Immunosuppressive therapy of lupus nephritis
ABSTRACT Aggressive immunosuppressive therapy should be considered for patients with proliferative lupus nephritis as the risk for progression to end stage renal disease is high. Intermittent intravenous cyclophosphamide therapy improves renal survival; longer duration of therapy is associated with fewer relapse of nephritis and decreased risk of diminished renal function. While azathioprine therapy does not differ statistically from steroids alone in prolonging renal survival, this therapy may be considered in patients with few risk factors for progression to renal insufficiency. Methylprednisolone as a single therapy does not prolong renal survival compared with regimens including cyclophosphamide. Plasmapheresis remains under study but has not shown additional benefit in treatment of severe lupus nephritis. The potential roles for cyclosporin A and mycophenylate mofetil in the therapy of proliferative lupus nephritis remain to be defined. Supportive care including rigorous control of hypertension, consideration of angiotensin receptor inhibition or blockade to reduce proteinuria and prolong renal function, control of hyperlipidemia, prevention of osteoporosis, and prevention of pregnancy remain important clinical goals. Current research efforts focus on genetic and socioeconomic factors involved in racial differences in expression of lupus nephritis, hormonal manipulation to preserve gonadal function during cyclophosphamide therapy, and the potential impact on lupus activity of estrogen-containing oral contraceptives or postmenopausal hormone replacement therapy.
- SourceAvailable from: Senad Bajramovic[Show abstract] [Hide abstract]
ABSTRACT: Serial sample labeling • Management of quantitative information • Samples handling by robot • Processing measurement data • Reporting (delivering findings) • Planning of laboratory resources • Quality monitoring • Communication with other informa-tion systems Integrated process like this assures the laboratory information management system (LIMS), which connects the in-struments, resources and personnel in a wide unique network within the most important link, is a link computer -auto analyzer. During this is necessary to use the central laboratory computer, which works with multiple terminals in real time and on which micro computers can be linked as peripheral computers. The purpose of laboratory automation is to increase pro-ductivity, which is specifically defined as the collection and reporting the results of tests in a period of time in order to achieve maximum accuracy and precision of mea-surements without the expansion of re-sources and increase of labor costs. The main reasons for the introduction of LIMS are: • Increased number of findings requests • Increased number of complex analyses • Increased number of unnecessary analyses • Emergency of demands • Loss of professional staff time on ad-ministrative jobs Inability to work more seriously on professional and scientific analysis of test and experiments results. The number of completed clinical-lab-oratory analyses in the developed coun-tries shows a high rate of growth which annually ranges from 10-17%, showing increase in the number of tested persons and the number of analysis by a patient. This phenomenon is a result of the prog-ress of medical science but also the tech-nological revolution in the field of labo-ratory equipment and biochemistry im-mune diagnostics. Serial labeling of samples is done im-191-196 SUMMARY Introducrion: Computers and information technology significantly improve the work in various laboratories (clinical-biochemistry, hematology, immunology, cytology, etc) since it automates the testing and speeds up delivery of findings. The number of completed clinical-laboratory analysis in the developed countries shows high rate of growth that annually ranges from 10-17. Systemic lupus erythematosus is the disorder of immune regulation which is mani-fested by activation of T and B lymphocytes, production of antibodies, and the formation of immune complex causing damage to tissues. SLE is a disease that progresses over time and has been intriguing to the doctors for more than a century while holding being a prototype of autoimmune disease. Kidney function loss is the most serious complication of SLE which represents a threat for long-term survival. Goal: The aim is to show the clinical and labora-tory parameters of lupus nephritis and principle of therapeutic protocol for the treatment of lupus nephritis using aggressive immunosuppressive therapy at the Institute of Nephrology of Clinical Center of the Sarajevo University by monitoring activity of disease. Patients and methods: Randomized retrospective study includes 14 patients with SLE and lupus nephritis that are treated at the Institute of Nephrology of Clinical Center University of Sarajevo in the period from the beginning of 2000 to 2003. Discussion: In our retrospective study, all patients were females with mean age of 34.5±13.5 years. Mean age at the beginning of SLE was 30.5±12.5 years. Most often clinical manifestations observed in patients with SLE are general ones (85.7%) -skeletal muscle (64.3%), skin (78.6%), hematologic (64.3), cardiac and pulmonal (42.9), neurologic (21.4%), thrombosis (35.7%), eye (14.3%) and abortion (7%). Conclusion: Females in reproductive age have SLE and lupus nephritis more frequently , which indicates that hormonal status (estrogen) has important role in illness pathogenesis. Most relevant parameters in evaluation of illness activity are the levels of complement components C3 and C4, level of antidsDNA, activity of urine sediment and proteinuria level. Aggressive immunosuppressive therapy that includes corticosteroids and cyclophosphamide, with control of side effects and its prevention, and duly treatment can lead to improvement of clinical symptoms and improvement of patient life. As long as new therapeutic modalities and more efficient treatment of autoimmune illnesses is not available, the greatest impact on mortality and morbidity can be achieved by monitoring late manifestations and treatment of extracranial manifestations that can lead to kidney function loss.
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ABSTRACT: The treatment of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) can be difficult and complex owing to the variety of nervous system manifestations that can occur, which include peripheral nerve disease, headaches, seizures, cerebrovascular disease, chorea, transverse myelitis, and psychiatric and cognitive disorders. Many of these manifestations can result from metabolic abnormalities or infection or as side effects of medications. Thus, in any patient with suspected NPSLE, it is crucial to exclude secondary causes of the presenting symptoms before assuming that they are due to NPSLE. It is especially important to exclude infection because this is a common cause of both morbidity and mortality in patients with systemic lupus erythematosus (SLE). Symptoms such as anxiety and depression may or may not be related to disease activity. Treatment decisions are based on accurate diagnosis of the specific NPSLE manifestation, which is usually made using tools such as brain imaging, electroencephalography, cerebrospinal fluid analysis, nerve conduction studies, or special serologic tests (eg, determination of antiphospholipid or antiribosomal P antibody levels). It is also important to assess the degree of other SLE- mediated systemic disease activity in a patient with neurologic manifestations to determine if activation of systemic disease activity is also occurring. This is done by measuring complement levels, anti-double-stranded DNA levels, complete blood count, and urinalysis. For some NPSLE manifestations (eg, infrequent seizures, headaches, depression, anxiety, or peripheral neuropathy) that appear without activation of systemic disease, symptomatic treatment is appropriate. For others (eg, psychosis, delirium, or transverse myelopathy without other obvious cause), treatment with high-dose glucocorticoids with or without cyclophosphamide is appropriate whether there is evidence of other systemic disease activity or not. In general, the activity and severity of the leading organ manifestations dictate pharmacologic treatment.Current Treatment Options in Neurology 10/2000; 2(5):473-485. DOI:10.1016/S1541-9800(09)70195-4 · 2.18 Impact Factor
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ABSTRACT: To compare the pharmacokinetics of subcutaneous and intravenous fludarabine in patients with lupus nephritis. Open-label, randomized, crossover trial conducted with a phase I-II trial. Government research hospital. Five patients with lupus nephritis. Fludarabine 30 mg/m2/day was administered either subcutaneously or as a 0.5-hour intravenous infusion for 3 consecutive days. All patients received oral cyclophosphamide 0.5 g/m2 on the first day of each cycle. Plasma samples were collected before and 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the first dose. Urine was collected at 6-hour intervals for 24 hours. Plasma and urine were analyzed for fluoro-arabinofuranosyladenine (F-ara-A), fludarabine's main metabolite, using high-performance liquid chromatography. Compartmental techniques were used to determine the pharmacokinetics of F-ara-A; a linear two-compartment model best described them. Comparison of the pharmacokinetics between subcutaneous and intravenous administration was done by using a Wilcoxon signed rank test. No significant differences were found between subcutaneous and intravenous administration in median (interquartile range) maximum concentrations of 0.51 (0.38-0.56) and 0.75 (0.52-0.91) mg/L, respectively, or in fitted area under the concentration-time curves from 0-24 hours of 4.65 (4.17-4.98) and 4.55 (3.5-4.94) mg x hour/L, respectively. Bioavailability of F-ara-A after subcutaneous dosing was approximately 105% of the bioavailability after intravenous administration. Differences in renal clearance and percentage of dose excreted in urine for subcutaneous and intravenous administration were nonsignificant. No injection site reactions were seen with subcutaneous dosing. Subcutaneous and intravenous administration of fludarabine appear to have similar pharmacokinetics in patients with lupus nephritis. Subcutaneous injection may offer a convenient alternative to intravenous administration.Pharmacotherapy 06/2001; 21(5):528-33. DOI:10.1592/phco.21.6.528.34549 · 2.20 Impact Factor