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.

Role of mycophenolate mofetil in the treatment of lupus nephritis.

Mycophenolate mofetil (MMF) is an immunosuppressive drug successfully used for the prevention of acute and chronic rejection of renal allografts, as well as in the therapy of glomerular disorders. We treated three groups of patients with lupus nephritis: the first group of patients had a high histologic activity index (AI), 13.4 +/- 2.34; the second group of patients had a high histologic chronicity index (CI), 6.0 +/- 0.7; and the third group consisted of only two patients, one with low AI (3.5) and another with low CI (1.5). The patients were treated for 2 years. MMF was initiated at a dose of 2 g/daily for the first 6 months and the dose was decreased to 1.5 g/daily for the further 18 months. Steroids, 0.4 mg/kg/day, were the concomitant therapy for the first 6 months, with slow tapering for the further 18 months. Patients with high AI presented significant decrease of serum creatinine after 2 years, 286 +/- 112.95 to 131.2 +/- 44.65 micromol/L. Two of the patients, with acute oligoanuria, were withdrawn from dialysis treatment. Significant improvement was also noted, 6.97 +/- 1.81 to 0.9 +/- 0.31 g/day. Patients with high CI had nonsignificant decrease of serum creatinine, 178.5 +/- 47.73 to 129.25 +/- 22.88 micromol/L, and significant improvement of proteinuria, 4.63 +/- 1.57 to 1.14 +/- 0.39 g/day. The patient with low AI showed recovery of renal function (serum creatinine from 196 to 72 micromol/L) and alleviation of proteinuria, 7.93 to 3.4 g/day. The patient with low CI did not respond to the therapy and renal function slowly worsened. MMF has emerged as a promising therapeutic approach for both the induction and maintenance phase in patients with lupus nephritis.

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.

Bioelectric impedance in the estimation of hemodynamic and fluid status in dialysis patients.

In order to estimate the hemodynamic and fluid changes, "dry body weight" and intradialytic stability, electric bioimpedance cardiography was performed in 37 dialysis patients during dialysis procedure, i.e. before, at 2 h and after dialysis. The following parameters were estimated: systemic vascular resistance index-fl. Ohm/m2 (SVRI), mean arterial pressure-Torr (MAP), thoracic fluid conductivity/Ohm (TFC), cardiac index-L/min/m2 (CI), left cardiac work index-kg m/m2 (LCWI) and ejection fraction % (EF). Results were compared with changes in total body water estimated by the urea kinetic model (UKM). The patients were divided into three groups: normotensive (n = 12), hypertensive (n = 15) and hypotensive (n = 10). EF was increased in all the three groups, but only in hypotensives this change was significant (from 40.5 +/- 9.1 to 50.2 +/- 5.41, p < 0.01). The changes in other hemodynamic parameters (CI, LCWI, SVRI) did not reach statistical significance. TFC decreased significantly in all the three groups: normotensive from 0.056 +/- 0.009 to 0.048 +/- 0.009 (p < 0.001), hypotensive from 0.043 +/- 0.009 to 0.035 +/- 0.058 (p < 0.001) and hypertensive from 0.054 +/- 0.016 to 0.045 +/- 0.014 (p < 0.001). These changes were accompanied by a significant decrease in total body water (TBW): from 34.05 +/- 4.19 to 32.72 +/- 4.51 in the hypotensive group, from 34.06 +/- 7.18 to 32.91 +/- 7.27 in the normotensive group, and from 38.92 +/- 7.06 to 37.59 +/- 7.04 in the hypertensive group. The technique was found to be simple, noninvasive and helpful for the estimation of individual hemodynamic changes during dialysis procedure.

Long-term diuretic therapy in patients with chronic renal failure.

Ten patients with chronic renal failure from different genesis (serum creatinine levels 150-200 mumol/l), were evaluated from the aspect of the effect of the diuretic therapy. The effects of furosemide (FUR) and polythiazide (POL) were assessed after 3-month application. The mean values of the estimated parameters before treatment, after 3-month administration of FUR as a monotherapy and after the next 3 months simultaneously used (FUR + POL), presented a stable increase of the diuresis, without statistically significant changes of the global renal function, and triglyceride disorders. On the contrary, the improvement of calciuria through combined using of furosemide and polythiazide is statistically and clinically significant.

[The importance of the metacarpal bone index in the evaluation of uremic osteopathy]. / Znacaj indeksa metakarpalnih kostiju u procenu uremijske osteopatije.

71 patients with chronic renal failure were analysed. The patients were treated (N1 = 32) and not treated (N2 = 39) with chronic intermittent hemodialysis. In all analysed patients and in the control group of 20 patients sex and age matched to the examined groups) the outside (D) the inner diameter of the middle II metacarpal bone of the dominant hand was measured (a precision of 0.1 mm was reached using Yashio, Japan, magnifying glass) and the following "metacarpal" indexes were calculated: 1. Garn's Index:--thickness in the cortical bone in mm (D-d) 2. Nordin's score:--percentage of the cortical bone [formula: see text] 3. Garw's area:--cortical bone surface [formula see text] 4. The quantity of the corical bone thickness and the bone surface [formula: see text] From the results received by the analysis it could be noted that the tested patients with chronic renal failure, regardless of chronic intermittent chronic dialyses, showed a negative interdependence on the relation: "PTH-metacarpal index", that indicates the conclusion that the bone destruction is greater if the levels of plasma C-iPTH are higher. The similar can be noticed with the comparison of the C-iPTH-value of the periostitic lacunas in the cortex of the iliac bone (r = 0.64, i.e. higher concentration of C-iPTH agrees with larger surface of lacunar periostitis). Finally, the thickness of the outer cortex of the iliac bone is smaller if the values of C-iPTH are higher (r = 0.12, patients treated with hemodialysis).