Tacrolimus Intrapatient Variability on Graft Outcomes in Adherent Renal Transplantation Patients: A Cross-Sectional Study.

INTRODUCTION: Tacrolimus is the mainstem of immunosuppressive therapy in kidney transplant patients. It has high intrapatient variability (Tac-IPV), which has been reported to affect graft function by predisposing patients to rejection or nephrotoxicity. We conducted this study with the aim of assessing the influence of Tac-IPV on 2-year graft function, biopsy-proven rejection, and infections in compliant renal recipients. METHODS: In this single-center retrospective analytic cross-sectional study, 250 patients who underwent transplantation from March 21, 2018, to March 20, 2020 and had at least three outpatient tacrolimus trough levels on the same daily dose 6 to 12 months after transplantation were recruited. Tac-IPV was defined as a coefficient variation of > 15%. Graft function, biopsy-proven rejection, cytomegalovirus (CMV) and BK virus viremia, and calcineurin inhibitor (CNI) toxicity were evaluated. RESULTS: Of 202 transplant recipients, 128 were included with a mean age of 45.48 ± 13.14 years. The median Tac-IPV was 13.28% with 43.75% of patients with Tac-IPV > 15%. There were no significant differences in graft function, rejection, CNI toxicity, and CMV viremia among the groups during the 24-month study (P > .05).  However, BK viremia was significantly higher among patients with Tac-IPV > 15% (13 vs. 2.9%, P = .042). The risk of antibody mediated rejection alone (22.7 vs. 2.9%) or any kind of rejection (22.7 vs. 11.8%) was significantly higher in patients with higher Tac-IPV, and in those who had mean trough levels below 7 ng/mL (P = .015, .032; respectively). CONCLUSION: Tac-IPV is low in adherent patients (with the median of 13.28%) and maintaining tacrolimus trough level above 7 ng/mL can overcome the adverse graft outcome of Tac-IPV in compliant kidney transplant recipients. DOI: 10.52547/ijkd.7815.

Prognostic Value of Blood Pressure Responsiveness in Hemodialysis for Cardiovascular Mortality, Development of A New Predictive Equation.

INTRODUCTION: Cardiovascular disease is considered as the main cause of mortality and morbidity in HD-patients and AS is a fundamental cause. This study was conducted to investigate whether intradialytic BP changes can use as a surrogate clinical marker. METHODS: Fifty-one patients on maintenance hemodialysis, for at least 12 hours per week, were included in a prospective cohort study. Intradialytic BP was measured using validated automated device. PWV was performed to assess Augmentation Index (AIx) as marker of arterial stiffness. All measurements were repeated in alive individuals after 5 years of follow-up. Patients with 5% reduction of intradialytic BP were considered as HD-responsive and Several statistical analyses were employed based on responsiveness to HD. RESULTS: After 5-year follow-up the findings demonstrated BP response to HD was an important and independent determinant of mortality (P < .05). Augmentation index (AIx) (P < .05), heart rate (P < .05), and calcium phosphate product (P < .05) as well as log PTH (P < .05) were significantly different between two responsive and non-responsive to HD. Pearson's Correlation studies revealed a significant relationship between the BP response to HD and heart rate (r = 0.4, P < .05), LVEF (r = -0.4, P < .05) and PTH (r = -0.3, P < .05). BP response to HD and log-PTH remained significant even after age and gender adjustment (P < .05). CONCLUSION: BP-response to HD can use as a clinical and surrogate marker of AS which is significantly associated with mortality and LVEF. Arterial stiffness and intradialytic BP can predict the changes in Ejection Fraction (EF). DOI: 10.52547/ijkd.6810.

In vitro and in vivo investigation of PLA/PCL scaffold coated with metformin-loaded gelatin nanocarriers in regeneration of critical-sized bone defects.

Large bone defects constitute a major challenge in bone tissue engineering and usually fail to heal due to the incomplete differentiation of recruited mesenchymal stem cells (MSCs) into osteogenic precursor cells. As previously proposed, metformin (MET) induces differentiation of MSCs into osteoblastic lineages in vitro. We fabricated a Poly (lactic acid) and Polycaprolactone (PLA/PCL) scaffold to deliver metformin loaded gelatin nanocarriers (MET/GNs) to critical-sized calvarial bone defects in a rat model. The scaffolds were evaluated regarding their morphology, porosity, contact angle, degradation rate, blood compatibility, biomechanical, cell viability and their osteogenic differentiation. In animal study, the defects were filled with autograft, scaffolds and a group was left empty. qRT-PCR analyses showed the expression level of osteogenic and angiogenic markers considerably increased in MET/GNs-PLA/PCL. The in vivo results showed that MET/GNs-PLA/PCL improved bone ingrowth, angiogenesis and defect reconstruction. Our results represent the applicability of MET/GNs-PLA/PCL for successful bone regeneration.