Renal replacement therapy in Sweden.

OBJECTIVE: The Swedish Registry for Active Treatment of Uraemia (SRAU) was founded in 1991 with the objective of documenting demographic data on patients treated for end-stage renal disease (ESRD). The aim of this study was to describe the prevalence, incidence, comorbidity risk factors and survival of patients with ESRD who underwent dialysis treatment and/ or kidney transplantation in Sweden between 1991 and 2002. MATERIAL AND METHODS: All dialysis and transplant units (n = 65) presently report to the SRAU and almost all patients are reported and followed until death. RESULTS: The prevalence of patients on dialysis and transplantation, being approximately 750 per million population (PMP), has increased by 75% in 12 years. The recent annual rise is approximately 3% (200 patients). The incidence has been stable since 1997 at approximately 125 patients PMP. In 2002, there were 1113 new patients, the majority of whom were aged > or =65 years. Their original kidney disease was most often diabetic nephropathy (23.7%), with nephrosclerosis (19.0%) being the second most common disease. The total number of renal transplantations performed has decreased to some extent. The overall 5-year patient survival rate was 23.1% in patients on dialysis and 85.5% after kidney transplantation. The major cause of death was cardiovascular disease (48%) and an increasing frequency of malignancy after transplantation (26%) was noted. CONCLUSION: The prevalence of ESRD has nearly doubled since 1990 and the number of new patients being referred for dialysis has increased. These patients are becoming older, with a large proportion having non-renal complicating diseases. Survival after transplantation was excellent. The shortage of cadaveric donors in Sweden in recent years and increasing mortality from malignant disease after transplantation are issues of great concern.

Double-blind, placebo-controlled study of growth hormone treatment in elderly patients undergoing chronic hemodialysis: anabolic effect and functional improvement.

Elderly patients with end-stage renal disease often have protein and/or caloric malnutrition that severely affects general well-being and mortality. Uremia is associated with resistance to the action of growth hormone (GH). This resistance could be of clinical importance in elderly dialysis patients. In the present study, the effects of GH treatment were assessed in elderly patients receiving chronic hemodialysis. Twenty hemodialysis patients with a mean age of 71.7 years (range, 53 to 92 years) were included on a 6-month, randomized, double-blind, placebo-controlled trial of GH treatment. The dose of GH was 66.7 microgram/kg, administered subcutaneously three times weekly immediately after each dialysis session. Body composition was measured using total-body potassium levels, computed tomography of the lower leg, and bioelectrical impedance analysis. Serum albumin concentrations and handgrip strength were also measured. GH treatment increased the serum concentration of insulin-like growth factor-I (IGF-I), IGF-I/IGF-binding protein-3 ratio, fat-free mass, and the serum concentration of albumin compared with placebo. The number of patients with serum albumin levels less than 40 g/L was reduced by a factor of three in the GH-treated group. Handgrip strength increased in response to GH treatment compared with placebo. Six months of GH treatment in elderly hemodialysis patients produced anabolic effects, with improved muscle performance. Also, the number of patients with low albumin levels was markedly reduced, indicating improved nutritional status and/or attenuated catabolism. These are all important beneficial effects for individual patient outcomes.

Pharmacokinetics of transperitoneal insulin transport.

Seven type I insulin-dependent diabetic patients on continuous ambulatory peritoneal dialysis treatment were selected for this study. Each patient participated in three different 6-hour 'single-dwell' studies on 3 consecutive days. A mean dose of 33 +/- 1.3 U Insulin Actrapid Human was given intraperitoneally each day. The procedures for intraperitoneal insulin administration were: (1) with 1,000 ml Ringer lactate; (2) with 1,000 ml 3.86% glucose-containing dialysate, and (3) into an empty peritoneal cavity. The calculation of the intraperitoneal volume was done with a single injection indicator dilution technique in which 100 kBq radioiodinated serum albumin (RISA) was added into the fluid prior to instillation. Free insulin and glucose were analyzed at 16 time intervals in blood and in dialysate during each dwell. After drainage the peritoneal cavity was rinsed with 1,000 ml Ringer lactate followed by two consecutive 5-hour exchanges with 2,000 ml glucose-containing dialysate. Recovery of insulin and RISA was measured in rinsing fluid and in sampled dialysate during the 6-hour dwell. The kinetic calculations made for insulin were disappearance rate (mU/min) from the peritoneal cavity, and appearance rate in circulating blood. After drainage and rinsing, 66.0 +/- 10 and 71.8 +/- 9.8% of the insulin instilled had disappeared after 6 h from the glucose fluid and from the Ringer solution respectively and did not differ significantly. However, the estimated disappearance rate from the peritoneal cavity was significantly higher in Ringer than in glucose from the time interval 120 to 360 min. A high and peak-shaped insulin concentration in the plasma was found following insulin injection into an empty peritoneal cavity, and was significantly higher than when insulin was dissolved in a 1,000-ml fluid volume. However, a higher blood concentration was also found when Ringer was instilled than when a hyperosmolal glucose solution was instilled. A high first-pass elimination in the liver is suggested. In conclusion, fluid volume and also the osmolality of the solution in the peritoneal cavity decreases the transport rate, but not the bioavailability of insulin given intraperitoneally. Both a high peak shape and a continuous insulin appearance in blood can be achieved. It is suggested that there is a high first-pass elimination of insulin during absorption from the peritoneal cavity. However, the values are uncertain and extended investigations must be done.

Ambulatory 24-hour blood pressure and peptide balance in hemodialysis patients.

Blood pressure regulation during intermittent hemodialysis treatment involves many different mechanisms. Eight normotensive patients without antihypertensive drugs on intermittent hemodialysis treatment, mean age 50 years, were studied with 24-hour blood pressure measurements. Atrial natriuretic peptide (ANP) and neuropeptide Y (NPY) were determined concomitantly. Eight control individuals matched for age and sex were investigated in the same way. A significant increase of both systolic and diastolic blood pressure, heart rate and pathological circadian rhythm was seen among the dialysis patients. High levels of ANP were found before and after dialysis. NPY showed steady state levels through the 24 hours and did not differ between the two groups. Overhydration is a probable cause of the disturbed blood pressure regulation and increased ANP-values.

Measurement of glomerular filtration rate by single-injection, single-sample techniques, using 51Cr-EDTA or iohexol.

Clearance calculations based on single sample determinations from 51Cr-EDTA samples 180 min after giving radioisotope showed a correlation coefficient of 0.992 to clearance calculations after multiple sampling of 51Cr-EDTA. The range of clearance determinations in 108 patients varied from 4 to 141 ml/min, 1.73 m2 BA. Twenty patients had clearance values below 20 ml/min, 1.73 m2 BA. Clearance calculations from single samples of iohexol from 180 min values showed a correlation coefficient of 0.986 to clearance calculations after multiple sampling of 51Cr-EDTA. These calculations were based on samples from 122 patients with clearance values varying from 4 to 139 ml/min, 1.73 m2 BA. No adverse reactions were registered during the study. This study confirms the reliability of single sample methods for clearance calculations at all levels of renal function.

Islet cell antibodies, but not glutamic acid decarboxylase antibodies, are decreased by plasmapheresis in patients with newly diagnosed insulin-dependent diabetes mellitus.

The effects of plasmapheresis on islet autoantibody levels, C-peptide (beta-cell function), and hemoglobin-A1c (HbA1c, metabolic control) were tested in a prospective blinded study of 18 newly diagnosed insulin-dependent diabetes mellitus (IDDM) patients randomly assigned to receive plasmapheresis (P), carried out as double filtration, or sham (S) treatment at diagnosis and 3 months thereafter. At diagnosis, 6 of 8 patients (75%) in group P and 9 of 10 patients (90%) in group S had islet cell antibodies (ICA), whereas 4 of 8 (50%) and 7 of 10 (70%) patients, respectively, had glutamic acid decarboxylase antibodies (GAD65-Ab), with no significant differences between the groups in ICA and GAD65-Ab levels. After 6 months, P patients showed significantly lower ICA levels than S patients (11 +/- 6 and 128 +/- 47 Juvenile Diabetes Foundation International Units, respectively; P < 0.02) due to an increase in ICA levels in 8 of 9 (88%) of the S patients not seen in P patients (P < 0.002). Concurrently, HbA1c stabilized in P, but not in S, patients and was significantly lower by 24 months (6.58 +/- 0.54% vs. 9.76 +/- 1.21%; P < 0.05). Moreover, fasting C-peptide increased significantly (214 +/- 11 pmol/L; P < 0.05) over the first 6 months in P. After the initial 6 months, ICA levels tended to decrease in all patients and were not detected after 60 months. GAD65-Ab levels were not influenced by plasmapheresis and, also in contrast to ICA, increased significantly (P < 0.05) in the whole study population after 60 months. In fact, 4 initially negative patients became GAD65-Ab positive after diagnosis (in 2 patients > 24 months after diagnosis). We conclude that plasmapheresis of newly diagnosed IDDM patients does not change subsequent GAD65-Ab levels, but ICA are significantly decreased with associated improved C-peptide and HbA1c levels.

Well-informed patients with end-stage renal disease prefer peritoneal dialysis to hemodialysis.

One hundred and one azotemic patients, from March 1988 to March 1992, expected to be in need of active treatment of uremia within the next 6 months, were invited to four information meetings concerning conservative treatment of uremia, hemodialysis, peritoneal dialysis, and transplantation. Eighty-three percent of the invited patients attended. Another 13 started active treatment of uremia after receiving individualized information. At the end of the observation period, 37 of 97 patients had chosen continuous ambulatory peritoneal dialysis (CAPD), and 23 hemodialysis. Twenty-nine had not yet decided which mode of active treatment of uremia they wanted, and 4 patients had died. Patients choosing CAPD had a mean age of 52 years, compared to 59 years for those choosing hemodialysis. Thirty-six of 37 patients who had chosen CAPD and 19 of 23 patients who had chosen hemodialysis had started treatment. The cumulative patient and technique survival at 12 months for CAPD was 92% and 66%, and for hemodialysis 70% and 70%, respectively. The patients were asked to give their views on their choice of active treatment of uremia and the information meetings once they had started treatment. Eighty-six percent of the patients did not want to change their chosen therapy, and 88% of the patients found the information provided adequate. When patients with renal insufficiency are given adequate information, the majority prefer peritoneal dialysis to hemodialysis and are very satisfied with their choice.

Quantitative analysis of islet glutamic acid decarboxylase p64 autoantibodies in insulin-dependent diabetes mellitus.

Autoantibodies against the beta-cell M(r) 64,000 protein (p64), recently identified as an isoform of glutamic acid decarboxylase (GAD), are prevalent in patients with insulin-dependent diabetes mellitus (IDDM). Dog islets were found to represent an abundant source of native p64 allowing the study of antigen-antibody interactions in IDDM. A quantitative, standardized assay for p64 antibodies based on dog islets was developed and evaluated. Utilizing dog and human islets the p64 antibodies were detected in 17/19 (89%) new onset 15-32-year-old patients, compared to 15/19 (79%) in a rat islet assay. ICA were detected in 15/19 (79%) patients and correlated with the presence of p64 antibodies (rs = 0.59, P < 0.004) but not with age at onset, sex, or C-peptide levels. Sensitivity therefore is improved with the dog islet p64 antibody assay which will allow future studies requiring native p64 antigen in larger quantities are possible based on our findings.

Inhibition of herpes simplex virus production in vitro by cyclosporin A.

Nontoxic concentrations of Cyclosporin A (CyA) dose-dependently inhibited herpes simplex virus (HSV) production in resting monkey kidney cells. The block was at the step of virus DNA synthesis as assessed by [3H]thymidine incorporation and by dot blot hybridization of infected cell DNA using a cloned 32P-labelled HSV DNA fragment (BamHI X) as probe. This was further supported by analysis of HSV protein synthesis in the presence of CyA as assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis and Western blot. A relative accumulation of HSV alpha- (e.g., ICP 4) and beta 1-proteins (e.g., ICP 6 and 8) was found, whereas HSV gamma 1-proteins were slightly decreased and gamma 2-proteins were markedly decreased by CyA. The production of thymidine kinase and DNA polymerase was decreased when CyA was added to HSV infected cells. The sensitivity to CyA was not escaped by thymidine kinase nor DNA polymerase deficient mutants. Passage of HSV in presence of CyA did not result in induction of drug resistance.

The role of paid work in Swedish chronic dialysis patients--a nation-wide survey: paid work and dialysis.

The role of paid work in chronic illness has been investigated in this nation-wide study of all Swedish-speaking patients on chronic dialysis above the age of 16 years, who were not too tired or severely ill to participate and who had been treated for at least 3 months. Young age and female gender were consistently associated with increased prevalence of self-reported depression, poor psychological health, psychosomatic symptoms and sleep disturbance. In multivariate analyses paid work, strong emotional support, and care at intermediate or small units were independently associated with a good quality of life. Chronic dialysis patients who did paid work (19.6% of the patients below 65 years of age) perceived their work as more socially supportive than did men and women in the normal working population. It may be concluded that paid work is of particular importance to this patient group because it may give extra social support to patients whose social network is in general rather poor.

Grading of exit sites cannot predict peritonitis in patients on CAPD.

Grading of exit sites was performed at 265 routine outpatient visits of 28 patients starting CAPD between January 1988 and February 1990, with a total observation time of 398.5 months to December 1990. Six patients had no peritonitis episode. The remaining 22 patients suffered from 43 peritonitis episodes. Fifty-eight per cent of these were caused by Staphylococcus epidermidis. Eighty-six per cent of the examinations of exit sites of patients with peritonitis episodes showed 0 to 1 point on an arbitrary grading scale of up to 9 points. Staphylococcus aureus was found after bacterial culture from exit site smears in 3 cases. All were adequately treated. None of these cases showed any peritonitis episodes with this bacteria. No relationship could be found between the grading of the exit site at routine outpatient clinic visits and the appearance of a peritonitis episode. Grading of exit sites is of clinical importance but cannot predict the appearance of peritonitis.