Severe blood pressure changes are well known in hemodialysis. Detection and prediction of these are important for the well-being of the patient and for optimizing treatment. New noninvasive methods for this purpose are required. The pulse wave transit time technique is an indirect estimation of blood pressure, and our intention is to investigate whether this technique is applicable for hemodialysis treatment. A measurement setup utilizing lower body negative pressure and isometric contraction was used to simulate dialysis-related blood pressure changes in normal test subjects. Systolic blood pressure levels were compared to different pulse wave transit times, including and excluding the cardiac preejection period. Based on the results of these investigations, a pulse wave transit time technique adapted for dialysis treatment was developed and tried out on patients. To determine systolic blood pressure in the normal group, the total pulse wave transit time was found most suitable (including the cardiac preejection period). Correlation coefficients were r = 0.80 ± 0.06 (mean ± SD) overall and r = 0.81 ± 0.16 and r = 0.09 ± 0.62 for the hypotension and hypertension phases, respectively. When applying the adapted technique in dialysis patients, large blood pressure variations could easily be detected when present. Pulse wave transit time is correlated to systolic blood pressure within the acceptable range for a trend-indicating system. The method's applicability for dialysis treatment requires further studies. The results indicate that large sudden pressure drops, like those seen in sudden hypovolemia, can be detected. © The Japanese Society for Artificial Organs 2005.

In this study we evaluated pathogenetic factors and possible mediators of renal and systemic disorders where immunologic mechanisms might be of importance.

An abberant immunoglobulin and IgG-subclass distribution was detected in 103 patients with primary and secondary glomerulonephritis as well as in 38 patients with the systemic disease primary Sjögren 's syndrome or purpura hypergammaglobulinemica (elevated IgG1 and low IgG2 ).

The drug hydralazine, an anti-hypertensive, was considered to cause renal disease on an immunologic base in 17 patients, with autoantibody production (mainly ANA and antibodies to myeloperoxidase).

Dialysis-patients showed adequate antibody responses to vaccination against pneumococci but low responses against hepatitis B, while the IgG-subclass response of the hepatitis B antibody (anti-HBs) was low, but not shown to be significantly different from that of healthy adults.

A therapeutical removal of igG-antibodies with immunoadsorption or plasmapheresis was considered to have a possible adjuvant effect to medical immunosuppressive treatment alone in 44 patients with rapidly progressive glomerulonephritis.

Hepatitis C virus (HCV) is common in dialysis patients and renal transplant recipients. In 20 anti-HCV positive sera from 1988-91 recombinant immunoblott assay (RIBA) was positive in 8 cases and indeterminate in 7, while HCV RNA was present in 13/20 tested sera. In October 1991 17% of our hemodialysis patients were verified or suspected carriers while 11% were verified or suspected carriers in January 1997. Genotype 2b was found in 13/24 tested cases and in 7 amplifiable 2b sequences a strong phylogenetic relationship occurred. In 8 out of 12 RIBA-3 indeterminate sera HCV-RNA was still positive. Awareness and preventive measures limited transmission between patients.

Indeterminate RlBA-results should, also with modem assays, be regarded with caution due to the relative immunodeficiency of uremic patients.

In conclusion renal and systemic diseases may affect the serum immunoglobulins and immunoglobulin G-subclasses, while a study of the specific antibody subclass distributions (anti-HBs) showed no difference in renal (dialysis) patients and healthy adults. Medication (hydralazine) and infection may be triggering factors of various forms of glomerulonephritis. Uremia affects the antibody responses to hepatitis C in dialysis patients. The extent of renal disease as well as the possibility of therapeutic removal of antibodies is also important for the immunologic responses of such disorders.

Background: Antibodies present in coeliac disease may occur in IgA-nephropathy. This raises the question of food intolerance in the disease. Evidence for a true correlation between the two disorders has however been scarce.

Design: Sera from 89 patients with IgA-nephropathy and 13 other patients with IgA deposits in the glomeruli of kidney biopsies were analysed for IgA-antibodies to gliadin, endomysium and tissue transglutaminase (92/102 patients).

Results: Eleven out of 89 (12.4%) of the patients with IgA-nephropathy and five of the 13 others (38%) had elevated titres of IgA-antibodies to gliadin but, in all cases but one, normal IgA-antibodies to endomysium. Patients with IgA-nephropathy and elevated IgA-antibodies to gliadin had elevated total serum IgA more frequently than patients who had not (p<0.01). Two patients with IgA-nephropathy and one with Hennoch Schönlein's purpura had elevated IgA-antibodies to tissue transglutaminase.

Small bowel biopsy in 7 out of 11 IgA-antibodies to gliadin positive patients with IgA-nephropathy was pathologic in three cases (two with Marsh I). One patient with chronic glomerulnephritis also had Marsh I.

Conclusions: We found no increased frequency of verified coeliac disease in 89 patients with IgA-nephropathy. Two patients with IgA-nephropathy and one patient with chronic glomerulonephritis with IgA deposits in the kidney biopsy had a Marsh I histopathology. The findings suggest a possible link of celiac disease to IgA-nephropathy and a role for antibodies to food antigens in this disorder.

We examined the response to hepatitis B vaccination in dialysis patients, and evaluated our vaccination program to hepatitis B virus. No new cases of hepatitis B occurred during the study period, i.e. from 1980 and onwards. Sera were analyzed for anti-HBs in 25 dialysis patients vaccinated at least three times against hepatitis B and 53 health care staff vaccinated three times. The IgG subclass distribution of antibodies to hepatitis B surface antigen (anti-HBs) was determined in 11 dialysis patients and in 45 healthy controls. The antibody response to pneumococci was determined in 29 vaccinated patients.

Results: Ten of 25 (40%) of the dialysis patients had anti-HBs when both tests after the third and/or fourth injections were considered. In four patients a fourth injection was cancelled due to transplantation or bad health, while such data were lacking in 8 cases. In staff 49/53 (93%) of the persons responded with anti-HBs production. In anti-HBs positive patients and controls a significant difference in the response of healthy adults was observed in anti-HBs IgG 1 (p<0.001) vs all other IgG subclasses. Dialysis patients had low levels, or negative findings, in all cases, with lgGI as the highest proportion found (3/11 patients). An antibody response to pneumococcal vaccination was registred in 25 out of 29 dialysis patients (in all 86 %).Dialysis patients respond poorly to hepatitis B vaccine. An anti-HBs subclass response mainly restricted to IgG I was observed in healthy adults, while dialysis patients had low or negative test results affecting all subclasses.

The findings suggest a general deficit in the ability to produce anti-HBs rather than a deficit in the production of a specific subclass of this antibody. Moreover, RBV-vaccination schedules in renal transplant recipients should be started early, as some patients otherwise, due to transplantation or bad health, may not receive a fourth injection.

The antibody response to pneumococcal vaccination indicates that the antigen involved is important in vaccination responses in dialysis patients.

Background. Hepatitis C is frequent problem in dialysis wards.

Design.  A long time (1989–97) follow up of hepatitis C virus (HCV) infection in a Swedish nephrology unit was performed with anti-HCV screening, confirmatory antibody tests, viral RNA detection and molecular characterization. Case histories were reviewed with focus, onset of infection, liver morbidity and mortality.

Results.  In October 1991, 10% (19 of 184) of the patients in the unit (haemodialysis-, peritoneal dialysis and transplanted patients) were verified or suspected HCV carriers, whilst the number at the end of 1996 was 8% (13 of 157). Most patients were infected before 1991 but only in one case from a known HCV-infected blood donor. No new HCV infections associated with haemodialysis occurred during the study period. A total of 13 of 24 viremic patients had HCV genotype 2b, a pattern suggesting nosocomial transmission. This was further supported by phylogenetic analysis of HCV viral isolates in seven. HCV viremia was also common in patients with an incomplete anti-HCV antibody pattern as 8 of the 12 indeterminant sera were HCV-RNA positive.

Conclusions.  Awareness, prevention, identification of infected patients and donor testing limited transmission. Indeterminant recombinant immunoblot assays (RIBA)-results should be regarded with caution as a result of the relative immunodeficiency in uremic patients. Our data indicate nosocomial transmission in several patients.

Clinical and laboratory findings and drug history were studied in 17 patients with suspected hydralazine-associated nephritis, five of whom only had renal disease, while twelve also had extrarenal manifestations. Renal biopsies revealed extracapillary proliferative or focal segmental proliferative glomerulonephritis in 10 patients, and tubulo-interstitial nephritis in five patients. Antinuclear antibody (ANA) was found in 16 patients, but none of the 14 patients tested had antibodies to DNA. Tests for antibodies to myeloperoxidase (anti-MPO) and antibodies to neutrophil cytoplasm antigen (ANCA) were performed by ELISA. Twelve of the 14 patients tested had anti-MPO; five of these 14 patients had ANCA, while one had borderline levels. These findings suggest that hydralazine facilitates the induction of a systemic disease with multiple autoantibody production.

We studied history, renal histopathology and microbiology of an epidemic of acute glomerulonephritis associated with throat infections and uncommon culture results in four neighbour families. A 40-year-old man (index patient) was referred to a university hospital for dialysis and kidney biopsy due to a suspected acute glomerulonephritis. An acute tonsillitis had preceded the condition. Penicillin treatment had been started four days before the discovery of renal failure. Throat swabs were positive for β-hemolytic streptococci, group C (GCS). GCS were also found in throat cultures from his wife and two of their children. The bacteria were typed as Streptococcus constellatus. A third child had S. constellatus expressing Lancefield antigen group G. A neighbour and two of his children fell ill the following week with renal involvement. Throat swabs from both these children were positive for S. constellatus. His third child had erythema multiforme and S. constellatus in the throat while a fourth child had β-hemolytic streptococci group A, Streptococcus pyogenes. Kidney biopsies on the index patient and his neighbour showed an acute diffuse prolipherative glomerulonephritis compatible with acute post-streptococcal nephritis and microbiological analysis of renal tissue revealed in both cases S. pyogenes and S. constellatus. The families had had much contact and had consumed unpasteurized milk from our index patient's farm. In four of seven persons in two additional neighbouring families S. constellatus was found in throat swabs during the same month while two persons carried Streptococcus anginosus expressing the Lancefield C antigen. In conclusion spread of S. constellatus coincided with the occurrence of four cases of acute glomerulonephritis. The two biopsied patients had both S. pyogenes and S. constellatus present in renal tissue. The epidemic either suggested that the outbreak of glomerulonephritis was due to S. pyogenes but coincided with the transmission and colonization of S. constellatus or that the S. constellatus strains were highly pathogenic or nephritogenic and that this organism can be transmitted in such cases.

Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF-23), hepatocyte growth factor (HGF), interleukin-6 (Il-6), high-sensitivity C-reactive protein (hs-CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF-23 and HGF with the earlier recognized inflammatory markers Il-6 and hs-CRP or suPAR. All patients studied had significantly elevated levels of FGF-23, HGF, hs-CRP and suPAR as compared to the controls. Il-6 and hs-CRP correlated for patients (R=0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il-6 and Ln CRP (R 0.28-0.37). Ln FGF-23 correlated only with Ln HGF (r=-0.25) in controls. Ln HGF correlated with ln suPAR (r=0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF-23 with the recognized inflammatory markers Il-6, hs-CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il-6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF-23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.

Hepatitis B is a well known problem in dialysis units. We therefore examined the historical frequency of hepatitis B carriers in our unit, our vaccination program to hepatitis B virus (HBV), the response to hepatitis B vaccine, the IgG subclass response of anti-HBs and the response and IgG subclass response to pneumococcal vaccination (another vaccine) in dialysis patients. From 1970 and onwards 23 HBV carriers were found, but no new cases of hepatitis B occurred during the study period, i.e. from 1980 and onwards.Only one of the carriers was alive by the end of 2001. In four patients liver disease(in one of them liver cirrhosis) may have been a concomitant cause of death. The antibody response to hepatitis B vaccine was significantly lower in patients than in staff. In four patients a fourth injection was cancelled due to transplantation and bad health, while such data were lacking in 8 cases. In anti-HBs positive patients and controls a significant difference in the response of healthy adults was observed in anti-HBs IgG1 (p<0.001) vs all other IgG subclasses. Dialysis patients had low levels, or negative findings, in all cases, with IgG1 as the highest proportion found (3/11 patients). An antibody response to pneumococcal vaccination was registered in 25 out of 29 dialysis patients (in all 86 %). The IgG-subclass vaccination response to pneumococci in 28 dialysis patients was mainly IgG2 and IgG1 but also occurred in IgG3 and IgG4. Prevaccination antibody levels of the controls were higher in IgG1 and IgG2 (p< 0.01) (n=21) than in dialysis patients (n=28). Hepatitis B is nowadays a rare, but still dangerous disease in nephrology units. Dialysis patients have a reduced response to hepatitis B vaccine and vaccination schedules should be started early as some patients otherwise may not receive a fourth injection. The adequate antibody response to pneumococcal vaccination mainly due to IgG2 and IgG1 antibodies indicates that the antigen involved is important in vaccination responses in dialysis patients.

In this paper, the influence from patient anamnesis and haemodialysis session specifications onto the relationship between obtained ultra violet (UV) absorbance and urea concentration in the spent dialysate were discussed. A characterisation of the relationship was done by an intercept value and a slope. Recently, a new a dialysate monitoring device, using UV- absorbance, been developed by our group which has found a relationship between the UV- absorbance and waste products in the dialysate but this relationship vary between patients. In the present investigation, 13 patients performing totally 84 sessions were characterised using 31 possible affecting parameters. Using a multi-regression analysis 11 parameters were found significant as affecting parameters. In a novel mathematical model approach the obtained UV- absorbance and incorporating possible affecting parameters we could predict urea concentration from the UV-absorption in the spent dialysate in the total material of patients and dialysis sessions. For all the 84 sessions R2 between 0.938 and 0.996 were obtained. A performed analysis of variance rejects the assumption of equal conditions for the relationship between diabetics and non-diabetics patients in the material (F=5.2 for intercept and F=14.4 for slope). The urea concentration could be estimated with an accuracy of 11% (one standard deviation) which is normally clinically sufficient. The non-invasive UV -absorption method therefore seems to have great potential for monitoring and control haemodialysis sessions.

2-Mercaptopropionylglycine (2-MPG, tiopronin) has been used successfully in the treatment of cystinuria despite the lack of knowledge of its pharmacokinetics. Therefore methods based on high-performance liquid chromatography and fluorometric detection were developed for quantitative analysis. The total, non-protein-bound, and free (thiolic) tiopronin were measured in plasma using this method.

The phannacokinetic disposition of tiopronin in plasma after intravenous administration was best described by a three exponential function. Plasma concentration time-curves of total tiopronin exhibited a rapid distribution phase, a B-phase corresponding to renal excretion, and a long terminal elimination phase. The latter was the result of strong disulphide binding of tiopronin to proteins. The non-protein-bound tiopronin was eliminated faster judging by its early appearance in urine. Mean bioavailability was 63 % in healthy volunteers with great interindividual variability (range 33-91%).

Multiple dosing studies gave similar pharrnacokinetic parameters as for single dose studies and studies on patients with renal impaitment elucidated the renal clearance of the drug. In vitro studies showed a slow dissolution of the drug dosage form employed. A metabolite, 2-mercaptopropionic acid, was identified and its pharmacokinetics was investigated. The mechanism of action of the drug is discussed based on the results of measuring free tiopronin in plasma.

Primary Sjögren's syndrome (SS) is characterised by inflammation in the lacrimal and salivary glands. The kidneys may be involved, e.g. tubulointerstitial nephritis (TIN) and distal renal tubular acidosis (dRTA). dRTA is often associated with hypocitraturia, and both represent risk factors for the development of urolithiasis. The present investigations were undertaken to evaluate renal tubular function (including -dRTA), glomerular filtration rate (GFR), renal histopathology and mechanisms of stone formation, as well as the serum IgG subclass pattern in patients with SS. Furthermore, patients presenting with urolithiasis and dRTA in absence of sicca symptoms, as well as patients with urolithiasis andhypocitraturia, were studied with respect to autoantibodies and clinical features of SS.

Renal tubular dysfunction, such as dRTA; impaired urine concentrating ability; hypocitraturia; and decreased tubular reabsorption of phosphate (1RP%), was conunonly detected in the SS-patients. Tubular proteinuria (al-microglobulin) and tubular enzymuria (NAG) were primarily associated with decreased GFR.

GFR, investigated with 5Icr-EDTA plasma clearance, was below the reference limit in 33% of SS-patients. An inverse correlation was found between GFR and the extent of tubulointerstitial nephritis (adjusted CTIN score). Decreased GFR was mostly due to TIN, although urolithiasis and upper urinary tract infections may have contributed in some patients.

TIN was demonstrated in most biopsied patients with SS, and the histopathological picture was characterised by mainly focal interstitial inflanunation, tubular atrophy, interstitial fibrosis and a varying extent of glomerular sclerosis.

Fourty-one percent of the SS-patients had formed at least one stone, and calcium phosphate was the main constituent in most stones. All stone formers had dRTA, and most of them had hypocitraturia. Urinary calcium and urate excretion was also significantly higher than in non-stone formers.

The SS-patients often had low serum levels of IgG2, despite high levels of total IgG. Low levels of IgG2 were sometimes associated with infections. A high IgG lngG2 ratio indicated autoimmune disease.

Of 10 patients presenting with urolithiasis and dRTA, anti-SS-A antibodies were detected in eight. Subjective sicca symptoms subsequently developed l-48 years after the presentation of urolithiasis, and objective signs of SS were found in 7 patients.

In a large population of hypocitraturic stone formers, ANA and anti-SS-A antibodies were commonly detected in the women but not in the men. Four of 14 evaluated hypocitraturic women with anti-SS-A antibodies or ANA, fulfilled the criteria for SS.

In conclusion, the present investigations show that 24-hour urinary excretion of citrate is a valuable tool for detection of renal disease in SS, slightly-moderately decreased GFR is not unusual in SS-patients with. renal disease, the "adjusted CTIN score" can be a useful tool for quantifying the extent of tu'bulointerstitial nephritis, and the urine composition in stone formers with SS is similar to that of other dRT A-patients.

The possibility of a Sjögren-related renal disease charcterised by urolithiasis and/or dRTA and antibodies to SS-A, regardless of whether subjective sicca symptoms are present or not, is hypothesised.

Total IgG and IgG subclasses were studied in 34 patients with primary Sjogren's syndrome and 4 with hypergammaglobulinemic purpura. Total IgG was elevated in 30/34 patients with Sjogren's syndrome. IgG1 increase was responsible for the main part of total IgG increase, contrasting with low levels of IgG2. The difference in IgG1/IgG2 ratio between 38 patients as a group and 40 normal controls was statistically highly significant, but was not seen in all patients. Six patients had markedly low levels of IgG2, but only two had severe repeated respiratory infections. These observations probably reflect selective autoantibody restiction to the IgG1 subclass. We conclude that patients with Sjogren's syndrome may be IgG2 subclass deficient despite elevated levels of total IgG, but also that such deficiency in most instances does not cause a tendency to infections. IgG subclass analysis may be of value to characterize polyclonal IgG increase, since IgG1 subclass predominance often indicates autoimmune disease.

PURPOSE:

The aim of this work was to describe a new optical method for monitoring solutes in a spent dialysate using absorption of UV radiation.

METHOD:

The method utilises UV-absorbance determined in the spent dialysate using a spectrophotometrical set-up. Measurements were performed both on collected dialysate samples and on-line. During on-line monitoring, a spectrophotometer was connected to the fluid outlet of the dialysis machine, with all spent dialysate passing through a specially-designed cuvette for optical single-wavelength measurements. The concentrations of several substances of various molecular sizes, electrical charge, transport mechanism, etc. were determined in the dialysate and in the blood using standard laboratory techniques. The correlation coefficient between UV-absorbance of the spent dialysate and concentration of the substances in the spent dialysate and in the blood was calculated from data based on the collected samples.

RESULTS:

The obtained on-line UV-absorbance curve demonstrates the possibility to follow a single hemodialysis session continuously and to monitor deviations in the dialysator performance using UV-absorbance. The experimental results indicate a very good correlation between UV-absorbance and several small waste solutes removed such as urea, creatinine and uric acid in the spent dialysate and in the blood for every individual treatment at a fixed wavelength of 285 nm. Moreover, a good correlation between the UV-absorbance and substances like potassium, phosphate and beta2-microglobulin was obtained. The lowest correlation was achieved for sodium, calcium, glucose, vitamin B12 and albumin.

CONCLUSIONS:

A technique for on-line monitoring of solutes in the spent dialysate utilising the UV-absorbance was developed. On-line monitoring during a single hemodialysis session exploiting UV-absorbance represents a possibility to follow a single hemodialysis session continuously and monitor deviations in dialysis efficiency (e.g. changes in blood flow and clearance). The UV-absorbance correlates well to the concentration of several solutes known to accumulate in dialysis patients indicating that the technique can be used to estimate the removal of retained substances.

Background. Mineral bone disorder (MBD) is a common complication of chronic kidney disease (CKD) even during the early stages. Bone alkaline phosphatase (BALP) is a marker of bone fort-nation and plays a pivotal role in the mineralization process. Three BALP isoforms (B/I, B1 and B2) have been identified in healthy individuals and a fourth isoform (B1x) has been discovered in serum from dialysis patients. We investigated these BALP isoforms, type I procollagen intact amino-terminal propeptide (PINP), carboxy-terminal telopeptide of type I collagen (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRACP5b), as well as bone mineral density (BMD) in predialysis CKD patients. Methods. PINP, CTX, TRACP5b and BALP isoforms were analysed in serum from 46 patients within CKD stages 3-5. BMD was determined by dual-energy x-ray absorptiometry. Results. PINP, TRACP5b and the BALP isoforms, B/I, B1 and B2, were independent predictors of total hip BMD in all patients. Furthermore, B/I predicted osteopaenia in the hip and in the distal 1/3 of the radius in CKD stage 3. The B1x isoform was detected in nine patients (20%), who had lower GFR, higher phosphate and calcium x phosphate product. Conclusion. We found an association of BALP isoforms and other markers of bone turnover with total hip BMD, which predominantly comprises trabecular bone. The association of the new BALP isoform B1x with risk factors for vascular calcification leads us to hypothesize a possible role for B1x in this process. The significance of the BALP isoforms in CKD remains to be further explored in experimental and clinical settings in conjunction with bone histomorphometry.

BACKGROUND:

The primary aim of this study was to assess whether a fixed protocol, using a specially trained team, for intermediate follow-up to fulfillment of guideline targets is non-inferior to conventional follow-up in the care of uraemic patients. A secondary aim was to investigate possible impact on patient outcome.

METHODS:

The cohort comprised 424 patients from seven centers. Inclusion criteria were either serum creatinine exceeding 200 µmol/l or calculated clearance below 30 ml/min, representing CKD 4 or 5a. Six centers followed a standardized protocol (group 1). One center provided controls (group 2). The study design was prospective and interventional. The variables measured were blood hemoglobin, bicarbonate, calcium, phosphate, intact parathyroid hormone, albumin, renal function variables, blood pressure and RAAS blockade. The number of patients achieving the set goals was analyzed as a time trend to determine if the intervention resulted in an improvement.

RESULTS:

At baseline, group 1 had significantly lower GFR and higher serum creatinine, calcium, phosphate, calcium × phosphate product and bicarbonate, lower mean arterial pressure (MAP), systolic blood pressures and less use of RAAS. During the intervention, group 1 improved in the direction of guidelines for blood hemoglobin, albumin, bicarbonate and MAP. Outcome of secondary endpoints gave a risk of death of 30% in both groups, while the risk of renal replacement therapy was higher in group 1.

CONCLUSIONS:

However, the time to renal replacement therapy was significantly shorter in the intervention group, indicating that other variables than guideline achievements are important for the patient.

Uremisk klåda är ett stort problem hos patienter med avancerad njursvikt. En enkätstudie på dialyspatienter visade att omfattningen av problemet var större än förväntat. Att tillfredställande behandla uremisk klåda är svårt och många olika behandlingsalternativ finns. Den enda behandlingen som är riktigt effektiv är njurtransplantation.

The intestinal permeability has been investigated in experimental chronic and acute uremia in rats. The permeability and the mucosal ability to exclude larger molecules have been measured using differently sized polyethylene glycols (PEG 400 and 1000: mean weights of 400 and 1000 dalton, range 326-1162 dalton). The permeation (uptake) of the differently sized molecules has been estimated from the urinary recovery of the PEGs after oral administration of the permeability markers. The effects of two different diets (high-and low-protein) have been studied inexperimental chronic uremia and in normal rats. The renal excretion of the PEGs after intravenous administration has also been investigated in chronic uremic rats. Furthermore, the effect of experimental acute uremia on intestinal brush border peptidases, disaccharidases and mucosal morphology have been studied. Finally has the urinary recovery of PEGs been investigated in patients with renal insufficiency compared to healthy subjects.

The urinary recovery of PEGs was reduced after intravenous administration in chronic uremic rats. The relative excretion of the smaller PEGs was, however, increased compared to the larger ones in the uremic rats. The opposite was found in the control rats. Intestinal permeability, measured as an increased urinary recovery after oral administration of larger PEGs, was increased in chrortic uremic rats.

The overall urinary recovery of the PEG molecules was reduced in patients with renal insufficiency. However, the relative excretion of the differently sized PEGs indicated a relative increased uptake of larger molecules also in uremic patients suggesting a more permeable gut.

An opposite pattern was seen in experimental acute uremic rats, reduced urinary recovery along with a relative decreased excretion of larger molecules compatible with a less permeable gut.

Moreover, both in the chronic uremic and in the control rats treated with low-protein diet was a reduction of intestinal permeability seen.

Increased activity of brush border peptidases was found in acute uremic rats. Minor morphological changes, shortening of the microvilli of the enterocytes in the small intestine were also observed. On the other hand, no alterations of the disaccharidases were measured.

In conclusion, the change in intestinal permeability indicates a more leaky mucosal barrier in chronic uremia. Functional alterations i.e. increased peptidase activity was seen in acute uremic rats. A more leaky gut might allow potentially toxic, infectious and immunogenic substances to pass more freely over the mucosa in chronic uremia.

Objective. To study the patency and complications associated with the Dialock, an access device for haemodialysis. Material and methods. The records of seven Swedish patients who were treated with the Dialock access device between 2000 and 2004 were studied retrospectively. Results. A total of 10 Dialock devices were used in seven patients. The mean period of patency was 16.3±13.8 months. Major complications observed were bleeding in the dose pocket in three patients and infection in four. Three patients experienced no complications. The 1-year patency was similar to that of a newly created arteriovenous fistula used in our unit. Conclusions. In spite of the associated complications, the Dialock is an acceptable access device for haemodialysis patients with vascular access problems. Although the Dialock is no longer available on the market, similar access devices may be of importance in the future. © 2007 Taylor & Francis.

Purpose: To propose a technique for standardizing volume-rendering technique (VRT) protocols and to compare this with maximum intensity projection (MIP) in regard to image quality and diagnostic confidence in stenosis diagnosis with magnetic resonance angiography (MRA). Material and Methods: Twenty patients were examined with MRA under suspicion of renal artery stenosis. Using the histogram function in the volume-rendering software, the 95th and 99th percentiles of the 3D data set were identified and used to define the VRT transfer function. Two radiologists assessed the stenosis pathology and image quality from rotational sequences of MIP and VRT images. Results: Good overall agreement (mean κ=0.72) was found between MIP and VRT diagnoses. The agreement between MIP and VRT was considerably better than that between observers (mean κ=0.43). One of the observers judged VRT images as having higher image quality than MIP images. Conclusion: Presenting renal MRA images with VRT gave results in good agreement with MIP. With VRT protocols defined from the histogram of the image, the lack of an absolute gray scale in MRI need not be a major problem. © 2005 Taylor & Francis.

A therapeutic removal of antibodies may be achieved by immunoadsorption (IA) or by plasma exchange (PE). The aim of this prospective randomised study was to compare the efficacy of these different techniques with regard to treatment of patients with rapidly progressive glomerulonephritis (RPG) having at least 50% crescents. Forty-four patients with a RPG were included for treatment either by IA or PE (with albumin as substitution for removed plasma). All patients were additionally treated with immunosuppression. A median of 6 sessions of PEs were performed in 23 patients compared with 6 IAs in 21 patients. Goodpasture's syndrome (GP) was present in 6 patients (PE 3, IA 3). All of them started and ended in dialysis, two died. Among the remaining 38 patients (26 men, 12 women) 87% had antibodies to ANCA. Creatinine clearance for PE versus IA were at a median at start 17.1 and 19.8 ml/min, and at 6 months 49 and 49 ml/min, respectively. At 6 months 7 of 10 patients did not need dialysis (remaining: IA 0/5 and PE 2/5, n.s.). The extent of improvement did not differ between the groups. Three patients died during the observation period of 6 months (IA 2; PE 1, on HD). Although no difference was found between the IA or the PE group this study shows that the protocol used was associated with an improved renal function in most patients (except for Goodpasture's syndrome) whereas 70% of them could leave the dialysis program.

The objective of the following work was to study the apoptosis inducing effect of puromycin in MCF-7 breast cancer cells and compare this effect with cycloheximide and emetine, 2 other inhibitors of protein synthesis. We also wished to investigate if the apoptosis modulating effect of insulin-like growth factor-1 (IGF-I) was similar for the 3 inhibitors. An immunological assay, quantifying mono- and oligonucleosome fragments and morphological criteria after nuclear staining, were used to study apoptosis. Protein synthesis was measured by incorporation of 3H-leucine in the cells, and solution hybridization and Western blot were performed to estimate IGF-I receptor m-RNA and IGF-I receptor protein respectively. Puromycin at 0.5 μg/ml induced a high level of apoptosis in MCF-7 breast cancer cells, although there was still a non-negligible amount of synthesized protein. In the case of cycloheximide and emetine, apoptosis occured when protein synthesis was almost completely blocked. IGF-I at a concentration of 10 ng/ml significantly reduced the level of apoptosis induced by puromycin, emetine, or cycloheximide. We also noticed a parallel increase in 3H-leucine incorporation when apoptosis induced by puromycin was lowered as an effect of IGF-I, in contrast to cycloheximide and emetine where IGF-I reduced the apoptosis level without increasing the 3H-leucine incorporation. At a higher concentration of puromycin (5. 7 μg/ml), which blocked protein synthesis, IGF-I at 10 ng/ml did not reduce apoptosis. The level of IGF-I receptor m-RNA was not influenced by the use of a concentration of puromycin (0.5 μg/ml) inducing a high degree of apoptosis. These results suggest, that reduction of puromycin-induced apoptosis by IGF-I occurs simultaneously with increased protein synthesis, in contrast to emetine and cycloheximide. Furthermore it would appear that puromycin-induced apoptosis is not caused by reduced levels of IGF-I receptors.

There is evidence suggesting that IgA nephropathy (IgAN) is an immunological disease. The role of FILA class II DR beta 1 (DRB1) has previously not been well studied. The aim of our study was to investigate the association of HLA-DRB1 variants with IgAN in a Swedish Caucasian cohort. Our study consisted of 213 patients with biopsy proven IgAN, all of self-reported Caucasian ancestry. As a control cohort, 1569 healthy subjects from the same population in Sweden were included. HLA-DRB1 low-resolution genotyping was performed and odds ratios were calculated to assess the risk. less thanbrgreater than less thanbrgreater thanIn an allelic model the HLA-DRB1*03 and *10, demonstrated association for IgAN after correction for multiple comparison, with subsequent OR = 0.54 (95% CI 0.37-0.78) and 3.44 (95% Cl 1.67-7.07). When the influence of risk allelic groups was adjusted for protective allelic groups and vice versa, only a protective effect of HLA-DRB1*03 remained significant. less thanbrgreater than less thanbrgreater thanIn conclusion, the variants of HLA-DRB1 were associated with IgAN of which the HLA-DRB1*03 revealed a strong protective effect for IgAN. Our data replicates finding from other Caucasian populations and suggest that involvement of adaptive immunity may be of importance in the development of the disease.

Background. There is growing evidence of genetic risk for susceptibility to IgA nephropathy. Among several candidate genes related to immunological regulation in renal tissue, TGFB1 is known to be a contributor to proliferation and the development of fibrosis. Methods. We analysed several SNPs in a region of this gene using 212 DNA samples from biopsy-proven IgA nephropathy patients, 146 men and 66 women and 477 healthy age-matched controls (321 men and 156 women) from the same population in Sweden. Results. Frequencies of four out of five selected SNPs (rs6957, rs2241715, rs1800471, rs1982073 and rs1800469) were found to significantly differ between male patients and male controls in a co-dominant model (corrected P andlt;= 0.05) and of two SNPs (rs1982073 and rs1800469) in the allelic model (P andlt;= 0.05 in 100 000 permutation test). Haplotype analysis for five selected SNPs revealed a significant association of TGGCG with protective effect (P = 0.0012, empirical P = 0.006, 100 000 permutations) and of CT-GTA with susceptibility effect (P = 0.0018, empirical P = 0.008, 100 000 permutations). In our study, no association with TGFB1 variations was found when comparing female patients and female controls. No association was found for TGFB1 markers with disease progression for selected individuals from the patients group. In addition, meta-analysis performed for SNP rs1982073 for combined patients and controls from our study together with published data from two independent studies showed a significant association. Conclusions. Our experimental data together with the meta-analysis suggest TGFB1 as an important candidate gene for further biological studies of IgA nephropathy and as a possible target for therapy. Our data also indicate a possibility of a gender effect in the genetic background of IgA nephropathy.

Background:

Several methods are available to determine Kt/V, from predialysis and postdialysis blood samples to using on-line dialysate urea monitors or to ionic dialysance using a conductivity method. The aim of this study is to compare Kt/V calculated from the slope of the logarithmic on-line ultraviolet (UV) absorbance measurements, blood urea Kt/V, dialysate urea Kt/V, and Kt/V from the Urea Monitor 1000 (UM; Baxter Healthcare Corp, Deerfield, IL).

Methods:

Thirteen uremic patients on chronic thrice-weekly hemodialysis therapy were included in the study. The method uses absorption of UV radiation by means of a spectrophotometric set-up. Measurements were performed on-line with the spectrophotometer connected to the fluid outlet of the dialysis machine; all spent dialysate passed through a specially designed cuvette for optical single-wavelength measurements. UV absorbance measurements were compared with those calculated using blood urea and dialysate urea, and, in a subset of treatments, the UM.

Results:

Equilibrated Kt/V (eKt/V) obtained with UV absorbance (eKt/Va) was 1.19 ± 0.23; blood urea (eKt/Vb), 1.30 ± 0.20, and dialysate urea (eKt/Vd), 1.26 ± 0.21, and Kt/V in a subset measured by the UM (UM Kt/V) was 1.24 ± 0.18. The difference between eKt/Vb and eKt/Va was 0.10 ± 0.11, showing a variation similar to the difference between eKt/Vb and eKt/Vd (0.03 ± 0.10) and in a subset between eKt/Vb and UM Kt/V (−0.02 ± 0.11).

Conclusion:

The study suggests that urea Kt/V can be estimated by on-line measurement of UV absorption in the spent dialysate.

The Fc-alpha receptor (Fc alpha R/CD89) is involved in IgA complex formation and may affect the development of IgA nephropathy (IgAN). In this study, we tested the genetic variations of the CD89 gene in relation to disease susceptibility in IgAN and the expression of soluble CD89 (sCD89) in sera of patients with IgAN and in controls. There was a significant difference between the levels of sCD89-IgA complexes, measured by sandwich enzyme-linked immunosorbent assay (ELISA), in 177 patients with IgAN with and without disease progression at the time of first diagnosis. No such difference was found in 42 patients with other renal diseases. The patients with IgAN without disease progression had stable but high levels of sCD89 over 5-15 years of follow-up in contrast to stable but low levels of sCD89 in the disease progression group. Moreover, levels of sCD89 complexes were correlated with one of the five CD89 genetic variants in 212 patients with IgAN and 477 healthy Caucasians; the single-nucleotide polymorphism (SNP) rs11084377 was significantly associated with a lower expression of sCD89. However, no association between CD89 gene polymorphisms and susceptibility to IgAN was detected. Thus, we found an association between the levels of sCD89-IgA complexes in serum and the severity of IgAN, and a possible genetic component in regulating the production or expression of sCD89.

Several in vitro and animal studies suggest effects of nicotine on the immune system, but little evidence exists regarding the in vivo immunomodulation of nicotine in humans. The increased use of nicotine replacement therapy to aid smoking cessation claims further understanding of how nicotine affects blood leukocytes. This is of particular importance when nicotine therapy is used in diseases associated with alterations of the immune system, such as chronic renal failure. The present study evaluates the acute effects of nicotine infusion (NI) on some immunoregulatory functions in seven healthy subjects and seven patients with renal failure. All subjects were nicotine users and had refrained from using nicotine for 36h before NI. Blood was collected before, immediately after, and 2h after NI. Plasma concentrations of intercellular adhesion molecule-1 (ICAM-1) and the cytokines interleukin-2 (IL-2), IL-4, IL-10, interferon-? and RANTES were measured using specific immunoassays. The generation of reactive oxygen species (ROS) induced by formyl-methionyl-leucyl-phenylalanine (fMLP), Ristocetin, adenosine 5'-diphosphate, or collagen was registered in whole blood as luminol-dependent chemiluminescence. Except for fMLP, these compounds induce leukocyte ROS generation by platelet mediated mechanisms. NI did not significantly affect the levels of the cytokines and ICAM-1 in any group. The peak and the persistent ROS production, induced by collagen and Ristocetin, was lower at some time points in patients with renal failure as compared to healthy subjects. Also in patients with renal failure, both peak height and persistent ROS generation induced by Ristocetin were reduced immediately after NI. Thus, nicotine inhibits some of the platelet-mediated activation of leukocyte ROS generation, and may be associated with platelet defects in renal failure.

Objective. The aim of this study was to describe the sleep--wake cycle, sleep quality, fatigue and Health Related Quality of Life (HRQoL) measured with questionnaires, actigraphy and a sleep diary during a one-week period in patients undergoing peritoneal dialysis (PD) treatment at home. A further aim was to explore differences compared with patients with coronary artery disease (CAD) and individuals from the general population. Material and methods. In this study one-week actigraphy registration, four questionnaires (Uppsala Sleep Inventory, SF-36, FACIT-fatigue, International Restless Legs Study Groups form) and a sleep diary were used. Results. Data from 68 participants and 470 nights were collected. PD patients (n == 28) had more fragmented sleep (p andlt; 0.001) and worse sleep efficiency (SE%) (p andlt; 0.0001) than the CAD (n == 22) and the population (n == 18) groups. Pruritus (57%), restless legs (46%) and fatigue (89%) were prevalent in PD patients. Pruritus correlated with fragmented sleep (r == --0.45, p == 0.01) and SE (r == --0.49, p == 0.01). In HRQoL, the physical component score was decreased in the PD and CAD groups (p andlt; 0.01) compared to the population group. Conclusions. To the authors knowledge this study is the first to demonstrate that PD patients have deteriorated sleep, with serious fragmentation measured by a one-week actigraphy registration. Further, PD patients exhibit worse sleep quality than CAD patients and individuals in the population. Evaluation of sleep in clinical practice is highly recommended since PD patients are vulnerable individuals with extended self-care responsibilities and at risk for comorbidity secondary to insufficient sleep. Future research on whether PD patients sleep problems and fatigue can be improved by an individual non-pharmacological intervention programme is required.