Search

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 modem, 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 - α and β) 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. [ABSTRACT FROM AUTHOR]

Introduction: Total dialysate calcium concentration has an important influence on calcium metabolism in bicarbonate high-flux dialysis. The aim of the study is to investigate the influence of different dialysate calcium concentrations on serum concentration of ionised calcium and on the balance of total dialysate calcium., Materials and Methods: A total of 20 stable aneuric patients on chronic bicarbonate high-flux haemodialysis with a frequency of 4 hours, 3 times per week with two different concentrations of total dialysate calcium (tdCa) were included in the study. Dialysis in the first session was performed with total dialysate calcium of 1.25 mmol/L, and at the next session with dialysate calcium of 1.5 mmol/L. The serum concentrations of total and ionized calcium were determined before and after each dialysis session. The balance of total dialysate calcium was measured on the dialysate side., Results: Serum concentration of total calcium before and after haemodialysis did not show any significant difference in HD with a total dialysate calcium of 1.25 mmol/L (2.40 ± 0.19 mmol/L before HD and 2.46 ± 0.15 mmol/L after HD). Serum ionized calcium in HD with tdCa 1.25 significantly decreased after HD (1.16 ± 0.09 mmol/L before HD to 1.08 ± 0.04 mmol/after HD, p < 0.05). The total serum calcium significantly increased after HD in comparison to HD with tdCa of 1.5 mmol/L (2.40 ± 0.15 mmol/L to 2.65 ± 0.16 mmol/L, p < 0.05). The concentration of serum ionized calcium did not increase significantly in HD with tdCa 1.50 mmol/L (1.16 ± 0.08 mmol/L to 1.20 ± 0.05 mmol/L). Average values of total dialysate calcium balance (gradient of diffusion between dialysate and patient) were negative in tdCa 1.25 (1.38 ± 0.08 mmol/L versus 1.48 ± 0.43 mmol/L), but in HD with tdCa 1.5 were slightly positive (1.56 ± 0.07 mmol/L versus 1.52 ± 0.07)., Conclusion: The use of total dialysate calcium of 1.5 mmol/L is beneficial because balance values of total dialysate calcium are slightly positive, but serum concentration of ionized calcium stays in the normal range.

The aim of this study was to evaluate the clinical course of patients with Wegener's granulomatosis (WG) with renal involvement, to examine histopatological form seen in renal biopsies and present follow-up of the patients. A retrospective analysis was carried out of 18 patients presenting with WG and active renal disease at the University Nephrology Department, Ss. Cyril and Methodius University, Skopje, R. Macedonia. All patients were ANCA positive and had a percutaneous renal biopsy taken on their admission. 12 patients were male, 6 female, aged 48.61±13.77 (M±SD). All had extrarenal symptoms prior to admission. Oligoanuria was present in 7/18 (38.9%) of the patients, serum urea levels of the whole group were 40.67±18.13 mmol/l (M±SD) and for serum creatinine 691.06±384.93 µmol/l (M±SD). Necrotizing glomerulonephritis with crescents was present in 11/18 (61.11%) of the patients, the others presented diffuse proliferative extracapillary glomerulonephritis. All patients were treated with steroids and cyclophosphamide, and plasmapheresis was performed in 7/18 (38.9%) of the patients. Probability rate for surviving after one month was 0.6111 and after three months 0.3889 (Kaplan-Meier). The current treatment of WG in our study did not prevent serious complications and development of ESRD in a large number of our patients. This systemic disorder is still a serious problem and early diagnosis and alternative strategies for the management of the disease will be an important objective for further studies.

The Oxford classification for the pathological classification of a glomerular disease in IgA nephropathy was established and published in 2009. Four of the pathological variables: 1) mesangial hypercellularity score, 2) segmental glomerulosclerosis, 3) endocapillary hypercellularity and 4) tubular atrophy/interstital fibrosis were presented as having value in predicting renal outcome in this glomerular disease. These features were recommended to be taken into account for predicting the outcome. In our study, we correlated these four variables with the outcome of the disease in 40 adult patients with IgA nephropathy. Standard histopathologic procedure was used to determine four variables as 0/1. The results were compared with renal outcome, clinical data were obtained from the out-patient files of the patients. The whole follow-up period was 3-27 years. The average survival of the whole group was 10.8±7.47 years (M±SD). Mesangial hypercellularity was confirmed to be associated with the renal outcome (p=0.047), as well as glomerular sclerosis (p=0.009), endocapillary hypercellularity (p=0.001) and tubular atrophy/interstitial fibrosis (p=0.045). When we analysed only patients with a severe form of the disease (nephrotic syndrome; patients treated with immunosuppression), the survival of the patients was associated only with the degree of tubulointerstitial changes (p=0.018). Analysing separately patients with mild clinical form, we found only a predictive value of segmental glomerulosclerosis on renal survival.

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.

Colour Doppler duplex ultrasonography (CDUS) has allowed noninvasive assessment of alterations of vascular perfusion showing general perfusion in colour. Since 1996, ultrasound examination by a duplex Doppler apparatus has been performed with an HDI 3000, ATL machine. We have retrospectively evaluated all patients (pts) with colour Doppler duplex examination for the last three years. Resistive indexes (RIs) are measured in each kidney using the existing software capabilities of the scanner. A total of 2581 CDUS examinations were performed over the past three years; in 2005 - 883 pts, in 2006 - 908 pts and in 2007 - 790 pts. Most of these examinations were on transplant pts. In 98 cases we examinated chronic rejection reactions, in 58 cases acute rejection and in 38 cases we postulated renal artery stenosis or thrombosis. We used CDUS to determine whether the RI can be used as a predictor in pts with Diabetic Nephropathy; in 108 cases we found an increased RI > 0.68. There is a positive correlation between the RI and the severity of arteriolosclerosis in the majority of pts, 331, where we found nephroarteriolosclerosis (RI > 0.64). In 52 cases renal artery stenosis was suspected (0.04 differences between RI on right and left renal artery). Acute renal failure was suspected in 53 cases. According to neoplasms, pathological, marked increased vascularization was noticed in 34 cases suspected for renal carcinoma, in 46 cases suspected of testicular tumours, 19 cases suspected of prostate neoplasm and in 32 cases suspected of tumours in other localizations. In combination with patient history, clinical and laboratory examination CDUS provides very useful information in accomplishing the diagnosis.

We used duplex Doppler analysis to determine whether the intrarenal RI can be used as a predictor in patients with diabetic nephropathy. Intrarenal resistive index (RI) values were obtained from intraparenchimal arteries of both kidneys, either the arcuate or interlobar arteries. Clinical parameters and renal function were also evaluated at baseline and after three and six months. Forty patients with diabetic nephropathy were divided into two groups based on their intrarenal RI values: group 1 had values of >or=70 and group 2 had values <70. Progression of renal function (delta creatinine clearance, delta CCr) was estimated by linear regression of the slope of decline of CCr plotted against time. At baseline, sixteen patients (40%) had an intrarenal RI value >or=70. Eight patients (50%) of them had a decline in renal function after six months. In comparison, among patients with intrarenal RI values <70 (n=24), only 2 had a decline in renal function. In multivariate regression analysis, proteinuria, lower baseline CCr and RI were independent predictors of declining renal function. An intrarenal RI value of >or=70 identifies diabetic patients at risk of progressive renal disease. The RI of interlobar arteries seems to be a dependable marker of intrarenal changes and can be used as a non-invasive, easily available parameter of the evolution in patients with advanced clinical diabetic nephropathy.

Glomerulonephritis (GN) is a major cause of renal failure. This study sought to determine whether intrarenal injection of rat mesenchymal stem cells (MSC) can preserve renal function in a progressive rat model of GN. Early in GN (day 10), fluorescently labeled rat MSC localized to more than 70% of glomeruli, ameliorated acute renal failure, and reduced glomerular adhesions. Fifty days later, proteinuria had progressed in controls to 40 +/- 25 mg/d but stayed low in MSC-treated rats (13 +/- 4 mg/d; P < 0.01). Renal function on day 60 in the MSC group was better than in medium controls. Kidneys of the MSC group as compared with controls on day 60 contained 11% more glomeruli per 1-mm(2) section of cortex but also significantly more collagen types I, III, and IV and alpha-smooth muscle actin. Approximately 20% of the glomeruli of MSC-treated rats contained single or clusters of large adipocytes with pronounced surrounding fibrosis. Adipocytes exhibited fluorescence in their cytoplasm and/or intracellular lipid droplets. Lipid composition in these adipocytes in vivo mirrored that of MSC that underwent adipogenic differentiation in vitro. Thus, in this GN model, the early beneficial effect of MSC of preserving damaged glomeruli and maintaining renal function was offset by a long-term partial maldifferentiation of intraglomerular MSC into adipocytes accompanied by glomerular sclerosis. These data suggest that MSC treatment can be a valuable therapeutic approach only if adipogenic maldifferentiation is prevented.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis. Some patients reach end-stage renal failure (ESRF), others experience an indolent course. We aimed the study to examine the association of risk factors with the progression to renal failure. Eighty patients diagnosed with IgAN by renal biopsy (RB) were studied. Baseline clinical and demographic data were reviewed. Severity of histological involvement was scored as H. S. Lee's grading system. The mean age of patients at biopsy was 36.65 +/- 8.83 years with predominance of men (male : female, 58 : 22). Patients were followed-up from 6 months to 23 years (276 months). An end-point was defined as the date when patient underwent their first haemodialysis or their last visit of follow-up. The differences in means between groups were compared by independent samples t-tests or one-way analysis of variance (ANOVA). Kaplan-Meier survival curves and Cox regression models were used to analyze the time course from renal biopsy to end points. The largest subclasses were grade I and II, with 31 patient each. Subclass III was observed in 12 patents. Subclass IV and V were found in 3 patients each. During the follow-up period, all patients with grade IV and V (after 6-48 months), five patients grade I (after 60-144 months), four patients grade II (after 48-84 months), and 7 patients from grade III (after 24-108 months) entered ESRD. Mean prioteinuria was 1.68 +/- 0.99 g/day. Macrohematuria had 32; microhematuria had 48 pts. The mean serum creatinine was 148.02 +/- 68.76 micromol/l. By multivariate analysis using the Cox regression model, grades, renal insufficiency and significant proteinuria were independent prognostic factors for progressive renal disease. At the end of follow-up, grades were significantly related to serum creatinine, proteinuria, hypertension and progressive renal disease. Renal biopsy in IgAN may be the most powerful predictor for renal outcome.

Membrane plasma exchange (PE) is a mode of extracorporeal blood purification. Since 1985 membrane PE has been in regular use at the Department of Nephrology, Medical Faculty of Skopje, R.Macedonia. In this paper we report on five years (2000-2004) of single centre plasma exchange activity. We performed 540 PE treatments (108 PE/per year) on 99 patients. The M/F ratio was 40/48. The patients underwent a median of 5.45 procedures (range, 1-16). The treated patients were from different Departments. Protocols for PE depend on the disease and its severity. PE were performed 2-4 times weekly using Gambro PF 2000 N filters with an adaptation of the Gambro AK10 dialysis machine or with the Gambro Prizma machine (2 cases). Blood access was achieved through femoral vein. Substitution was made with fresh frozen plasma and/or with 20% human albumin combined with Ringer's solution. An average amount of 2150 ml plasmafiltrate per treatment (respectively 30 to 40 ml plasmafiltrate/kg body weight) was eliminated. Most therapeutic procedures were performed on patients from the Department of Neurology. 63.6% of all patients were referred for Myasthenia gravis and the Guillian Barre syndrome. The total number of procedures per year has remained fairly stable, corresponding to a median of 5.4 treatments/100 000 inhabitants. We observed hypocalcaemia in 8% of the patients, urticarial reactions in 7.3%, pruritic reactions in 12%, and hypotension/headache in 6.8%. No major procedural complications were seen.

Patients with rapidly progressive glomerulonephritis who are positive for anti-neutrophil cytoplasmic antibody (ANCA) or anti-glomerular basement membrane (GBM) antibodies may develop chronic renal failure leading to end-stage renal disease (ESRD) within days or weeks. The early serologic detection of auto-antibodies associated with ANCA and anti-GBM diseases will be helpful in preventing ESRD. We evaluated the combined ANCA-GBM dot-blot strip assay (Biomedical Diagnostics, Brugge, Belgium) in 30 consecutive patients with biopsy proven glomerulonephritis (GN). MPO- and PR3-ANCA were detected in 5 and 2 samples, respectively. Three samples were positive for both MPO- and PR3-ANCA (all 3 had focal segmental necrotizing GN). One patient was diagnosed as having Goodpastures' syndrome (the only anti-GBM positive result) and two had Wegener's granulomatosis (the two PR3-ANCA positive results). Two additional samples were equivocal: positive for MPO-ANCA and PR3-ANCA, respectively. Patients positive only for MPO-ANCA had only limited extrarenal organ manifestations. Anti-PR3 positive patients with necrotizing glomerulonephritis had a more dramatic deterioration of their renal function at diagnosis. Radiographically, these patients had nodular or pneumonia-like lesions. Acute respiratory failure necessitating mechanical ventilation was developed in one GBM positive patient. In conclusion, the ANCA-GBM dot-blot is a useful screening tool in situations where conventional ANCA testing is not readily available.

Background: Cyclin-dependent kinase (CDK) inhibition is a new therapeutic approach to proliferative glomerulonephritides. CDK2 is required for G(1)/S transition and DNA synthesis and is inhibited by CYC202 (R-roscovitine). Since podocytes express CDK2 in nephritis and since loss of podocytes contributes to glomerulosclerosis, the rationale of the present study was to test whether CDK2 inhibition is safe in instances of podocyte injury., Methods: Rats with passive Heymann nephritis, a model of membranous glomerulonephritis, were treated (day 3 to 30) with vehicle, low (25 mg/kg/day), or high (50 mg/kg/day) doses of CYC202., Results: On day 27, blood pressure was normal in nephritic controls and was dose-dependently reduced by CYC202. Urinary albumin excretion did not differ between the groups on days 9, 16, 23, and 30. To investigate podocyte injury, we assessed the glomerular de novo expression of desmin, which was markedly up-regulated in almost all passive Heymann nephritis glomeruli but was not significantly different between the three groups. No tubulointerstitial de novo expression of desmin or alpha-smooth muscle actin (alpha-SMA), or tubulointerstitial monocyte/macrophage infiltration was noted in any group. Biologic activity of CYC202 was evident in the form of a dose-dependent decrease in the number of glomerular and tubulointerstitial mitotic figures as compared to vehicle alone. Glomerular immunostaining for cyclin D1, a marker for G(0) to G(1) transition, was significantly decreased in CYC202 treated groups at day 9., Conclusion: Whereas inhibition of CDKs by CYC202 reduced intrarenal cell proliferation in passive Heymann nephritis it did not aggravate podocyte damage, suggesting that this novel therapeutic approach is safe in renal diseases characterized by podocyte injury.