Surgical margin status outcome of intraoperative indocyanine green fluorescence-guided laparoscopic hepatectomy in liver malignancy: a systematic review and meta-analysis.

BACKGROUND: Hepatectomy stands as a curative management for liver cancer. The critical factor for minimizing recurrence rate and enhancing overall survival of liver malignancy is to attain a negative margin hepatic resection. Recently, Indocyanine green (ICG) fluorescence imaging has been proven implemental in aiding laparoscopic liver resection, enabling real-time tumor identification and precise liver segmentation. The purpose of this study is to conduct a systematic review and meta-analysis to ascertain whether ICG-guided laparoscopic hepatectomy yields a higher incidence of complete tumor eradication (R0) resections. METHODS: The search encompassed databases such as PubMed, Cochrane Library database, Scopus, ScienceDirect, and Ovid in April 2024, in strict adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies involving patients with malignant liver lesions who underwent ICG-guided laparoscopic hepatectomy and reported R0 resection outcomes were eligible for inclusion in this review. RESULTS: In a total of seven studies, involving 598 patients, were included in the meta-analysis. The ICG demonstrated a significantly elevated R0 resection rate compared to the non-ICG group [98.6% (359/364) vs. 93.1% (339/364), odds ratio (OR) = 3.76, 95% confidence intervals (CI) 1.45-9.51, P = 0.005]. Notably, no heterogeneity was observed (I2 = 0%, P = 0.5). However, the subtype analysis focusing on hepatocellular carcinoma [98.2% (165/168) vs. 93.6% (161/172), OR = 3.34, 95% CI 0.94-11.91, P = 0.06) and the evaluation of margin distance (4.96 ± 2.41 vs. 2.79 ± 1.92 millimeters, weighted mean difference = 1.26, 95% CI -1.8-4.32, P = 0.42) revealed no apparent differences. Additionally, the incidence of overall postoperative complications was comparable between both groups, 27.6% (66/239) in the ICG group and 25.4% (75/295) in the non-ICG group (OR = 0.96, 95% CI 0.53-1.76, P = 0.9). No disparities were identified in operative time, intraoperative blood loss, postoperative blood transfusion, and length of hospital stay after the surgery. CONCLUSIONS: The implementation of ICG-guided laparoscopic hepatectomy can be undertaken with confidence, as it does not compromise either intraoperative or postoperative events. Furthermore, the ICG-guided approach is beneficial to achieving a complete eradication of the tumor during hepatic resection. TRIAL REGISTRATION: PROSPERO registration number CRD42023446440.

Should we abandon therapeutic drug monitoring of tacrolimus in whole blood and move to intracellular concentration measurements?

The measurement of whole blood (WB) concentrations has been the primary method for therapeutic drug monitoring of tacrolimus since its introduction in the field of organ transplantation. However, >99% of tacrolimus measured in WB is bound to erythrocytes and plasma proteins, which are the pharmacologically inactive fractions. The pharmacologically active fractions, the free (or unbound) tacrolimus in plasma and the intracellular tacrolimus, make up 1% or less of the WB concentration. The mechanism of action of tacrolimus is to inhibit the enzyme calcineurin within T lymphocytes and, therefore, measuring the intralymphocytic tacrolimus concentration may better reflect its pharmacodynamic effects and better correlate with clinical outcomes. However, studies on intracellular tacrolimus concentrations have shown conflicting results. In this review, we argue that we need to overcome the analytical limitations of current assays for the measurement of intracellular tacrolimus before moving this technique into the clinical setting. The validity and standardization of the cell isolation process before the measurement of the intracellular tacrolimus concentration is as important as the measurement itself but has received little attention in our view. Recent evidence suggests that the addition of an inhibitor of P-glycoprotein, an efflux transporter expressed on lymphocytes, prevents the expulsion of tacrolimus during the cell isolation process. Refining the technique for the intracellular tacrolimus concentration measurement should be the focus followed by clinical evaluation of its association with rejection risk.

Clinical validation and comparison of the Comprehensive Complication Index and Clavien-Dindo classification in predicting post-operative outcomes after cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: The Comprehensive Complication Index (CCI) is an instrument used to measure cumulative post-operative complications. Our study aimed to validate the CCI after cytoreductive surgery for primary advanced-stage epithelial ovarian cancer, and to compare its diagnostic performance with the Clavien-Dindo classification. METHODS: This prospective cohort study classified post-operative complications according to the Clavien-Dindo classification and the CCI. Logistic regression was used to determine the association between both classifications with intensive care unit admission, prolonged length of hospital stay (defined as stays longer than the 75th percentile of all stays in this study), 30-day readmission, and time to initiating chemotherapy after surgery >42 days. Area under the receiver operating characteristic curves (AUC) were used to assess the discriminative performance of each classification. RESULTS: A total of 300 patients were included in the analysis. Most patients (n=255, 85%) underwent interval cytoreductive surgery. Complete cytoreduction was achieved in 235 (78%) patients. Overall, 30-day post-operative complications classified by the Clavien-Dindo classification occurred in 147 (49%) patients. Severe complications (grade ≥3a) occurred in 51 (17%) patients. Approximately 30% (n=82) had multiple complications. The CCI showed an excellent correlation with the Clavien-Dindo classification (r=0.906, p<0.001). In comparison with the Clavien-Dindo classification, the proportion of patients classified with severe complications increased from 17% to 30% when stratified with the CCI, and 20% of patients were diagnosed with a CCI score that correlated with a higher Clavien-Dindo classification grade. On regression analysis, both Clavien-Dindo classification and CCI had associations with intensive care unit admission, prolonged length of hospital stay, 30-day readmission, and time to chemotherapy >42 days (all p<0.05). AUC demonstrated that CCI (0.842, 95% CI 0.792 to 0.893) and Clavien-Dindo classification (0.813, 95% CI 0.762 to 0.864, p<0.001) had a good diagnostic performance for prolonged length of hospital stay. CONCLUSIONS: Both the Clavien-Dindo classification and CCI showed significant associations with all surgical outcomes. However, the cumulative complications score of the CCI demonstrated a more superior discriminative performance than the Clavien-Dindo classification for prolonged length of hospital stay in advanced-stage epithelial ovarian cancer.

Metabolic effects of kidney donation: A Bayesian analysis of matched cohorts.

The kidney is a notable site of glycolysis, gluconeogenesis, and fatty acid oxidation. Loss of a kidney after kidney donation might, therefore, affect the glucose and lipid metabolism of the donors. This matched cohort study investigated the effect of nephrectomy on glucose and lipid metabolisms using Bayesian hypothesis testing. There were 77 pairs of matched donor-control pairs in the present study. Clinical and laboratory data of the participants, at baseline and 1-year, were extracted from electronic medical records. Comparisons between donor and control groups were performed using the Bayesian independent samples t-test or Bayesian Mann-Whitney test. The Bayes Factor for alternative hypothesis over null hypothesis (BF10 ) was used to compare the two competing hypotheses. The BF10 of 3 or more was considered evidence for the alternative hypothesis. Comparing changes from baseline to 1-year between donors and controls, the BF10 of triglycerides, high-density lipoprotein cholesterol (HDL-C), triglyceride-glucose (TyG) index of insulin resistance, and estimated glomerular filtration rate (eGFR) were 7.95, 3.96, 30.13, and 1.32 x 1041 , respectively signifying that the change of these variables in the donors differed from those in the controls (alternative hypothesis). Triglyceride, HDL-C, and TyG index of the donors increased more than those of the controls while eGFR of the donor decreased more than that of the controls. Our data suggest that triglycerides and insulin resistance increase after donor nephrectomy. Kidney donors should be informed about these metabolic changes and should adhere to lifestyle recommendations that may mitigate insulin resistance.

Lipopolysaccharide Tolerance Enhances Murine Norovirus Reactivation: An Impact of Macrophages Mainly Evaluated by Proteomic Analysis.

Because of endotoxemia during sepsis (a severe life-threatening infection), lipopolysaccharide (LPS) tolerance (the reduced responses to the repeated LPS stimulation) might be one of the causes of sepsis-induced immune exhaustion (the increased susceptibility to secondary infection and/or viral reactivation). In LPS tolerance macrophage (twice-stimulated LPS, LPS/LPS) compared with a single LPS stimulation (N/LPS), there was (i) reduced energy of the cell in both glycolysis and mitochondrial activities (extracellular flux analysis), (ii) decreased abundance of the following proteins (proteomic analysis): (a) complex I and II of the mitochondrial electron transport chain, (b) most of the glycolysis enzymes, (c) anti-viral responses with Myxovirus resistance protein 1 (Mx1) and Ubiquitin-like protein ISG15 (Isg15), (d) antigen presentation pathways, and (iii) the down-regulated anti-viral genes, such as Mx1 and Isg15 (polymerase chain reaction). To test the correlation between LPS tolerance and viral reactivation, asymptomatic mice with and without murine norovirus (MNV) infection as determined in feces were tested. In MNV-positive mice, MNV abundance in the cecum, but not in feces, of LPS/LPS mice was higher than that in N/LPS and control groups, while MNV abundance of N/LPS and control were similar. Additionally, the down-regulated Mx1 and Isg15 were also demonstrated in the cecum, liver, and spleen in LPS/LPS-activated mice, regardless of MNV infection, while N/LPS more prominently upregulated these genes in the cecum of MNV-positive mice compared with the MNV-negative group. In conclusion, defects in anti-viral responses after LPS tolerance, perhaps through the reduced energy status of macrophages, might partly be responsible for the viral reactivation. More studies on patients are of interest.

Association Between the Intracellular Tacrolimus Concentration in CD3 + T Lymphocytes and CD14 + Monocytes and Acute Kidney Transplant Rejection.

BACKGROUND: Intracellular tacrolimus concentration in peripheral blood mononuclear cells (PBMCs) (TAC [PBMC] ) has been proposed to better represent its active concentration than its whole blood concentration. As tacrolimus acts on T lymphocytes and other white blood cells, including monocytes, we investigated the association of tacrolimus concentration in CD3 + T lymphocytes (TAC [CD3] ) and CD14 + monocytes (TAC [CD14] ) with acute rejection after kidney transplantation. METHODS: From a total of 61 samples in this case-control study, 28 samples were obtained during biopsy-proven acute rejection (rejection group), and 33 samples were obtained in the absence of rejection (control group). PBMCs were collected from both cryopreserved (retrospectively) and freshly obtained (prospectively) samples. CD3 + T lymphocytes and CD14 + monocytes were isolated from PBMCs, and their intracellular tacrolimus concentrations were measured. RESULTS: The correlation between tacrolimus whole-blood and intracellular concentrations was poor. TAC [CD3] was significantly lower than TAC [CD14] (median 12.8 versus 81.6 pg/million cells; P < 0.001). No difference in TAC [PBMC] (48.5 versus 44.4 pg/million cells; P = 0.82), TAC [CD3] (13.4 versus 12.5 pg/million cells; P = 0.28), and TAC [CD14] (90.0 versus 72.8 pg/million cells; P = 0.27) was found between the rejection and control groups. However, freshly isolated PBMCs showed significantly higher TAC [PBMC] than PBMCs from cryopreserved samples. Subgroup analysis of intracellular tacrolimus concentrations from freshly isolated cells did not show a difference between rejectors and nonrejectors. CONCLUSIONS: Differences in TAC [CD3] and TAC [CD14] between patients with and without rejection could not be demonstrated. However, further optimization of the cell isolation process is required because a difference in TAC [PBMC] between fresh and cryopreserved cells was observed. These results need to be confirmed in a study with a larger number of patients.

Effects of phosphate binders on bone biomarkers and bone density in haemodialysis patients.

AIM: The incidences of osteoporosis, fracture and vascular calcification increase concordantly with the progression of chronic kidney disease (CKD). CKD-mineral bone disease (CKD-MBD) induced by hyperphosphatemia is a major pathophysiologic mechanism. The effects of phosphate binders on bone turnover biomarkers and bone mineral density (BMD) in haemodialysis patients are still inconclusive. Our aim is to demonstrate the effects of these phosphate binders on different aspects of CKD-MBD. METHODS: We conducted a prospective cohort of 65 haemodialysis patients to investigate the effect of 12-month monotherapy of phosphate binders composing calcium-based phosphate binders (CPB) or non-calcium-based phosphate binders (NCPB), including sevelamer and lanthanum, on bone turnover biomarkers and BMD changes. The performance of bone turnover biomarkers to predict low BMD was attentively determined. RESULTS: When compared with CPB, NCPB use was associated with higher levels of bone turnover biomarkers. NCPB was also associated with lower BMD at lumbar and distal radius. Total procollagen type 1N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase 5b (TRAP5b) provided the best performance for diagnosing low BMD in haemodialysis patients. CONCLUSION: Switching from CPB to NCPB might increase bone biomarkers and prevent the development of adynamic bone disease. On the contrary, NCPB should be cautiously used in haemodialysis patients who already had low BMD. P1NP, BALP and TRAP5b could be used to guide the appropriate management, including anti-resorptive and anabolic medications, and predict low BMD in haemodialysis patients treated with phosphate binders.

Risk factors and clinical outcomes of tuberculosis among kidney transplant recipients in high endemic country.

BACKGROUND: Tuberculosis (TB) is considered as a challenge issue in solid organ transplant recipients because of high morbidity and mortality. Active TB after transplant mostly occurs from reactivation of latent infection. Understanding risk factors and clinical information of TB may provide an appropriate prevention and treatment strategies in this specific patient population, however data from high endemic area is scarce. METHODS: A matched single-center, case-control study was conducted in our institute. Cases were defined as newly diagnosed confirmed or clinical active TB in patients who underwent kidney transplant (KT) between April 1992 and October 2018. For each case, 5 controls were matched by age and sex. Risk factor associated with TB was determined using univariate and multivariate conditional logistic regression. RESULTS: Between study period, KT was performed in 787 patients. Twenty-seven patients (3.43%) were diagnosed with active TB including 20 confirmed and 7 clinical diagnosed cases. The global incidence of TB in our population was 315 cases per 100 000 patients per year. Among 27 cases, pulmonary involvement was the most common (48.1%) followed by disseminated (18.5%), extrapulmonary (14.8%), pleura (11.1%) and pleuropulmonary (7.4%) TB. Allograft rejection was significantly associated with active TB (P < .001). The median onset duration of infection was 17 months (IQR, 4-59 months) after KT. Twenty-four (88.9%) patients received rifampicin containing regimen for treatment with median duration of 10 months (IQR, 6-12 months). All patients were cured after complete treatment, however those with TB remained having unfavorable outcomes including higher all-cause mortality and graft loss. CONCLUSIONS: Incidence rate of TB in KT recipients is higher than normal population. Allograft rejection was identified as a significant risk factor. Increase unfavorable outcomes including graft loss and mortality were also observed among patients with TB.

A case of successful treatment of severe COVID-19 pneumonia with favipiravir and tocilizumab in post-kidney transplant recipient.

We report a case of COVID-19 in kidney transplant patient in Thailand. A 58-year-old 2 years post-kidney transplant recipient, with maintenance immunosuppression of tacrolimus, mycophenolate mofetil (MMF), and prednisolone, presented with acute diarrhea which followed by fever on day 12. Symptoms of pneumonia together with lymphopenia from complete blood count were developed on day 7 after onset of fever with the x-ray finding of bilateral multifocal patchy infiltration. COVID-19 infection has been confirmed by reverse real-time polymerase chain reaction (PCR) in nasal swab as well as found in stool. Darunavir together with ritonavir, hydroxychloroquine, azithromycin, and favipiravir was initiated on the first day of admission at primary hospital. Patient has been transferred to our hospital on day 2 of admission in which tacrolimus together with MMF was discontinued. High-flow nasal cannula oxygen therapy was required on days 4-5 of hospitalization. Tocilizumab was administered after rising of serum IL-6 level. Symptoms of pneumonia were improved in which no oxygen treatment required from day 10 of hospitalization. Drug interaction between tacrolimus and anti-viral treatment leads to severely high level of tacrolimus which caused reversible acute kidney injury (AKI) after supportive treatment.

Tenofovir alafenamide nephrotoxicity: a case report and literature review.

BACKGROUND: Tenofovir alafenamide (TAF), a novel prodrug of tenofovir (TFV), has become the preferred drug for the treatment of HIV-1 and chronic hepatitis B infection in clinical practice. Results from clinical trials showed that it had better renal and bone mineral outcomes compared to tenofovir disoproxil fumarate (TDF). However, as we have seen with TDF, side effects from the new medication can be more prevalent and recognized after extensive use in real world situations. Sporadic cases of acute kidney injury in patients using TAF have started to emerge. CASE PRESENTATION: We report a case of 49-year-old Thai, HIV treatment-experienced female with hypertension presented with worsening renal function after switching her antiretroviral regimen from TDF, emtricitabine (FTC), and lopinavir/ritonavir (LPV/r) to TAF, FTC and dolutegravir (DTG) for 3 months. Kidney biopsy showed distinctive picture of tenofovir nephrotoxicity with acute tubular injury and mitochondrial injury. The possible causes of acute kidney injury and nephrotoxicity from TAF for this patient were discussed. We have extensively reviewed all published case reports of TAF-associated nephrotoxicity and summarized the essential information in this article. CONCLUSION: Although TAF has less nephrotoxicity compared with TDF; renal function should always be monitored after the initiation of both drugs. Future large cohort studies are required to identify the risk factors of TAF-associated nephrotoxicity and to design an effective preventive strategy.

Urinary Extracellular Vesicles Are a Novel Tool to Monitor Allograft Function in Kidney Transplantation: A Systematic Review.

Extracellular vesicles (EVs) are nanoparticles that transmit molecules from releasing cells to target cells. Recent studies link urinary EVs (uEV) to diverse processes such as infection and rejection after kidney transplantation. This, and the unmet need for biomarkers diagnosing kidney transplant dysfunction, has led to the current high level of interest in uEV. uEV provide non-intrusive access to local protein, DNA, and RNA analytics without invasive biopsy. To determine the added value of uEV measurements for detecting allograft dysfunction after kidney transplantation, we systematically included all related literature containing directly relevant information, with the addition of indirect evidence regarding urine or kidney injury without transplantation. According to their varying characteristics, uEV markers after transplantation could be categorized into kidney-specific, donor-specific, and immune response-related (IR-) markers. A few convincing studies have shown that kidney-specific markers (PODXL, ion cotransporters, SYT17, NGAL, and CD133) and IR-markers (CD3, multi-mRNA signatures, and viral miRNA) could diagnose rejection, BK virus-associated nephropathy, and calcineurin inhibitor nephrotoxicity after kidney transplantation. In addition, some indirect proof regarding donor-specific markers (donor-derived cell-free DNA) in urine has been demonstrated. Together, this literature review provides directions for exploring novel uEV markers' profiling complications after kidney transplantation.

Bone turnover markers predict type of bone histomorphometry and bone mineral density in Asian chronic haemodialysis patients.

BACKGROUND: Although the levels of intact parathyroid hormone (iPTH) are well-controlled following the Kidney Disease Outcomes Quality Initiative guideline, the incidence of osteoporosis and fracture are still high in haemodialysis (HD) patients. This study was conducted to investigate the correlation between bone turnover markers, bone mineral density (BMD), and bone histomorphometry in HD patients. METHODS: Twenty-two chronic HD patients were enrolled. Serum levels of bone turnover markers were measured. Double tetracycline-labelled iliac crest bone specimens were evaluated using specialized a computer program (Osteomeasure). The types of bone histomorphometry were classified based on turnover, mineralization and volume. BMD and coronary artery calcification were also determined. RESULTS: Bone histomorphometry revealed osteitis fibrosa (50%), adynamic bone disease (45%) and mixed uremic osteodystrophy (5%). Serum iPTH level predicted high bone turnover with area under the receiver operating characteristic (ROC) of 0.833 (95% CI = 0.665-1.000, P = 0.008). Serum TRAP-5b also had ROC of 0.733 (95% CI = 0.517-0.950, P = 0.065). In addition, when using serum iPTH (cut-off 484.50 ng/mL) or serum TRAP-5b (cut-off 1.91 pg./mL) to predict high turnover, the sensitivity was 0.917. On the other hand, when both iPTH and TRAP-5B were above these cut-off, the specificity was 1.000. Low BMD and severe vascular calcification were commonly identified. However, there were no significant correlations between bone biomarkers and BMD or severe vascular calcification. CONCLUSION: Although iPTH levels were close to the target of Kidney Disease Outcomes Quality Initiative guideline, abnormal bone histomorphometry, BMD, and severe vascular calcification are still common. Bone biopsy is still crucially required as an accurate diagnostic tool in providing optimal guide for the treatment. © 2019 Asian Pacific Society of Nephrology.

Maximizing anti-HBs seroresponsiveness in kidney transplant waitlist patients: A tertiary-center perspective
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BACKGROUND: Patients on dialysis are at risk of hepatitis B virus (HBV) infection, and antibodies against the hepatitis B surface antigen (anti-HBs) ≥ 10 IU/L are required. However, a high percentages of HBV vaccine nonresponders have been reported. We aimed to determine the optimal HBV vaccination protocol. MATERIALS AND METHODS: Kidney transplant waitlisted patients were followed for 12 months and categorized into two groups. Group A included patients with sustained anti-HBs ≥ 10 IU/L who did not require vaccination. Group B consisted of patients with anti-HBs < 10 IU/L who were treated with a course of 4 double-dose HBV vaccinations. Without seroconversion after the first course, a second course was initiated. A third course, coadministered with the tetanus-diphtheria (Td) vaccine, was performed upon failure of the second course. RESULTS: A total of 266 patients were included, 140 were categorized into group A and 126 into group B. Higher serum phosphorus, hemoglobin, and antibodies against the hepatitis core antigen (anti-HBc) were associated with sustaining anti-HBs ≥ 10 IU/L without vaccination. Diabetes mellitus (DM) was associated with the need for vaccination. For group B, 107 patients required 1 course of vaccination, 15 patients required 2 courses, and 4 patients required the third course with Td vaccine coadministration. Long dialysis vintage and low hemoglobin level were associated with seroconversion failure after the first course. CONCLUSION: Serum phosphorus, hemoglobin, DM, anti-HBc, and dialysis vintage were associated with the anti-HBs seroresponsiveness and sustainability. Our 3-course of 4 double-dose HBV vaccines regimen (with Td vaccine in the final course) conferred immunity to all patients.

The Cytochrome P450 3A5 Non-Expressor Kidney Allograft as a Risk Factor for Calcineurin Inhibitor Nephrotoxicity.

BACKGROUND: Tacrolimus is mainly metabolized by cytochrome P450 3A5 (CYP3A5), which is expressed in the liver. However, CYP3A5 is also expressed in the kidney tissue and may contribute to local tacrolimus clearance in the kidney allograft. We aimed to evaluate the association between the allograft CYP3A5 genotype and transplant outcomes. METHODS: We conducted a retrospective cohort study at the King Chulalongkorn Memorial Hospital, Thailand, comparing 2 groups of donor and recipient CYP3A5 genotypes, the expressor (*1/*1 and *1/*3) and the non-expressor (*3/*3). The primary outcomes were allograft complications including calcineurin inhibitor (CNI) nephrotoxicity and acute rejection episode. RESULTS: Of the 50 enrolled patients, 21 donors were expressors and 29 donors were the non-expressors. Tacrolimus trough concentrations were similar between the 2 genotypes. The incidence of CNI nephrotoxicity was higher in recipients with non-expressor donor genotype compared with the expressor donor genotype (72.4 vs. 33.3%, p = 0.006). CNI nephrotoxicity incidence was not different when recipient's genotypes were compared. Multivariate analysis from Cox-regression showed a hazard ratio of 3.18 (p = 0.026) for CNI nephrotoxicity in the non-expressor compared with the expressor donor. The recipient CYP3A5 genotypes did not significantly contribute to CNI nephrotoxicity. Kaplan-Meier analysis demonstrated the lowest CNI nephrotoxicity-free survival in recipients with the expressor genotype who received allograft from the non-expressor donors (p = 0.005). CONCLUSION: In conclusion, our results suggest that donor CYP3A5 non-expressor genotype (*3/*3) is a risk for CNI nephrotoxicity.

Therapeutic drug monitoring of mycophenolic acid and clinical outcomes of lupus nephritis: a systematic review and meta-analysis.

INTRODUCTION: Mycophenolic acid (MPA) is a primary immunosuppressive agent used in the treatment of lupus nephritis (LN). While therapeutic drug monitoring (TDM) of MPA is well established in organ transplantation, its role in LN treatment remains uncertain. Our objective was to review and summarise current knowledge on TDM of MPA in the LN treatment. METHODS: A systematic search was conducted in the online databases, specifically targeted patients diagnosed with LN receiving MPA treatment. The included studies had to report both MPA pharmacokinetic parameters and renal outcomes. A random-effects model meta-analysis was conducted to assess the relationship between clinical responses and MPA pharmacokinetics. RESULTS: A total of 1507 studies were initially screened, resulting in the inclusion of 16 studies for meta-analysis, encompassing 433 patients. The response group exhibited significantly higher MPA area under the concentration-time curve (AUC) compared with the non-response group (51.44±21.73 mg·h/L vs 30.30±16.24 mg·h/L). The weighted mean difference (WMD) of MPA-AUC between responders and non-responders was 16.83 mg·h/L (95% CI 10.59 to 23.06; p<0.001). Similarly, trough concentration (C0) of MPA showed a strong association with renal response, evidenced by C0 values of 2.50±1.73 mg/L in the response group vs 1.51±1.33 mg/L in the non-response group (WMD 1.37 mg/L; 95% CI 0.77 to 1.97; p<0.001). There was no significant relationship identified between MPA-AUC and adverse events. CONCLUSION: This meta-analysis emphasised the meaningful correlation between MPA AUC and C0 with renal response in LN treatment. Randomised controlled trials are necessary to validate this approach and determine its superiority over fixed dosing in the context of LN treatment.

A Randomized Controlled Study of Efficacy and Safety of Accelerated Versus Standard Hepatitis B Vaccination in Patients With Advanced CKD.

Introduction: Hepatitis B virus (HBV) vaccination is crucial for seronegative patients with advanced chronic kidney disease (CKD) for protection during dialysis while preparing for transplantation. A standard regimen for HBV vaccination requires 24 weeks to be completed. An accelerated HBV vaccination regimen completed within 8 weeks has shown early effective seroconversion in healthcare workers. However, data for patients with advanced CKD are limited. Methods: A randomized controlled trial was conducted in patients with advanced CKD (estimated glomerular filtration rate [GFR] <30 ml/min per 1.73 m2) and patients on dialysis. The patients were randomly assigned to either a standard HBV vaccination regimen (Engerix B; 40 µg at 0, 4, 8, and 24 weeks) or an accelerated regimen (40 µg at 0, 1, 4, and 8 weeks). The hepatitis B surface antibodies (anti-HBs) were measured at 12, 28, and 52 weeks. Seroconversion were defined as anti-HBs ≥10 IU/l. Results: At 12 weeks, among the intention-to-treat (ITT) population of 133 participants (65 in the accelerated and 68 in the standard groups), the accelerated group demonstrated significantly higher rates of seroconversion (83.08% vs. 63.24%, P = 0.01). In the per-protocol (PP) analysis of 125 patients (62 in the standard and 63 in the accelerated groups), the accelerated group exhibited higher seroconversion rate compared with the standard group (85.71% vs. 69.35%, P = 0.03). At 28 and 52 weeks, the seroconversion rates were similar between the 2 groups. Conclusion: In patients with advanced CKD, the accelerated HBV vaccination regimen demonstrated a significantly higher seroconversion rate at 12 weeks of vaccination. This finding suggests that the accelerated regimen is an effective option to achieve rapid seroconversion before initiating hemodialysis or before undergoing kidney transplantation.

Pathological Approach to Kidney Allograft Infection.

Infectious agents can pose a significant challenge in kidney transplantation, as they have the potential to cause direct infections in the transplanted kidney. These infections can lead to a decline in kidney function and reduce the longevity of the transplanted kidney. Common post-transplant allograft infections include bacterial pyelonephritis and the BK virus infection, while adenovirus, JC virus, and cytomegalovirus are less frequent but can also lead to significant allograft dysfunctions. The histopathological features of these infections are characterized by the infiltration of inflammatory cells in the kidney interstitial area and the presence of viral nuclear inclusions or cytopathic changes in the renal tubular epithelial cells. The confirmation of causative organisms can be achieved by immunohistochemical staining or the visualization of viral particles using electron microscopic examination. However, these methods typically require a longer turnaround time and are not readily available in developing countries, unlike standard hematoxylin-eosin staining. Notably, the differential diagnosis of interstitial inflammation in kidney allografts almost always includes T cell-mediated rejection, which has a different treatment approach than allograft infections. The aim of this review was to prompt clinicians to identify diverse pathological alterations as observed in kidney allograft biopsies, thereby facilitating further investigations and the management of suspected kidney allograft infections.