Search

Background: Uraemia and chronical haemodialysis are associated with an abnormal growth hormone (GH)-insulin-like growth factor (IGF) axis which may contribute to malnutrition and renal bone disease. Short-term studies have shown a beneficial effect of treatment with recombinant human growth hormone (rhGH) on nutritional status in patients on haemodialysis. In the present study, we evaluated the effect of rhGH on bone and mineral metabolism. [ABSTRACT FROM PUBLISHER]

HLA-DRB1*03:201 differs from HLA-DRB1*03:01 in exon 3 at codon 178 resulting in a proline to serine substitution., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hepatic lipid metabolism is highly dynamic, and disruption of several circadian transcriptional regulators results in hepatic steatosis. This includes genetic disruption of the glucocorticoid receptor (GR) as the liver develops. To address the functional role of GR in the adult liver, we used an acute hepatocyte-specific GR knockout model to study temporal hepatic lipid metabolism governed by GR at several preprandial and postprandial circadian timepoints. Lipidomics analysis revealed significant temporal lipid metabolism, where GR disruption results in impaired regulation of specific triglycerides, nonesterified fatty acids, and sphingolipids. This correlates with increased number and size of lipid droplets and mildly reduced mitochondrial respiration, most noticeably in the postprandial phase. Proteomics and transcriptomics analyses suggest that dysregulated lipid metabolism originates from pronounced induced expression of enzymes involved in fatty acid synthesis, β-oxidation, and sphingolipid metabolism. Integration of GR cistromic data suggests that induced gene expression is a result of regulatory actions secondary to direct GR effects on gene transcription., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Macrophages play an important role in the development of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). In this study, we investigated the hepatic expression of the macrophage scavenger receptor CD163 and the plasma level of its shed soluble form (sCD163) in patients with obesity and NASH, non-NASH NAFLD (NAFL), or healthy livers (no NAFLD)., Methods: Paired liver biopsies and plasma samples were collected from 61 patients with obesity (body mass index ≥35). Hepatic expression of CD163 was analyzed by immunohistochemistry and data-independent acquisition mass spectrometry, whilst plasma levels of sCD163 were determined by enzyme-linked immunosorbent assay and data-independent acquisition mass spectrometry. NAFLD stage and activity were assessed using the Kleiner fibrosis and NASH Clinical Research Network (NAS-CRN) scoring system., Results: sCD163 turned out as a promising predictor of NASH with an area under the receiver-operating characteristic curve of 0.78 [0.65;0.92] ( P  = .0008 ). sCD163 increased with more severe NAFLD both in univariate (odds ratio [OR] = 3.31[1.80;6.11], P < .001) and multivariable ordinal logistic regression adjusting for NAFLD risk factors (OR = 2.02 [1.03;3.97], P  = .042 ). On the other hand, hepatic expression of CD163 was negatively associated with more severe NAFLD in univariate ordinal logistic regression determined by immunohistochemistry (OR = 0.91[0.84;0.98], P  = .015 ) and proteomics (OR = 0.13[0.02;0.80], P  = .028 ). Taking NAFLD risk factors into account, hepatic expression of CD163 was only associated with the fibrosis stage (OR = 0.01 [0.0003;0.21], P  = .004 ). Accordingly, hepatic CD163 surface expression and sCD163 were negatively correlated (rho = -0.478, P  = .0001 )., Conclusion: An increased plasma sCD163 and a concurrent decreased hepatic expression of CD163 are strongly associated with NAFLD in obese patients., (© 2023 The Authors.)

Liver fibrosis is a strong predictor of long-term mortality in individuals with metabolic-associated fatty liver disease; yet, the mechanisms underlying the progression from the comparatively benign fatty liver state to advanced non-alcoholic steatohepatitis (NASH) and liver fibrosis are incompletely understood. Using cell-type-resolved genomics, we show that comprehensive alterations in hepatocyte genomic and transcriptional settings during NASH progression, led to a loss of hepatocyte identity. The hepatocyte reprogramming was under tight cooperative control of a network of fibrosis-activated transcription factors, as exemplified by the transcription factor Elf-3 (ELF3) and zinc finger protein GLIS2 (GLIS2). Indeed, ELF3- and GLIS2-controlled fibrosis-dependent hepatokine genes targeting disease-associated hepatic stellate cell gene programs. Thus, interconnected transcription factor networks not only promoted hepatocyte dysfunction but also directed the intra-hepatic crosstalk necessary for NASH and fibrosis progression, implying that molecular "hub-centered" targeting strategies are superior to existing mono-target approaches as currently used in NASH therapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Efficient genome editing methods are essential for biotechnology and fundamental research. Homologous recombination (HR) is the most versatile method of genome editing, but techniques that rely on host RecA-mediated pathways are inefficient and laborious. Phage-encoded single-stranded DNA annealing proteins (SSAPs) improve HR 1,000-fold above endogenous levels. However, they are not broadly functional. Using Escherichia coli, Lactococcus lactis, Mycobacterium smegmatis, Lactobacillus rhamnosus and Caulobacter crescentus, we investigated the limited portability of SSAPs. We find that these proteins specifically recognize the C-terminal tail of the host's single-stranded DNA-binding protein (SSB) and are portable between species only if compatibility with this host domain is maintained. Furthermore, we find that co-expressing SSAPs with SSBs can significantly improve genome editing efficiency, in some species enabling SSAP functionality even without host compatibility. Finally, we find that high-efficiency HR far surpasses the mutational capacity of commonly used random mutagenesis methods, generating exceptional phenotypes that are inaccessible through sequential nucleotide conversions.

The aim of this study was to study the efficiency and the adverse effects of 2 or 4 IU/m2/day of growth hormone (GH) in the first year and 4 IU/m2/day in the second. Of 29 growth-retarded children with chronic renal failure (CRF) (aged 3.4-15.1 years), 23 completed the first year of therapy, and 16 completed the second year. Height velocity SDS (HVSDS) increased in the first year in the low-dose group with 3.0, and 3.8 in the high-dose group. In the second year, HVSDS increased by 1.3 in the low-dose group and by 2.1 in high-dose group (p < 0.05). The IGF-I/IGFBP-3 ratio rose identically during the first year (p < 0.01). The retarded bone age did not advance inappropriately. The integrated insulin levels (AUC) increased significantly after 1 year of therapy in both groups. HbA1c, levels did not change. The number of adverse events was highest in the low-dose group, in which one patient developed overt insulin dependent diabetes mellitus. In conclusion, glucose metabolism should be monitored in children with CRF during rhGH-treatment. GH therapy in our patients resulted in a significant increase in height velocity with no inappropriate bone age progression and few serious adverse effects, all without relation to the dose of rhGH. The low start dose (2 IU/m2/ day) was of no advantage compared to the high dose.

Background: Many adult patients in chronic hemodialysis exhibit malnourishment and muscle wasting, which in some may be due partly to blockage of the biological action of growth hormone and the somatomedines. Growth hormone (GH) promotes protein synthesis, and long-term treatment with growth hormone has induced an augmentation in lean body-mass (LBM) in normal elderly persons, in persons with GH deficiency as well as growth improvement in uremic children. The purpose of this study was to evaluate the effect of long-term GH treatment on soft tissues in hemodialyzed patients by dual-energy X-ray absorptiometry (DXA) with special regard to the improvement in lean body mass and fat mass (FM)., Design: The study was double-blinded, randomized, and placebo-controlled. Twenty enfeebled patients in chronic hemodialysis were treated by subcutaneous injections of biosynthetic human GH (4 IU/m2 per day) or placebo, given every evening for 6 months. Soft tissues as LBM and FM, were measured by DXA scan, and height, and weight were recorded before, and after 6 months treatment. Serum concentration of insulin-like growth factor (IGF-I) and type III collagen N-terminal propeptide (PIIINP) were analyzed at baseline and after 2, 4 and 6 months., Results: Six months of GH therapy induced a total FM reduction of 3.05 +/- 0.75 kg (mean +/- SEM) (p < 0.001) (n = 9) corresponding to 25% of the total fat mass. The reduction in fat was most marked at the trunk, i.e. 1.39 +/- 0.41 kg (p < 0.001) corresponding to 40% of the total FM reduction. Total LBM increased by 3.14 +/-0.41 kg (p < 0.001) in the GH group. Regional changes for arm, truncus and leg in GH group amounted to 0.22 +/- 0.06 kg (p < 0.001), 1.64 +/- 0.37 kg (p < 0.001) and 0.51 +/- 0.06 kg (p < 0.001), respectively. In contrast, total body weight remained unchanged. Serum IGF-I increased from 199 +/- 14.8 microg/l to 527 +/- 111 microg/l (p < 0.0001) at month 6, and the serum PIIINP from 7.8 +/- 1.3/microg/l to 14.3 +/- 2.1 microg/l (p < 0.001) in the GH-treated group. In the placebo group (n = 11) there were no significant changes in FM, LBM or PIIINP while serum IGF-I decreased from 285 +/- 36 microg/l to 219 +/- 35 microg/l (p < 0.01) after 6 months treatment., Conclusions: Six months of GH therapy to patients with chronic renal failure resulted in marked changes of the soft tissue with an increase in LBM, and reduction of FM particularly at the trunk. The data imply that GH-induced changes in body composition are maintained with long-term therapy. Very few side-effects of GH treatment were observed, and no serious ones were encountered, though the dosage were 2 to 3 times higher than the one given to GH-insufficient, non-uremic persons, and the serum IGF-I concentrations during treatment equalized those seen in acromegalia. This indicates the existence of a reduced biological effect of GH and IGF-I in uremic persons.

Background: Adult patients with chronic renal failure (CRF) often show symptoms as fatigue, wasting, and reduced working capacity with concomitant findings of reduced cardiac performance and muscle mass. This state may in part be caused by an imbalance in the somatostatin/somatomedine axis resulting in increased catabolism. During an attempt to correct this catabolic state by administration of exogenous growth hormone, cardiac muscle mass and performance were studied., Methods: In a double-blind, placebo-controlled 6-month study comprising 20 adult enfeebled hemodialysis patients, 9 patients were treated with a single daily subcutaneous injection of recombinant human growth hormone (rhGH) 4 IU/m2 and 11 with placebo injections. Left ventricular muscle mass (LVM) and ejection fraction (EF) were evaluated by echocardiography and the maximal working capacity (MWC) was measured by a bicycle exercise test performed before and after the treatment period. Supplementary electrocardiography (ECG) was performed before and after 6-month treatment., Results: Median LVM increased significantly from 172 to 220 g (p = 0.03) in the rhGH-treated group, while an insignificant decrease was observed in the placebo group from 281 to 200 g (p = 0.3). The EF showed no significant changes in the two groups. MWC showed a slight, insignificant decrease in both groups. From ECG no significant ST deviations were found and no significant changes regarding B-Hb, blood pressure or pulse were observed in the two groups. Irregular heart rhythm aggravated in one patient during the first month of treatment with rhGH, but was overcome by a -blocking agent., Conclusion: The treatment with rhGH of adult chronic hemodialysis patients for 6 months increased the left ventricular mass significantly, but without any effect on ejection fraction or maximal working capacity. No electrocardiographic signs of ischemia were associated with the increasing muscle mass and only one patient developed symptoms that might relate to ischemia. No changes in B-Hb, blood pressure or pulse were observed during the treatment period.

Background: Growth deficiency and malnutrition in uremic children are often caused by malfunction of the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis and can be corrected by treatment with GH. The purpose of this study was to evaluate the levels of GH, IGF-I and II and their binding proteins compared to changes in body composition in adult, enfeebled, uremic patients in chronic hemodialysis (HD), treated for 6 months with recombinant human growth hormone (rhGH)., Methods: 31 patients were included in a controlled, randomized, double-blinded study using either 4 IU/m2/day of rhGH or placebo injected subcutaneously every evening for 6 months., Results: Fasting levels of GH were normal at start and increased significantly from 2.2 to 13.5 microg/l (p = 0.01) within the first 4 months of rhGH treatment. Before treatment IGF-I was at the upper limit of normal range (130 to 220 microg/l) in both groups, and it increased significantly from 213 to 348 microg/l (p = 0.01) during rhGH treatment. IGF-II was above the normal range in both groups, and remained unchanged throughout. IGFBP-1 decreased in the rhGH-treated group from 53.1 to 24.7 microg/l (p = 0.004), while IGFBP-3 increased from 5620 to 7100 microg/l (p = 0.004). The molar ratio of IGF-I/IGFBP-3 increased significantly from 14 to 25% (p = 0.01), while the ratio decreased in the placebo group (p = 0.01). During the treatment with rhGH the patients increased their lean body mass (= muscle mass) by a median of 3.18 kg (range 0.82 to 5.12 kg) (p = 0.0001) while their fat mass decreased by a median of 3.33 kg (range 0.18 to 5.82 kg) (p = 0.004). Total body mass (= weight) remained stable. No significant changes were observed in the placebo group., Conclusion: The baseline GH and IGF-I concentrations were normal in malnourished HD patients. When treated with rhGH in a dosage as used in growth-retarded uremic children, IGF-I increased to the levels seen in acromegalic persons. IGF-I increased more than IGFBP-3 whereby its biological activity obviously improved. This was reflected in an increased muscle mass and a decreased fat mass. The rhGH treatment was well tolerated.

Background: Uraemia and chronical haemodialysis are associated with an abnormal growth hormone (GH)-insulin-like growth factor (IGF) axis which may contribute to malnutrition and renal bone disease. Short-term studies have shown a beneficial effect of treatment with recombinant human growth hormone (rhGH) on nutritional status in patients on haemodialysis. In the present study, we evaluated the effect of rhGH on bone and mineral metabolism., Methods: Twenty chronic malnourished patients on haemodialysis took part in a double-blind, placebo controlled trial with subcutaneous injections of rhGH (4 IU/m2/day) or placebo for 6 months., Results: During rhGH treatment, serum IGF-1 increased 264 +/- 52% (mean +/- SEM) (P < 0.008). There were no significant changes in biochemical markers of mineral metabolism (serum ionized calcium, phosphate and parathyroid hormone). Among markers of bone metabolism, there was a significant increase in serum procollagen type I C-terminal propeptide (maximum 155 +/- 8%, P < 0.001) and no significant changes in serum alkaline phosphatase. Bone densitometry showed a significant decrease in whole body bone mineral content (95.7 +/- 1.2%) after 6 months treatment. The effects on the proximal femur were not significant., Conclusion: The effects of 6 months treatment with rhGH seen in this study are best explained by a GH- or IGF-1-induced increased bone turnover. Long-term treatment in larger cohorts followed by bone densitometry and, preferentially, bone histomorphometry are needed to evaluate whether this is a beneficial effect in haemodialysis patients.

Using an ELISA technique, the aminopropeptide of type I procollagen (PINP) was measured in serum from patients with chronic renal failure treated with haemodialysis (HD) (n = 19) or continuous ambulatory peritoneal dialysis (CAPD) (n = 14), and compared to the commonly used bone markers. The serum concentrations for PINP, compared to healthy controls were significantly increased in both the HD-group (p < 0.00001) and the CAPD-group (p < 0.00001). In the HD-group a close correlation was found between PINP and parathyroid hormone (PTH) (R(s) = 0.745; p = 0.00026) and between PINP and total alkaline phosphatase (R(s) = 0.623; p = 0.004), but in the CAPD-group the corresponding p-values were 0.17 and 0.06 only. No significant difference was found between the HD and CAPD patients with respect to serum levels of PINP, PTH, total alkaline phosphatase, or ionized calcium. In the HD-patients, a significantly higher level of serum phosphate was found compared to in the CAPD-patients. The present study demonstrates a close correlation between PTH, total alkaline phosphatase and PINP, which indicates that PINP might be used as a marker for evaluating increased bone turnover in patients with chronic renal failure treated with haemodialysis, and perhaps also in patients treated with peritoneal dialysis, and that the ideal biochemical parameters to analyse changes in bone metabolism in these patients may be a combination of the initiating hormone (PTH) and PINP as a marker of the effect of PTH on bone metabolism.

In a double-blind, placebo-controlled trial of recombinant human growth hormone (rhGH) comprising 20 chronic enfeebled haemodialysed patients, the clinical benefit of daily growth hormone treatment for six months was evaluated. Nine patients (five male, four female) were treated with rhGH 4 i.u./m2/day and eleven with placebo (seven male, four female). Their mean age was 46.5 years (range 18-68). No difference in mean age was found between the groups. A significant increase in insulin-like growth factor I (IGF-I) was observed in the rhGH-treated group (200 to 527ng/ml, p = 0.01), while a decrease was noticed in the placebo group (285 to 219ng/ml, p = 0.02). S-GH did not change significantly in either group, and there were no differences between the two groups in terms of weight, haemoglobin, s-albumin, -urea or -creatinine, which all remained unchanged during the trial. Patients' lean body mass, as measured by DXA-scanning, increased significantly in the rhGH-treated group (43.4 to 46.7kg, p = 0.004), while no change was observed in the placebo group (44.9 to 45.2kg, p = 0.76). The changes in lean body mass between the two groups were significant, p = 0.001. Left ventricular muscle mass increased significantly (227 to 286g, p = 0.03) in the rhGH-treated group, but not in the placebo group (292 to 253g, p = 0.3). The changes in left ventricular muscle mass between the two groups were significant (p = 0.02). The maximal working capacity decreased slightly and insignificantly in both groups, when measured by bicycle ergometry. Isometric muscle contraction force and endurance did not change significantly in either group. Patients' opinion about the influence of the treatment on their general well-being and working capacity, evaluated blindly on a subjective scale, improved significantly in the rhGH-treated group (9.7 to 12.6, p = 0.02), while no change was experienced in the placebo group (9.9 to 10.7, p = 0.2). No difference was however demonstrable between the two groups (p = 0.4). Thus we conclude that adult patients in long-term haemodialysis treated with rhGH experienced an increase in their lean body mass and left ventricular muscle mass. This increase in muscle mass did not, however, improve muscle contraction force or endurance when measured objectively. The rhGH-treated patients nevertheless had a subjective feeling of a slight improvement in their general wellbeing.

Change in bone mineral content (BMC) was evaluated in a longitudinal trial comprising 12 women and 11 men with chronic renal disease treated with CAPD and 1-alpha-OH-D3 for 2 years. The patients served as their own controls. No patients were treated with steroids. Median age was 54 and 60 years for women and men respectively. No significant difference in 1-alpha-OH-D3 dosage or serum 1,25(OH)2D3 was found between the genders in the study period. Bone mineral content at the distal radius deteriorated significantly in the females with a median decrease of 12% over 2 years, i.e. approximately 6% per year (P < 0.001 and 95% confidence limits 8-20%). No significant change was noted in the males. There was no correlation between age and BMC change. Serum total alkaline phosphatase decreased nonsignificantly in both sexes. Total serum calcium increased significantly (P < 0.05) and serum phosphate decreased significantly (P < 0.05) in the women. Serum albumin and body weight decreased significantly in the males (P < 0.01 and P < 0.05) while no change was seen in the females. The demonstrated decrease in BMC in the female patients of approximately 6% per year exceeds the commonly observed loss of 1-2% per year in healthy women when measured with the same technique. Tentatively, the severe mineral loss in the women could indicate a sex-hormone-related disturbance in bone metabolism of uraemic females.

During long-term peritoneal dialysis (PD) treatment, the biocompatibility of the dialysis fluid is one of the factors that determine the functional integrity of the peritoneal mesothelium and stroma, and the alertness and functional capacity of the peritoneal host defense system. In vitro studies show that conventional acidic lactate-based PD solutions (LB fluids) are detrimental to some of the more important functions of the peritoneal cell system including mesothelial and white blood cells. The main toxic components of the fluids are the high hydrogen ion content (pH = 5-5.6), high lactate concentration, and osmolality. Some toxic side effects can be omitted using bicarbonate-based fluids (BB fluids), in which lactate has been replaced by bicarbonate and the pH has been normalized (7.2-7.4). The present paper is an overview of the biocompatibility tests and studies performed using bicarbonate-based continuous ambulatory peritoneal dialysis (CAPD) fluids. While the final long-term clinical evaluation of the BB fluids is still missing, biocompatibility tests indicate that these fluids are less toxic to many cell systems than the conventional acidic LB fluids. BB fluids with a high glucose content remain cytotoxic. The BB fluids are well tolerated in animal studies. Some BB fluids increase the ultrafiltration in short-term animal studies when compared with LB fluids. The few animal studies failed to demonstrate a better preservation of the peritoneal membrane integrity by BB fluids. The difference in cell toxicity between LB and BB fluids as measured in vitro also seems detectable during the first 30 min of intraperitoneal dwell in man.

To evaluate the initial antibiotic regime of cephalothin monotherapy in the treatment of peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD), the frequency of peritonitis was registered retrospectively together with the frequency of recurrent episodes and change of antibiotic. A median frequency of 0.96 episodes per year of dialysis was found. In 24% of the episodes no microorganism was cultured. 82% of the microorganisms were gram-positive cocci, 17% gram-negative rods. The frequency of recurrent episodes was 7%. The initial antibiotic treatment with cephalothin had to be changed in 33% of the cases due to microbial resistance. In another 33% the antibiotic treatment was changed to something with a narrower spectrum. More than one third of the resistant microorganisms were methicillin-resistant coagulase-negative staphylococci. With quick and reliable microbiological diagnostic technique that makes it possible to change the antibiotic treatment early, we find cephalothin to be a suitable initial monotherapy.

A theoretical analysis of the noise properties of an Er-doped superfluorescent fiber source is presented. The optimum fiber design with respect to the signal-to-noise ratio and output power is found.

Indications of some bio-incompatibility of fluids used for continuous ambulatory peritoneal dialysis (CAPD) have been found previously. We have tested cytotoxicity of an frequently used dialysis fluid, Dianeal, and a new bicarbonate-based dialysis fluid with a pH of 7.4, called 87b, in a model system of quiescent fibroblasts. The ATP level of the cells and release of lactate dehydrogenase was followed during incubation in the dialysis fluids. A marked cytotoxicity of Dianeal was found mainly due to a low pH (5.0-5.5) and to a minor degree because of the lack of potassium and glutamine. 87b was less cytotoxic but it also lacked potassium and glutamine.

Five different bicarbonate-based continuous ambulatory peritoneal dialysis (CAPD) solutions (pH: 7.0-7.4; bicarbonate: 10-27 mM; lactate: 20.8-6.7 mM) were produced in order to examine the cytotoxic effects of the different compositions. The migratory capacity of normal human polymorphonuclear (PMN) granulocytes after exposure to the solutions was used as a cytotoxicity assay. All the tested solutions reduced cellular function compared to a standard cell culture medium, but considerable differences between the solutions were observed. The optimal conditions for the PMN migration were at a pH of 7.0 and at bicarbonate and lactate concentrations of 20 mM and 12.5 mM, respectively. Bicarbonate concentrations of more than 25 mM were associated with reduced cellular function as were lactate concentrations of more than 15 mM. The most advantageous CAPD solution regarding cytotoxicity towards normal human PMN's is a combination of a lactate and bicarbonate-based solution, which has a bicarbonate concentration of approximately 20 mM, a lactate concentration of 12.5 mM, and a pH of approximately 7.2.

In a prospective study of intraperitoneal opsonins in 30 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), the IgG concentration, the fibronectin concentration, the specific antistaphylococcal antibody level, and the opsonic activity against Staphylococcus epidermidis were measured in peritoneal dialysis effluent from the initiation of CAPD and monthly for 6 months. Significant correlation was found between the four assays, but the interindividual and intraindividual variations were considerable. No statistically significant correlation was observed between susceptibility of the patients to CAPD-related infectious peritonitis and any of the above-mentioned parameters of humoral defense. We conclude that at the present time it is not feasible to use these assays for the establishment of prognosis with regard to peritonitis in CAPD.

Unlabelled: Human polymorphonuclear granulocytes (PMN) were tested for migration and phagocytosis after exposure to CAPD solutions and effluents sampled during the first hour of dialysis from patients treated with lactate or bicarbonate based CAPD-solutions. The effluents from the lactate based solutions (Dianeal and Lockolys) reduced the migration and enhanced the phagocytosis compared to values obtained in a standard cell culture medium. Both cell functions increased during the dialysis period. In contrast, the cell-function only changed slightly when 87b, a bicarbonate based CAPD-solution (pH = 7.4, [HCO3-) = 29mM), was employed. During the first 30 minutes, the cells performed at a higher level when exposed to the 87b effluent than when exposed to the lactate effluents. The observations further indicated that optimal conditions for PMNs are at a bicarbonate concentration of less than 20 mM and a lactate concentration of less than 15mM., In Conclusion: PMN migration is reduced by both lactate and bicarbonate based CAPD solutions and effluents collected during the first hour of dialysis. The bio-compatibility of CAPD solutions may be improved by combining the lactate and bicarbonate buffering systems in a solution with a concentration of less than 20 mM of bicarbonate and less than 15 mM of lactate.

Previous in vitro biocompatibility studies have shown bicarbonate-based continuous ambulatory peritoneal dialysis (CAPD) fluids to be superior to those based upon lactate/acetate. To evaluate these findings in vivo, 41 rabbits were subjected to CAPD for four weeks in a randomized prospective study using either Dianeal, a commercially available dialysis fluid containing lactate, or 87b, a bicarbonate-based CAPD fluid. Ten rabbits with CAPD catheters, which were flushed with a heparin solution every 36 hours, served as controls. None of the control rabbits showed clinical or histopathological signs of peritonitis, while 8 of 20 in the Dianeal group and 6 of 21 in the 87b group contracted peritonitis. Four rabbits in the Dianeal group had to be sacrificed early due to severe peritonitis. Post mortem examinations, including scanning and light microscopy, did not reveal any macroscopic or microscopic differences among the three groups of noninfected animals. No significant distinctions between the groups could be made for body temperature, weight gain, dialysate volume, dialysate differential leukocyte count, dialysate protein content, and food intake during the course of the study. In conclusion, the present animal model did not reveal any major difference in the biocompatibility between the lactate- and the bicarbonate-based CAPD fluids.

Peritonitis remains the major complication of continuous ambulatory peritoneal dialysis. A review is given of the clinical, microbiological, immunological, and pathogenic aspects of this problem and new fields of research for reducing the incidence of peritonitis are suggested.

Biochemical detection of neutrophils in peritoneal effluents by Cytur-test has been advocated as a fast and reliable bedside test when peritonitis is suspected in patients on continuous ambulatory peritoneal dialysis. The Cytur-test developed a light blue colour when the neutrophil count exceeded 10(8) l-1 in the dialysis effluents, while in urine the same reaction is seen at a neutrophil concentration of 10(7) l-1. The Cytur-test was inhibited by glucose at 25 g l-1 and by albumin at 10 g l-1. However, the median (range) concentrations of glucose and albumin of 60 dialysis effluents was 1.8 g l-1 (0.9-10.6 g l-1) and 1.1 g l-1 (0.3-5.2 g l-1) respectively. Thus, presence of glucose and albumin cannot be the only reason of the reduced reactivity of the Cytur-test in dialysis effluents when compared with urine.

The concentration of leukocytes and the fraction of neutrophil granulocytes are two important criteria in the diagnosis of peritonitis in continuous ambulatory peritoneal dialysis (CAPD). We have found that leukocytes are unstable in dialysis effluents, resulting in false low leukocyte concentrations if not counted immediately. At 25 degrees C the leukocyte count decreases 25%-30% in 4-6 hours. Sampling in tubes containing EDTA and storage at 4 degrees C make the leukocyte concentration stable for 6 hours, while the combination of EDTA and storage at 4 degrees C ensures stability for 24 hours. When samples are handled accordingly, concentrations as high as 2 x 10(8)/L are observed without any clinical signs of peritonitis, especially within the first months of CAPD-treatment. Thus, we suggest a leukocyte-concentration of 2 x 10(8)/L as the diagnostic limit for peritonitis. Concerning fraction of neutrophils a diagnostic limit of 0.50 still seems relevant.

In a double-blind, placebo-controlled trial of rHu-EPO (recombinant human erythropoietin) comprizing 19 haemodialysis patients (rHu-EPO: n = 9, placebo: n = 10) the patients' opinion about the influence of the treatment on the quality of life was investigated. At the commencement of the trial and after eight weeks, a score was registered by means of a structured interview with a range of 0-10 concerning the complaints most frequently expressed by haemodialysis patients. Erythropoietin was effective in the treatment of renal anaemia. In the therapeutic group, the mean haematocrit value increased from 0.206 to 0.338 (p less than 0.0005), while no change in the haematocrit value was observed in the placebo group. In the therapeutic group, significant decreases were found in the interview scores for fatigue, vertigo (p less than 0.001), dyspnoea (p less than 0.0025), muscular weakness (p less than 0.01) and palpitations (p less than 0.05). No significant differences were found in the placebo group. The treatment had no serious side-effects. On the basis of this material, it is concluded that erythropoietin treatment of haemodialysis patients is effective and that a marked improvement in the quality of life can be observed already after treatment for eight weeks.

In a prospective, randomised, double blind controlled trial the adverse reactions, food consumption, changes in blood chemistry including acid-base balance, and anthropometry were studied during two consecutive dialysis periods of 3 months, using either acetate- or bicarbonate-based dialysis fluids. Sixteen chronic, stable patients were included. The dialysis fluid sodium content was fixed at 140 mmol/l during all treatments. Patient complaints and adverse reactions were identical using the two dialysis fluids. No differences were observed regarding blood chemistry except for a less pronounced metabolic acidosis present during bicarbonate dialysis compared to acetate dialysis. A slight but insignificant increment in food consumption and nutritional status was noticed during bicarbonate dialysis. In conclusion, the use of a bicarbonate-based haemodialysis fluid offered no significant advantages compared to an acetate-based one in the haemodialysis of chronic, stable patients.

The alpha 1-acid glycoprotein (orosomucoid) concentration in the serum of 34 uremic patients on chronic hemodialysis was measured twice at intervals of 3 months. In 80% of the cases the concentrations are above normal. Furthermore, the examination showed a correlation between the concentrations at the first and at the second measurement. No change in se-orosomucoid concentration was observed during hemodialysis. We therefore conclude that orosomucoid cannot be used as an acute phase reactant among uremic patients in chronic hemodialysis neither is it very likely that the hyperlipidemia and accelerated atherosclerosis in hemodialysis patients are due to lack of orosomucoid.

Twenty patients on home peritoneal dialysis were studied during two years. The patients dialysed 4--5 times a week, using an average of 78 l dialysis fluid. The dialysis equipment used was either a simplified delivery system or a fully automatic dialysis machine. Despite clinical improvement, serum urea and serum creatinine levels were the same after 12 months of therapy as before. The patients' weight and serum albumin levels remained constant. Only 1 patient developed hyperparathyroidism, otherwise serum calcium levels ranged from normal to subnormal. Fifteen patients did not require blood transfusions. Twenty episodes of peritonitis occurred, an incidence of 0.58%. All patients carried out dialysis themselves without assistance. Three were working full-time, and 5 were able to look after their homes. The rest were able to take care of themselves. Four patients died from causes unrelated to peritoneal dialysis. In selected patients this mode of treatment provides an acceptable alternative to haemodialysis.

The effect of Periactin on the rejection course was examined in 36 kidney allograft recipients. Half of the patients were given 32 mg of Periactin daily as a supplement to the immunosuppressive treatment consisting of prednisone and azathioprine. The other half was given only the latter two medicaments. Rejection crises were treated with intravenous infusion with methylprednisolone. No beneficial effect of the Periactin treatment was demonstrable. Graft survival and kidney functions thus did not differ between the two groups within the first 90 days after the transplantation. The frequency of rejection, on the other hand, was significantly higher in the group treated with Periactin, especially within the first postoperative week. Periactin, apparently, does not offer any advantage as a supplement to the immunosuppressive treatment in human kidney transplantation.

The acid-base characteristics of two peritoneal dialysis solutions containing either lactate or acetate are compared and the time course of changes in intraperitoneal pH following instillation into the abdominal cavity is measured. The concentration of titratable acid (cTA) is 5.58 mmol/l or 7 times as high in solutions containing acetate as in those containing lactate (0.79 mmol/l). The buffer capacity, -dcTA/dpH, is 11.43 and 1.82 mmol/l, respectively. Following intraperitoneal instillation of 1.5 liter of the solutions, the time course is 2-3 times as long before intraperitoneal pH reaches 7 using acetate (18 min) as when using lactate (7 min). The above mentioned difference in acid-base characteristics as well as an individual acetate intolerance is supposed to be the cause for the development of abdominal pains and peritoneal irritation observed in some patients using acetate-containing solutions. 123 mmol/l of sodium bicarbonate is to be added to the acetate solution to raise the pH value from 5.6 to 7.4. Neutralization using sodium bicarbonate will thus result in sodium intoxication of the patient. The use of lactate instead of acetate for peritoneal solutions is advocated.

The frequency of urinary tract and wound infections was studied in 53 patients most of whom had received kidneys from donors without heart action. Urinary infection was demonstrated soon after the transplantation in 46 out of 47 with functioning kidneys. Recurrent infections took place during the first 3 months and still half of the patients were infected or under treatment 6 months after the operation. The urinary infection seems mainly to arise via indwelling catheters. Wound infections were demonstrated in 18 out of the 53 patients and in addition abscess formation took place in 9 of these. In the majority of the infected wounds previous infected drains were demonstrated. In all, 36 of the patients had infected drains, the use of which therefore is to be avoided.