Hemoglobin Levels Influence Pharmacokinetics of Tacrolimus in Kidney Transplant Patients

AbstractObjective: To determine the relationship between hemoglobin levels andpharmacokinetics of tacrolimus in Thai kidney transplant patients.Methods: The clinical data of 71 kidney transplant recipients at KingChulalongkorn Memorial Hospital, Bangkok were retrospectively collectedduring 1 to 6 months after initiation of tacrolimus treatment. The ratio ofdose to trough whole-blood concentrations of tacrolimus (D/Ctrough) wascalculated. Linear regression was used to determine the relationshipbetween hemoglobin levels and D/Ctrough.Results: Hemoglobin levels wereinversely associated with D/Ctrough (r = -0.41, P < 0.01). The relationshipcould be described as an equation (D/Ctrough (L/kg) = 26.38 - 1.44Hemoglobin (g/dl)). Furthermore, D/Ctrough was significantly higher in thepatients with low hemoglobin levels (<12 g/dL) than those with normalhemoglobin levels (11.10 8.73 vs 7.31 4.05 L/kg, respectively).Conclusion: The ratio of dose to trough concentrations of tacrolimussignificantly correlates with hemoglobin levels. We should considerhemoglobin levels of kidney transplant patients whenever modifying theirtacrolimus dosage.Keywords: hemoglobin, kidney transplant, pharmacokinetics, tacrolimusบทคัดย่อวัตถุประสงค์: เพื่อศึกษาหาความสัมพันธ์ระหว่างระดับ hemoglobin และเภสัชจลนศาสตร์ของยา tacrolimus ในผู้ป่วยไทยที่ได้รับการปลูกถ่ายไต วิธีการศึกษา: ทำการศึกษาแบบย้อนหลังในผู้ป่วยปลูกถ่ายไต จำนวน 71 คน ที่มาติดตามการรักษา ณ โรงพยาบาลจุฬาลงกรณ์ กรุงเทพ โดยเก็บข้อมูลระดับความเข้มข้นยาจากเวชระเบียน ในระยะ 1 ถึง 6 เดือนหลังได้รับยา tacrolimus คำนวณหาค่าสัดส่วนขนาดยาต่อความเข้มข้นของยา tacrolimus ในเลือดที่เวลาก่อนให้ยามื้อถัดไป (D/Ctrough) และหาความสัมพันธ์ระหว่างระดับ hemoglobin และ D/Ctrough โดยการวิเคราะห์ความถดถอยเชิงเส้น ผลการศึกษา: จากการศึกษาพบว่า ระดับ hemoglobin มีความสัมพันธ์เชิงลบกับค่า D/Ctrough (r = -0.41, P < 0.01) และได้สมการทำนายค่าสัดส่วนขนาดยาต่อความเข้มข้นยาคือ D/Ctrough (L/kg) = 26.38 - 1.44 Hemoglobin (g/dl) นอกจากนั้นค่า D/Ctrough ใน กลุ่มผู้ป่วยที่มีระดับ hemoglobin ต่ำกว่า 12 กรัม/ดล. มีค่าสูงกว่ากลุ่มผู้ป่วยที่มีระดับ hemoglobin ปกติอย่างมีนัยสำคัญทางสถิติ (11.10 8.73 และ 7.31 4.05 L/kg ตามลำดับ). สรุป: ค่าสัดส่วนขนาดยาต่อความเข้มข้นของยา tacrolimus ที่เวลาก่อนให้ยามีความสัมพันธ์กับระดับ hemoglobin การเปลี่ยนแปลงของระดับ hemoglobin อาจช่วยในการปรับขนาดใช้ยา tacrolimus ให้มีความปลอดภัยและประสิทธิผลดีในผู้ป่วยปลูกถ่ายไตคำสำคัญ: hemoglobin, kidney transplant, pharmacokinetics, tacrolimus

A machine learning strategy for predicting localization of post-translational modification sites in protein-protein interacting regions

Definitions of true positives (TP), false positives (FP), true negatives (TN), and false negatives (FN) in this study. (DOCX 18 kb

A randomized controlled trial of comparative effectiveness between the 2 dose and 3 dose regimens of hepatitis a vaccine in kidney transplant recipients.

Hepatitis A virus (HAV) is able to cause a spectrum of illnesses ranging from no symptom to fulminant hepatitis which may lead to acute kidney injury. Although hepatitis A vaccine is recommended in non-immune solid organ transplant recipients who live in or travel to endemic areas, the standard 2-dose vaccination regimen demonstrated less favorable immunogenicity among these population. The 3-dose regimen showed higher response rate and immune durability in patients with human immunodeficiency virus. However, this strategy has never been studied in solid organ transplant recipients. A single-center, open-labeled, computer-based randomized controlled trial (RCT) with a 2:1 allocation ratio was conducted from August 2017 to December 2018. The study compared the seroconversion rate after receiving 2- or 3-dose regimen of hepatitis A vaccine at 0, 6 and 0, 1, 6 months, respectively, in non-immune kidney transplant recipients. A total of 401 adult kidney transplant recipients were screened for anti-HAV IgG and 285 subjects had positive results so the seroprevalence was 71.1%. Of 116 seronegative recipients, 93 (80.2%) completed vaccination; 60 and 33 participants completed 2- and 3-dose vaccination, respectively. The baseline characteristics were comparable between both groups. The seroconversion rate at 1 month after vaccination was 51.7% in the standard 2-dose regimen and 48.5% in the 3-dose regimen (p = 0.769). Overall, the seroconversion rate appeared to be associated with high estimated glomerular infiltration rate, high serum albumin, and low intensity immunosuppressive regimen. Seroconversion rate after hepatitis A vaccination in kidney transplant recipients was less favorable than healthy population. Three-dose regimen did not show superior benefit over the standard 2-dose regimen. Other strategies of immunization may increase immunogenicity among kidney transplant recipients

ITGAM is associated with disease susceptibility and renal nephritis of systemic lupus erythematosus in Hong Kong Chinese and Thai

ITGAM was recently found to be associated with systemic lupus erythematosus (SLE) in populations of not only European ancestry, but also in Hispanic- and African-Americans, Mexicans and Colombians. The risk alleles in the gene, however, were found to be monomorphic in two Asian populations examined: Japanese and Korean. In this study, using a collection of 910 SLE patients and 2360 controls from Chinese living in Hong Kong, analyzed by both genome-wide association and direct sequencing, we confirmed the association of the same risk alleles in ITGAM with the disease. These findings were further replicated in the Thai population with 278 patients and 383 ethnicity- and geography-matched controls. Subphenotype stratification analyses showed significantly more involvement of the gene in patients with renal nephritis and neurological disorders. Although our results support a pivotal role by rs1143679 (R77H) in disease association, our data also suggests an additional contribution from rs1143683, another non-synonymous polymorphism in this gene (A858V). Therefore, despite the low-allele frequencies of the risk alleles of the gene in our two Asian populations, ITGAM was confirmed to be a risk factor related to disease susceptibility and probably severe manifestations of SLE