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Effectiveness of renoprotective approaches for persistent proteinuria in lupus nephritis: more than just immunosuppression.
Castro, M, Ugolini-Lopes, M, Borba, EF, Bonfá, E, Seguro, LPC
Lupus. 2018;(14):2215-2219
Abstract
OBJECTIVE The objective of this study is to evaluate the efficacy of a tightly controlled renoprotective protocol in systemic lupus erythematosus (SLE) patients with persistent proteinuria. METHODS Thirteen SLE patients with nephritis and persistent proteinuria (>1 g/24 hours) were included. The protocol consisted of regular clinical evaluations every two weeks to assess blood pressure (BP, target <130/80 mmHg), adherence to therapy, diet and smoking. No change in immunosuppressive drugs was allowed but reduction of glucocorticoid dose was permitted if indicated. Clinical, laboratory and treatment evaluations were performed at baseline and at the end of the study (after three months). RESULTS SLE patients had a mean age of 37.85 ± 7.68 years and disease duration of 9.85 ± 7.29 years. At baseline, patients had a mean duration of maintenance therapy of 10.38 ± 7.56 months, 12 with mycophenolate mofetil (92.3%) and one with azathioprine (7.7%). At least one dose optimization of antihypertensive regimen was required in all patients during the study. Seven patients (53.8%) had BP>130/80mmHg at baseline. At the end, 11 patients (84.6%) achieved stable BP target; 92.3% were using an angiotensin-converting enzyme inhibitor, 53.9% an angiotensin receptor blocker, and 46.2% were using combined therapy. All patients had a significant reduction in proteinuria levels (2.26 ± 1.09 vs 0.88 ± 0.54 g/24 hours, p < 0.001) and 61.5% achieved proteinuria <1 g/24 hours. A significant decrease in mean prednisone dose was observed (10.96 ± 6.73 vs 5.38 ± 3.36 mg/day, p = 0.013) as well as mean Systemic Lupus Erythematosus Disease Activity Index score (4.38 ± 0.72 vs 3.08 ± 1.86, p = 0.043). No significant changes were identified in serum creatinine, albumin, potassium, complement 3 and complement 4 levels ( p > 0.05). CONCLUSION This study provides evidence that a tightly controlled renoprotective protocol is effective in reducing persistent proteinuria in lupus nephritis. The concomitant reduction of prednisone without any change in immunosuppression reinforces the importance of strategies beyond the treatment of nephritis activity.
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The influence of thiamazole, lithium carbonate, or prednisone administration on the efficacy of radioiodine treatment ((131)I) in hyperthyroid patients.
Oszukowska, L, Knapska-Kucharska, M, Makarewicz, J, Lewiński, A
Endokrynologia Polska. 2010;(1):56-61
Abstract
INTRODUCTION The effects of selected drugs (see below) on the efficacy of ((131)I) radioiodine therapy were examined. MATERIAL AND METHODS The study involved 200 hyperthyroid patients, treated with radioactive iodine. They were divided into five groups (40 persons in each). In Group I - patients were administered (131)I and thiamazole; in Group II they were given - (131)I and lithium carbonate; in Group III they were given - (131)I only (the assumed absorbed dose - 150-200 Gy, the same as in Groups I and II, for which Group III was a control group); in Group IV they were given - (131)I and prednisone; and in Group V they were given - (131)I only (250-350 Gy, the same as in Group IV, for which Group V was a control group). Therapeutic results were analyzed after six months based on clinical and hormonal status. The evaluation also included effects of the initial hormonal status on the outcome of (131)I therapy in Groups II and IV (v. respective controls, i.e. Groups III and V); such analysis was not performed in Group I because all the patients in that group were initially hyperthyroid. RESULTS In 145 patients (72.5%) the therapy with (131)I was effective. In 55 patients (27.5%) the therapy was ineffective. The application of thiamazole during the peritherapeutic period in patients treated with 131I reduced the effectiveness of radioiodine, while lithium carbonate had no effect on the therapy outcome. Prednisone increased the effectiveness of the therapy with (131)I. Normalisation of the initial concentration of TSH was advantageous for the (131)I therapeutic outcome only when the assumed absorbed doses of 150-200 Gy were applied, while being of no avail for doses above 250 Gy. CONCLUSIONS The present results indicate the necessity of careful analysis of administered drugs in hyperthyroid patients while qualifying them to (131)I therapy. The initial concentration of TSH has no effect on the efficacy of radioiodine therapy in cases where absorbed doses are regarded to be ablative. (Pol J Endocrinol 2010; 61 (1): 56-61).
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A combination treatment of prednisone, aspirin, folate, and progesterone in women with idiopathic recurrent miscarriage: a matched-pair study.
Tempfer, CB, Kurz, C, Bentz, EK, Unfried, G, Walch, K, Czizek, U, Huber, JC
Fertility and sterility. 2006;(1):145-8
Abstract
OBJECTIVE To compare a combination treatment of prednisone, aspirin, folate, and progesterone with no treatment in women with idiopathic recurrent miscarriage (IRM). DESIGN Matched-pair study. SETTING Academic research institution. SUBJECT(S): Women with a history of IRM, defined as three or more consecutive miscarriages before 20 weeks' gestation without associated anatomic, cytogenetic, hormonal, and infectious pathologies or antiphospholipid syndrome. INTERVENTION(S): Eighty of 210 eligible women consented to participate and were treated with prednisone (20 mg/d) and progesterone (20 mg/d) for the first 12 weeks of gestation, aspirin (100 mg/d) for 38 weeks of gestation, and folate (5 mg every second day) throughout their pregnancies. Fifty of 80 women became pregnant; they were compared with 52 women with IRM (matched for age and number of miscarriages), who became pregnant without treatment during the same observation period. MAIN OUTCOME MEASURE(S): Live birth rate, complications of pregnancy, such as preeclampsia, premature birth, and intrauterine growth restriction, and therapy-related side effects. RESULT(S): The overall live birth rates of the treatment and control groups were 77% (40 of 52) and 35% (18 of 52) (P=.04). The rates of first and second trimester miscarriage among the treatment and control groups were 19% (10 of 52) and 0 (0 of 52), and 63% (33 of 52) and 2% (1 of 52), respectively (P=.09 and P=1.0, respectively). The median gestational age at birth and median birth weight did not differ between the groups. We observed two and three cases of premature birth among the treatment and control groups, respectively (P=.3) and no cases of intrauterine growth restriction and Cushing's disease. Of 80 women who started treatment, one woman had an ectopic pregnancy and one woman terminated her pregnancy due to fetal chromosome aberration (trisomy 18). Three women stopped treatment due to nausea, depression, and tachycardia. CONCLUSION(S): A combination treatment of prednisone, aspirin, folate, and progesterone is associated with a higher live birth rate compared with no treatment in women with IRM.
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Prednisone metabolism in recipients of kidney or liver transplants and in lung recipients receiving ketoconazole.
Jeng, S, Chanchairujira, T, Jusko, W, Steiner, R
Transplantation. 2003;(6):792-5
Abstract
BACKGROUND Actual prednisone exposure in low-dose prednisone regimens, in part determined by cytochrome P450 metabolism, has been shown to be important for allograft survival. METHODS Prednisolone (the principal active metabolite of prednisone) metabolism was determined in eight nontransplant patients and in transplant recipients receiving oral prednisone maintenance therapy (20 kidney and 6 liver recipients receiving cyclosporine [CsA] and eight lung recipients receiving ketoconazole and CsA or tacrolimus [FK506]). RESULTS Prednisolone area under the curve (AUC)-dose-normalized (PNAUCn) to 1 mg/kg was 8,288+/-1,513 ng.hr/mL in kidney recipients, versus 4,826+/-999 ng/mL per hr in healthy subjects (P<0.001); it was also increased in liver recipients versus healthy subjects (11,456+/-1,214 ng.hr/mL, P<0.001). Liver recipients also metabolized prednisolone more slowly than kidney recipients (P<0.001). PNAUCn in lung recipients was similar in kidney recipients despite the effect of ketoconazole to slow CsA metabolism. In kidney transplant recipients, the rate of CsA metabolism was correlated with the rate of prednisolone metabolism (r=0.54, P=.026). Basal cortisol levels in all transplant recipients were lower than in healthy subjects, suggesting more prednisolone exposure in transplant patients. CONCLUSIONS Prednisolone metabolism is slower in solid-organ transplant recipients than in healthy subjects. The slower metabolism of prednisolone, particularly in liver recipients, may help explain the immunologic effectiveness of low-dose prednisone regimens in these patients.
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Effect of glucocorticoid therapy on energy intake in children treated for acute lymphoblastic leukemia.
Reilly, JJ, Brougham, M, Montgomery, C, Richardson, F, Kelly, A, Gibson, BE
The Journal of clinical endocrinology and metabolism. 2001;(8):3742-5
Abstract
Despite a widespread belief that glucocorticoid therapy is associated with positive energy balance and excess weight gain there is a dearth of quantitative evidence about its effects and the underlying mechanisms of any effects. The primary aim of the present study was to quantify the effect of dexamethasone and prednisone treatment on energy intake in children treated for childhood acute lymphoblastic leukemia. A secondary aim was to test for differences in excess weight gain between patients treated using the 2 glucocorticoids. We measured energy intake in 26 patients (mean +/- SD age, 6.3 +/- 2.3 yr) during a 5-d period "on" steroids and again in the week before steroid treatment. Changes in body mass index from diagnosis to 1 and 2 yr postdiagnosis were expressed as SD scores. Steroid treatment was associated with a significant increase in energy intake of approximately 20% (mean paired difference, 1.7 MJ/d; SD, 2.8; 95% confidence interval, 0.7-2.8 MJ/d), with no significant difference between the 2 steroids. The mean change in body mass index SD score was +0.38 (SD, 1.10; P < 0.05) to 1 yr and +0.68 (SD, 1.38; P < 0.05) to 2 yr, with no significant difference between the 2 groups of patients. Glucocorticoid treatment in childhood acute lymphoblastic leukemia increases energy intake markedly, and this effect contributes to the excess weight gain and obesity characteristic of patients being treated for acute lymphoblastic leukemia.