Exploring Symptom Clusters in Chinese Patients with Diabetic Kidney Disease: A Network Analysis.

Purpose: The research on symptom management in patients with diabetic kidney disease (DKD) has shifted from separate symptoms to symptom clusters and networks recently. This study aimed to evaluate the unpleasant symptoms of DKD patients, and to investigate how these symptom clusters could affect patients. Methods: 408 DKD patients were recruited in this cross-sectional study. The symptoms of DKD patients were measured using the modified Dialysis Symptom Index. Network analysis was employed to evaluate the symptom network and the characteristics of individual nodes, while factor analysis was utilized to identify symptom clusters. Results: Blurred vision was the most prevalent symptom among DKD patients. The symptoms identified as the most distressing, severe, and frequent were light headache or dizziness, arteriovenous fistula/catheterization pain, and diarrhea, respectively. Five symptom clusters were obtained from factor analysis, and the most central symptom cluster in the entire symptom network was sexual dysfunction. Conclusion: This study identified five symptom clusters in Chinese DKD patients, with sexual dysfunction emerging as the most central cluster. These findings carry significant clinical implications, underscoring the necessity of assessing symptom clusters and their associations to enhance symptom management in DKD patients. Further research is essential to elucidate the underlying mechanisms of symptoms and to clarify the associations among symptoms in DKD patients across different disease trajectories or treatment modalities.

Characterization of the novel HLA-DRB1*16:76 allele in a Chinese individual.

The HLA-DRB1*16:76 allele differs from HLA-DRB1*16:02:01 by one nucleotide substitution (A > G) at position 37 in exon 1.

The impact of pretransplant suspected HLA antibody on the long-term outcome of the graft kidney: A retrospective cohort study.

INTRODUCTION: The preoperative examination of kidney transplantation includes HLA antibody screening to initially determine the presence of preexisting donor-specific antibody (DSA) that mediates hyperacute rejection. Recipients with positive HLA antibodies require further HLA specificity analysis to type the antigen and determine the antigen mismatches between the donor and recipient. However, recipients with suspected antibodies would have no further HLA specificity analysis. It is unclear whether suspected HLA antibodies would affect renal graft function. This study aimed to explore the impact of pretransplant suspected HLA antibody on the long-term outcome of the graft kidney and thus determine the necessity of routinely performing the HLA specificity analysis in recipients with suspected HLA antibodies preoperatively. METHODS: This is a single-center retrospective cohort study. 179 kidney transplant recipients (KTRs) were included and further divided into HLA antibody-negative group (Group 1) and HLA antibody-suspected groups (Group 2) based on the result of the pretransplant HLA antibody screen test. And the antibody-suspected group was further divided into a low-mismatched group (Group A) and a high-mismatched group (Group B) according to the HLA specificity analysis. We tracked the renal function indexes, biochemical indexes, and posttransplant adverse events within 5 years after transplantation and explored the necessity of further HLA specificity analysis in recipients with pretransplant suspected HLA antibodies. RESULTS: There was no statistically significant difference in demographics between HLA antibody-negative group and HLA antibody-suspected groups. At 5 years of follow-up, the KTRs in HLA antibody-negative group had significantly higher eGFR levels, lower serum creatinine levels, and less urinary protein compared to those in antibody-suspected group. Meanwhile, the KTRs in low-mismatched group also had significantly higher eGFR levels, lower serum creatinine levels, and less proteinuria compared to those in high-mismatched group. Correlation analysis showed that the age of KTRs, urinary protein levels and the load capacity of HLA mismatches were associated with eGFR levels of KTRs at 5 year posttransplant. CONCLUSION: KTRs with suspected HLA antibodies before kidney transplantation have worse graft function than the preoperative HLA antibody-negative recipients in the long-term posttransplant follow-up. The specific load capacity of HLA mismatches, the age of the recipient and the urinary protein was found to be negatively correlated with long-term posttransplant renal outcomes. It is necessary to undergo further HLA specificity analysis for recipients with suspected HLA antibodies in HLA antibody screen test to explicit HLA mismatches and improve long-term posttransplant outcomes.

Vitamin D supplementation reduced blood inflammatory cytokines expression and improved graft function in kidney transplant recipients.

Background: Chronic allograft dysfunction(CAD) is the leading cause of graft loss in kidney transplant recipients (KTRs). Inflammatory process is believed to be one of the major contributors to CAD. The aim of this study is to explore the anti-inflammatory effect of vitamin D (VD) supplementation in KTRs and its role in the graft function improvement(protection). Methods: A retrospective cohort of 39 KTRs with chronic antibody mediated rejection(CAMR)or stable renal function and a prospective cohort of 42 KTRs treated or untreated with VD were enrolled. Serum levels of vitamin D metabolism and serum inflammatory cytokines, renal graft function, and routine blood biomarkers were tested and dynamically tracked within 12 months post-transplant. Results: Compared with the stable group, the CAMR group exhibited significantly elevated serum levels of inflammatory cytokines IL-1ß, IFN-γ, IL-2, IL-10, IP-10, and HMGB1 (P <0.05). The supplementation of vitamin D effectively increased the serum concentration of vitamin D in kidney transplant recipients (KTRs) in the treated group. During the course of treatment, the treated group exhibited a gradual increase in eGFR levels, which were significantly higher than those observed in the untreated group at 12 months post-transplant (p<0.05). Notably, as eGFR improved, there was a significant decrease in levels of IL-1ß, IFN-γ, IL-2, IL-10, IP-10 and HMGB1 in the treated group compared to the untreated group (P<0.05). Conclusion: This study confirmed that immune-inflammation is a crucial factor in the development of CAD in KTRs.VD deficiency impairs its anti-inflammatory activity. By assisting in the regulation of excessive immune inflammation and restoration of immune homeostasis, effective VD supplementation contributes to protection and maintenance of graft function in KTRs.

Case report: Dynamic antibody monitoring in a case of anti-recombinant human erythropoietin-mediated pure red cell aplasia with prolonged course after kidney transplantation.

Anti-erythropoietin (anti-EPO) antibody-mediated pure red cell aplasia (PRCA) is a rarely seen disease. Anti-EPO antibodies were mostly found in patients with chronic kidney disease who received recombinant human erythropoietin (rHuEPO) injections subcutaneously. The treatment against anti-EPO antibody-mediated PRCA included discontinuation of rHuEPO, immunosuppressive agents, intravenous immunoglobulin, plasmapheresis, or kidney transplantation. We reported a case of kidney transplant recipient with anti-EPO antibody-mediated PRCA, who had no trend of recovery after stopping rHuEPO, receiving regular induction and maintenance immunosuppressive regimens. He was further given 6 consecutive plasmapheresis sessions, cyclophosphamide, and adjusted maintenance immunosuppressive regimen into cyclosporine, sirolimus and prednisone. We monitored his anti-EPO antibody levels with a self-created simple mixing test. At 10 months post kidney transplant, his anti-EPO antibody finally turned negative, and his reticulocyte count dramatically increased. Cyclosporine, sirolimus and prednisone combined with roxadustat eventually alleviated the patient's anti-EPO antibody-mediated PRCA. Our self-created simple mixing test for anti-EPO antibody titer was very helpful in disease monitoring and therapeutic guidance.

Cholecalciferol supplementation effectively improved tertiary hyperparathyroidism, FGF23 resistance and lowered coronary calcification score: a prospective study.

Introduction: Tertiary hyperparathyroidism (THPT) and vitamin D deficiency are commonly seen in kidney transplant recipients, which may result in persistently elevated fibroblast growth factor 23 (FGF23) level after transplantation and decreased graft survival. The aim of this study is to evaluate the effect of vitamin D supplementation on THPT, FGF23-alpha Klotho (KLA) axis and cardiovascular complications after transplantation. Materials and methods: Two hundred nine kidney transplant recipients were included and further divided into treated and untreated groups depending on whether they received vitamin D supplementation. We tracked the state of THPT, bone metabolism and FGF23-KLA axis within 12 months posttransplant and explored the predictors and risk factors for intact FGF23 levels, KLA levels, THPT and cardiovascular complications in recipients. Results: Vitamin D supplementation significantly improved FGF23 resistance, THPT and high bone turnover status, preserved better graft function and prevented coronary calcification in the treated group compared to the untreated group at month 12. The absence of vitamin D supplementation was an independent risk factor for THPT and a predictor for intact FGF23 and KLA levels at month 12. Age and vitamin D deficiency were independent risk factors for coronary calcification in recipients at month 12. Conclusion: Vitamin D supplementation effectively improved THPT, FGF23 resistance and bone metabolism, preserved graft function and prevented coronary calcification after transplantation.

Anncaliia algerae Microsporidiosis Diagnosed by Metagenomic Next-Generation Sequencing, China.

We report a case of Anncaliia algerae microsporidia infection in an immunosuppressed kidney transplant recipient in China. Light microscopy and transmission electron microscopy initially failed to identify A. algerae, which eventually was detected by metagenomic next-generation sequencing. Our case highlights the supporting role of metagenomic sequencing in early identification of uncommon pathogens.

Food Literacy and Its Associated Factors in Non-Dialysis Patients with Chronic Kidney Disease in China: A Cross-Sectional Study.

PURPOSE: Nephrology professionals' understanding of food literacy (FL) and influencing factors is significant for nutrition management, which is key to controlling disease progress among non-dialysis patients with chronic kidney disease (CKD). However, few studies have explored FL in CKD patients. Hence, this study aimed to investigate the level of FL of non-dialysis patients with CKD and to analyze influencing factors in China. PATIENTS AND METHODS: A total of 203 CKD patients without dialysis were recruited from August to December 2020 to participate in a cross-sectional study. Food literacy was assessed by a modified short food literacy questionnaire for adults. Related influencing factors were measured by the motivation for dietary self-control scale and the satisfaction with dietary behavior scale. Data were also collected regarding patients' health information-seeking behavior (four items), satisfaction and compliance with dietary advice from healthcare professionals (two items), and demographics and clinical diagnoses. RESULTS: The mean age of patients was 44.5 years (range 18 to 75), and 42.5% were male. Most (50.2%) were in stages 1-2 of CKD. The mean FL score of these patients was 38.75±0.38. The multivariable linear regression analysis shows that secondary educational level (ß=0.221, p=0.004), motivation for controlling diet (ß=0.198, p=0.003), satisfaction with dietary behaviors (ß=0.319, p<0.001), and health information-seeking behavior (ß=0.146, p=0.019) were significant influencing factors. CONCLUSION: Food literacy of Chinese CKD patients without dialysis should be improved. Patients with higher education levels exhibit more active information-seeking behaviors, have greater satisfaction with dietary behaviors, and their motivation for dietary self-control is more likely to be associated with better FL. Healthcare workers should be aware of factors influencing FL and attempt to integrate assessment of FL into routine food-related education for CKD patients.

Soluble Tim-3/Gal-9 as predictors of adverse outcomes after kidney transplantation: A cohort study.

BACKGROUND: In our previous study, serum soluble T-cell immunoglobulin and mucin structure-3 (sTim-3) and galactosin-9 (sGal-9) were found to be associated with renal function after kidney transplantation. However, it is unclear whether these two indicators can predict adverse outcomes after transplantation. METHODS: Ninety-one recipients of kidney transplantation were enrolled and divided into a stable group and an adverse outcome group (consisting of biopsy-proven rejection, graft loss, death and clinically diagnosed rejection). The expression levels of sTim-3 and sGal-9 before (pre-Tim-3 and pre-Gal-9) and one month after transplantation (post-Tim-3 and post-Gal-9) were measured by ELISA. RESULTS: The level of pre-Tim-3 was significantly higher in the stable group than in the adverse outcome group [median (range), 2275 (840-4236) pg/mL vs. 1589 (353-3094) pg/mL, P = 0.002]. The level of post-Gal-9 was significantly lower in the stable group than in the adverse outcome group [median (range), 4869 (1418-13080) pg/mL vs. 6852: (4128-10760) pg/mL, P = 0.003]. The areas under the curve (AUCs) for pre-Tim-3 and post-Gal-9 were 0.737 (P = 0.002) and 0.751 (P = 0.003), respectively, better than AUC of post-eGFR (0.633) (P = 0.071), according to the receiver operating characteristic (ROC) curve. Through Cox regression analysis, including pre-Tim-3, post-Gal-9, post-eGFR, sex, age, BMI of recipients and donors, pre-Tim-3 and post-Gal-9 were independent risk factors for adverse outcomes after kidney transplantation (P = 0.016, P = 0.033, respectively). CONCLUSION: Serum sTim-3 and sGal-9 can predict adverse outcomes within two years after kidney transplantation.

Beneficial effect of roxadustat on early posttransplant anemia and iron utilization in kidney transplant recipients: a retrospective comparative cohort study.

Background: Although posttransplant anemia (PTA) is a common complication after kidney transplant, it has not been thoroughly evaluated for appropriate treatment. Roxadustat can stimulate erythropoiesis by increasing erythropoietin (EPO) production and improving the utilization of iron. However, there are currently a few case reports describing its effect on PTA in kidney transplant recipients (KTRs). Our purpose was to evaluate the efficacy and safety of roxadustat in KTRs with PTA. Methods: In this retrospective study, KTRs with early PTA were divided into a roxadustat group, erythropoiesis-stimulating agent (ESA) group, and untreated group (neither roxadustat nor ESA) according to the treatment prescribed by their physicians. We compared the levels of hemoglobin (Hb), creatinine, lipids, hepcidin, intact fibroblast growth factor 23 (iFGF23) and iron-related indices, at baseline and different time points posttransplant. Outcome was assessed at both month 3 and month 12 posttransplant. Adverse events during the treatment course were also recorded. Results: A total of 57 KTRs were included (n=22 roxadustat group, n=13 ESA group, n=22 untreated group). There was no difference in age, sex, body mass index, dialysis method and duration, donor type among three groups at baseline. The mean Hb levels at month 3 posttransplant (128.00±19.62 vs. 118.59±11.60 g/L, P=0.048) and the average change in Hb levels from week 2 to month 3 (48.05±22.53 vs. 31.45±12.96 g/L, P=0.005) in the roxadustat group were significantly higher than those in the untreated group. However, there was no significant difference in the above indices between the roxadustat and ESA groups. At month 3, the total iron binding capacity (TIBC) and levels of transferrin were significantly higher while levels of ferritin, hepcidin and iFGF23 were significantly lower in the roxadustat group than in other groups (P<0.05). No significant difference was found in creatinine or estimated glomerular filtration rate (eGFR) levels among the three groups at month 3. During the follow-up, no adverse events related to roxadustat were reported. Conclusions: Administration of roxadustat in KTRs with early PTA could elevate Hb levels effectively and safely by enhancing endogenous EPO production and improving iron utilization. Further randomized studies with larger sample size are necessary to verify our results.

Role of serum CXCL9 and CXCL13 in predicting infection after kidney transplant: A STROBE study.

ABSTRACT: Chemokines are majorly involved in inflammatory and immune responses. The interferon-γ-inducible chemokines C-X-C motif chemokines 9 and 10 (CXCL9 and CXCL10) are considerably associated with Th1 cells and monocytes, and their expression levels rapidly increase during the early episodes of renal allograft rejection and various infectious diseases. CXCL13 is one of the most potent B-cell and T follicular helper-cell chemoattractants. The expression of CXCL13 in the presence of infection indicates an important chemotactic activity in multiple infectious diseases. C-C motif chemokine ligand 2 (CCL2) can attract monocytes and macrophages during inflammatory responses. However, there are no studies on the role of these chemokines in posttransplant infection in kidney transplant recipients.In this study, CXCL9, CXCL10, CXCL13, and CCL2 were analyzed using the Bio-Plex suspension array system before transplant and 30 days after transplant.The serum levels of CXCL9 and CXCL13 30 days after kidney transplant were associated with infection within 1 year after transplant (P = .021 and P = .002, respectively). The serum levels of CXCL9 and CXCL13 before surgery and those of CCL2 and CXCL10 before and after surgery were not associated with infection within 1 year after transplant (P > .05). The combination of postoperative day (POD) 30 CXCL9 and postoperative day 30 CXCL13 provided the best results with an area under the curve of 0.721 (95% confidence interval, 0.591-0.852), with a sensitivity of 71.4% and specificity of 68.5% at the optimal cutoff value of 52.72 pg/mL.As important chemokines, CXCL9 and CXCL13 could be used to predict the occurrence of infection after kidney transplant.

Pre-transplant donor HBV DNA+ and male recipient are independent risk factors for treatment failure in HBsAg+ donors to HBsAg- kidney transplant recipients.

BACKGROUND: In order to reduce the burden on organ shortage around the world, using potential infectious donor might be an option. However, scarce evidences have been published on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg) + donors to HBsAg- recipients [D (HBsAg+)/R(HBsAg-)] without hepatitis B virus (HBV) immunity. Here, we reported the results of D(HBsAg+/HBV DNA- or +)/R(HBsAg-) living KTx recipients with or without HBV immunity. METHODS: We retrospectively identified 83 D(HBsAg+)/R(HBsAg-) living KTx recipients, and 83 hepatitis B core antibody (HBcAb) + living donors to HBcAb- recipients [D(HBcAb+)/R(HBcAb-)] were used as control group by reviewing medical archives and propensity score matching. Treatment failure (defined as any HBV serology conversion, liver injury, graft loss, or recipient death) is the primary endpoint. RESULTS: Twenty-four donors (28.9%) were HBV DNA+, and 20 recipients had no HBV immunity in the D(HBsAg+)/R(HBsAg-) group pre-transplantation. HBV prophylaxis was applied in all D(HBsAg+)/R(HBsAg-) recipients, while none was applied in the D(HBcAb+)/R(HBcAb-) group. We observed a significant higher treatment failure in D(HBsAg+)/R(HBsAg-) than D(HBcAb+)/R(HBcAb-) group (21.7% vs. 10.8%, P < 0.001). Interestingly, no significant difference was found between groups on HBV seroconversion, liver and graft function, rejection, infection, graft loss, or death. However, 2/20 recipients without HBV immunity in the D(HBsAg+)/R(HBsAg-) group developed HBV DNA+ or HBsAg+, while none observed in the D(HBcAb+)/R(HBcAb-) group. HBV DNA+ donor and male recipient were significant risk factors for treatment failure. CONCLUSION: D(HBsAg+)/R(HBsAg-) should be considered for living kidney transplantation, but with extra caution on donors with HBV DNA+ and male candidates.

Kidney Transplantation From Hepatitis B Surface Antigen (HBsAg)-Positive Living Donors to HBsAg-Negative Recipients: Clinical Outcomes at a High-Volume Center in China.

BACKGROUND: Data on kidney transplantation (KTx) from hepatitis B surface antigen (HBsAg)-positive (HBsAg+) donors to HBsAg-negative (HBsAg-) recipients [D(HBsAg+)/R(HBsAg-)] are limited. We aimed to report the outcomes of D(HBsAg+)/R(HBsAg-) KTx in recipients with or without hepatitis B surface antibody (HBsAb). METHODS: Eighty-three D(HBsAg+)/R(HBsAg-) living KTx cases were retrospectively identified. The 384 cases of KTx from hepatitis B core antibody-positive (HBcAb+) living donors to HBcAb-negative (HBcAb-) recipients [D(HBcAb+)/R(HBcAb-)] were used as the control group. The primary endpoint was posttransplant HBsAg status change from negative to postive (-- →+). RESULTS: Before KTx, 24 donors (28.9%) in the D(HBsAg+)/R(HBsAg-) group were hepatitis B virus (HBV) DNA positive, and 20 recipients were HBsAb-. All 83 D(HBsAg+)/R(HBsAg-) recipients received HBV prophylaxis, while no D(HBcAb+)/R(HBcAb-) recipients received prophylaxis. After a median follow-up of 36 months (range, 6-106) and 36 months (range, 4-107) for the D(HBsAg+)/R(HBsAg-) and D(HBcAb+)/R(HBcAb-) groups, respectively, 2 of 83 (2.41%) D(HBsAg+)/R(HBsAg-) recipients and 1 of 384 (0.26%) D(HBcAb+)/R(HBcAb-) became HBsAg+, accompanied by HBV DNA-positive (P = .083). The 3 recipients with HBsAg-→+ were exclusively HBsAb-/HBcAb- before KTx. Recipient deaths were more frequent in the D(HBsAg+)/R(HBsAg-) group (6.02% vs 1.04%, P = .011), while liver and graft function, rejection, infection, and graft loss were not significantly different. In univariate analyses, pretransplant HBsAb-/HBcAb- combination in the D(HBsAg+)/R(HBsAg-) recipients carried a significantly higher risk of HBsAg-→+, HBV DNA-→+, and death. CONCLUSIONS: Living D(HBsAg+)/R(HBsAg-) KTx in HBsAb+ recipients provides excellent graft and patient survivals without HBV transmission. HBV transmission risks should be more balanced with respect to benefits of D(HBsAg+)/R(HBsAg-) KTx in HBsAb-/HBcAb- candidates.

Individualized Preconditioning for ABO-Incompatible Living-Donor Kidney Transplantation: An Initial Report of 48 Cases from China.

BACKGROUND ABO-incompatible (ABOi) living-donor kidney transplantation (KTx) is well established in developed countries, but not yet in China. MATERIAL AND METHODS We developed individualized preconditioning protocols for ABOi KTx based on initial ABO antibody titers. After propensity score matching of ABOi with ABO-compatible (ABOc) KTx, post-transplant outcomes were compared. RESULTS Between September 2014 and June 2018, 48 ABOi living-donor KTx candidates received individualized preconditioning, and all underwent subsequent KTx (median initial ABO titers: 16 for IgM and 16 for IgG). Thirty-one recipients (64.6%) were preconditioned with rituximab (median dose: 200 mg, range: 100-500 mg). Among 37 patients (77.1%) who received pre-transplant antibody removal, the median number of sessions of antibody removal required to achieve ABOi KTx was 2 (range: 1-5), which was conducted between days -10 and -1. Eleven ABOi recipients (22.9%) were preconditioned with oral immunosuppressants alone. Hyperacute rejection led to the loss of 2 grafts in the ABOi group. After a median follow-up of 27.6 months (ABOi group) and 29.8 months (ABOc group), there were no significant differences in graft/recipient survival, rejection, and infection. There were marginally higher rates of severe thrombocytopenia (<50×109/L) (P=0.073) and delayed wound healing (P=0.096) in ABOi recipients. CONCLUSIONS Our individualized preconditioning protocol evolved as our experience grew, and the short-term clinical outcomes of ABOi KTx did not differ from those of matched ABOc patients. ABOi KTx may be a major step forward in expanding the kidney living-donor pool in China.

Effects of Wuzhi Capsules on Blood Concentration of Tacrolimus in Renal Transplant Recipients.

BACKGROUND Tacrolimus is a widely used immunosuppressant in renal transplant recipients. It was demonstrated in rats and healthy volunteers that Wuzhi capsules could inhibit metabolism and maintain blood concentration of tacrolimus. However, there are no clinical studies of Wuzhi capsules in renal transplant recipients. This research aimed to assess the effect of Wuzhi capsules on the blood concentration of tacrolimus in renal transplant recipients. MATERIAL AND METHODS A total of 158 Chinese renal transplant recipients receiving tacrolimus with or without Wuzhi capsules were included in this retrospective study. The cohort study included 126 recipients, with 86 recipients receiving Wuzhi capsules (WZCs) and the other 40 recipients not receiving WZCs. Another 32 recipients were involved in a self-control study. RESULTS Dose- and body weight-adjusted trough concentrations (C0/D/W) of tacrolimus in the WZC group were found to be significantly higher than that in the non-WZC group (P<0.05). The improvement of C0/D/W by administration of Wuzhi capsules was more significant in CYP3A5 expressers than in non-expressers following subgroup analysis. Furthermore, the WZC group had a remarkably higher proportion of subjects who reached target tacrolimus concentration than in the non-WZC group, both in CYP3A5 expressers (P=0.01) and non-expressers (P<0.001). Multiple linear regression analysis and self-control analysis confirmed the positive impact of Wuzhi capsules on tacrolimus concentration (P<0.001). CONCLUSIONS Wuzhi capsules can increase tacrolimus trough concentration without adverse effects on allograft function, especially in CYP3A5 expressers. Efficient and convenient immunosuppressive effects on renal transplant recipients can be achieved by treatment including administration of Wuzhi capsules.

Assessment of serum Tim-3 and Gal-9 levels in predicting the risk of infection after kidney transplantation.

Infection remains a major cause of morbidity and mortality after kidney transplantation (KT). Reliable biomarkers to predict post-transplant infection are lacking. We investigated the predictive performance of pre- and post-transplant levels of T-cell immunoglobulin and mucin domain-3 (Tim-3) and Galectin-9 (Gal-9), two pleiotropic immunomodulatory molecules, in early identification of infection. Serum Tim-3 and Gal-9 were paired measured before and 30 days after transplantation (PTD 30) in 95 KT recipients (KTRs). The decline rates of Tim-3 and Gal-9 were calculated relative to pre-transplant levels. KTRs with infection history had significantly higher levels of PTD 30 Tim-3 and Gal-9, and slower decrease rates of Gal-9 compared to non-infected recipients, while no difference was observed between two groups regarding pre-transplant levels. The AUCs for predicting 1-year post-transplant infection were 0.653 and 0.711 for post-transplant Tim-3 and Gal-9, 0.664 and 0.670 for relative Tim-3 and Gal-9, respectively. After adjusting for potential confounders, PTD 30 Tim-3, Gal-9 and relative Gal-9 remained as independent risk factors for post-transplant infection. Our results suggested that PTD 30 Tim-3 and Gal-9 and relative decrease of Gal-9 were promising predictors for identifying KTRs with high risk of infection, while pre-transplant Tim-3 and Gal-9 showed no predictive power to infection.

Comparison of urine and blood NGAL for early prediction of delayed graft function in adult kidney transplant recipients: a meta-analysis of observational studies.

BACKGROUND: Neutrophil gelatinase-assoicated lipocalin (NGAL) appears to be a promising proximal tubular injury biomarker for early prediction of delayed graft function (DGF) in kidney transplant recipients. However, its predictive values in urine and blood were varied among different studies. Here, we performed the meta-analysis to compare the predictive values of urine NGAL (uNGAL) and blood NGAL (bNGAL) for DGF in adult kidney transplant recipients. METHODS: We systematically searched Medline, Cochrane library and Embase for relevant studies from inception to May 2018. The summary receiver operating characteristic (SROC) curves, the pooled sensitivity, specificity and diagnostic odds ratio (DOR) were used to evaluate the prognostic performance of uNGAL and bNGAL for the identification of DGF. RESULTS: A total of 1036 patients from 14 eligible studies were included in the analysis. 8 studies focused on NGAL in urine and 6 reported NGAL in serum or plasma. The composite area under the ROC (AUC) for 24 h uNGAL was 0.91 (95% CI, 0.89-0.94) and the overall DOR for 24 h uNGAL was 24.17(95% CI, 9.94-58.75) with a sensitivity of 0.88 (95% CI, 0.75-0.94) and a specificity of 0.81 (95% CI, 0.68-0.89). The composite AUC for 24 h bNGAL was 0.95 (95% CI, 0.93-0.97) and the overall DOR for 24 h bNGAL was 43.11 (95% CI, 16.43-113.12) with a sensitivity of 0.91 (95% CI, 0.81-0.96) and a specificity of 0.86 (95% CI, 0.78-0.92). CONCLUSIONS: Urine and serum/plasma NGAL were valuable biomarkers for early identification of DGF in kidney transplantation. In addition, the bNGAL was superior to uNGAL in early prediction of DGF.

Correlation of CYP2C19 genotype with plasma voriconazole exposure in South-western Chinese Han patients with invasive fungal infections.

The aim of this study was to investigate the correlation between CYP2C19 genotype and dose-adjusted voriconazole (VCZ) trough concentrations (C0/dose).We analyzed the correlation between CYP2C192(681G>A), CYP2C193(636G>A), and CYP2C1917(-806C>T) genetic polymorphisms and the dose-corrected pre-dose concentration (C0/dose) in 106 South-western Chinese Han patients.The frequencies of variant alleles of CYP2C192, 3, and 17 were 29.7%, 4.25%, and 0.92%. For 49.3% of the VCZ samples, the therapeutic window between 1.5 and 5.5 µg/ml was reached. Following the first dose VCZ measurement, in subsequent samples the proportion of VCZ C0 within the therapeutic window increased, suggesting effective therapeutic drug monitoring (TDM) (P = .001). The VCZ C0 was significantly different (P = .010) between patients with normal metabolism (NMs), intermediate metabolism (IMs), and poor metabolism (PMs). The VZC C0/dose was 12.2 (interquartile range (IQR), 8.33-18.2 µg·ml/kg·day), and 7.68 (IQR, 4.07-16.3 µg·ml/kg·day) in PMs and IMs patients, respectively, which was significantly higher than in NMs phenotype patients (4.68; IQR, 2.51-8.87 µg·ml/kg·day, P = .008 and P = .014).This study demonstrated that the VCZ C0/dose was significantly influenced by the CYP2C19 genotype in South-western Chinese Han patients. In this patient population, more over-exposure was observed in patients with a CYP2C19 genotype associated with poor or intermediate metabolism. CYP2C19 genotype-based dosing combined with TDM will support individualization of VCZ dosing, and potentially will minimize toxicity and maximize therapeutic efficacy.

A Low Fixed Tacrolimus Starting Dose Is Effective and Safe in Chinese Renal Transplantation Recipients.

BACKGROUND We investigated whether a low fixed Tac starting dose regimen could lead to a better achievement of Tac target concentrations, as well as an effective immunosuppressive treatment, in Chinese kidney transplant recipients (KTRs). MATERIAL AND METHODS We collected whole-blood and serum samples from 189 KTRs and the Tac starting dose was 2, 2.5, or 3 mg/day. Information on Tac C0, dose, body weight, body mass index (BMI), Scr, eGFR, and CYP3A5 genotypes were collected from a routine therapeutic drug monitoring database. The correlation between Tac C0 and body weight (or BMI) was investigated by calculating the goodness of fit. Multivariable logistic regression was performed to estimate the independent associated factors. RESULTS The patients with 3 mg per day of Tac had higher C0 at day 7 compared to those with 2 or 2.5 mg. For patients receiving the same Tac starting dose, no significant difference was found in Tac C0 at day 7 among different body weight or BMI groups. There was no significant difference in Scr or eGFR at 1 year after transplant, nor was there a significant difference in the rates of DGF or AR at post-transplant day 30 among different Tac starting dose groups or among the 3 Tac C0 range groups. CYP3A5 genotype and Tac initial dose were independently associated with Tac C0. CONCLUSIONS CYP3A5 genotype and Tac initial dose were independently associated with Tac C0 in renal transplant recipients. Our results suggest that a low Tac target C0 range (5-8 ng/ml) with a low fixed starting dose (3 mg/day) would be safe and effective among Chinese KTRs.

Soluble Tim-3 and Gal-9 are associated with renal allograft dysfunction in kidney transplant recipients: A cross-sectional study.

BACKGROUND: T cell immunoglobulin mucin-3 (Tim-3) has been reported to participate in the regulation of immune response and the induction of allograft tolerance. However, the association between Tim-3 and renal allograft dysfunction is unclear. We studied the expression of cellular and soluble Tim-3 (sTim-3), soluble galectin-9 (sGal-9) and carcinoembryonic antigen-related cell adhesion molecule-1 (sCEACAM-1) in kidney transplantation recipients (KTRs) to explore their roles in allograft dysfunction. METHODS: 96 KTRs (53 with stable graft and 43 with graft dysfunction) and 30 healthy controls (HC) were enrolled. Among the KTRs, 55 used Tacrolimus (TAC) and 41 used Sirolimus (SRL). In the dysfunction group, 29 recipients have undergone graft biopsy and 14 were classified as biopsy-proven rejection (BPR). Cellular Tim-3 was determined by flow cytometry. sTim-3 was determined by ELISA. sGal-9 and sCEACAM-1 were determined by Bio-Plex® suspension array system. RESULTS: KTRs with renal dysfunction showed significantly higher levels of sTim-3 and sGal-9 but similar levels of cellular Tim-3 and sCEACAM-1 compared with stable recipients. Correlation analysis revealed that estimated glomerular filtration rate (eGFR) was negatively associated with sTim-3 and sGal-9. Both BPR and non-BPR groups showed comparable levels of Tim-3, Gal-9 and CEACAM-1. Moreover, SRL group showed significantly higher levels of sCEACAM-1 than TAC and HC groups. CONCLUSIONS: sTim-3 and sGal-9 were promising biomarkers for allograft dysfunction, but unable to differentiate allograft rejection from other causes of renal dysfunction in KTRs. Moreover, long-term administration of sirolimus would up-regulate sCEACAM-1 level, while exert similar regulatory effects on Tim-3 and Gal-9 compared to tacrolimus.