OBJECTIVETo systematically evaluate the clinical effects of cyclosporine A (CsA) and tacrolimus, which are calcineurin inhibitors, on lupus nephritis.

METHODIn this study, the clinical trials on treatment of lupus nephritis with cyclosporine A and tacrolimus published until May 2010 were searched at www.guideline.gov, www.nice.org.uk, mdm.ca/cpgsnew/cpgs/index.asp, www.show.scot.nhs.uk, www.nzgg.org.nz, www.eguid elines.co.uk, www.gin.net, Cochrane library, EMBASE, MEDLINE, Wanfang database, Chinese Journal full-text Database, Chongqing Weipu Database by using the methods of Cochrane systematic review. At the same time the information from related journals, professional data and network were hand-searched. The homogeneous evaluation was performed by meta-analysis.Statistical analysis of clinical data was performed by using RevMan 4.2 software provided by the Cochrane Collaboration.

RESULTA total of 214 reports were found, while only 7 randomized controlled trials met the inclusion criteria, 4 of them were on the treatment with CsA (treatment group) and cyclosporine (CTX) group (control group), and 3 of them were the on treatment with FK506 (treatment group) and CTX group (control group). There were 148 reports in the treatment of CsA and CTX group, while 185 reports in the treatment of FK506 and CTX group. Both CsA and tacrolimus group could decrease daily urinary protein. Tacrolimus group was good at reducing daily urinary protein as compared with CTX group, and the difference was statistically significant (Z = 2.8, P = 0.005), but there was no significant difference between CsA and CTX groups (Z = 1.08, P = 0.28). Tacrolimus group was good at complete remission as compared with CTX group (Z = 3.64, P = 0.0003), partial remission was similar in both groups (Z = 0.53, P = 0.6), and tacrolimus group was good at total remission (Z = 2.2, P = 0.03). There was no significant difference between CsA and CTX group in side effect within a short period, while FK506 had less side-effect than CTX group.

CONCLUSIONCompared with the treatment with CTX, tacrolimus was good at reducing daily urinary protein. CsA and CTX were similar in reducing daily urinary protein in the treatment of lupus nephritis. Tacrolimus resulted in better total remission than CTX and had less side effect. CsA and CTX groups were similar in side effect. On the whole, calcineurin inhibitor could significantly decrease daily urinary protein, and tacrolimus was better in treatment and had less side-effect than CTX. However, large scale, multicenter, well-designed clinical trials should be adopted to further confirm the conclusions.

Calcineurin Inhibitors ; Cyclosporine ; therapeutic use ; Enzyme Inhibitors ; therapeutic use ; Humans ; Lupus Nephritis ; drug therapy ; Tacrolimus ; therapeutic use

Anemia, Aplastic ; drug therapy ; immunology ; Animals ; Antilymphocyte Serum ; immunology ; therapeutic use ; Calcineurin Inhibitors ; immunology ; therapeutic use ; Humans ; Immunoglobulins ; immunology ; therapeutic use ; Lymphocytes ; drug effects ; immunology ; Swine

OBJECTIVETo evaluate safety and efficacy of conversion of calcineurin inhibitors (CNI) to sirolimus (SRL) therapy for treatment of new-onset diabetes after kidney transplantation (NODAT).

METHODSOf 321 kidney transplant recipients, 34 patients who developed NODAT (10.59%) were divided into 3 groups to receive continued CNI therapy at a reduced dose (group A, 14 cases), sirolimus conversion therapy (group B, 12 cases), or oral hypoglycemic drugs (group C, 12 cases). All the patients had dietary and exercise therapies, and insulin injections were given in patients with postprandial (2 h) blood glucose over 14.0 mmol/L. The patients were followed up regularly for 5 years.

RESULTSThe mean blood glucose level was 13.02∓1.74 mol/L upon the diagnosis of NODAT in the 34 patients without significant differences between the 3 groups. At 6 months of therapy, fasting plasma glucose levels in the 3 groups decreased to 8.05 ∓2.45, 7.45∓2.44, and 9.30∓3.89 mmol/L, repsectively; at 12 months, blood glucose became normal in both groups A and B, but the patients in group A needed a greater daily insulin dose (P<0.05). In group B, the mean serum creatinine level was 165.1∓61.82 mmol/L at the conversion and lowered to 150∓53.05 mmol/L at 5 years (P<0.05), which were similar to those in group A at the two time points (152∓43.05 and 145.88∓53.05 mmol/L, respectively; P>0.05). In group C, creatinine level further increased after medication with oral hypoglycemic drugs. At 5 years, the patient and graft survival rates were 100% and 75% in group A, respectively, similar to those in group B (83.4% and 68%, respectively; P>0.05); group C showed lower patient and graft survival rates than groups B and C.

CONCLUSIONConversion from CNI to SLR therapy can significantly the metabolism of patients with NODAT without increasing the risk of acute graft rejection.

Blood Glucose ; Calcineurin Inhibitors ; therapeutic use ; Diabetes Mellitus ; Graft Rejection ; prevention & control ; Humans ; Hypoglycemic Agents ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; Sirolimus ; therapeutic use

Lupus nephritis (LN), a severe manifestation of systemic lupus erythematosus, poses a substantial risk of progression to end-stage renal disease, with increased mortality. Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids, mycophenolate mofetil, and calcineurin inhibitors. Although therapeutic regimens have evolved over the years, they have inherent limitations, including non-specific targeting, substantial adverse effects, high relapse rates, and prolonged maintenance and remission courses. These drawbacks underscore the need for targeted therapeutic strategies for LN. Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity. This review provides an overview of the current evidence on targeted therapies for LN, elucidates the biological mechanisms of responses and failure, highlights the challenges ahead, and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.
Humans ; Calcineurin Inhibitors/therapeutic use* ; Immunosuppressive Agents/therapeutic use* ; Lupus Erythematosus, Systemic/drug therapy* ; Lupus Nephritis/pathology* ; Mycophenolic Acid/therapeutic use*

Calcineurin inhibitors (CNI), including oral cyclosporin A and tacrolimus, are intensive immunosuppressants that are extensively used in the treatment of rheumatic and immunologic diseases in China. CNI selectively inhibit the activation and proliferation of T lymphocytes and the transcription of cytokines [such as tumor necrosis factor-α, interleukin (IL)-6, and IL-17] through inhibiting the activation of calcineurin in cells and reducing the release of IL-2. To standardize the use of CNI in the field of rheumatic and immunologic diseases, this consensus statement was developed by the National Clinical Research Center for Dermatologic and Immunologic Diseases (Peking Union Medical College Hospital), in conjunction with the Chinese Association of Rheumatology and Immunology Physicians, the Chinese Research Hospital Association, the Rheumatology and Immunology Professional Committee, and the Chinese Association of Rehabilitation Medicine. The 2011 Oxford Centre for Evidence-Based Medicine Levels of Evidence was used to rate the quality of the evidence and the strength of the recommendations, and the RIGHT (Reporting Items for practice Guidelines in HealThcare) checklist was followed to report the consensus. The consensus offers recommendations addressing nine clinical challenges to Chinese clinicians. The primary objective of this consensus is to deliver scientific and detailed guidance on CNI for Chinese clinicians, and to improve the quality of patient-centered medical services.
Humans ; Calcineurin Inhibitors/pharmacology* ; Immunosuppressive Agents/therapeutic use* ; Tacrolimus/pharmacology* ; T-Lymphocytes ; Immune System Diseases ; Rheumatic Diseases/drug therapy*

OBJECTIVETo observe the effect of sirolimus-based immunosuppression administered on heart transplant recipients with chronic renal dysfunction.

METHODSFrom June 2004 to December 2008, standard calcineurin inhibitors (CNI)-based immunosuppressive regimen was changed to reduced-dose CNI plus sirolimus due to CNI-related chronic renal dysfunction in 20 out of 138 cardiac transplant recipients at Fuwai Hospital. The standard immunosuppressive regimen included steroid, CNI (cyclosporine or tacrolimus), and mycophenolate mofetil or azathioprine. Sirolimus was started at 0.75 - 1.50 mg/d with titration to achieve levels of 5 - 15 µg/L, and CNI dose was reduced gradually to 1/2-2/3 of the baseline level. Patients were followed for changes in renal function, lipid level and clinical side effects related to immunosuppressive therapy. Endomyocardial biopsy (EMB) was performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB was also performed at 3 months after regimen change within 1 year post-transplantation or when rejections were suspected in patients beyond 1 year post-transplantation. Echocardiography was performed for monitoring purpose.

RESULTSThe mean follow-up after regimen change was (7.9 ± 6.3) months. Final sirolimus dose was (0.89 ± 0.22) mg/d and blood drug level was (7.6 ± 3.8)µg/L. Cyclosporine dose was reduced from (191.7 ± 60.0) mg/d to (123.6 ± 34.8) mg/d, with blood drug concentration reduced from (175.5 ± 58.0) µg/L to (111.9 ± 56.0) µg/L in 18 patients (P < 0.01). Tacrolimus average dose was reduced from 4.25 mg/d to 3.00 mg/d, with blood drug concentration reduced from 13.5 µg/L to 10.5 µg/L in 2 patients. Serum creatinine level fell from (160.4 ± 25.5) µmol/L to (134.4 ± 26.8) µmol/L (P < 0.01) and urea nitrogen fell from (13.8 ± 4.7) µmol/L to (10.4 ± 3.0) µmol/L (P < 0.01) at one month after regimen change. Twenty two EMBs were performed in 11 patients within 1 year post-transplant, there were 4 episodes of acute rejected (ISHLT grade 2). Twenty patients are all alive and cardiac function was normal. The most common side effect was hyperlipidemia, and triglycerides, total cholesterol and low density lipoprotein levels were significantly increased at 1 month post regimen change (P < 0.05 or P < 0.01). Leukocyte, hemoglobin and platelet as well as liver function remained unchanged at 1 month post regimen change (all P > 0.05).

CONCLUSIONOur results show that change from CNI-based immunosuppressive regimen to reduced-dose CNI plus sirolimus is an effective and safe approach for the management of patients with CNI-related chronic renal dysfunction, leading to an improvement in renal function without compromise in anti-rejection efficacy and with tolerable side effects.

Calcineurin Inhibitors ; Female ; Heart Transplantation ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Kidney Failure, Chronic ; drug therapy ; Male ; Middle Aged ; Retrospective Studies ; Sirolimus ; therapeutic use

OBJECTIVETo observe the effect of total ginsenosides (TG) on monocrotaline (MCT) induced right ventricular hypertrophy rats, and to explore its correlation with calcineurin (CaN) pathway.

METHODSFifty male Sprague Dawley rats were randomly divided into the normal control group, the MCT model group, and the low, middle, high dose TG treatment groups, 10 in each group. All medication was performed by peritoneal injection for 18 days. Right ventricular peak systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and right ventricular weight/body weight (RVW/BW) were measured. Intracellular free calcium concentrations were measured by Ca2+ fluorescence indicator Fura2/AM. The atrial natriuretic factor (ANF) and CaN mRNA expression of the myocardial tissue were quantitatively analyzed by Real-time PCR. The protein expression of CaN was detected by Western blot.

RESULTSCompared with the MCT model group, preventive treatment of TG at the 3 doses could significantly reduce RVSP, RVHI, RVW/BW, and ANF mRNA expression, and decrease Ca2+ concentration in myocardial cells, CaN mRNA and protein expression in the myocardial tissue.

CONCLUSIONTG could obviously improve MCT-induced right ventricular hypertrophy, which was possibly achieved through suppressing MCT-activated CaN signal transduction.

Animals ; Atrial Natriuretic Factor ; Calcineurin ; metabolism ; Calcineurin Inhibitors ; therapeutic use ; Ginsenosides ; therapeutic use ; Heart Ventricles ; Hypertrophy, Right Ventricular ; drug therapy ; metabolism ; Male ; Monocrotaline ; Myocardium ; Myocytes, Cardiac ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Signal Transduction

Calcineurin Inhibitors (CNIs) and Corticosteroids have been the main immunosuppressive agents in solid organ transplantation. Many studies have confirmed the positive impacts of withdrawal/avoidance of these agents, separately, on their side effect profiles. A pilot study was performed avoiding both agents among low-immunological-risk living donor kidney transplant recipients at a single center. Seventeen recipients were maintained on the double avoidance protocol during the study period beginning July 2002 through December 2003. Three rejection episodes occurred (out of ten) among related donor kidney recipients and six episodes (out of seven) among unrelated donor kidney recipients. Although most of the rejections were reversed with a short course of corticosteroids, the protocol was revised to exclude the unrelated donor kidney recipients. There were higher incidences of wound complications among recipients who received the initial loading dose of Sirolimus. Double avoidance of CNIs and corticosteroids is possible in living donor kidney transplant recipients with an acceptable incidence of rejection. Proper management of the side effects of Sirolimus could further minimize the incidence of rejection. A multi-center randomized study is recommended in order to recognize the benefits of avoiding CNIs and corticosteroids in renal transplant recipients.
Adrenal Cortex Hormones ; Adult ; Aged ; Antibodies, Monoclonal/*therapeutic use ; Calcineurin/antagonists & inhibitors ; Chimeric Proteins/*therapeutic use ; Drug Therapy, Combination ; Enzyme Inhibitors ; Female ; Glucocorticoids/*therapeutic use ; Humans ; Immunosuppressive Agents/*therapeutic use ; *Kidney Transplantation ; *Living Donors ; Male ; Methylprednisolone/*therapeutic use ; Middle Aged ; Mycophenolic Acid/*analogs & derivatives/*therapeutic use ; Pilot Projects ; Sirolimus/*therapeutic use

INTRODUCTIONAtopic dermatitis is a common, chronic pruritic condition affecting both children and adults, which has a negative impact on the quality of life. These guidelines were developed by an expert workgroup appointed by the Dermatological Society of Singapore, to provide doctors with information to assist in the management of their patients with atopic dermatitis. The workgroup members are experienced dermatologists with interest and expertise in eczemas.

MATERIALS AND METHODSWorkgroup members arrived at a consensus on the topics to be included. Relevant studies from the literature were assessed for best evidence, supplemented by the collective experience of the workgroup.

RESULTSFor mild atopic dermatitis, emollients, mild potency topical steroids and topical calcineurin inhibitors are recommended. For moderate-to-severe atopic dermatitis, the use of emollients, moderate-to-potent topical steroids, topical calcineurin inhibitors, wet dressings, antimicrobials for secondary skin infection, phototherapy, and systemic therapy (e.g. prednisolone, cyclosporine, azathioprine or methotrexate) may be warranted. Patients with moderate-to-severe atopic dermatitis should be managed in conjunction with a dermatologist.

CONCLUSIONGood outcomes can be achieved with an individualised therapeutic approach combined with adequate patient and parental education.

Administration, Cutaneous ; Adrenal Cortex Hormones ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Azathioprine ; therapeutic use ; Calcineurin Inhibitors ; therapeutic use ; Coinfection ; complications ; drug therapy ; Cyclosporine ; therapeutic use ; Dermatitis, Atopic ; complications ; immunology ; therapy ; Dermatology ; Disease Management ; Emollients ; therapeutic use ; Food Hypersensitivity ; immunology ; Humans ; Immunosuppressive Agents ; therapeutic use ; Methotrexate ; therapeutic use ; Patient Education as Topic ; Phototherapy ; Practice Guidelines as Topic ; Referral and Consultation ; Severity of Illness Index ; Singapore

OBJECTIVETo investigate the efficacy of conversion from calcineurin-inhibitor (CNI) to rapamycin in liver recipients with CNI-associated renal insufficiency.

METHODSThis retrospective study examined the liver transplant recipients who had switched from CNI to rapamycin between January 2004 and June 2008 in the first affiliated hospital of Sun Yat-sen University. The data of renal function before and after the conversion were analyzed by Wilcoxon sum rank test, and rapamycin-related adverse effects were also observed.

RESULTSCompared with that before conversion, the renal funtion 4 months after the conversion improved significantly (P<0.05). The blood lipid level 3 months after the conversion increased significantly (P<0.05) but were well controlled.

CONCLUSIONRapamycin can be used safely as a good alternative in liver transplant recipients with CNI-related renal insufficiency.

Adult ; Aged ; Calcineurin Inhibitors ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Renal Insufficiency ; drug therapy ; etiology ; Retrospective Studies ; Sirolimus ; therapeutic use ; Young Adult