Lipid accumulation-induced hepatocyte senescence regulates the activation of hepatic stellate cells through the Nrf2-antioxidant response element pathway.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease globally. Elderly individuals are at a higher risk of developing NAFLD with severe clinical outcomes. Although NAFLD is closely related to liver aging, the role of hepatocyte senescence in the progression of NAFLD, especially in the development of fibrosis, is still unclear. The early stage of NAFLD is mainly characterized by lipid accumulation in hepatocytes, which could lead to severe oxidative stress, causing cellular senescence. In the present study, hepatocytes cultured in the presence of free fatty acids to induce lipid deposition were used as a hepatocyte senescence model in vitro. Senescent hepatocytes significantly increased the activation of co-cultured primary hepatic stellate cells (HSCs) and the expression of pro-fibrosis molecules. Moreover, the antioxidant regulator nuclear factor erythroid 2-related factor 2 (Nrf2) that was upregulated in senescent hepatocytes was found to be related to the activation of co-cultured HSCs. The Nrf2 agonist sulforaphane, which upregulated the transcriptional activity of the Nrf2-antioxidant response element (ARE) pathway, remarkably inhibited hepatocyte senescence and its activation effect on HSCs. However, the liver tissue obtained from non-alcoholic steatohepatitis (NASH) mice with Nrf2 knockdown showed decreased antioxidation and significant liver senescence and fibrosis. In conclusion, this study confirmed that lipid accumulation induces hepatocyte senescence, which leads to HSC activation and development of hepatic fibrosis. Increasing the activity of the Nrf2-ARE antioxidant pathway in senescent hepatocytes elicited the opposite effect, suggesting that targeting Nrf2 may prevent or delay the progression of aging-related liver fibrosis in NASH.

Secretory galectin-3 induced by glucocorticoid stress triggers stemness exhaustion of hepatic progenitor cells.

Adult progenitor cell populations typically exist in a quiescent state within a controlled niche environment. However, various stresses or forms of damage can disrupt this state, which often leads to dysfunction and aging. We built a glucocorticoid (GC)-induced liver damage model of mice, found that GC stress induced liver damage, leading to consequences for progenitor cells expansion. However, the mechanisms by which niche factors cause progenitor cells proliferation are largely unknown. We demonstrate that, within the liver progenitor cells niche, Galectin-3 (Gal-3) is responsible for driving a subset of progenitor cells to break quiescence. We show that GC stress causes aging of the niche, which induces the up-regulation of Gal-3. The increased Gal-3 population increasingly interacts with the progenitor cell marker CD133, which triggers focal adhesion kinase (FAK)/AMP-activated kinase (AMPK) signaling. This results in the loss of quiescence and leads to the eventual stemness exhaustion of progenitor cells. Conversely, blocking Gal-3 with the inhibitor TD139 prevents the loss of stemness and improves liver function. These experiments identify a stress-dependent change in progenitor cell niche that directly influence liver progenitor cell quiescence and function.

Lipid-injured hepatocytes release sOPN to improve macrophage migration via CD44 engagement and pFak-NFκB signaling.

BACKGROUND: The key characteristics in the pathogenesis of nonalcoholic steatohepatitis (NASH) are hepatic lipotoxicity, inflammatory cell infiltration (activated macrophages, in part), and varying degrees of fibrosis. The fatty acid palmitate (PA) can cause hepatocyte cellular dysfunction, but whether and how this process contributes to macrophage-associated inflammation is not well understood. This study aimed to explore whether lipid-injured hepatocytes result in the secretion of osteopontin (sOPN), and how sOPN induces macrophage migration to steatosis hepatocytes. METHODS: Human hepatocellular carcinoma HepG2 cells were incubated with PA to establish the lipotoxicity in hepatocytes model in vitro. The released sOPN was isolated, characterized, and applied to macrophage-like cells differentiated from the human monocytic cell line THP-1 cells. C57BL/6 mice were fed either chow or a diet high in fructose-fat-glucose (FFG) to induce NASH in vivo. Some NASH model mice were also given siSPP1 for two weeks to inhibit the expression of OPN. Related tissues were collected and analyzed by histology, immunofluorescence, ELISA, qRT-PCR, and western blotting. RESULTS: PA upregulated OPN expression and release in human hepatocytes, which drove the migration of macrophages. Incubation of HepG2 cells with palmitate increased mRNA expression and secretion of OPN in cell culture supernatants. Compared with the BSA and siSPP1 groups, treatment with the supernatant derived from PA-treated hepatocytes promoted macrophage migration and activation. The sOPN induction of macrophage migration occurred via CD44 engagement and activation of the pFak-NFκB signaling pathway. Likewise, administration of siSPP1 to NASH mice inhibited the expression and release of OPN, which was associated with decreased liver dysfunction, inflammatory cell infiltration, and even fibrosis. CONCLUSIONS: sOPN, which is released from lipid-injured hepatocytes, emerges as a cytokine driving the migration of macrophages, contributing to an inflammatory response in NASH.

Identifying SLC27A5 as a potential prognostic marker of hepatocellular carcinoma by weighted gene co-expression network analysis and in vitro assays.

BACKGROUND: The incidence and mortality rates of hepatocellular carcinoma are among the highest of all cancers all over the world. However the survival rates are relatively low due to lack of effective treatments. Efforts to elucidate the mechanisms of HCC and to find novel prognostic markers and therapeutic targets are ongoing. Here we tried to identify prognostic genes of HCC through co-expression network analysis. METHODS: We conducted weighted gene co-expression network analysis with a microarray dataset GSE14520 of HCC from Gene Expression Omnibus database and identified a hub module associated with HCC prognosis. Function enrichment analysis of the hub module was performed. Clinical information was analyzed to select candidate hub genes. The expression profiles and survival analysis of the selected genes were performed using additional datasets (GSE45267 and TCGA-LIHC) and the hub gene was identified. GSEA and in vitro experiments were conducted to further verify the function of the hub gene. RESULTS: Genes in the hub module were mostly involved in the metabolism pathway. Four genes (SLC27A5, SLC10A1, PCK2 and FMO4) from the module were identified as candidate hub genes according to correlation analysis with prognostic indicators. All these genes were significantly down-regulated in tumor tissues compared with non-tumor tissues in additional datasets. After survival analysis and network construction, SLC27A5 was selected as a prognostic marker. GSEA analysis and in vitro assays suggested that SLC27A5 downregulation promoted tumor cell migration via enhancing epithelial-mesenchymal transition. CONCLUSION: SLC27A5 is a potential biomarker of HCC and SLC27A5 downregulation promoted HCC progression by enhancing EMT.

A retrospective cohort study of preoperative lipid indices and their impact on new-onset diabetes after liver transplantation.

BACKGROUND: The correlation between preoperative lipid profiles and new-onset diabetes after transplantation (NODAT) remains relatively unexplored in liver transplant recipients (LTRs). Thus, we aimed to investigate the preoperative lipid profiles in Chinese LTRs and evaluate the different influences of preoperative total cholesterol, total triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol on the development of NODAT in both sexes. METHODS: A total of 767 Chinese LTRs from Zhongshan Hospital were retrospectively evaluated. NODAT was defined according to the American Diabetes Association guidelines; the relationship between each preoperative lipid index and NODAT development was analyzed separately in men and women. RESULTS: Pretransplant hypotriglyceridemia was observed in 35.72% of the total LTRs. In men, only the preoperative TG level was significantly associated with incident NODAT after adjusting for potential confounders (hazard ratio 1.37, 95% confidence interval 1.13-1.66, P = .001). There was a nonlinear relationship between the preoperative TG level and NODAT risk. The risk of NODAT significantly increased with preoperative a TG level above 0.54 mmol/L (log-likelihood ratio test, P = .043). In women, no significant association was observed. CONCLUSION: Among male LTRs, a higher preoperative TG level, even at a low level within the normal range, was significantly and nonlinearly associated with an increased risk of NODAT.

Curcumol suppresses RANKL-induced osteoclast formation by attenuating the JNK signaling pathway.

Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage lineage, have a unique role in bone resorption, and are considered a potential therapeutic target in the treatment of such pathologic bone diseases as osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we demonstrate that curcumol, one of the major components of the essential oil of Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is prominently reduced in the presence of curcumol. Furthermore, the molecular mechanism of action was investigated, and curcumol inhibited osteoclastogenesis by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling, which was further identified in rescue studies by means of anisomycin, a JNK signaling-specific activator. Taken together, these findings suggest that curcumol suppresses RANKL-induced osteoclast differentiation through the JNK/AP-1 signaling pathway, and may be useful as a therapeutic treatment for bone resorption-associated diseases.

Aged microbiota exacerbates cardiac failure by PPARα/PGC1α pathway.

The dysbiosis of gut microbiota with aging has been extensively studied, revealing its substantial contribution to variety of diseases. However, the impact of aged microbiota in heart failure (HF) remains unclear. In this study, we employed the method of fecal microbiota transplantation (FMT) from aged donors to investigate its role in the context of HF. Our results demonstrate that FMT from aged donors alters the recipient's gut microbiota composition and abundance. Furthermore, FMT impairs cardiac function and physical activity in HF mice. Aged FMT induces metabolic alterations, leading to body weight gain, impaired glucose tolerance, increased respiratory exchange ratio, and enhanced fat accumulation. The epicardium of aged FMT recipients shows fat accumulation, accompanied by cardiomyocyte hypertrophy, cardiac fibrosis and increased cellular apoptosis. Mechanistically, aged FMT suppresses the PPARα/PGC1α signaling pathway in HF. Notably, activation of PPARα effectively rescues the metabolic changes and myocardial injury caused by aged FMT. In conclusion, our study emphasizes the role of the PPARα/PGC1α signaling pathway in aged FMT-mediated HF.

Butyrate promotes C2C12 myoblast proliferation by activating ERK/MAPK pathway.

Sarcopenia has garnered considerable interest in recent years as ageing-associated diseases constitute a significant worldwide public health burden. Nutritional supplements have received much attention as potential tools for managing sarcopenia. However, the specific nutrients responsible are still under-investigated. In the current study, we first determined the levels of short chain fatty acids (SCFAs) and intestinal flora in the feces of elderly sarcopenia subjects and elderly healthy individuals by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Then cell viability detection, flow cytometry and transcriptome analysis were adopted to experimentally evaluate the effect and the underlying mechanism of SCFA on C2C12 cells proliferation in vitro. The results suggested that patients with sarcopenia exhibited decreased levels of butyrate. And butyrate may stimulate C2C12 myocyte proliferation via promoting G1/S cell cycle transition. Transcriptomic analyses pointed to upregulation of the Mitogen-activated protein kinase (MAPK) signaling pathway in butyrate-treated cells. In addition, the above proliferative phenotypes could be suppressed by the combination of ERK/MAPK inhibitor. A combined transcriptomic and metabolomic approach was applied in our study to investigate the potential effect of microbiota-derived butyrate yield on muscular proliferation which may indicate a protective effect of nutritional supplements.

Ileal FXR-FGF15/19 signaling activation improves skeletal muscle loss in aged mice.

Sarcopenia is the age-related decrease in skeletal muscle mass, and current therapies for this disease are ineffective. We previously showed that ileal farnesoid X receptor (FXR)-fibroblast growth factor 15/19 (FGF15/19) signaling acts as a regulator of gut microbiota to mediate host skeletal muscle. However, the therapeutic potential of this pathway for sarcopenia is unknown. This study showed that ileal FXR-FGF15/19 signaling was downregulated in older men and aged male mice due to changes in the gut microbiota and microbial bile acid metabolism during aging. In addition, the intestine-specific FXR agonist fexaramine increased skeletal muscle mass and improve muscle performance in aged mice. Ileal FXR activation increased skeletal muscle protein synthesis in a FGF15/19-dependent way, indicating that ileal FXR-FGF15/19 signaling is a potential therapeutic target for sarcopenia.

Depletion of gut microbiota induces skeletal muscle atrophy by FXR-FGF15/19 signalling.

Background: Recent evidence indicates that host-gut microbiota crosstalk has nonnegligible effects on host skeletal muscle, yet gut microbiota-regulating mechanisms remain obscure.Methods: C57BL/6 mice were treated with a cocktail of antibiotics (Abx) to depress gut microbiota for 4 weeks. The profiles of gut microbiota and microbial bile acids were measured by 16S rRNA sequencing and ultra-performance liquid chromatography (UPLC), respectively. We performed qPCR, western blot and ELISA assays in different tissue samples to evaluate FXR-FGF15/19 signaling.Results: Abx treatment induced skeletal muscle atrophy in mice. These effects were associated with microbial dysbiosis and aberrant bile acid (BA) metabolism in intestine. Ileal farnesoid X receptor (FXR)-fibroblast growth factor 15 (FGF15) signaling was inhibited in response to microbial BA disturbance. Mechanistically, circulating FGF15 was decreased, which downregulated skeletal muscle protein synthesis through the extracellular-signal-regulated protein kinase 1/2 (ERK1/2) signaling pathway. Treating Abx mice with FGF19 (human FGF15 ortholog) partly reversed skeletal muscle loss.Conclusions: These findings indicate that the BA-FXR-FGF15/19 axis acts as a regulator of gut microbiota to mediate host skeletal muscle.

Oleate Ameliorates Palmitate-Induced Impairment of Differentiative Capacity in C2C12 Myoblast Cells.

A common observation in metabolic disorders and aging is the elevation of free fatty acids (FFAs), which can form ectopic fat deposition and result in lipotoxicity. Ectopic fat deposition of skeletal muscle has been recognized as an important component of aging, frailty, and sarcopenia. Previous studies have suggested that lipotoxicity caused by FFAs mainly stemmed from saturated fatty acids and decreased unsaturated/saturated fatty acid ratio in serum are also observed among metabolic disorder patients. However, the different effects of saturated fatty acids and unsaturated fatty acids on skeletal muscle are not fully elucidated. In this study, we verified that palmitate (PA), a saturated fatty acid, could lead to impaired differentiative capacity of C2C12 myoblasts by affecting Pax7, MyoD, and myogenin (MyoG), which are master regulators of lineage specification and the myogenic program. Then, oleate (OA), a monounsaturated fatty acid, were added to culture medium together with PA. Results showed that OA could ameliorate the impairment of differentiative capacity in C2C12 myoblast cells. In addition, we found PI3K/Akt signaling pathway played an important role during the process by RNA sequencing and bioinformatics analysis. The positive effect of OA on myoblast differentiative capacity disappeared if PI3K inhibitor LY294002 was added. In conclusion, our study showed that PA could destroy differentiative capacity of C2C12 myoblasts by affecting the expression of Pax7, MyoD, and MyoG, and OA could improve this impairment through PI3K/Akt signaling pathway.

Secretory Galectin-3 promotes hepatic steatosis via regulation of the PPARγ/CD36 signaling pathway.

Galectin-3 (Gal3) is an essential regulator of a number of metabolic disorders. Previous studies have established that Gal3 is a positive regulator of inflammation, fibrosis, and insulin resistance. However, its function in the early pathogenesis of hepatic lipid accumulation in non-alcoholic fatty liver disease (NAFLD) remains unresolved. Here, we demonstrate the presence of significantly upregulated extracellular concentrations of Gal3 in the fatty livers of high-fat diet (HFD)-induced mice. Systemic inhibition of Gal3 by injection of TD139 reduced the accumulation of lipid in the livers of HFD-fed mice, accompanied by the decreased expression of CD36 and peroxisome proliferator-activated receptor-gamma (PPARγ). Treatment with Gal3 protein elicited the opposite response in palmitic acid (PA)-induced HepG2 hepatocytes. It was additionally discovered that Gal3 positively regulates CD36 transcription by increased activation of PPARγ, thereby increasing fatty acid uptake, resulting in hepatic steatosis. In conclusion, the present study confirmed the roles of Gal3 in hepatic lipid metabolism in both in vitro and in vivo studies and revealed that Gal3 is a secretory protein that promotes hepatic steatosis through the PPARγ-CD36-dependent pathway, suggesting that targeting Gal3 may represent a potential therapeutic approach for the treatment of NAFLD and related metabolic disorders.

Interleukin-2 receptor antagonists: Protective factors against new-onset diabetes after renal transplantation.

BACKGROUND: The aim of the present study was to examine the association between interleukin-2 receptor antagonists (IL-2Ra) and new-onset diabetes after transplantation (NODAT) among renal transplant recipients (RTRs). METHODS: Between January 1993 and March 2014, 915 patients underwent renal transplantation at Zhongshan Hospital. In all, 557 RTRs were included in the present retrospective cohort study. The incidence of NODAT in this cohort was determined and multivariate Cox regression analysis was used to evaluate the risk factors for NODAT and to show the association between IL-2Ra use and NODAT development among RTRs. The cumulative incidence of NODAT was compared between groups treated with or without IL-2Ra. RESULTS: The mean ±SD postoperative follow-up was 5.08 ±3.17 years. The incidence of NODAT at the end of follow-up was 20.3%. After adjusting for potential confounders in the multivariate logistic regression (i.e. age, sex, body mass index, history of smoking, family history of diabetes, duration of dialysis, type of dialysis, donor type, recovery of graft function, acute rejection, hepatitis B or C or cytomegalovirus infection, fasting plasma glucose levels before and 1 week after transplantation, preoperative total cholesterol and triglyceride levels, daily dose of glucocorticoid, immunosuppressive regimen type, and immunosuppressant concentration after transplantation), IL-2Ra use was found to be related to a reduced incidence of NODAT. CONCLUSIONS: Use of IL-2Ra is associated with protection against the development of NODAT in RTRs.

Donor liver steatosis: A risk factor for early new-onset diabetes after liver transplantation.

AIMS/INTRODUCTION: To investigate whether donor liver steatosis increases the incidence of new-onset diabetes after transplantation (NODAT) in liver transplant recipients. MATERIALS AND METHODS: We retrospectively analyzed liver transplant recipients at Zhongshan Hospital, Shanghai, China, from April 2001 to December 2014. The final analysis involved 763 patients. The cumulative incidence of NODAT at 1, 3, 5 and 10 years after liver transplantation was investigated. Furthermore, according to the findings of donor liver biopsy before transplantation, patients were divided into steatotic and non-steatotic donor liver groups, and NODAT incidence was compared between these groups. Multivariate Cox regression was used to explore the risk factors for NODAT in the patients. RESULTS: Of the 763 donors, 309 (40.5%) had liver steatosis. At the end of follow up, 130 (42.1%) patients in the steatotic donor liver group developed NODAT, an incidence that exceeded that in the non-steatotic donor liver group (P = 0.001). The cumulative incidence of NODAT among all patients at 1, 3, 5, and 10 years after transplantation was 33, 43, 50 and 56%, respectively. The cumulative incidences of NODAT at 1, 3, 5 and 10 years in the steatotic donor liver group were significantly higher than those in the non-steatotic donor liver group (P = 0.003). Multivariate Cox regression analyses showed that donor liver steatosis was an independent risk factor for NODAT among liver transplant recipients, after other potential risk factors were adjusted for (hazard ratio 1.774, 95% confidence interval: 1.025-3.073; P = 0.041). CONCLUSIONS: Donor liver steatosis increases NODAT incidence among liver transplant recipients.

Effect of interleukin-2 receptor antagonists on new-onset diabetes after liver transplantation: A retrospective cohort study.

BACKGROUND: The aim of the present retrospective observational study was to examine the effect of interleukin-2 receptor antagonists (IL-2Ra) on new-onset diabetes after transplantation (NODAT) in liver transplant recipients. METHODS: Pre- and postoperative clinical data of 781 patients undergoing liver transplantation between April 2001 and December 2014 at Zhongshan Hospital, Fudan University, were analyzed. Patients were divided into two groups depending on the use of IL-2Ra (IL-2Ra and non-IL-2Ra). The cumulative incidence of NODAT was compared between the IL-2Ra and non-IL-2Ra groups and the effect of IL-2Ra on the incidence of NODAT in liver transplant recipients was evaluated. RESULTS: Of the 781 patients in the study, 451 received IL-2Ra. During follow-up, 138 (41.8%) and 137 (30.4%) patients in the non-IL-2Ra and IL-2Ra groups, respectively, developed NODAT (P = 0.001). The cumulative incidence of NODAT at 1, 3, 5, and 8 years after transplantation in the IL-2Ra group was 30%, 38%, 45%, and 54%, respectively; these values were substantially lower than corresponding values for the non-IL-2Ra group (P < 0.05). Cox regression analyses showed that IL-2Ra was a protective factor against NODAT development (odds ratio 0.685; 95% confidence interval 0.473-0.991; P = 0.044). This was independent of age, sex, donor type, hepatitis virus infection, body mass index, history of hypertension, preoperative liver function, preoperative fasting plasma glucose, total cholesterol, and total triglyceride levels, severity of liver cirrhosis, acute rejection, initial immunosuppressant regimen type, and postoperative immunosuppressant levels. CONCLUSION: In conclusion, IL-2Ra reduces the risk of NODAT in liver transplant recipients.

New-onset diabetes after liver transplantation and its impact on complications and patient survival.

BACKGROUND: The aim of the present study was to investigate the incidence and risk factors of new-onset diabetes after transplantation (NODAT) in liver transplant recipients and the influence of NODAT on complications and long-term patient survival. METHODS: We examined 438 patients who underwent liver transplantation between April 2001 and December 2008 and were not diabetic before transplantation. RESULTS: The mean (± SD) follow-up duration was 2.46 ± 1.62 years. The incidence of NODAT 3, 6, 9, 12, 36, and 60 months after transplantation was 44.24%, 25.59%, 23.08%, 25.17%, 17.86%, and 18.18%, respectively. Multifactor analysis indicated that preoperative fasting plasma glucose (FPG) levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an interleukin-2 receptor (IL-2R) antagonist reduced the risk of NODAT. Compared with the no NODAT group (N-NODAT), the NODAT group had a higher rate of sepsis and chronic renal insufficiency. Mean survival was significantly longer in the N-NODAT than NODAT group. Cox regression analysis showed that pre- and/or postoperative FPG levels, tumor recurrence or metastasis, and renal insufficiency after liver transplantation were independent risk factors of mortality. Pulmonary infection or multisystem failure were specific causes of death in the NODAT group, whereas patients in both groups died primarily from tumor relapse or metastasis. CONCLUSIONS: Preoperative FPG levels and donor liver steatosis were independent risk factors for NODAT, whereas administration of an IL-2R antagonist reduced the risk of NODAT. Patients with NODAT had reduced survival and an increased incidence of sepsis and chronic renal insufficiency. Significant causes of death in the NODAT group were pulmonary infection and multisystem failure.

Influencing factors of new-onset diabetes after a renal transplant and their effects on complications and survival rate.

OBJECTIVE: To discuss the onset of and relevant risk factors for new-onset diabetes after a transplant (NODAT) in patients who survive more than 1 year after undergoing a renal transplant and the influence of these risk factors on complications and long-term survival. METHOD: A total of 428 patients who underwent a renal transplant between January 1993 and December 2008 and were not diabetic before surgery were studied. The prevalence rate of and relevant risk factors for postoperative NODAT were analyzed on the basis of fasting plasma glucose (FPG) levels, and differences in postoperative complications and survival rates between patients with and without NODAT were compared. RESULTS: The patients in this study were followed up for a mean of 5.65 ± 3.68 years. In total, 87 patients (20.3%) developed NODAT. Patients who converted from treatment with CSA to FK506 had increased prevalence rates of NODAT (P <0.05). Multi-factor analysis indicated that preoperative FPG level (odds ratio [OR]  =  1.48), age (OR  =  1.10), body mass index (OR  =  1.05), hepatitis C virus infection (OR  =  2.72), and cadaveric donor kidney (OR  =  1.18) were independent risk factors for NODAT (All P <0.05). Compared with the N-NODAT group, the NODAT group had higher prevalence rates (P < 0.05) of postoperative infection, hypertension, and dyslipidemia; in addition, the survival rate and survival time of the 2 groups did not significantly differ. CONCLUSION: Among the patients who survived more than 1 year after a renal transplant, the prevalence rate of NODAT was 20.32%. Preoperative FPG level, age, body mass index, hepatitis C virus infection, and cadaveric donor kidney were independent risk factors for NODAT. Patients who converted from treatment with CSA to FK506 after a renal transplant had aggravated impairments in glycometabolism. Patients with NODAT were also more vulnerable to postoperative complications such as infection, hypertension, and hyperlipidemia.