scholarly journals Steroid-Resistant Kidney Transplant Rejection: Diagnosis and Treatment

2001 ◽  
Vol 12 (suppl 1) ◽  
pp. S48-S52
Author(s):  
H. ANDREAS BOCK
Keyword(s):  
Mycophenolate Mofetil ◽  
Transplant Rejection ◽  
Steroid Treatment ◽  
Steroid Resistance ◽  
Temporary Increase ◽  
Success Rates ◽  
Steroid Resistant ◽  
First Line Therapy ◽  
Postrenal Failure ◽  
Pulse Steroid

Abstract. Decreases in transplant function may be attributable to a variety of conditions, including prerenal and postrenal failure, cyclosporin A (CsA) toxicity, polyoma nephritis, recurrent glomerulonephritis, and rejection. The diagnosis of rejection should therefore be made on the basis of a transplant biopsy of adequate size, before the initiation of any therapy. Pulse steroid treatment (three to five 0.25- to 1.0-g pulses of methylprednisolone, administered intravenously) is the usual first-line therapy and has a 60 to 70% success rate, although orally administered prednisone (0.25 g) may be just as efficacious. Even if reverted, any rejection should trigger an at least temporary increase in basal immunosuppression, consisting of an increase in CsA or tacrolimus target levels, the addition of steroids or an increase in their dosage, the addition of mycophenolate mofetil, or a switch from CsA to tacrolimus. The addition of rapamycin or its RAD derivative may fulfill the same purpose. Steroid resistance should not be assumed before the fifth day of pulse steroid treatment, although histologic features of vascular rejection may indicate the need for more aggressive treatment earlier. Steroid-resistant rejection is traditionally treated with poly- or monoclonal antilymphocytic antibodies, with success rates of 60 to 70%. Their potential benefit must be carefully balanced against the risks of infection and lymphoma. More recently, mycophenolate mofetil has been successfully used to treat steroid-resistant rejection, but only of the interstitial (cellular) type. Switching from CsA to tacrolimus for treating recurrent or antibody-resistant rejection is successful in approximately 60% of cases. Plasmapheresis and intravenously administered Ig have been used in some desperate cases, with surprising success. Because none of the available drugs has a significantly better profile of therapeutic versus adverse effects, the possible benefits of continued rejection therapy must be continuously balanced with the potential for serious, sometimes fatal, side effects.

Influence of mycophenolate mofetil on BTLA and ICOS signaling in renal transplant rejection

2010 ◽  
Vol 34 (8) ◽  
pp. S70-S70
Author(s):  
Yan Wang ◽  
Chuan Tian ◽  
Chun Mei Wang ◽  
Chun Guang Fan ◽  
Gang Liu
Keyword(s):  
Mycophenolate Mofetil ◽  
Renal Transplant ◽  
Transplant Rejection ◽  
Renal Transplant Rejection

scholarly journals Lung macrophages drive mucus production and steroid-resistant inflammation in chronic bronchitis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kristina Andelid ◽  
Karolina Öst ◽  
Anders Andersson ◽  
Esha Mohamed ◽  
Zala Jevnikar ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Chronic Bronchitis ◽  
Cross Talk ◽  
Alveolar Macrophages ◽  
Ex Vivo ◽  
Bronchial Epithelial Cells ◽  
Steroid Resistance ◽  
Bronchial Epithelial ◽  
Steroid Resistant ◽  
Copd Patients

Abstract Background Patients with chronic obstructive pulmonary disease (COPD) frequently suffer from chronic bronchitis (CB) and display steroid-resistant inflammation with increased sputum neutrophils and macrophages. Recently, a causal link between mucus hyper-concentration and disease progression of CB has been suggested. Methods In this study, we have evaluated the steroid sensitivity of purified, patient-derived sputum and alveolar macrophages and used a novel mechanistic cross-talk assay to examine how macrophages and bronchial epithelial cells cross-talk to regulate MUC5B production. Results We demonstrate that sputum plug macrophages isolated from COPD patients with chronic bronchitis (COPD/CB) are chronically activated and only partially respond to ex vivo corticosteroid treatment compared to alveolar macrophages isolated from lung resections. Further, we show that pseudo-stratified bronchial epithelial cells grown in air–liquid-interface are inert to direct bacterial lipopolysaccharide stimulation and that macrophages are able to relay this signal and activate the CREB/AP-1 transcription factor complex and subsequent MUC5B expression in epithelial cells through a soluble mediator. Using recombinant protein and neutralizing antibodies, we identified a key role for TNFα in this cross-talk. Conclusions For the first time, we describe ex vivo pharmacology in purified human sputum macrophages isolated from chronic bronchitis COPD patients and identify a possible basis for the steroid resistance frequently seen in this population. Our data pinpoint a critical role for chronically activated sputum macrophages in perpetuating TNFα-dependent signals driving mucus hyper-production. Targeting the chronically activated mucus plug macrophage phenotype and interfering with aberrant macrophage-epithelial cross-talk may provide a novel strategy to resolve chronic inflammatory lung disease.

Successful Treatment of Steroid-Resistant Minimal Change Disease with Mycophenolate Mofetil

2002 ◽  
Vol 22 (5-6) ◽  
pp. 569-572 ◽  
Author(s):  
András Mogyorósi ◽  
H. Robert Lippman ◽  
George M. Feldman
Keyword(s):  
Mycophenolate Mofetil ◽  
Successful Treatment ◽  
Minimal Change Disease ◽  
Minimal Change ◽  
Steroid Resistant

scholarly journals Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes

Gut ◽  
1999 ◽  
Vol 45 (3) ◽  
pp. 382-388 ◽  
Author(s):  
S D Hearing ◽  
M Norman ◽  
C S J Probert ◽  
N Haslam ◽  
C M Dayan
Keyword(s):  
Ulcerative Colitis ◽  
T Lymphocytes ◽  
Disease Severity ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Steroid Treatment ◽  
Steroid Resistance ◽  
Severe Ulcerative Colitis ◽  
Steroid Sensitivity

BACKGROUNDUp to 29% of patients with severe ulcerative colitis (UC) fail to respond to steroid treatment and require surgery. Previous studies have failed to show a clear correlation between failure of steroid treatment in severe UC and measures of disease severity. The reasons for treatment failure therefore remain unknown.AIMTo investigate the hypothesis that patients with severe UC who fail to respond to steroid treatment have steroid resistant T lymphocytes.METHODSEighteen patients with severe UC were studied. After seven days’ treatment with high dose intravenous steroids they were classified as complete responders (CR), incomplete responders (IR), or treatment failures (TF). Within 48 hours of admission blood was taken and the antiproliferative effect of dexamethasone on phytohaemagglutinin stimulated peripheral blood T lymphocytes was measured. Maximum dexamethasone induced inhibition of proliferation (Imax) was measured.RESULTSIn vitro T lymphocyte steroid sensitivity of TF and IR patients was significantly less than that of CR patients. Both TF and 3/5 IR patients had an Imax of less than 60%; all CR patients had an Imax of greater than 60%. No significant correlation was seen between response to treatment and disease severity on admission. When in vitro T lymphocyte steroid sensitivity was remeasured three months later, there was no difference between the groups.CONCLUSIONSResults suggest that T lymphocyte steroid resistance is an important factor in determining response to steroid treatment in patients with severe UC and may be more predictive of outcome than disease severity.

scholarly journals Clinical and laboratory features that differentiate familial from sporadic focal segmental glomerulosclerosis in adolescents and adults

2021 ◽  
Vol 6 (1) ◽  
pp. 1-5
Author(s):  
Maria Goretti Polito ◽  
Michelle Tiveron Passos ◽  
Danilo Euclides Fernandes ◽  
Gianna Mastroianni-Kirsztajn
Keyword(s):  
Serum Albumin ◽  
Focal Segmental Glomerulosclerosis ◽  
Steroid Resistance ◽  
End Stage Kidney Disease ◽  
Steroid Resistant ◽  
Best Management ◽  
Segmental Glomerulosclerosis ◽  
Laboratory Features ◽  
Adolescents And Adults ◽  
End Stage

Background: Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage kidney disease in children and adults. Although most cases are sporadic (s), familial (f) presentation is also described. The purpose of the present study was to establish clinical and laboratory profiles of fFSGS vs. primary sFSGS, contributing to the distinguishing diagnosis in clinical practice and best management, in particular when mutation analysis is not available. Methods: Demographic, clinical and laboratorial parameters were studied in 124 patients 12 years and older with FSGS, subdivided in sFSGS (n=89) and fFSGS (n=35). Results: General and clinical features were similar, as well as serum creatinine at disease presentation. Proteinuria levels were more frequently ≥ 3g/day in sFSGS (63.8%) than in fFSGS (44%, p=0.080), and serum albumin levels were < 3.0 g/dL in 45.8% and 20%, respectively (p=0.046). The groups were statistically different regarding steroid resistance, corresponding to 60% in sFSGS and 100% in fFSGS (p=0.001). Conclusions: The studied groups were clinically similar, except that proteinuria tended to be higher (nephrotic range) and serum albumin was lower in sFSGS vs. fFSGS. In addition, all treated fFSGS patients were steroid resistant. At presentation it is important to characterize if the patient has fFSGS, that will contribute to further disease management, and disease history will be the first clue for such differential diagnosis.

EFFECT OF OKT3 IN STEROID-RESISTANT RENAL TRANSPLANT REJECTION

1995 ◽  
Vol 59 (3) ◽  
pp. 347-351 ◽  
Author(s):  
JAMES J.B. PETRIE ◽  
RUSSELL J. RIGBY ◽  
CARMEL M. HAWLEY ◽  
MICHAEL G. SURANYI ◽  
MICHAEL WHITBY ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Transplant Rejection ◽  
Steroid Resistant ◽  
Renal Transplant Rejection

scholarly journals MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD

Blood ◽  
2018 ◽  
Vol 131 (25) ◽  
pp. 2846-2855 ◽  
Author(s):  
Hannah Major-Monfried ◽  
Anne S. Renteria ◽  
Attaphol Pawarode ◽  
Pavan Reddy ◽  
Francis Ayuk ◽  
...  
Keyword(s):  
Clinical Response ◽  
Acute Gvhd ◽  
Steroid Treatment ◽  
Prognostic Biomarkers ◽  
Long Term Outcomes ◽  
Steroid Resistant ◽  
Key Points ◽  
Better Than

Key Points Biomarker scores generated after 1 week of steroid treatment of GVHD are prognostic. Biomarkers reflect prognosis better than early clinical response to GVHD treatment.

Mycophenolate Mofetil after Rituximab for Childhood-onset Complicated Frequently-relapsing or Steroid-dependent Nephrotic Syndrome

2021 ◽  
pp. ASN.2021050643
Author(s):  
Kazumoto Iijima ◽  
Mayumi Sako ◽  
Mari Oba ◽  
Seiji Tanaka ◽  
Riku Hamada ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Mycophenolate Mofetil ◽  
Treatment Failure ◽  
Treatment Period ◽  
Immunosuppressive Agents ◽  
Steroid Resistance ◽  
Rank Test ◽  
Childhood Onset ◽  
Steroid Dependent ◽  
Steroid Dependent Nephrotic Syndrome

Background. Rituximab is the standard therapy for childhood-onset complicated frequently-relapsing or steroid-dependent nephrotic syndrome (FRNS/SDNS). However, most patients redevelop FRNS/SDNS following peripheral B cell recovery. Methods. We conducted a multicenter, randomized, double-blind, placebo-controlled trial to examine whether mycophenolate mofetil (MMF) administration after rituximab can prevent treatment failure (FRNS, SDNS, steroid resistance, or use of immunosuppressive agents or rituximab). Thirty-nine patients (per group) were treated with rituximab, followed by either MMF or placebo until Day 505 (treatment period). The primary outcome was time to treatment failure (TTF) throughout the treatment and follow-up periods (until Day 505 for the last enrolled patient). Results. TTFs were clinically but not statistically significantly longer among patients given MMF after rituximab than among patients receiving rituximab monotherapy (median: 784.0 vs. 472.5 days, hazard ratio (HR): 0.593, 95% confidence interval (CI): 0.336-1.049, log-rank test: P=0.0694). Because most patients in the MMF group presented with treatment failure after MMF discontinuation, we performed a post-hoc analysis limited to the treatment period and found that MMF after rituximab prolonged the TTF and decreased the risk of treatment failure by 80% (HR: 0.202, 95% CI: 0.081-0.503). Moreover, MMF after rituximab reduced the relapse rate and daily steroid dose during the treatment period by 74% and 57%, respectively. The frequency and severity of adverse events were similar in both groups. Conclusions. Administration of MMF after rituximab may sufficiently prevent the development of treatment failure and is well tolerated, although the relapse-preventing effect disappears after MMF discontinuation.

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