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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

How to combine antirejection drugs and which is the optimal dose of steroids and calcineurin inhibitors beyond the first year after kidney transplantation to maintain adequate immunosuppression without major side effects are far from clear. Kidney transplant patients on steroid, cyclosporine (CsA), and azathioprine were randomized to per-protocol biopsy (n = 30) or no-biopsy (n = 29) 1 to 2 yr posttransplant. Steroid or CsA were discontinued or reduced on the basis of biopsy to establish effects on drug-related complications, acute rejection, and graft function over 3 yr of follow-up. Serum creatinine, GFR (plasma clearance of iohexol), RPF (renal clearance of p-aminohippurate), CsA pharmacokinetics, and adverse events were monitored yearly. At the end, patients underwent a second biopsy. Per-protocol biopsy histology revealed no lesions (n = 5, steroid withdrawal), CsA nephropathy (n = 13, CsA discontinuation/reduction), or chronic rejection (n = 12, standard therapy). Reducing the drug regimen led to overall fewer side effects related to immunosuppression as compared with standard therapy or no-biopsy. Steroids were safely stopped with no acute rejection or graft loss. Complete CsA discontinuation was associated with acute rejection in the first four patients. Lowering CsA to low target CsA trough (30 to 70 ng/ml) never led to acute rejection or major renal function deterioration. Biopsy patients on conventional regimen had no acute rejection, one graft loss, no significant change in GFR, and significant RPF decline. No-biopsy controls: no acute rejection, one graft loss, significant decline of GFR and RPF. By serial biopsy analysis, severe lesions did not develop in patients with steroid discontinuation in contrast to patients on standard therapy over follow-up. CsA reduction did not adversely affect histology. Per-protocol biopsy more than 1 yr after kidney transplantation is a safe procedure to guide change of drug regimen and to lower the risk of major side effects.
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PMID:Renal transplantation: can we reduce calcineurin inhibitor/stop steroids? Evidence based on protocol biopsy findings. 1292 40

Proteinuria plays a causal role in the progression of IgA nephropathy (IgAN). A previous controlled trial showed that steroids are effective in reducing proteinuria and preserving renal function in patients with IgAN. The objective of this study was to evaluate the long-term effectiveness of steroids in IgAN, examine the trend of proteinuria during follow-up (starting from the hypothesis that the degree of reduction in proteinuria may influence IgAN outcome), and evaluate how histologic scores can influence steroid response. A secondary analysis of a multicenter, randomized, controlled trial of 86 adult IgAN patients who were receiving supportive therapy or intravenous methylprednisolone plus oral prednisone for 6 mo was conducted. Ten-year renal survival was significantly better in the steroid than in the control group (97% versus 53%; log rank test P = 0.0003). In the 72 patients who did not reach the end point (doubling in baseline serum creatinine), median proteinuria significantly decreased (1.9 g/24 h at baseline, 1.1 g/24 h after 6 mo, and 0.6 g/24 h after a median of 7 yr). In the 14 progressive patients, proteinuria increased from a median of 1.7 g/24 h at baseline to 2.0 g/24 h after 6 mo and 3.3 g/24 h after a median of 5 yr. Steroids were effective in every histologic class. Cox multivariate regression analyses showed that, in addition to steroids, a low baseline histologic score, a reduction in proteinuria after 6 mo, and no increase in proteinuria during follow-up all were independent predictors of a beneficial outcome. Steroids significantly reduce proteinuria and protect against renal function deterioration in IgAN. The histologic picture and proteinuria during early and late follow-up improve the prediction of outcome, but considerable variability remains outside the model.
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PMID:Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. 1469 68

A 28 years old male on chronic hemodialysis for 40 months due to a IgA crescentic glomerulonephritis developed pancytopenia (hematocrit 16%, white blood cell count 3,800 mm3 and platelets 11,000 mm3. The bone marrow aspirate showed erythropoietic hyperplasia. Hemolytic anemia, folate or vitamin B12 deficiency and paroxysmal nocturnal hemoglobinuria were ruled out. Steroids were given with a transient elevation of red cells and platelets, which lasted only for some weeks. Afterwards, intravenous immunoglobulin was given without benefit. Two months after, a bone marrow biopsy and a bone marrow magnetic resonance imaging showed severe aplasia. Cyclosporine was started with a rapid increase in blood cells count. Eight months later, he received a renal transplant from a cadaveric donor. Immunosupression was achieved with cyclosporine, prednisone and mycofenolate mofetil. The patient required hemodialysis for the first three weeks and a mild acute cellular rejection was treated with methylprednisolone. At discharge, 6 weeks later, serum creatinine was 2.4 mg/dl and creatinine clearance 37.6 ml/min. During the first months after transplant, platelet count and hemoglobin decreased and a bone marrow biopsy showed only mild hypoplasia. Four months after renal transplant the hematocrit was 43%, white blood cell count 6,600 mm3 and platelets, 150,000 mm3 and did not change during the first year of follow up.
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PMID:[Bone marrow aplasia during hemodialysis successfully treated with cyclosporine. Report of one case]. 1547 2

The long-term benefit of steroid withdrawal on patient and graft survival is unproven. Steroids were stopped within the first year after kidney transplantation in 223 consecutive low-risk patients initially treated with thymoglobulin and triple-drug therapy. The 15-year actuarial graft survival rate was 83.9%. Risk factors for graft loss were: proteinuria (hazard ratio [HR]: 6.96, P = 0.0003), creatinine >130 micromol/L (HR: 3.37, P = 0.01), recipient age <35 years (HR: 5.31, P = 0.001), and no mycophenolate mofetil (MMF) treatment (HR: 8.83, P = 0.04). Interestingly, recipient age and no MMF treatment were not risk factors in higher-risk patients in whom steroids were continued. The 2-year incidence of acute rejection following steroid withdrawal was 12.1%; the graft survival rate was lower in this group (71.1%). Our findings indicate that late steroid withdrawal results in excellent long-term outcome in most low-risk patients, but it should be attempted with caution in younger patients and when MMF is not used.
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PMID:Recipient age and mycophenolate mofetil as the main determinants of outcome after steroid withdrawal: analysis of long-term follow-up in renal transplantation. 1621 Sep 79

Steroids have been a mainstay of immunosuppressive regimens in renal transplantation despite their adverse effects. The introduction of new immunosuppressant has improved the survival rates and prompted trials of steroid withdrawal. We conducted a randomized prospective study to compare steroid withdrawal at 6 months post-transplant between tacrolimus + mycophenolate mofetil (MMF) (FK group) versus cyclosporine A + MMF (CsA group). Steroid was withdrawn at 6 months post-transplant under the condition of no rejection episode proven by biopsy and maintenance of serum creatinine level <2.0 mg/dl. Fourteen recipients were excluded because of acute rejection within 6 months or protocol violation. Steroid could be tapered off in 62 in FK group and 55 in CsA. Three cases in FK group and five in CsA had acute rejection within another 6 months after steroid withdrawal (P > 0.05). At 12 months, the incidence of post-transplant diabetes was 18.6% vs. 8.0% in FK and CsA group. And hypercholesterolemia was presented in 8.5% vs. 2.0%, hypertension in 47.5% vs. 56.0%, and serum creatinine level 1.18 +/- 0.24 mg/dl vs. 1.18 +/- 0.20 mg/dl, respectively (P > 0.05). Steroid withdrawal may be carried out successfully using both FK and CsA with MMF, but long-term follow-up is necessary.
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PMID:Steroid withdrawal in living donor renal transplant recipients using tacrolimus and cyclosporine: a randomized prospective study. 1677 69

The usefulness of icodextrin-containing peritoneal dialysis (PD) solution for the management of body fluid and blood pressure has been reported. However, icodextrin PD solution is a foreign solution in the body, and the possible induction of intraperitoneal inflammation has been reported. In this study, we investigated at 6-month intervals the influence of icodextrin solution on peritoneal permeability and inflammatory reactions in patients in whom glucose solution had been changed to icodextrin solution for the overnight dwell. We enrolled 9 anuric PD patients (5 men, 4 women) of mean age 58 +/- 5.9 years (range: 45.6-64.8 years) into the study. The patients' mean duration of PD was 61.9 +/- 42 months (range: 6.7-142.5 months). The cause of end-stage renal disease was chronic glomerulonephritis in all patients. For evaluation ofperitoneal permeability, we performed peritoneal equilibration tests (PETs) immediately after an overnight dwell and determined the dialysate-to-plasma ratios of creatinine (D/P Cr), beta2-microglobulin (D/P beta2m), albumin (D/P Alb), immunoglobulin G (D/P IgG), and alpha2-macroglobulin (D/P alpha2m). We also measured interleukin-6 (IL-6) and fibrinogen degradation products (FDPs) in overnight effluent as indices of inflammation and of the fibrinolysis-coagulation system. The evaluation was performed every 6 months for 24 months. The FDPs in effluent increased significantly at 6 months after the change to icodextrin solution, and IL-6 tended to increase. The D/P beta2m, D/P Alb, D/P IgG, and D/P alpha2m all significantly increased in the course of follow-up. In the PETs, the D/P Cr increased slightly, but the change was nonsignificant. At 30 months after the change to icodextrin solution, 1 patient was diagnosed as having a risk of encapsulating peritoneal sclerosis (pre-EPS). In this patient, rapid increases in IL-6, D/P Cr and macromolecular and small molecular D/P by PET were noted after the change to icodextrin solution. Steroids were administered after the diagnosis of pre-EPS, with the result that the IL-6 level rapidly decreased and the D/P Cr and D/P of small molecules and macromolecules slightly decreased. Icodextrin dialysis solution increased peritoneal permeability. Although the cause was unclear, icodextrin may have changed peritoneal reactivity. Long-term use of icodextrin PD solution requires further investigation.
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PMID:Impact on peritoneal membrane of use of icodextrin-based dialysis solution in peritoneal dialysis patients. 1698 33

Equol production, isoflavone excretion, and the salivary estradiol profile among 36 females, native Irish Caucasian volunteers following ingestion of 200mL soymilk is reported. The soymilk contained daidzein (73+/-6.7mg) and genistein (86+/-10.2mg). Volunteers provided personal and family medical history. Dietary analysis revealed that all volunteers regularly consumed soy-based or soy-supplemented food products. The mean age, mean age at menarche, and body mass index of volunteers were 46.6+/-12.3 years, 13.1 years and 26.1, respectively. The average number of children per volunteer was 2.13. Twelve (34%) of the volunteers were found to be first-degree relatives of breast cancer patients. Following consumption of the soymilk, equol was detected in the urine of 18 (51%) of the volunteers. Mean urinary daidzein and genistein concentrations during the hours following soymilk ingestion were 13.5 and 16.7microg/mg creatinine, respectively, however, some volunteers excreted little (less than 4.0microg/mg) or no isoflavone. Salivary estradiol in most (24) volunteers had decreased from 51.5+/-28.67pmol/L pre-ingestion to 29.75+/-16.13pmol/L 5h after drinking the soymilk. However, the salivary estradiol in 12 subjects (34%) increased from 33.76+/-13.4pmol/L to 137.4+/-65.64pmol/L over the same period. Individuals whose salivary estradiol increased had significantly less children (1.58 (P<0.05)), were more likely to (a) return urine samples with low isoflavone content (50.3% compared to 25%), (b) to be equol producers (67% compared to 41.7%), and (c) to be first-degree relatives of breast cancer patients (41.7% compared to 25%). Volunteers who reported a first-degree link to breast cancer were more likely to have a higher body mass index (29.0 compared to 26.1 (P<0.05)), to be equol producers (75% compared to 51%), and to excrete isoflavones in low quantities only (60% compared to 50%). First-degree relatives also had fewer children (1.75 (P<0.05)). The results indicate a significant, distinctive variation in equol production, isoflavone excretion and salivary estradiol profile among individual volunteers following ingestion of soymilk.
Steroids 2007 Jan
PMID:Equol producer status, salivary estradiol profile and urinary excretion of isoflavones in Irish Caucasian women, following ingestion of soymilk. 1715 87

Heart transplant recipients treated with long-term calcineurin inhibitors (CNIs) experience significant nephrotoxicity and transplant vasculopathy. Signal proliferation inhibitors might prevent the development of transplant vasculopathy. In an open, prospective pilot study, 33 primary heart transplant recipients received tacrolimus (Tac) and sirolimus (rapamycin, Rapa) with steroids. To reduce both nephrotoxicity and transplant vasculopathy at the same time, both Tac and Rapa exposure was kept low (6 to 8 ng/ml). Steroids were withdrawn successfully from all patients within 6 months. Just one acute rejection occurred at 54 days post-transplant, resulting in 0.03 acute rejection episode per patient at 1-year (primary end-point) and 2-year follow-up. Transplant vasculopathy assessed by angiogram was absent at 2 years. Graft and patient survival were 100% at 1 and 2 years. Accordingly, the survival estimate for freedom from first acute rejection, transplant vasculopathy, graft loss or death was 0.97 at 1 and 2 years. The regimen was well tolerated with only 3 patients requiring a change of study medication. Mean serum creatinine increased during the first year but returned to baseline at 2 years.
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PMID:Low-dose tacrolimus/sirolimus and steroid withdrawal in heart recipients is highly efficacious. 1754 83

Steroids are still the mainstay of therapy in primary chronic glomerulonephritis (PCGN), regardless of underlying disturbance or pathology. Moreover, relationship between known abnormalities and disease manifestation is stochastic, therefore treatment continues to be empirical. It is not known whether responsiveness is related to immune phenotype. We performed flowcytometric lymphocyte (Ly) phenotyping (CD19, CD3, CD3CD4, CD3CD8, CD56/16) on 16 patients (pts) (12M, 4F), mean age 37.6+/-13 years with primary chronic glomerulonephritis (PCGN): minimal change disease (MCD)--6 pts, focal and segmental glomerulosclerosis (FSGS)--4 pts, mesangial proliferative glomerulonephritis--5 pts, mesangiocapillary glomerulonephritis--1 pt, before and at 7 days of oral Prednisone 1 mg/kg/day (in 2 divided doses). Before steroids: 4/16 pts(25%) had elevated BP; 9/16(56.2) showed nephrotic proteinuria. Serum creatinine was >1.2 mg% in 6/16(37.5%). At 7 days WBC count increased (13,079.37+/-4966.4/microl vs. 8021.25+/-2077.4/microl; p=0.0007), Ly percentage (%) decreased (20.30+/-9% vs. 29.9+/-10.4%; p=0.0095), while absolute (abs.) Ly count remained unchanged. Both CD19 Ly% and CD19 Ly abs. count increased (16.13+/-6.5% vs. 9.52+/-3.7%; p=0.0015, and 410.012+/-29.7/microl vs. 223.56+/-123.8/microl; p=0.0077, respectively). NK (natural killer)% decreased (9.15+/-5.2% vs. 14.19+/-7.1%; p=0.0296). CD3, CD3CD4, CD3CD8 Ly subsets and CD4/CD8 ratio showed no change. Variation in proteinuria (2.88+/-2.1 g/24 h vs. 3.45+/-1.7 g/24 h; p=0.4) did not reach statistical significance (Wilcoxon-Mann-Whitney). In 11 pts we performed an additional analysis at 1 month. Compared to levels before steroids, there was an increase in WBC, CD19 Ly% and CD19 Ly abs. count and a decrease in NK% and NK abs. count. Other Ly subsets and CD4/CD8 ratio remained unchanged. Variation in clinical parameters (proteinuria, serum Creatinine, BP) did not reach statistical significance. Changes in Ly profile precede changes in clinical parameters and thus are divergent. While our patients proved to be early non-responders, further studies to elucidate whether profile changes provide for response specification are warranted.
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PMID:The effect of steroids on lymphocyte profile in primary chronic glomerulonephritis. Empirical or tailored therapy? 1763 Feb 6

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.
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PMID:Role of mycophenolate mofetil in the treatment of lupus nephritis. 1791 58


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