Prednisone/cyclophosphamide treatment in adult-onset autosomal dominant familial focal segmental glomerulosclerosis (FSGS 1).
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Biomedical subjects
Publications and source records attributed to L Grcevska.
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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.
There is now controlled evidence that a 6-month course with methylprednisolone and chlorambucil may favour remission of the nephrotic syndrome and may significantly improve the 10-year kidney survival in patients with idiopathic membranous nephropathy. We analyzed the outcome of 15 nephrotic patients (proteinuria 7.06 +/- 1.07 g/d), stage II-III membranous nephropathy, aged 37.93 +/- 2.32, 8 males and 7 females, with normal serum creatinine (62.8 +/- 2.34 micromol/l), followed > 10 years after the treatment. It consisted of 1g i.v. methylprednisolone for three consecutive days, followed by oral steroids 0.4 mg/kg/d and chlorambucil 0.2 mg/kg/d monthly, alternatively. 10 patients, age and sex matched, who refused any treatment of any reason, represented the control group. Complete remission was defined as protein loss of 0.2 g/d, partial 0.2-2 g/d with normal creatinine and renal dysfunction as increase in plasma creatinine. The follow-up period was between 10 and 20 years. Complete remission after the treatment was noted in 9/15, partial in 4/15, and 2/15 patients did not respond. 10-year survival rate of the whole group was 100%, 15-year - 86.7%, i.e. two patients with persistent nephrotic syndrome developed end-stage renal failure after 12 years. 13/15 patients (complete, partial remission) were followed > 15 years without development of end-stage renal failure. One patient (female, 32) developed idiopathic thrombocytopenia after 8 years. 3 patients (complete remission) were followed > 20 years, they are still without proteinuria. 10-year survival rate of untreated patients was 40%. It is concluded that in nephrotic patients with stage II-III membranous nephropathy steroids/chlorambucil therapy may be effective in favoring remission and in preserving renal function.
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.
The aim of the present study was to identify subclinical and borderline rejections as well as histological markers of chronic allograft nephropathy (CAN) among protocol biopsies performed at 1 and 6 months after living related kidney transplantation to assess their possible implications for graft function. Twenty paired allograft biopsies performed at 1 and 6 months were reviewed according to the Banff scoring scheme. The mean ages of donors and recipients were 59.6 +/- 13.8 and 34.4 +/- 8.7 years, respectively. Among all biopsies only 10% (4/40) showed no histopathological lesions. At the first month borderline rejection was shown in 35% and subclinical rejection in 10% of patients. At 6 months the proportion of findings was even higher, namely, 40% and 30%, respectively. When divided according to donor age, donors above 55 years showed a mean CAN score of 2.33 +/- 1.56 which increased to 5.0 +/- 2.26 on the 6 month biopsy (214.3%). Unexpectedly, the proportion of these changes in the younger donor group also increased by 173.3%, which might have been explained by the greater number of borderline and subclinical rejections in the younger donor group at the 1 month biopsy. In conclusion, 1 month biopsy may be valuable to determine borderline and subclinical rejection and to prognosticate the outcome of renal allograft function. Our findings suggest a greater susceptibility of histological deterioration among the older donor population. However, the presence of an untreated rejection in the younger donor pool leads to a rapid impairment of the graft function accelerating the process of chronic allograft nephropathy.
BACKGROUND: Renal diseases other than diabetic nephropathy can be found in diabetic patients who have undergone renal biopsy. Various forms of primary and secondary glomerular diseases were reported, but membranoproliferative glomerulonephritis was rare. METHODS: Analyzing data at our Department for the past three years, we noted 18 patients with primary membranoproliferative glomerulonephritis and 4 associated with diabetic nephropathy. RESULTS: Nodular glomerulosclerosis with diffuse membranoproliferative glomerulonephritis was registered in two patients and a diffuse form of diabetic nephropathy with a combination of segmental and diffuse changes characteristic of membranoproliferative glomerulonephritis in the other two patients. CONCLUSIONS: Analyzing what can be common for these two diseases we can conclude that they are at least three disorders: 1. hyperperfusion injury, hallmark for the diabetic nephropathy, but also with the highest incidence in membranoproliferative glomerulonephritis than in the other glomerulonephritides; 2. mesangial matrix expansion, and; 3. thickening of all extracellular membranes.
Glomerulonephritis (GN) is one of the most frequent causes of end-stage renal disease. Recurrent GN can occur very early after transplantation in up to 20% of renal-allograft recipients and should be considered with late graft dysfunction in 2-5%. Importantly, diagnosis of a clinically silent recurrence of the disease will pass undetected unless transplant centers have a policy of protocol biopsies. In addition, the classification of the type of recurrent GN should be done with data on electron microscopy and immunofluorescence, in order to promote prompt treatment and a strategy for long-term graft survival. The aim of our paper was to present a few typical cases of recurrent GN, showing the actuality of the problem in living related kidney transplant recipients and to ascertain the importance of precise and timely diagnosis by protocol biopsy. Recurrent focal segmental glomerular sclerosis (FSGS) in childhood is associated with the highest number of graft loss. The treatment of recurrent FSGN is difficult, so prophylactic plasmapheresis prior to transplantation appeared to be more effective in preventing recurrence than plasmapheresis after transplantation, especially in population of children. Mesangio proliferative GN type II is the second most frequent recurrent GN, followed by type I. Here, it is of paramount importance to classify the type of the disease. The family of the patient at risk for recurrent GN, a candidate for living related kidney transplantation, should be informed for the expected outcome and their voluntary decision whether to proceed with transplantation should be awaited.
BACKGROUND: All patients with thymomatous Myasthenia Gravis (MG) should undergo early and total thymectomy, but controversy abounds in the choice of chronic immunosuppressive agents. The value of plasmaexchange (PE) in MG has been clearly established in preoperative preparation and treatment of myasthenic crisis. Whether PE may be used in the chronic long-term therapy of patients with thymomatous MG in addition to conventional immunosuppressive agents and cholinesterase inhibitors is yet to be answered. CASE HISTORY: We present a 40-year old woman with an 11 year history of MG. Thymectomy was done during the first year of the disease and the histopathologic finding was thymoma. To sustain clinical remission after thymectomy she continued with immunosuppression with methylprednisolone and cyclosporin A (or azathioprine) in addition to cholinesterase inhibitors. Despite the almost continuous immunosuppression, the disease course continued with fluctuating myasthenic weakness which few times progressed to myasthenic crisis requiring mechanical ventilation. During myasthenic crisis we performed 6-8 plasmapheresis at 2-3 day intervals in addition to conventional immunosuppressive therapy. The disease rapidly worsened in January 2000 and we started with intermittent plasmapheresis (3-6 procedures at 2-3 day intervals, every 6-8 weeks) in order to sustain remission. With this therapeutic protocol, during 20 months follow-up we managed to prevent myasthenic crisis and to avoid ventilatory support. CONCLUSIONS: Plasmaexchange could be used as a successful and safe therapeutic tool in chronic long-term therapy in addition to conventional immunosuppressive agents to sustain remission in patients with MG. This is particularly important in the treatment of patients with thymomatous MG because they have an increased frequency of myasthenic crisis and often respond poorly an to immunosuppression with steroids or other immunosuppressants.
The duration of diabetes mellitus and the presence of hyperglycaemia were thought to be important in the development of nodular glomerulosclerosis. We report on 3 patients without overt diabetes, but with glucose intolerance, all male, aged 43-66 years, with histological features of diabetic glomerulosclerosis. The nodular form was present in 2 patients and the diffuse form in 1. These cases suggest that factor(s) other than hyperglycaemia are responsible for diabetic renal damage.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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Many important aspects of the therapeutic approach to patients with idiopathic membranous nephropathy are still controversial. There are several reports that the effectiveness of therapy depends on histological staging and severity of interstitial mononuclear cell infiltration. We used several different treatments in 39 patients with stage II to III primary membranous nephropathy with proteinuria more than 2.5 g/d, without hypertension and chronic renal failure at biopsy. Ten patients were not treated, 13 were treated with only steroids, 13 with alternate use of steroids and chlorambucil, and three with cyclosporine A. The follow-up period was 5 to 10 years. Statistics included Kruskall-Wallis and one-way ANOVA analysis. A significant decrease in proteinuria was noted in patients treated with steroids (P < 0.01), from 8.45 +/- 1.04 g/d (mean +/- SEM) to 1. 42 +/- 0.45 g/d after follow-up of 5 years and in patients treated with steroids and chlorambucil (12.9 +/- 2.4 g/d [mean +/- SEM] to 2. 46 +/- 1.38 g/d). Compared with patients treated with steroids (15. 3%) and patients treated with steroids and chlorambucil (15.3%), untreated patients had a high frequency of chronic renal failure after 5 years of follow-up (70%) and had a significant increase in mean serum creatinine (P = 0.008). We conclude that steroid therapy alone, or associated with chlorambucil, is effective in patients with stage II to III membranous nephropathy. Patients responded with a decrease of proteinuria and stable renal function during the long-term follow-up period. The group of patients treated with cyclosporine A was too small to analyze.
In 1986, Weiss et al reported a group of patients with nephrotic syndrome, progressive chronic renal failure, and the histopathologic features of glomerular capillary collapse. Similar lesions are often described in human immunodeficiency virus (HIV) nephropathy. We evaluated 893 consecutive nontransplant renal biopsies performed in our department and the follow-up of the patients at our outpatient service. Sixteen specimens were identified with the pathological features of collapsing glomerulopathy (focal segmental or global glomerular capillary collapse and visceral epithelial cell hyperplasia), with no evidence of HIV infection and/or intravenous drug abuse. Their clinical characteristics were analyzed and compared with a group of 29 patients with noncollapsing focal segmental glomerulosclerosis (FSGS). The follow-up period of both patient groups was 5 +/- 1.46 years. The Kaplan-Meier life table method was used to present survival of the patients. The age of both groups was similar, 34 +/- 4 years (mean +/- standard error of the mean) for patients with collapsing glomerulopathy and 35 +/- 3 years for those with FSGS. The serum creatinine level was greater in patients with collapsing glomerulopathy (183 +/- 31 micromol/L) compared with those with FSGS (115 +/- 18 micromol/L), but the difference was not significant (P = 0.0504). The difference in proteinuria was not significant (P = 0.7668); it was 5.83 +/- 0.74 g/d in patients with collapsing glomerulopathy and 5.42 +/- 0.84 g/d in those with focal sclerosing glomerulonephritis. The difference in systolic (P = 0.4) and diastolic blood pressure (P = 0.556) was also not significant. Survival of the patients with collapsing glomerulopathy was worse than that of patients with FSGS (P = 0.025). Renal function survived 5 years in 40% of the patients with FSGS, but patients with collapsing glomerulopathy had no renal function survival. Our data suggest that idiopathic collapsing glomerulopathy is a distinct clinicopathologic entity with similar clinical features to focal sclerosing glomerulonephritis, but a worse prognosis and a rapidly progressive course toward end-stage renal disease.