Renal histopathology and clinical course in patients with Wegener's granulomatosis--single centre experience from the Republic of Macedonia.

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.

Doppler ultrasonography: a tool for nephrologists--single centre experience.

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.

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.

Progression of diabetic nephropathy: value of intrarenal resistive index (RI).

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.

Therapeutic apheresis in the Republic of Macedonia - our five years experience (2000-2004).

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.

ANCA-GBM dot-blot test in diagnosis of patients with glomerulonephritis.

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.

IgA nephropathy: 23 years of follow-up.

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.