Kidney Transplant Patients Research Articles

Kidney disease and reproductive health.

Understanding the relationship between reproductive health and kidney function is important to provide holistic care for people living with kidney disease. Chronic kidney disease (CKD) has negative impacts on both male and female fertility owing to factors including inflammation, hormonal dysregulation, reduced ovarian reserve, reduced sperm quality and sexual dysfunction. However, pregnancy is achievable for most cisgender women with kidney disease, including kidney transplant recipients and patients on dialysis. CKD in pregnancy is associated with health risks to the mother and child, including increased risk of progression of kidney disease, hypertensive complications of pregnancy, and neonatal complications including fetal growth restriction, preterm birth and stillbirth. However, with appropriate pre-pregnancy counselling, fertility assessment and support, health optimization, and evidence-based antenatal care, the majority of patients will achieve a good outcome. Medication safety should be reviewed before and during pregnancy and lactation, weighing the risk of disease flare against potential adverse effects on the offspring. Important areas for further research include the optimal timing of delivery and the short- and long-term cardiovascular and renal impacts of pregnancy in patients with CKD, as well as long-term kidney and cardiovascular outcomes in their offspring.

Clinical characteristics and outcomes of kidney transplantation in autosomal dominant polycystic kidney disease patients.

Kidney transplantation (KT) is the best kidney replacementtreatment for autosomal dominant polycystic kidney disease (ADPKD). We aimed to investigate the clinical characteristics and outcomes of KT in ADPKD patients compared to those in non-ADPKD patients. We retrospectively analyzed KT recipients in two Korean transplantation centers from 2005 to 2020. Propensity score-matching and Cox regression analysis were used to assess the clinical outcomes of ADPKD compared to non-ADPKD and identifyprognostic factors influencing outcomes in ADPKD. Among a total of 4452 KT patients, 189 (4.2%) were ADPKD patients. Median age at transplantation was 53.0 and 47.0 in ADPKD and non-ADPKD patients, respectively. In both groups, living-donor KT was more common than deceased-donor KT. The ADPKD group had a 4.09-fold higher risk of post-transplant diabetes mellitus and a 1.65-fold higher risk of post-transplant infection compared to the non-ADPKD group; however, subjects with ADPKD had similar risk of rejection, graft failure, and mortality. In the ADPKD group, kidney volume decreased after KT, irrespective of kidney volume status (Mayo classification), while the size of hepatic cysts increased. Neither kidney volume nor nephrectomy of native kidneys were associated with risk of infection, graft failure, or mortality in the ADPKD group. ADPKD patients have a higher risk of post-transplant diabetes mellitus and infection than non-ADPKD patients, with no significant impact of kidney volume or nephrectomy on post-transplant outcomes.

The incidence and risk factors of post-transplant diabetes mellitus in living donor kidney transplantation patients: a retrospective study

BackgroundPost-transplant diabetes mellitus (PTDM) is a well-known complication of kidney transplantation that significantly impacts recipient morbidity and mortality. Over the recent years, the incidence of PTDM has increased considerably worldwide. Therefore, the primary purpose of this study was to evaluate the incidence and risk factors for PTDM in living donor kidney transplantation patients in Riyadh, Saudi Arabia.MethodsA retrospective cohort study was conducted at a tertiary transplant center in Riyadh, Saudi Arabia, and data were extracted between February 2016 and March 2022. Patients aged ≥ 18 years who underwent renal transplant with at least one year of post-transplant follow-up were included in the analysis, and their medical records were comprehensively reviewed. Patients < 18 years of age, history of diabetes mellitus, other organ transplants, or those who underwent transplantation outside the Kingdom of Saudi Arabia were excluded from the study.ResultsThe study included 247 living donor kidney transplant patients, with a mean age of 39.5 ± 14.6 years. 17.0% of the patients were diagnosed with PTDM. Patient age and fasting glucose levels at 6-months and 12-months after transplantation were found to be significant risk factors for the development of PTDM.ConclusionAn increased occurrence of PTDM emphasizes the importance of identifying high-risk patients prior to transplantation and implementing early interventions to prevent potential complications that could affect graft and patient survival.

Anti-PD-1 immunotherapy for the treatment of metastatic urothelial carcinoma in a kidney transplant recipient: a case report

BackgroundImmune checkpoint inhibitor (ICI) therapy has been widely investigated in urothelial carcinoma; however, the utility of ICI therapy in the treatment of organ transplant recipients with metastatic urothelial carcinoma (mUC) is unclear. We herein report the first case of a first-line anti-programmed cell death-1 (anti-PD-1) monotherapy for a kidney transplant patient with mUC.Case presentationA 71-year-old woman who received a kidney transplant in 2003 was diagnosed with urothelial carcinoma in 2018. After operation of the tumor, the patient developed local recurrence at the site of the right kidney and bladder and multiple distant metastases in May 2020. Considering the intolerance of chemotherapy and high tumor mutation burden, we administered the anti-PD-1 agent tislelizumab (200 mg every three weeks). Partial response was achieved after two cycles of therapy and sustained until 18th cycles. There were no signs of kidney graft rejection. The immunotherapy was temporarily stopped after the 18th course because of a suspicious immune-related pneumonitis and was continued in December 2021.ConclusionsThis case demonstrates the feasibility of safely achieving stable cancer control in a kidney transplant patient with mUC without encountering graft rejection by using single-agent anti-PD-1 treatment.

Use of a Facebook Support Group for Kidney Transplant Patients

Background: Facebook groups have been used to foster social support of transplant patients. Examining the use and content strategies for generating member interactions within transplant-specific groups can inform how we leverage these groups to expand access to social support resources. This study characterizes the use of a closed Facebook group for kidney transplant patient support linked to a hospital in Buffalo, NY to identify the most engaging content. Methods: The sample consisted of 387 individuals (372 patients/family, eight transplant professionals, and seven community advocates) and the administrator. Content analysis was conducted of posts and comments made to the group. Descriptive measures of post content associated with interactions (reactions and comments) were computed. Results: Between 5/2020 and 5/2023, there were 484 posts with 8233 interactions (2793 comments, 5440 reactions). Half of the posts (n = 241) were made by the administrator, 166 (34%) by patients/family, 70 (14%) by community advocates, and 7 (1%) by transplant professionals. Content analysis revealed that post types with the most interactions were personal experiences, monthly transplant volume, and monthly new members added; the least interactions involved posts about holidays, observances, and information. Conclusions: The interaction metrics varied according to the content strategies used by members and provided insights into the types of content members interact with.

Exploring Condition-Specific Variability in the Ureteral Stent Microbiome

(1) Background: Indwelling ureteral stents are commonly used urological devices to maintain ureteral patency, yet they have been associated with complications such as infections. Some studies have shown that bacteria adhere to and create an antimicrobial-resistant biofilm on stents. One factor that may impact biofilm formation is the original condition informing stent placement, such as kidney stones and renal allografts. Both kidney stones and renal allografts are independently associated with infection, yet the differential stent microbiomes of these populations remain poorly characterized. Our objective was to characterize these microbiomes in order to inform urological health practice and help prevent ureteral stent-associated infections. (2) Methods: Stents were collected from kidney stone and renal transplant recipients undergoing routine cystoscopic stent removal. Microbial DNA was extracted from stents and analyzed using 16S Next Generation Sequencing. Descriptive statistics, alpha diversity, and beta diversity methods were used for statistical analysis. (3) Results: The microbiome of ureteral stents in kidney stone and transplant patients is composed of unique species, each with different biofilm-forming abilities. (4) Conclusions: Our findings demonstrate that the microbiome of stents differs based on preceding condition. It is important to conduct future studies that explore this microbiome further to understand what type of stent-associated infection someone may develop based on their initial condition.

Successful eculizumab treatment as an adjunctive therapy to desensitization in ABO-incompatible living donor kidney transplantation and its molecular phenotypes

IntroductionABO-incompatible (ABOi) kidney transplantation (KT) has become an important option to overcome organ shortage. Plasmapheresis/rituximab-based desensitization therapy has successfully reduced anti-ABO antibody levels and suppressed antibody-mediated rejection (AMR) in ABOi KT. However, high titers of anti-ABO antibodies in some patients are refractory to standard desensitization, leading to loss of KT opportunities or AMR.MethodsEculizumab treatment was used an adjunctive therapy to rescue high-titer ABOi KT patients refractory to plasmapheresis/rituximab-based desensitization. Molecular phenotypes of allograft biopsies and cellular phenotypes of peripheral blood mononuclear cells of eculizumab group were compared with those of control groups using the Banff Human Organ Transplant gene panel and flow-cytometric analysis, respectively.ResultsThe initial titers of anti-ABO antibodies in the two patients were 1:512 and &amp;gt;1:1024; the final pre-transplant titers after desensitization were 1:128 and 1:64. Both patients received eculizumab from KT day to two or four weeks post-KT and maintained stable renal function up to one-year post-transplantation without overt infection, despite early episodes of probable AMR or borderline T cell-mediated rejection. Molecular phenotype analysis revealed that gene expression patterns in the ABOi KT with eculizumab group overlapped with those in the ABOi KT with AMR group more than in the ABOi KT without AMR group, except for complement pathway-related gene expression. Anti-ABO antibody titers decreased to low levels 1–3 months post-transplant in the eculizumab group in parallel with decreasing anti-B-specific B cells.ConclusionsShort-term eculizumab therapy is promising for rescuing ABOi KT recipients with high anti-ABO antibody titers refractory to plasmapheresis-based desensitization therapy.

Cryptosporidium spp. Infection in Adult Kidney Transplant Patients: A Systematic Review and Meta-Analysis

Cryptosporidium spp. Infection in Adult Kidney Transplant Patients: A Systematic Review and Meta-Analysis

The use of metabolomics and machine learning algorithms to predict post-transplant diabetes mellitus in renal transplant patients on Tacrolimus therapy.

Tacrolimus (TAC) has significantly improved kidney graft survival following transplantation, though it is associated with adverse side effects. The most prevalent complication resulting from excessive TAC exposure is the onset of de novo diabetes mellitus (DM), a condition that can negatively impact both renal graft function and patient outcomes. De novo DM is linked to an increased risk of chronic transplant dysfunction, as well as cardiovascular morbidity and mortality. Although the underlying mechanisms remain unclear, emerging research in the field of omics shows promise. The aim of this study was to investigate the metabolomic profile of kidney transplant patients who developed de novo DM, in comparison to those who did not, following TAC exposure, using untargeted metabolomic analysis through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and machine learning algorithms. A cohort of 34 kidney transplant patients on a Tacrolimus regimen for at least 6 months was enrolled in the study, with serum samples collected from each patient. Comprehensive profiling of serum metabolites was performed, enabling the classification of patients into de novo diabetes mellitus and non diabetes groups. The metabolomic analysis of serum was conducted using UHPLC-MS. Of the 34 patients, 16 were diagnosed with TAC-induced diabetes. A total of 334 metabolites were identified in the serum samples, of which 10 demonstrated a significant correlation with the de novo diabetes mellitus group. Most of these metabolites were linked to alterations in lipid metabolism. The application of metabolomics in kidney transplant patients undergoing a Tacrolimus regimen is both feasible and effective in identifying metabolites associated with de novo diabetes mellitus. This approach may provide valuable insights into the metabolic alterations underlying TAC-induced diabetes.

Prospective study on immune function in renal transplant patients during perioperative period: A prospective cohort study.

Delayed graft function (DGF) is a type of acute renal failure that is closely linked to the immune system. The objective of this study is to investigate immune trends during the perioperative period of renal transplantation and compare the variations between patients with DGF and immediate graft function (IGF). A total of 48 kidney transplant patients were enrolled. Parameters including stimulated adenosine triphosphatase concentrations (sATP), nonstimulated ATP concentrations, white blood cells, and lymphocyte count were assessed. Patients were categorized into the DGF or IGF group. Clinical information and changes in immune markers were compared. Receiver operating characteristic analysis was performed to determine the sensitivity and specificity in predicting DGF. Additionally, separate immune function analyses were conducted for the 3 infection cases. Following induction immunosuppressive therapy, white blood cells, and neutrophil count showed a significant initial increase followed by a gradual decline. Lymphocyte count, nonstimulated ATP concentrations, and sATP exhibited an initial significant decrease followed by a slow recovery. Immune markers between the DGF and IGF groups were significantly different at day 4 after renal transplantation. Only sATP levels at day 4 after renal transplantation (area under the curve = 0.731, sensitivity = 0.864, specificity = 0.684) demonstrated predictive value for DGF occurrence. Among the 3 infection cases, 2 cases exhibited persistently decreased sATP levels and died within the first month and 6 months, while the remaining case showed a recovery of sATP levels at D9 and survived. These findings indicate that sATP level can potentially serve as a biomarker reflecting the impact of immunosuppressants. Poor recovery of sATP may be associated with DGF, infection, or even mortality.

Impact of Pelvic Calcification Severity on Renal Transplant Outcomes: A Prospective Single-Center Study.

Background: Vascular calcifications (VC) are increasingly prevalent in patients with chronic kidney disease. This study aimed to assess the incidence of iliac artery calcifications in kidney transplant (KT) patients and explore the relationship between iliac VC burden measured by pelvic calcification score (PCS) and renal transplant outcomes. Methods: This prospective study involved 79 KT recipients. VC quantification, using a pre-transplant computed tomography (CT) scan, was performed by assessing calcifications in the common and external iliac arteries bilaterally, resulting in an overall PCS ranging from 0 (no calcifications) to 44 (extensive calcifications). Based on PCS values, patients were divided into three equal-sized groups: PCS Group 1 (PCS 0-4), PCS Group 2 (PCS 5-19), and PCS Group 3 (PCS > 19). Post-transplant outcomes tracked for at least 1 year were patient and graft survival, graft function (urea, creatinine, MAG-3 clearance), and incidence of MACE during the first post-transplant year. Results: Calcifications were present in at least one arterial segment in 61 patients (77.2%). One-year patient survival was 95%, and one-year graft survival was 92.4%. Patients in PCS Group 3 had significantly lower one-year patient and graft survival compared to those in PCS Group 1 and 2 (p = 0.006 and p = 0.008, respectively). MACE and renal function indicators 1-year post-transplant were similar across all PCS groups. Conclusions: Our study demonstrated that a significant majority of KT recipients exhibited iliac VC during pre-transplant CT assessments. Patients in PCS Group 3 exhibited significantly lower one-year patient and graft survival rates compared to those in PCS Groups 1 and 2, indicating that this subgroup may require more intensive post-transplant monitoring and management.

Cross-cultural validation of the Spanish version of the Kidney AlloTransplant Immunosuppressive Therapy Adherence Questionnaire (KATITA-25)

The KATITA-25 (Kidney AlloTransplant Immunosuppressive Therapy Adherence) Questionnaire is a multidimensional self-administered scale developed in Brazilian Portuguese that measures the predisposition for non-adherence to immunosuppressive medication in candidate patients for kidney transplantation, in the pre-transplant setting. The aim of this study was the cross-cultural validation of the Spanish version of the KATITA-25 scale. The translation/back-translation method was used, followed by cognitive interviews and a pre-test. The Spanish version of KATITA-25 was administered to 163 candidate patients for kidney transplantation from 2 kidney transplant centres and 2 dialysis centres in Catalonia, Spain. The scale was re-administered to the first 79 patients included into the study, after a 2 to 4 weeks interval. Internal consistency was assessed using Cronbach’s alpha, test–retest reliability with the intraclass correlation coefficient (ICC); construct validity with goodness of fit indices after confirmatory factor analysis using structural equation modelling. The Cronbach’s alpha of the Spanish version was 0.83, the ICC was 0.86. Confirmatory factor analysis showed adequate fit of the structural model. Overall, the analytical results closely resembled those obtained in the validation of the original scale. In conclusion, this cross-cultural validation study showed adequate reliability and construct validity of the Spanish version of the KATITA-25 questionnaire.

Tacrolimus Dose Requirement in De Novo Adult Kidney Transplant Patients Treated With Adoport® Can Be Anticipated.

All the factors potentially influencing tacrolimus dose requirement and combinations thereof have never been thoroughly investigated, precluding accurate prediction of tacrolimus starting dose. This prospective, non-interventional, multicenter study in de novo adult kidney transplant recipients over the first year after transplantation aimed to investigate the factors influencing tacrolimus dose-standardized trough blood concentration (C0/D) over the first week post-transplant (D4-D7, primary objective), D8-M3 and M3-M12 (secondary objectives). Statistical analysis employed mixed linear models with repeated measures. Eighteen sites enrolled 440 patients and followed them up for 9.5 ± 4.1months. Age at baseline (p = 0.0144), end-stage renal disease (p = 0.0092), CYP3A phenotype (p < 0.0001), dyslipidemia at baseline (p = 0.0031), hematocrit (p = 0.0026), total bilirubin (p = 0.0261) and plasma creatinine (p = 0.0484) independently increased with log(C0/D) over D4-D7, explaining together 72.3% of the interindividual variability, and representing a robust model to estimate tacrolimus initial dose. Donor age and CYP3A phenotype were also influential over D8-M3 and M3-12, in addition to recipient age. Corticosteroids, diabetes at baseline, and ASAT yielded inconstant results between D8-M3 and M3-M12. We found no ethnicity effect when CYP3A phenotype was accounted for, and no food effect. Intra-individual variability over M3-M12 was moderate, and significantly lower in patients with chronic hepatic disorder (p = 0.0196) or cancer (p = 0.0132).

Sedentary Lifestyle Is a Modifiable Risk Factor for Cognitive Impairment in Patients on Dialysis and after Kidney Transplantation

Background: Chronic kidney disease (CKD) is a risk factor for cognitive impairment (CI), and this risk is the highest in patients with end-stage kidney disease (ESKD). As a multifactorial disease, CI may be influenced by several potentially modifiable lifestyle and behavioral factors that may reduce or increase the risk of dementia. The aim of this study was to evaluate the associations between the known modifiable risk factors for dementia and the risk of CI in patients with ESKD treated with renal replacement therapy. The Charlson Comorbidity Index and the risk of CI in patients with ESKD were also assessed. Methods: In this cross-sectional study, 225 consecutive patients with ESKD treated with different modalities of renal replacement therapy were assessed for cognitive decline using the Addenbrooke’s Cognitive Examination (ACE III) test. Information was also collected on modifiable risk factors for dementia, medical history and demographics. Results: This study included 117 patients after kidney transplantation (KT) and 108 patients with ESKD undergoing peritoneal dialysis and hemodialysis. The prevalence of modifiable risk factors for dementia differed between the groups; KT patients were more likely to be physically active, residing in cities with populations of less than 500,000 inhabitants, and were less likely to suffer from depression. Furthermore, the KT group had a lower Charlson Comorbidity Index score, indicating less severe comorbidities, and a lower risk of CI (3.6 ± 1.67 vs. 5.43 ± 2.37; p = 0.001). In both the KT and dialysis groups, patients with CI were more likely to have a sedentary lifestyle (45% vs. 9%, p = 0.001 and 88% vs. 48%, p = 0.001, respectively), whereas lower educational attainment and depression had a significant negative impact on ACE III test results, but only in KT patients. Finally, cognitive function in dialysis patients was negatively affected by social isolation and living in urban areas. Conclusions: Modifiable risk factors for dementia, particularly a sedentary lifestyle, are associated with a higher risk of CI in patients treated with different renal replacement therapy modalities. As CI is an irreversible condition, it is important to identify lifestyle-related factors that may lead to dementia in order to improve or maintain cognitive function in patients with ESKD.

Population pharmacokinetics of tacrolimus whole blood and peripheral blood mononuclear cell concentrations in stable kidney-transplanted patients.

Therapeutic drug monitoring of tacrolimus based on whole blood drug concentrations is routinely performed. The concentration of tacrolimus in peripheral blood mononuclear cells (PMBCs) is likely to better reflect drug exposure at the treatment target site. We aimed to describe the relationship between tacrolimus whole blood and PBMC concentrations, and the influence of patient characteristics on this relationship by developing a population pharmacokinetic model. We prospectively enrolled 63 stable adult kidney-transplanted patients and collected dense (12-h, n = 18) or sparse (4-h, n = 45) pharmacokinetic profiles of tacrolimus. PBMCs were isolated from whole blood (Ficoll density gradient centrifugation), and drug concentrations in whole blood and PBMCs were analysed using liquid chromatography-mass spectrometry. Patient genotype (CYP3A4/5, ABCB1, NR1I2) was assessed with PCR. Population pharmacokinetic modelling and statistical evaluation was performed using NONMEM. Tacrolimus whole blood concentrations were well described using a two-compartment pharmacokinetic model with a lag-time and first-order absorption and elimination. Tacrolimus PBMC concentrations were best estimated from whole blood concentrations with the use of a scaling factor, the ratio of whole blood to PBMC concentrations (RC:PBMC), which was the extent of tacrolimus distribution into PBMC. CYP3A5*1 non-expressors and NR1I2-25 385T allele expressors demonstrated higher RC:PBMC ratios of 42.4% and 60.7%, respectively. Tacrolimus PBMC concentration could not be accurately predicted from whole blood concentrations and covariates because of significant residual unexplained variability in the distribution of tacrolimus into PBMCs and may need to be measured directly if required for future studies.

Associations between Kidney Disease Progression and Metabolomic Profiling in Stable Kidney Transplant Recipients-A 3 Year Follow-Up Prospective Study.

Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results: The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m2 vs. 55.8 mL/min/1.73 m2, p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found (F (1,70) = 5.15, p = 0.026), with an R2 of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = -0.250 and p = 0.04, citric acid with r = -0.296 and p = 0.014, formic acid with r = -0.349 and p = 0.004, and glycine with r = -0.306 and p = 0.01). Conclusions: some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites.

Frequency of human leukocyte antigen compatibility and graft rejection in kidney transplant patients from living donors

Frequency of human leukocyte antigen compatibility and graft rejection in kidney transplant patients from living donors

9391 Clinical Accuracy Of Continuous Glucose Monitoring In Post-kidney Transplant Patients With Type 2 Diabetes

Abstract Disclosure: Q. Aziz: None. K. Batra: None. S. Fatima: None. J. Splinter: None. A.L. Champion: None. A.M. Kumar: None. K.E. Izuora: Research Investigator; Self; Novo Nordisk. Background: Continuous glucose monitoring (CGM) devices provide real time blood glucose data to guide therapy in patients with diabetes mellitus. Diabetic nephropathy is a major complication of diabetes which can eventually lead to End Stage Renal Disease (ESRD). Kidney transplant is a treatment option for ESRD and patients who undergo kidney transplant are exposed to anti-rejection therapy, including high-dose steroids, resulting in significant fluctuations in blood glucose. Having a reliable system for monitoring blood glucose continuously, such as a CGM, can provide valuable information to guide optimal diabetes management. Objective This study aims to compare the clinical accuracy of the CGM data with the Point of Care Testing (POCT) glucose values as a reference among post kidney transplant patients with Type 2 diabetes mellitus (T2DM). Methodology This study was conducted at an academic medical center from September 2023 to January 2024, enrolling subjects ≥ 18 years, diagnosed with T2DM , admitted for kidney transplant. Following informed consent, a blinded CGM (Freestyle Libre Pro®) was applied. We collected all POCT and serum glucose values and downloaded corresponding CGM glucose data. Using matched pairs between CGM and POCT glucose values, bias and absolute relative differences (ARD) were calculated. Based on the ARD, the Clarke error grid (CEG) analysis was conducted to quantify the clinical accuracy of CGM and POCT by assigning glucose data points into 5 zones A, B, C, D, and E. Summary statistics for numeric variables included mean and standard deviation, whereas categorical variables were described as counts and proportions. All analyses were performed using SAS, 9.4 version. Results: A total of 22 subjects were analyzed after excluding one patient due to CGM malfunction. Subjects were 58±9.69 years old, and 82% were males. The mean body mass index was 30±6.41 kg/m2 and mean HbA1c was 6.7 ± 1.07%, at baseline. The mean duration of diabetes and ESRD were 19±10.6 years and 3±2.27 years respectively. Average CGM wear time was 76±24.5 hours. The CEG comparing CGM values with POCT values showed 83.79% values in zone A, 15.29% in zone B (combined =99.08%) with the Mean Absolute Relative Difference (MARD) of 13.24%. The CEG comparing CGM values with serum glucose showed 83.1% values in zone A, 16.9% in zone B (combined =100%) with the MARD of 13.10%. Conclusion: Our results indicate that CGM values are comparable to the POCT and serum glucose values in post kidney transplant patients with T2DM receiving high dose steroids. Therefore, use of CGMs should be considered as a useful tool, providing timely information to guide prompt interventions and improve outcomes in this patient population. Presentation: 6/3/2024

Effect of cholecalciferol supplementation on PTH and increasing the glomerular filtration rate in kidney transplant patients at King Faisal Specialist Hospital and Research Center

The association between oral cholecalciferol and GFR has been identified in various renal transplant populations around the globe. This study aimed to evaluate the effect of oral cholecalciferol supplementation on the GFR and serum PTH levels, with other parameters in the Saudi kidney transplant population. A retrospective observational study was conducted on a cohort of 174 kidney recipients who underwent transplantation and had serum 25-Hydroxy VD level tests performed (2018-2022) at King Faisal Specialist Hospital and Research Center in Jeddah, KSA. Generalized and linear mixed effects regression models were conducted. The percentage of GFR &gt;60 (25.86% vs 78.16%, P&lt;.0001) and VD insufficiency (&lt; 30 ng/mL) (36.21% vs 6.90%, P&lt;.0001) were significantly different between pre-&amp; post-transplant periods, respectively. After adjustment, significant changes were found in post-transplant GFR, hemoglobin levels, serum creatinine levels, blood urea nitrogen levels, hematocrit levels, PTH levels, and VD 25-Hydroxy from the baseline. Calciferol 1000/2000 IU and 50,000 IU (P&lt;.0001) were significantly more effective in increasing the odds of having GFR &gt;60 as compared to other supplements (P=0.75). VD supplementations may be particularly beneficial in improving kidney function in kidney transplant patients, as this contributes to normalizing GFR levels and creatinine levels and reducing PTH levels.

B-297 Tacrolimus Concentrations in Envarsus vs Prograf Patients: An Evaluation of the Clinical Impact of LC-MS/MS and Immunoassay Methods on Tacrolimus measurement

Abstract Background Tacrolimus is a calcineurin inhibitor used as part of an immunosuppressive regimen in kidney and liver transplant patients to prevent graft-versus-host disease (GvHD) and requires therapeutic drug monitoring due to its narrow therapeutic index. Tacrolimus levels are commonly measured using two different methodologies - immunoassay and liquid chromatography tandem mass spectrometry (LC-MS/MS). A global proficiency study to assess and compare the measurement of trough levels by these two methodologies noted a positive bias with the ARCHITECT immunoassay which is likely due to the presence of tacrolimus metabolites. The aim of our study is to assess the impact of two different formulations of tacrolimus on the accuracy of its analytical measurement. While differences between immunoassay and LC-MS/MS results have been evaluated for immediate-release tacrolimus (Prograf), it has yet to be characterized for extended-release formulations such as Envarsus. The discrepancy between immunoassay and LC-MS/MS has clinical implications, as dosage modifications are based on measured concentrations, analytical variation may cause intervals of subtherapeutic or supratherapeutic exposure, increasing the risk of graft rejection or toxicity. Methods Development of an LC-MS/MS method for the simultaneous quantification of tacrolimus and its major metabolite, desmethyl tacrolimus, was performed in whole blood. Traceable calibrators and quality control material for tacrolimus and specimens supplemented with desmethyl tacrolimus were used to determine accuracy and precision. Tacrolimus concentrations were measured by LC-MS/MS and ARCHITECT immunoassay methods in excess whole blood specimens from patients treated with either Prograf or Envarsus. Measurement biases between LC-MS/MS and immunoassay methodologies were determined for both formulations of tacrolimus. Results External calibration curves for both tacrolimus and desmethyl tacrolimus were linear (R2&amp;gt;0.995), and the analytical measurement range (AMR) for tacrolimus spanned from 1.1 - 31.6 ng/ml. Calibrator and Quality control (QC) biases were within 15% of their target values throughout the AMR and within-run imprecision was less than 10% (n=25) for all calibrators and QCs. Between-run imprecision for Low, Mid, and High QC levels over a period of 2 weeks (n=5 days) was less than 10%. Comparative bias of tacrolimus concentrations between immunoassay and LC-MS/MS was significantly lower (P value=0.0074) for Envarsus (n=20 specimens) relative to Prograf (n=32 specimens). Conclusions The differential bias between immunoassay and LC-MS/MS in the measurement of tacrolimus in patients dosed with immediate-release versus extended-release formulations suggests that their distinct pharmacokinetic profile may impact the accuracy of the measurement. Therefore, applying observed measurement biases from different assays derived from Prograf patients to Envarsus patients and vice versa may result in erroneous estimation of tacrolimus concentrations.