First scientific meeting of Yugoslav nephrologists, Struga, Republic of Macedonia, 26-28.IX 1977--introduction to the development of nephrology--in former Yugoslavia.

The first scientific meeting of nephrologists in Yugoslavia with international participation was held in Struga, Republic of Macedonia, on Lake Ohrid, 26 to 28 September 1977. During the Third Symposium on Endemic Nephropathy, which was held in Nis on 5 to 8 November 1975 at the Radon Hotel, representatives of the nephrology sections of the republics founded the Yugoslav Society of Nephrology. Academician Vojislav Danilovic from Belgrade was elected as the Association's first President. It was decided that the first scientific meeting of Yugoslav Nephrologists be held in Struga, Macedonia, 1977, and the first Nephrology Congress in Belgrade in 1979. It was also agreed that congresses be held every four years, and to organize scientific meetings between congresses. In this way, the Nephrology Association of Yugoslavia gained the opportunity for a lot of activities every two years. The Proceedings of the First Scientific Meeting of Yugoslav Nephrologists contained 6 plenary lectures and 84 papers presented during the three sections of the scientific meeting, 31 about hypertension and kidneys, 19 about immunology in nephrology and 34 about dialysis. The first scientific meeting of Yugoslav nephrologists with international participation was the first major review of the achievements of Nephrology in Yugoslavia, assessment of its results, work incentives and the creation of a vision for future development. The meeting strengthened the ties among the colleagues, new acquaintances were created, and new ideas for further cooperation appeared.

Malnutrition inflammation complex syndrome in maintenance haemodialysis patients.

Malnutrition inflammation complex syndrome (MICS) occurs in maintenance haemodialysis (MHD) patients and is a strong predictor of morbidity and mortality in these patients. The aim of our study was to evaluate the influence of inflammation on the biochemical and anthropometrical parameters of the nutritional status in MHD patients. Our study was made on 154 patients (93 men and 61 women, mean age=54.7 yrs. and mean time on dialysis 84 months) over a period of 6 months. The indicator of inflammation, C-reactive protein (CRP), was measured monthly at the central laboratory by nephelometry. The assessment tools used to evaluate the influence of inflammation on the nutritional status in MHD patients were: serum albumin and cholesterol level, midarm circumference (MAC), midarm muscle circumference (MAMC), triceps skin fold thickness (TSF) and body mass index (BMI). Student's t-test was used for group mean comparison between men and women. Person's correlation r was used to determine the significance and the strength of associations. The CRP level was significantly greater in men than in women (12.9 vs. 7.97, p < 0.04). The CRP level showed a strong correlation only with the serum concentration of cholesterol (r=0.49, p < 0.000), and did not correlate with the serum albumin of the MHD patients. There was no correlation between the CRP level and the anthropometrical parameters of the MHD patients in our study. Two separate processes, inflammation and reduced protein intake, each separately contributed to causing a decrease in serum albumin concentration and anthropometrical measurements. The levels of acute phase proteins vary widely as opposed to the serum albumin level; for that reason, changes in the albumin catabolic rate or synthesis require a considerable time to become visible. The average value of the protein catabolic rate of the patients in our study was 1.01 g/kg/d, a value that showed adequate protein intake. These findings would suggest that clinical attention to the maintenance of adequate nutrition could blunt the effects of inflammation on both somatic and visceral protein stores.

Histomorphometric analysis of fibrosis in the renal interstitial compartment.

The interstitium is the extravascular intertubular space of the renal parenchyma, which provides structural support to the functional renal units and is included at the same time in nearly all renal functions. Alterations to this renal compartment have been found in almost all glomerular diseases. During the last thirty years the studies of a few groups of investigators have shown that the degree of the renal dysfunction is strongly correlated with the changes in the tubulointerstitial compartment. We made a morphometric study of a group of 10 renal biopsies, previously diagnosed as IgA nephropathy or membranoproliferative glomerulonephritis. For morphometric analysis we made colour extraction of the interstitial area on tissue sections stained with trichrom Masson using the LUCIA M-NIKON image analysing system with integrated software for statistical analysis of the data. We measured the surface of the marked fields and the results were expressed as a percentage of the total scanned area. The results were correlated with the serum creatinine at the time of biopsy. We found fibrosis occupying more than 10% of the tubulointerstitial surface in all 10 patients. Six of them had a moderate level of fibrosis, occupying more that 20% of the tubulointerstitial space. The statistical analysis of these results showed a significant correlation between the degree of the interstitial expansion and the serum creatinine. The results showing the correlation between these parameters will enable the quantitative histological analyses to be included in the process of the nephropathological diagnosis in order to evaluate the histological risk factors in glomerular diseases.

Approach to vascular access for hemodialysis: experiences from the Republic of Macedonia.

Eight thousand eight hundred and forty nine different vascular hemodialysis accesses were performed in the period from 1976 until 1999 at the Department of Nephrology, Skopje: 3,114 native arterial-venous fistula (AVF), 715 arterial-venous shunts (AVS), 4,964 temporary or permanent catheters (4,411/88.86% femoral, 410/8.26% subclavian, 143/2.88% jugular) and 56 PTFE vascular grafts. Femoral catheterization (4,312/86.86%) is the favoured solution if a temporary vascular dialysis access is taken into consideration. The most popular chronic dialysis angio-access in our country is native AVF (90.5% of 3,440 permanent dialytic vascular accesses). The tunneled subcutaneously positioned catheters as a permanent dialytic angio-access were present in 270 cases (7.9%): 99 in femoral veins (our original method), 123 in subclavian veins and 48 catheters in jugular veins. The synthetic vascular grafts-PTFE (polytetrafluoro-ethylene) represent only 1.6% of all dialysis angio-accesses. The number of preventive AVFs created in patients with preterminal end-stage renal disease eventually increased; from 14% in the eighties, 20.8% after 10 years and 31.50% in 1999. Most of the preventive AVFs are done in outpatients 71.8% in 1999. This year 44.4% of all chronic vascular access were created in the same way. We prefer femoral catheters for both temporary and permanent access because our results show that femoral catheterization has a lower rate of early complications when compared to the subclavian catheterization group; the rate of late complications (thrombosis, stenosis, infections) is lower or the same; infections in femoral catheterizations are less frequent, compared to subclavian and jugular ones. Our contributions in the field of vascular access surgery are the three original methods which are constantly used at the Department: 1. Combination of temporary (AVS) and permanent vascular access (AVF) using the same blood vessels, performed in one surgical act; 2. Tunneled femoral catheter as a permanent vascular access for hemodialysis (2 types: on the abdominal wall and on the infrainguinal region - thigh); 3. Reduction of hyper-flow in AVF without the operation of "banding", with ligation of the artery before arteriovenous anastomosis.

Dialysis in adults in year 2000 in the Republic of Macedonia.

1,019 adult patients with terminal renal failure were treated with dialysis (D) in the first part of the year 2000 in the Republic of Macedonia. 1,010 patients (99%) were treated with chronic intermittent (maintenance) hemodialysis (HD) while nine patients (1%) were on continuous ambulatory peritoneal dialysis (CAPD). For the children, a special peritoneal dialysis program was developed; 509 patients per million of the population (PMP) were on dialysis. The Republic of Macedonia is, therefore, among those central and eastern European countries with a higher PMP number in the treatment of end-stage renal disease, following Croatia, the Czech Republic and Slovenia. The patients were treated at 18 Centers in a network of HD Centers at a distance of 30-50 km. from their place of residence in order to facilitate their access to treatment and to work. All patients who have had symptoms indicating need for treatment with D were accepted for treatment. The government payed all the expenses of the treatment and the salaries of the staff. 56% were male and 44% were female patients. The youngest patient was aged 9 and the oldest was 82 years old. There has been an increase in the age of the patients on D as well as an increase in their number. In 1993 we had 727 patients being treated with D, and now we have 1,019 with a constant increase in the number of patients with ESRD and a need for D and renal transplantation. Mortality per year at the different Centers ranged from 8-19% in 1999 and the average is 12%. Glomerulonephritis (GN)--both primary and secondary--is the main cause of renal failure (RF) in some Centers up to 45%. Tubulo-interstitial disease follows GN. ADPKD patients constitute 9.4% with a difference among the Centers of 3-29%, and diabetic nephropathy is found in 10%, 5-15% in different Centers. 11-61% of patients have an unknown etiology. 352 patients are on treatment with human recombinant erythropoietin (rhuEPO) - in some Centers up to 60%. The mode of application was subcutaneous and the initial dose is 20 U/kg body weight and the mean maintenance dose of EPO per patient weekly is 4,000 U. The Cimino-Brescia arteriovenous fistula is being applied as a standard vascular access. The survival rate of our patients treated with maintenance HD at 5 years was 58%. CAPD and particularly renal transplantation are to be further developed as alternative methods in treating terminal renal failure.

Haemodialysis-membrane biocompatibility and mortality of patients with dialysis-dependent acute renal failure: a prospective randomised multicentre trial. International Multicentre Study Group.

BACKGROUND: There is controversy as to whether haemodialysis-membrane biocompatibility (ie, the potential to activate complement and neutrophils) influences mortality of patients with acute renal failure. We did a prospective randomised multicentre trial in patients with dialysis-dependent acute renal failure treated with two different types of low-flux membrane. METHODS: 180 patients with acute renal failure were randomly assigned bioincompatible Cuprophan (n=90) or polymethyl-methacrylate (n=90) membranes. The main outcome was survival 14 days after the end of therapy (treatment success). Odds ratios for survival were calculated and the two groups were compared by Fisher's exact test. Analyses were based on patients treated according to protocol (76 Cuprophan, 84 polymethyl methacrylate). FINDINGS: At the start of dialysis, the groups did not differ significantly in age, sex, severity of illness (as calculated by APACHE II scores), prevalence of oliguria, or biochemical measures of acute renal failure. 44 patients (58% [95% CI 46-69]) assigned Cuprophan membranes and 50 patients (60% [48-70]) assigned polymethyl-methacrylate membranes survived. The odds ratio for treatment failure on Cuprophan compared with polymethyl-methacrylate membranes was 1.07 (0.54-2.11; p=0.87). No difference between Cuprophan and polymethyl-methacrylate membranes was detected when the analysis was adjusted for age and APACHE II score. 18 patients in the Cuprophan group and 20 in the polymethyl-methacrylate group had clinical complications of therapy (mainly hypotension). INTERPRETATION: There were no differences in outcome for patients with dialysis-dependent acute renal failure between those treated with Cuprophan membranes and those treated with polymethyl-methacrylate membranes.

Autonomic neuropathy in hemodialysis patients treated with recombinant human erythropoietin.

Autonomic nervous system (ANS) function was evaluated in hemodialysis patients treated with recombinant human erythropoietin (rHu-EPO) before and after therapy, in an effort to evaluate the role of anemia in the genesis of autonomic dysfunction in chronic renal failure (CRF). Studies were conducted using a battery of five cardiovascular reflex tests: Valsalva maneuver, handgrip exercise, heart rate response to standing (30:15 index), post-Valsalva rise in blood pressure and postural drop in blood pressure. The patients were divided into two groups: group I consisted of 14 patients on maintenance hemodialysis treated with rHu-EPO for one year, and group II-13 hemodialysis patients treated with rHu-EPO for two years. The results of the tests were compared before and after the correction of anemia by rHu-EPO in each group, as well as with the control group of ten healthy subjects. Data show that renal anemia is not implicated in the genesis of ANS dysfunction in hemodialysis patients, since correction of same by rHu-EPO does not improve the autonomic dysfunction.

Increased silicon levels in dialysis patients due to high silicon content in the drinking water, inadequate water treatment procedures, and concentrate contamination: a multicentre study.

BACKGROUND: Although silicon is considered as an essential element, little is known about the basic effects and clinical significance of increased concentrations of the element in dialysis patients. METHODS AND RESULTS: In a multicentre study we found silicon levels in haemodialysis (HD) patients to be markedly increased. In these patients silicon concentrations were significantly higher than those noted in subjects with normal renal function as well as in patients with chronic renal failure not yet in dialysis and patients treated by continuous ambulatory peritoneal dialysis (CAPD). Moreover we noted that in both HD and CAPD patients mean silicon levels differed from one centre to another. Also, was there in the HD population a significant difference in serum silicon levels among patients from different countries. In HD patients differences in serum silicon levels were either due to the use of silicon contaminated dialysis fluids or an increased oral intake of the element mainly originating from the high silicon content of the drinking water. Silicon contamination of the dialysis fluid was found to be due to either the use of reverse osmosis membranes that insufficiently retain the element during water treatment or by the addition of concentrates containing high amounts of silicon. Using a recently developed high-performance liquid chromatographic/atomic absorption spectrophotometric (HPLC/ETAAS) hybrid technique, we found silicon in serum to be present as a low-molecular-weight non-protein-bound component, which in the presence of a low silicon dialysate is adequately removed during treatment. CONCLUSIONS: The clinical relevance of increased serum silicon levels is not yet known and as such deserves further investigation. In view of the controversy that exists on the element's assumed protective as well as toxic role in the development of some (aluminium-related) neurodegenerative diseases and its vital role in bone formation, monitoring of the silicon levels in serum, tap water, and dialysis fluids might become important.