Diabetics on dialysis in the Republic of Macedonia: A nationwide epidemiological study.

BACKGROUND: Incidence increase of diabetes mellitus (DM) has taken epidemic proportions in the world. Diabetic nephropathy (DN) is a most serious complication, taking a leading place as a factor in the progression of chronic kidney disease (CKD). Dialysis treatment of these patients is complex, expensive, and exerts an excessive burden on the health budgets of the affected countries. METHODS: We performed a nationwide precise observational study with the aim of analysing diabetics on dialysis in dialysis centres throughout the Republic of Macedonia (RM) in 2002 and in 2006; to compare the results from patients records; and to gather data on the epidemiology, clinical characteristics and complications of diabetes type 1 (DM1) and diabetes type 2 (DM2). RESULTS: The prevalence of HD patients in RM was 1114 vs 1074 in 2002 and 2006, respectively. Of these, 109 (9.78%) vs. 115 (10.71%) had DM in 2002 and 2006, respectively. The percentage of diabetics on dialysis between different centers varied between 3% to 21% vs. 2.4% to 22.07% in 2002 and 2006, respectively. The mean age of the patients was 58+/-10.29 vs. 56.5+/-10.71 in 2002 and 2006, respectively. Patients with DM1 were 19 (17.43%) vs. 15 (13.04%) and with DM2 were 90 (82.57%) vs. 100 (86.96%) in 2002 and 2006, respectively. 28 (25.68%) vs. 31 (26.96%) patients were on oral anti-diabetic drugs and 62 (57.21%) vs. 69 (60%) patients were on insulin in 2002 and 2006, respectively. Mean age of DM1 patients was 47+/-11.6 y. vs. 45+/-7.32 y. respectively and of DM2 was 60.37+/-8.33 y. vs. 61.14+/-10.23 y., in 2002 and 2006, respectively. Mean time of insulin treatment was 9.5+/-6.63 y. vs. 10.85+/-9.29 y. in 2002 and 2006. Mean Body Mass Index (BMI) was 26.4 vs. 23.49+/-4.74 kg/m2 in DM1 and 25.5 vs. 24.77+/-3.70 kg/m2 in DM2 patients in 2002 and 2006, respectively. Thrombosis of first arteriovenous fistulae (AVF) occurred in 41% vs. 25.22% in 2002 and 2006, respecttitvely. Hepatitis C virus (HCV) infection was confirmed in 57% vs. 44% of DM patients in 2002 and 2006, respectively. Most common co-morbidity in patients was hypertension, 91% vs. 80.87% in 2002 and 2006, respectively. CONCLUSION: The number of diabetics on dialysis in the Republic of Macedonia did not increase in the period from 2002 to 2006. In DM2 diabetics on dialysis the frequency of complications is higher and time on dialysis is shorter than in DM1 patients. Early detection of diabetic nephropathy by primary care physicians as well as collaborative treatment by diabetologists, nephrologists, cardiologists and ophthalmologists before and during dialysis are important for improvement of treatment and survival of diabetic patients on dialysis.

Dialysis and aphaeresis in the Republic of Macedonia "a success story".

The first haemodialysis (HD) in the Republic of Macedonia (RM) was performed in 1959 in a patient with acute renal failure (ARF) using Kolff-Brigham rotating drum artificial kidney at the Blood Transfusion Institute in Skopje. In 1965 the Renal Unit at the Dept. of Medicine, Medical Faculty, Skopje obtained a modern, new artificial "Websinger" kidney with sigma motor pump and possibilities for use of disposable Kolff "twin coil" dialyser. Between 1959 and 1971, HD was performed only in patients with ARF. In May 1971 at the Renal Unit, a Unit for chronic HD was founded and the program of maintenance haemodialysis (MHD) was started with five Stuttgart Fresenius machines and 12 patients dialysed on twin coil dialyzers. 1173 patients were treated in 18 HDC in the RM in 2007. 320 machines were used; 299 (93%) for bicarbonate HD and 21 (7%) for acetate HD. In all centers the water for HD was processsed by reverse osmosis. There was no reuse of dialysers. All patients received the same treatment. The patients received epoetin (recombinant human erythropoetin - alpha and beta) to maintain hemoglobin between 100 and 120 g/L. Our patients received epoetin between 62% and 100 % in HDC according the individual need. The Cimino - Brescia arterial-venous fistula was typically used as permanent vascular access. Prevalence of the HBV in patients on MHD varied between 6-28% in different centers. Prevalence of HCV in patients on MHD was between 37-78% in some centers. Nosocomial infection is probably one of causes of the so high prevalence of HCV in our patients. We do not have HIV infection in patients on MHD. The survival rate of our patients treated with MHD was 60% at 5 years, 37% at 10 years, 25% at 15 years and 9% at 20 years. PD was started in 1995 in children and in 1996 in adults. Now, there are 24 adult patients treated with PD. Since 1985 membrane PE has been in regular use. Most therapeutic procedures were performed on patients from the Dept. of Neurology. 1216 patients were on RRT in 2005. On HD were 1077 (89%), with transplanted kidney 121 (10%) and on PD - 18 (1%). 601, 4 patients were on RRT per million of population. The activity of the Macedonian nephrology societies helped a lot in the development of the nephrology and dialysis inviting distinguished nephrologists from Europe and the world and transferring the achievement of the world in our practice. Having in mind that CKD, ESRD and RRT are a great burden for the health budget, we need early diagnosis and treatment of CKD, i.e. prevention of kidney disease.

[The role of the von Willebrand factor in renal diseases and haemodialysis patients]. / Bioloskata aktivnost na fon Vilebranodoviot faktor kaj bubrezni i hemodijalizni bolni.

During a period of twenty years, the von Willebrand factor (VWf) biological activity was evaluated in 805 patients with vein thrombosis, diabetes mellitus, chronic renal failure and ischemic heart disease. The examined patients were 168 with vein thrombosis, 129 with diabetes mellitus, 412 with chronic renal failure (CRF), and 96 with ischemic heart disease. The biological activity was also determined in 104 haemodialysis patients using four different haemodialytic membranes: 30 on cuprophan membrane, 30 on polymethylmetacrylate membrane (PMMA), 24 on hemophane and 20 patients on polysulphone (PS) membrane. In 42 patients with arterio-venous fistula prone to thrombosis, the biological activity of the von Willebrand Factor was 178% in comparison to 106% in the control group. The biological activity of VWF was increased in patients with vein thrombosis (p < 0.02), in patients with diabetes mellitus (p < 0.01), CRF (p < 0.05), and in patients with ischemic heart disease (p < 0.01). The highest biological activity was found in patients on PMMA (p < 0.001), then cuprophan (p < 0.05) and hemophane membrane (p < 0.01), while the lowest increase of its concentration was noticed in patients on PS without statistical significance. In arteriovenous fistula prone to thrombosis patients biological activity of the von Willebrand Factor was significantly increased (p < 0.01). Our investigations show the importance of VWF as a marker of endothelial disfunction, a possible predictor of A-V fistula thrombosis, and a possible marker of haemodialysis membranes biocompatibility.

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.

Are ambulatory femoral catheters for hemodialysis a safe vascular access?

Femoral catheterization is fast and simple and associated with a low risk of complications. Those which occur can usually be managed easily. Femoral catheters are usually kept in place for a short period of a few days. We, instead, used femoral catheters (FC) as a temporary vascular access for a longer period of time (until the permanent vascular access matured) in inpatients and in outpatients on regular ambulatory hemodialysis who had a problem with their permanent access. We analyzed 59 patients with end-stage renal disease treated with hemodialysis (HD), divided into two groups. Of the group that started with hemodialysis (group I), only 16 patients were hospitalized during the maturation of native arterio-venous fistula (AVF). Duration time of the catheters was 15-47 days (average 32 days). The second group (group II) comprised 43 patients going on regular ambulatory hemodialysis who were discharged from hospital with femoral catheters. Duration time of catheters in this group was 13-183 days (average 44.2 days). Catheters were removed when AVF matured, or if a significant complication occured. We took blood culture from peripheral vein (BCP) and from catheter (BCC) on removal of the catheter, or when we suspected infection. Catheter tips (CT) were also sent for microbiological analysis. We monitored the clinical signs of infection. We compared microbiological results of BCP, BCC and CT from the two groups using chi-square test and we did not find any significant difference among the three types of findings (p<0.05). The FC was removed from one patient only from group II because of suspicion of catheter-related infection. Two pts were treated with antibiotics (AB) systemically and locally (AB was 'locked' in the catheter) because of febricity. When the catheters were removed the microbiological findings were sterile. We concluded that FC can be used without any problem for a longer period of time for ambulatory HD, with the provision of permanent care from a team specially trained for vascular access.

[Vascular access and chronic renal failure]. / Accès vasculaires et insuffisance rénale chronique.

From 1976 to 1999 a total of 8,849 surgical procedures for vascular access prior to dialysis were performed in the Department of nephrology at Skopje hospital (Macedonia). Cases included 3,114 native arteriovenous fistula (AVF), 715 arteriovenous shunts and 4,964 temporary or indwelling catheters (4,411 (88.86%) in the femoral vein, 410 (8.26%) in the subclavian vein, 143 (2.88%) in the jugular vein and 56 PTFE vascular grafts). Femoral catheterization is the favoured solution for repeated dialysis (90.50% of the 3,440 procedures for indwelling vascular access). Subcutaneous indwelling catheters were used in 270 (7.90%) cases, with vascular access taking place in either the femoral (99 cases), subclavian (123 cases) or jugular vein (48 cases). Biosynthetic vascular grafts represent only 1.6% of all procedures for vascular access. The number of preventive AVFs has been increasing steadily from 14% in the 1980s to 20.8% in the 1990s and 31.50% in 1999. The majority of preventive AVFs (71.80%) and a large number of other surgical procedures for vascular access (44.40%) are performed in day hospital.

Hantaan virus infection with acute renal failure.

We report on 10 patients with acute renal involvement in Hantaan virus infection observed at the Department of Nephrology, Faculty of Medicine, Skopje, Republic of Macedonia, during a period of 3 years (October 1987-July 1990). Eight patients were male and 2 were female, aged 37.5 +/- 4.8 years. The diagnosis of Hantaan virus infection was proven by an indirect immunofluorescent and ELISA test with a significant increase of the titer after a week to ranges from 1:512 to 1:2,048. Percutaneous renal biopsy was performed in 3 cases using standard procedures for optical and immunofluorescent microscopy. Fever, weakness, headache, conjunctival injection, hematuria, and lumbar pain were clinical features all patients had in common. Complete anuria was noted in 7 out of 10 and oliguria in the other 3 of the 10 cases with serum levels of creatinine 967 +/- 152.6 mumol/L. Other following laboratory findings were leukocytosis in 10 out of 10 patients, with neutrophylia, and reduction of serum sodium and potassium in 8 out of 10, and a decrease in serum complement C3 in 3 out of 10 patients. Percutaneous renal biopsy confirmed interstitionephritis in 2 out of 3 biopsied patients and acute diffuse proliferative glomerulonephritis in the third. Interstitial mononuclear infiltration with dominant T cells proven with monoclonal antisera (direct immunoperoxidase method) was present in all 3 cases. The outcome of the disease was good in 8 of the 10 patients with a development of polyuric phase and complete recovery of renal function later. One patient with interstitial lesions on biopsy developed chronic renal failure, and the other with a concomitant brucellosis died during the polyuric phase of the disease.

Different pathohistological presentations of acute renal involvement in Hantaan virus infection: report of two cases.

We present two patients with Hantaan virus infection, admitted to the Department of Nephrology, Skopje, at the same time, with the same clinical presentation (chills, fever, abdominal pain, hemorrhages, nausea, headache, proteinuria, hematuria, oliguria, acute renal failure) but with different pathohistological findings and different disease courses. In the first case diffuse proliferative glomerulonephritis was found, with a complete recovery of renal function after a month, with a mild proteinuria and erythruria during the second and the third month. In the second case, glomeruli were normal in general, with slight mesangial proliferation found in two out of twenty, but interstitial edema, lymphocyte infiltrations and tubular changes were noted. Complete recovery was not noted after 3 months of follow-up. The patient is now without hemodialysis treatment, with polyuria, in the stable phase of chronic renal failure which is not improving.