To investigate the postoperative serum triglyceride (TG) levels in predicting the risk of new-onset diabetes mellitus (NODM) in patients following allogeneic liver transplantation. One hundred and forty three patients undergoing allogeneic liver transplantation in Shanghai General Hospital from July 2007 to July 2014 were enrolled in this study. The NODM developed in 33 patients after liver transplantation. The curve of dynamic TG levels in the early period after liver transplantation was generated. Independent risk factors of NODM were determined by univariate and multivariant logistic regression analyses. The clinical value of TG in predicting NODM was analyzed by area under the ROC curve (AUC). Serum TG levels were gradually rising in the first week and then reached the plateau phase (stable TG, sTG) in patients after surgery. The sTG in NODM group were significantly higher than that in non-NODM group (=-2.31, <0.05). Glucocorticoid therapy (=4.054, <0.01), FK506 drug concentration in the first week after operation (=3.482, <0.05) and sTG (=3.156, <0.05) were independent risk factors of NODM. ROC curve analysis showed that the AUC of sTG in predicting NODM was 0.72. TG shows a gradual recovery process in the early period after liver transplantation, and the higher TG level in stable phase may significantly increase the risk of NODM in patients.
China/epidemiology* ; Diabetes Mellitus/etiology* ; Humans ; Liver Transplantation/adverse effects* ; Risk Factors ; Tacrolimus/adverse effects* ; Triglycerides

OBJECTIVETacrolimus (FK506) is an immunosuppressive drug, which is widely used to prevent rejection of transplanted organs. However, chronic administration of FK506 leads to hypertension in solid organ transplantation patients, and its molecular mechanisms are much more complicated. In this review, we will discuss the above-mentioned molecular mechanisms of FK506-induced hypertension in solid organ transplantation subjects.

DATA SOURCESThe data analyzed in this review were mainly from relevant articles without restriction on the publication date reported in PubMed. The terms "FK506" or "tacrolimus" and "hypertension" were used for the literature search.

STUDY SELECTIONOriginal articles with no limitation of research design and critical reviews containing data relevant to FK506-induced hypertension and its molecular mechanisms were retrieved, reviewed and analyzed.

RESULTSThere are several molecular mechanisms attributed to FK506-induced hypertension in solid organ transplantation subjects. First, FK506 binds FK506 binding protein 12 and its related isoform 12.6 (FKBP12/12.6) and removes them from intracellular ryanodine receptors that induce a calcium ion leakage from the endoplasmic/sarcoplasmic reticulum. The conventional protein kinase C beta II (cPKCβII)-mediated phosphorylation of endothelial nitric oxide (NO) synthase at Thr495, which reduces the production of NO, was activated by calcium ion leakage. Second, transforming growth factor receptor/SMAD2/3 signaling activation plays an important role in Treg/Th17 cell imbalance in T cells which toget converge to cause inflammation, endothelial dysfunction, and hypertension following tacrolimus treatment. Third, the activation of with-no-K(Lys) kinases/STE20/SPS1-related proline/alanine-rich kinase/thiazide-sensitive sodium chloride co-transporter (WNKs/SPAK/NCC) pathway has a central role in tacrolimus-induced hypertension. Finally, the enhanced activity of renal renin-angiotensin-aldosterone system seems to play a crucial role in the pathophysiology of FK506-induced hypertension.

CONCLUSIONFK506 plays a predominant role in the pathophysiology of hypertension in solid organ transplantation subjects.

Humans ; Hypertension ; chemically induced ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Organ Transplantation ; adverse effects ; Tacrolimus ; adverse effects ; therapeutic use

OBJECTIVES: To investigate the clinical effect of different immunosuppressive treatment regimens in children with ocular myasthenia gravis (OMG). METHODS: A retrospective analysis was conducted on 130 children with OMG who were treated in the Department of Neurology, Jiangxi Children's Hospital, from February 2018 to February 2023. According to the treatment regimen, they were divided into four groups: glucocorticoid (GC) group (n=29), mycophenolate mofetil (MMF) group (GC+MMF; n=33), methotrexate (MTX) group (GC+MTX; n=30), and tacrolimus (FK506) group (GC+FK506; n=38). Treatment outcomes and adverse reactions were compared among the groups. RESULTS: After 3 months of treatment, the FK506 group had significantly lower scores of Myasthenia Gravis Quantitative Scale and Myasthenia Gravis-Specific Activities of Daily Living than the other three groups (P<0.05). After 3 months of treatment, the FK506 group had a significantly lower dose of prednisone than the GC group, and after 6 and 9 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower dose of prednisone than the GC group (P<0.05). After 12 months of treatment, the MMF, MTX, and FK506 groups had a significantly lower incidence rate of GC-related adverse reactions than the GC group (P<0.05). CONCLUSIONS For children with OMG, the addition of various immunosuppressants can reduce the dosage of GC and adverse reactions. Among them, FK506 shows superior efficacy compared to other immunosuppressants in the early treatment of OMG.
Humans ; Child ; Prednisone/adverse effects* ; Tacrolimus/adverse effects* ; Retrospective Studies ; Activities of Daily Living ; Immunosuppressive Agents/adverse effects* ; Myasthenia Gravis/drug therapy* ; Glucocorticoids/therapeutic use* ; Mycophenolic Acid/adverse effects*

This study aimed to evaluate the efficacy and safety of mycophenolate mofetil (MMF) or tacrolimus (TAC) compared with azathioprine (AZA) as maintenance therapy for active lupus nephritis (ALN). Patients with ALN who responded to 24 weeks of induction treatment were enrolled. Patients who received MMF or TAC as induction therapy continued MMF or TAC treatment during the maintenance period, whereas those who received intravenous cyclophosphamide were subjected to AZA treatment. The primary endpoint was the incidence of renal relapse. Secondary endpoints included extrarenal flares and composite endpoints (deaths, end-stage renal disease, or doubling of serum creatinine levels). A total of 123 ALN patients (47 in the MMF group, 37 in the TAC group, and 39 in the AZA group) were enrolled. The median follow-up time was 60 months. Ten MMF-treated patients, ten TAC-treated patients, and eight AZA-treated patients experienced renal relapses (P = 0.844). The cumulative renal relapse rates in the MMF group (P = 0.934) and TAC group (P = 0.673) were similar to the renal relapse rate in the AZA group. No significant difference in the incidence of severe adverse event was observed among the groups. Long-term maintenance therapies with MMF or TAC might have similarly low rates of renal relapse and similar safety profiles compared with AZA.
Humans ; Mycophenolic Acid/adverse effects* ; Azathioprine/adverse effects* ; Tacrolimus/therapeutic use* ; Lupus Nephritis/complications* ; Immunosuppressive Agents ; Treatment Outcome ; Recurrence

Adjuvants, Immunologic ; adverse effects ; therapeutic use ; Azathioprine ; adverse effects ; therapeutic use ; Cyclosporine ; adverse effects ; therapeutic use ; Glucocorticoids ; adverse effects ; therapeutic use ; Humans ; Mycophenolic Acid ; adverse effects ; analogs & derivatives ; therapeutic use ; Tacrolimus ; adverse effects ; therapeutic use

Adult ; Cerebral Infarction ; etiology ; prevention & control ; Female ; Humans ; Immunosuppressive Agents ; adverse effects ; Intracranial Hemorrhages ; etiology ; prevention & control ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Tacrolimus ; adverse effects

Left ventricular hypertrophy associated with the use of tacrolimus is a rare complication of solid organ transplantation in adult recipients. We present a cardiac transplant recipient who developed severe concentric left ventricular hypertrophy with congestive heart failure related to myocardial hypertrophy on tacrolimus. Hypertrophy improved when the drug was discontinued and replaced with sirolimus.
Adult ; Cardiomyopathy, Hypertrophic ; chemically induced ; diagnosis ; Female ; Heart Transplantation ; adverse effects ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Middle Aged ; Tacrolimus ; adverse effects ; therapeutic use

PURPOSE: Tacrolimus has been widely used to prevent acute rejection in liver transplantation and it requires drug concentration monitoring due to narrow therapeutic index. The aim of this study is to define an adequate whole blood tacrolimus level to prevent acute rejection and drug toxicity in early postoperative days. METHODS: We reviewed 27 patients who underwent liver transplantation from November 1998 to January 2000 at the Department of Surgery, Seoul National University, College of Medicine. Tacrolimus plus steroid were used as initial immunosuppressive drugs. The trough whole blood tacrolimus level had been checked everyday from 2 days after transplantation by microparticle enzyme immunoassay (IMX Tacrolimus II assay). Acute rejection was confirmed by liver biopsy. We divided the patients into low level group (below median, n=13) and high level group (above median, n=14) according to average tacrolimus level within 30 days after transplantation. We compared the incidence of side effects between two groups. The average whole blood tacrolimus levels of the patients according to development of acute rejection were compared. The ratio of sex, age, donor status were also compared. RESULTS: 17 patients (63.0%) showed acute rejection within 30 days after transplantation. The median tacrolimus level of all patients within 30 days after transplantation was 11.39 ng/ml. The incidence of acute rejection in low level group (84.6%) was significantly higher than in high level group (42.9%) (P=0.046). The incidence of side effects between two groups was not different. Mean tacrolimus level of the patients without acute rejection within 30 days after transplantation (12.43+/-1.78 ng/ml) was significantly higher than that of the patients with acute rejection (10.81+/-1.17 ng/ml) (P=0.022). Daily average levels were different statistically on 7th (18.4+/-6.7 vs 10.7+/-3.3 ng/ml, P=0.009), 8th (16.0+/-6.7 vs 11.0+/-3.1 ng/ml, P=0.016), 23th (12.2+/-4.5 vs 9.0+/-2.5 ng/ml, P=0.030), 24th (13.7+/-3.2 vs 9.5+/-2.5 ng/ml, P= 0.009), 25th (13.5+/-3.0 vs 8.9+/-4.0 ng/ml, P=0.009) days after transplantation. Sex, age (adult or child) and donor status (living or cadevaric) didn't affect the development of acute rejection. CONCLUSION: The whole blood tacrolimus level should be kept near 15 ng/ml around 7 and 8 days after transplantation to prevent acute rejection in liver transplantation.
Biopsy ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Immunoenzyme Techniques ; Incidence ; Liver Transplantation* ; Liver* ; Seoul ; Tacrolimus* ; Tissue Donors

Female ; Humans ; Kaposi Varicelliform Eruption ; diagnosis ; etiology ; Middle Aged ; Rosacea ; drug therapy ; Tacrolimus ; adverse effects ; therapeutic use

BACKGROUNDWith the increase of survival in liver transplantation recipients, more patients are at a high risk of developing osteonecrosis, especially in the femoral head, due to immunosuppressive treatment. The purpose of this study was to report the incidence, possible risk factors, and outcome of symptomatic osteonecrosis of the femoral head (ONFH) in adult patients with current immunosuppressive agents and individual protocol after liver transplantation in China.

METHODSA retrospective analysis was performed on 226 adult patients who underwent orthotopic liver transplantation (OLT) at a single liver transplantation institution between January 2004 and December 2008. The posttransplant survival time (or pre-retransplantation survival time) of all the patients were more than 24 months. The possible pre- and post-transplantation risk factors of symptomatic ONFH were investigated and the curative effects of the treatment were also reported.

RESULTSThe incidence of ONFH was 1.33% in patients after OLT. ONFH occurred at a mean of (14 ± 6) months (range, 10 - 21 months) after transplantation. Male patients more often presented with osteonecrosis as a complication than female patients. The patients with lower pre-transplantation total bilirubin and direct bilirubin levels (P < 0.05). There was no difference in the cumulative dose of corticosteroids or tacrolimus between the patients with or without symptomatic ONFH. Patients were treated either pharmacologically or surgically. All patients showed a nice curative effect without major complications during the 18 - 63 months post-treatment follow up.

CONCLUSIONSThe symptomatic ONFH does not occur commonly after adult OLT in the current individual immunosuppressive protocol in China.

Adult ; Aged ; Cyclosporine ; adverse effects ; therapeutic use ; Female ; Femur Head Necrosis ; epidemiology ; etiology ; Humans ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Liver Transplantation ; adverse effects ; Male ; Methylprednisolone ; adverse effects ; therapeutic use ; Middle Aged ; Osteonecrosis ; epidemiology ; etiology ; Retrospective Studies ; Risk Factors ; Sirolimus ; adverse effects ; therapeutic use ; Tacrolimus ; adverse effects ; therapeutic use ; Young Adult