation to serum PTH or treatment modality. CONCLUSION: In CAPD patients low-calcium dialysate solutions can be used successfully over prolonged periods of time with stable control of serum calcium. The risk of hypercalcemia resulting from calcium-containing phosphate binders and the need to use aluminum-containing phosphate binders is markedly diminished. However, there is a certain risk that severe secondary hyperparathyroidism with long-term LCa therapy will develop, even if normocalcemia is maintained. Thus, LCa dialysis requires close and continuous monitoring of PTH and bone metabolism.

Adult↗

Factors affecting bicarbonate transfer with bicarbonate-containing CAPD solution.

OBJECTIVE: To evaluate bicarbonate fluxes across the peritoneal membrane and bicarbonate gain in patients treated with continuous ambulatory peritoneal dialysis (CAPD) using dialysis solutions with different bicarbonate concentrations. PATIENTS AND DESIGN: Ninety-seven exchanges, using different dwell times and glucose and bicarbonate concentrations were performed in 43 stable CAPD patients. Dialysate effluent bicarbonate concentration and volumes were measured at different dwell times. Net dialytic bicarbonate gain was calculated. Patients' acid-base status was determined at the middle of the dwell. RESULTS: In prolonged dwells (6-12 hours) the dialysate effluent bicarbonate concentration correlated with arterial plasma bicarbonate concentration (F = 129, p < 0.0001), but not with ultrafiltration rate or dialysis solution bicarbonate concentration. In 4-hour dwells, effluent bicarbonate concentration correlated with both plasma bicarbonate concentration and ultrafiltration rate (F = 32.52, p < 0.0001 and F = 4.4, p < 0.05, respectively). The effluent bicarbonate concentration may be predicted from the patient's plasma bicarbonate concentration and net ultrafiltration rate for either a 4-hour or prolonged (6-12 hours) dwell time. Net bicarbonate gain by the patient correlated with ultrafiltration rate, plasma bicarbonate, and dialysis solution bicarbonate concentration (F = 100.56, p < 0.0001 at 4 hours and F = 108.08, p < 0.0001 at 6-12 hours), with the ultrafiltration rate being the predominant parameter. CONCLUSIONS: The effluent bicarbonate concentration is related to plasma bicarbonate concentration, with ultrafiltration playing a marginal role only during short dwells. However, the ultrafiltration rate has a profound effect on net patient bicarbonate gain. Multiple linear regression analysis allows the prediction of the effect of acid-base status, ultrafiltration, dwell time, and dialysis solution bicarbonate content on net patient bicarbonate gain. It seems that bicarbonate content in the CAPD dialysis solution should be progressively increased with increasing solution osmolality.

Acid-Base Equilibrium↗

Clinical experience with a 39 mmol/L bicarbonate-buffered peritoneal dialysis solution.

OBJECTIVE: To investigate the effect on the patient's acid-base status of a 39 mmol/L bicarbonate-buffered continuous ambulatory peritoneal dialysis (CAPD) solution. DESIGN: This was an open, controlled, cross-over, two-center study in 9 patients. After three months of treatment with a 34 mmol/L bicarbonate-buffered solution (t0) patients were switched to a 39 mmol/L bicarbonate-containing solution for four weeks. At the end of the study period (t4) patients were again treated with a 34 mmol/L bicarbonate-buffered CAPD solution for one month (t8). RESULTS: Mean venous plasma bicarbonate level significantly increased during the study and decreased at the baseline level during the control period (t0 = 22.94 +/- 2.54, t1 = 26.74 +/- 3.07, t2 = 28.47 +/- 2.68, t3 = 28.11 +/- 3.56, t4 = 28.71 +/- 3.27, t8 = 24.94 +/- 2.56). Arterial blood pH and plasma bicarbonate significantly increased during the study and significantly decreased at the end of the control period (pH: t0 = 7.37 +/- 0.04, t4 = 7.42 +/- 0.04, t8 = 7.37 +/- 0.06. Bicarbonate: t0 = 21.97 +/- 2.57, t4 = 25.85 +/- 2.02, t8 = 21.87 +/- 2.89). The changes in plasma bicarbonate during the study period were inversely correlated with the metabolic acid production calculated from the protein catabolic rate and with the apparent distribution space for bicarbonate (ABS) of patients. CONCLUSIONS: The 39 mmol/L bicarbonate-buffered CAPD solution improved the patient's acid-base status. Potential undesirable metabolic alkalosis could be prevented by analyzing the ABS and the metabolic acid production of patients.

Acid-Base Equilibrium↗