Association of Coronary Calcium Score on Cardiac PET During Pre-Kidney Transplant Assessment with Persistent Hyperparathyroidism: A Retrospective Study.

BACKGROUND Secondary hyperparathyroidism and coronary calcifications are common complications in chronic kidney disease. However, the relation between coronary calcium score (CCS) and persistent hyperparathyroidism (pHPT) after kidney transplantation (KT) remains unknown. MATERIAL AND METHODS This was a single-center retrospective study of KT candidates from January 2017 to May 2020. We collected patients' demographics, cardiovascular (CV) risk factors, and the findings of pre-KT CV imaging. We also collected parathyroid hormone (PTH) values before KT, at 1-6 months, 6-12 months, and 12-24 months after KT. We defined pHPT as PTH ≥25.5 pmol/L after 12 months post-KT. RESULTS A total of 111 KT recipients (KTRs) with a mean age of 50.4 years were included, of which 62.2% were men and 77.5% were living-donor KTRs. Dialysis modality used before KT was peritoneal dialysis in 9.9% and hemodialysis in 82.9%. Dialysis vintage was 3±2.9 years. The prevalence of pHPT was 24.3% (n=27), and the prevalence of severe coronary calcifications (CCS >400 Agatston units) was 19.8% (n=22). PTH values at baseline, 1-6 months, 6-12 months, and 12-24 months were not different among between CCS >400 or CCS <400 groups. However, pHPT after KT was significantly more prevalent in KTRs with severe CCS (37% vs 14.3%, p=0.014). Severe CCS was associated with less improvement of PTH values after KT (r=0.288, p=0.020). Otherwise, the findings of cardiac PET and coronary angiogram were not significantly different between pHPT and non-pHPT patients. CCS >400 was independently associated with pHPT after transplant (aOR=18.8, P=0.012). CONCLUSIONS Severe CCS on pre-KT cardiac assessment is associated with pHPT after KT.

Beyond the First Year: Epidemiology and Management of Late-Onset Opportunistic Infections After Kidney Transplantation.

Late opportunistic infections (OI) occurring beyond the first year after kidney transplantation (KT) are poorly described and not targeted by prophylactic strategies. We performed a ten-year retrospective monocentric cohort study describing epidemiology, risk factors and impact of late OI occurring 1 year after KT. We included clinically symptomatic OI requiring treatment besides BK virus nephropathy. Control groups included early OI occurring in the first year after KT, and KT recipients without OI since KT and alive with a functional allograft at 1 year. Among 1066 KT recipients, 185 (19.4%) presented a first episode of OI 21.0 (8.0-45.0) months after KT: 120 late OI (64.9%) and 65 early OI (35.1%). Late OI were mainly viral (N = 83, 69.2%), mostly herpes zoster (HZ) (N = 36, 43.4%). Pneumocystis represented most late fungal infections (N = 12/25, 48%). Compared to early OI, we reported more pneumocystis (p = 0.002) and less invasive aspergillosis (p = 0.01) among late OI. Patients with late OI were significatively younger at KT (54.0 ± 13.3 vs. 60.2 ± 14.3 years, p = 0.05). Patient and allograft survival rates between late OI and control groups were similar. Only age was independently associated with mortality. While late OI were not associated with higher mortality or graft loss, implementing prophylactic strategies might prevent such infections.

Cost-utility analysis of pharmacogenomics-guided tacrolimus treatment in Austrian kidney transplant recipients participating in the U-PGx PREPARE study.

Chronic kidney disease (CKD) is a global health issue. Kidney failure patients may undergo a kidney transplantation (KTX) and prescribed an immunosuppressant medication i.e., tacrolimus. Tacrolimus' efficacy and toxicity varies among patients. This study investigates the cost-utility of pharmacogenomics (PGx) guided tacrolimus treatment compared to the conventional approach in Austrian patients undergone KTX, participating in the PREPARE UPGx study. Treatment's effectiveness was determined by mean survival, and utility values were based on a Visual Analog Scale score. Incremental Cost-Effectiveness Ratio was also calculated. PGx-guided treatment arm was found to be cost-effective, resulting in reduced cost (3902 euros less), 6% less hospitalization days and lower risk of adverse drug events compared to the control arm. The PGx-guided arm showed a mean 0.900 QALYs (95% CI: 0.862-0.936) versus 0.851 QALYs (95% CI: 0.814-0.885) in the other arm. In conclusion, PGx-guided tacrolimus treatment represents a cost-saving option in the Austrian healthcare setting.

Comprehensive geriatric assessment predicts listing for kidney transplant in patients with end-stage renal disease: a retrospective cohort study.

BACKGROUND: Comprehensive geriatric assessment (CGA) involves a formal broad approach to assess frailty and creating a plan for management. However, the impact of CGA and its components on listing for kidney transplant in older adults has not been investigated. METHODS: We performed a single-center retrospective study of patients with end-stage renal disease who underwent CGA during kidney transplant candidacy evaluation between 2017 and 2021. All patients ≥ 65 years old and those under 65 with any team member concern for frailty were referred for CGA, which included measurements of healthcare utilization, comorbidities, social support, short physical performance battery, Montreal Cognitive Assessment (MoCA), and Physical Frailty Phenotype (FPP), and estimate of surgical risk by the geriatrician. RESULTS: Two hundred and thirty patients underwent baseline CGA evaluation; 58.7% (135) had high CGA ("Excellent" or "Good" rating for transplant candidacy) and 41.3% (95) had low CGA ratings ("Borderline," "Fair," or "Poor"). High CGA rating (OR 8.46; p < 0.05), greater number of CGA visits (OR 4.93; p = 0.05), younger age (OR 0.88; p < 0.05), higher MoCA scores (OR 1.17; p < 0.05), and high physical activity (OR 4.41; p < 0.05) were all associated with listing on transplant waitlist. CONCLUSIONS: The CGA is a useful, comprehensive tool to help select older adults for kidney transplantation. Further study is needed to better understand the predictive value of CGA in predicting post-operative outcomes.

Sonographic Assessment of Renal Transplantation in Adult Saudi Patients: A Cross-Sectional Retrospective Study.

Kidney transplantation stands as a practical and cost-effective treatment option for end-stage renal disease patients, offering an improved quality of life with reduced morbidity when compared with hemodialysis. To evaluate the status of transplanted kidneys in Saudi patients, we conducted a retrospective single-center study at Jazan, Saudi Arabia, involving 46 adult renal recipients enrolled randomly from 2015 to December 2022. Using high-frequency ultrasound, we performed Duplex ultrasound examinations to assess renal allografts. The study revealed that the renal grafts exhibited normal length, with preserved cortical medullary differentiation (CMD) in 84.8% of cases and poor CMD in 15.2%. The echogenicity of the grafts remained normal in 69.6% of instances. Interestingly, we observed a significant rise in resistance index values as the graft duration increased (P = .04), whereas patients with abnormal creatinine levels displayed decreased peak systolic velocity and end-diastolic velocity. Notably, sonographic graft assessments unveiled complications, including perinephric fluid accumulation (8.7%), simple renal cysts (10.86%), hydronephrosis (8.7%), and one case of graft rejection. Receiver operating characteristics analysis for serum blood creatinine levels and abnormal parenchymal findings yielded fair to poor predictive accuracy, with varying sensitivity and specificity measures that lacked statistical significance. In conclusion, our study revealed that most Saudi renal transplant recipients exhibited grafts with normal echogenicity, preserved CMD, and limited perinephric fluid. This investigation provides valuable insights into sonographic changes and Doppler parameters of renal grafts, potentially aiding in the early detection of graft rejection and facilitating diagnostic and therapeutic planning.

Economic and humanistic burden in kidney transplant rejection: a literature review.

INTRODUCTION: Antibody-mediated rejection (ABMR) is a major cause of late kidney allograft failure, but its economic and humanistic impacts have not been well-characterized in the literature. AREAS COVERED: We reviewed available literature on economic burden (costs and healthcare resource use) and humanistic burden (health-related quality of life impacts [HRQOL] and utility estimates) in patients diagnosed with kidney transplant rejection; ABMR-specific studies were of particular interest. In total, 21 publications reporting economic and humanistic burden were included in the review; 9 of these reported ABMR-specific outcomes. The reviewed studies consistently showed a greater burden associated with ABMR-related transplant rejection than with non-ABMR transplant rejection. EXPERT OPINION: Evidence suggests greater economic burden and increased HRQOL impairment with ABMR-related kidney transplant rejection relative to non-ABMR, although small sample sizes and missing definitions for ABMR make meaningful comparisons between studies challenging. Because no International Classification of Diseases (ICD)-10 codes currently describe the etiologies of transplant rejection, it is difficult to characterize the burden of distinct types of transplant rejection. The paucity of high-quality data on the burden of ABMR in kidney transplant rejection demonstrates the need for more etiology-centric ICD-10 codes.

The medical cost and outcome of desensitization protocol in kidney transplantation recipients with high immunological risks.

BACKGROUND: Kidney transplantation is a well-established alternative in renal replacement therapy. Compared with hemodialysis, low-immunological-risk kidney transplantation can reduce the medical treatment costs associated with end-stage renal disease. However, there are few reports on whether high-immunological-risk kidney transplantation reduces the financial burden on governments. We investigated the medical costs of high-immunological-risk kidney transplantation in comparison with the cost of hemodialysis in Japan. METHODS: We compared the medical costs of high-immunological-risk kidney transplantation with those of hemodialysis. 15 patients who underwent crossmatch-positive and/or donor-specific antibody-positive kidney transplantations between 2020 and 2021 were enrolled in this study. The patients received intravenous immunoglobulin, plasmapheresis, and rituximab as desensitizing therapy. RESULTS: Acute antibody-mediated rejection was detected in nine (60%) recipients, while there were no indications of graft function deterioration during the follow-up. For each patient, the transplant hospitalization cost was 38 428 ± 8789 USD. However, the cumulative costs were 59 758 ± 10 006 USD and 79 781 ± 16 366 USD, at 12 and 24 months, respectively. Compared with hemodialysis (34 286 USD per year), high-immunological-risk kidney transplantation tends to be expensive in the first year, but the cost is likely to be lower than that of hemodialysis after 3 years. CONCLUSIONS: Although kidney transplantation is initially expensive compared with hemodialysis, the medical cost becomes advantageous after 3 years even in kidney transplant recipients with high immunological risk.

Differences in the epidemiology, management and outcomes of kidney disease in men and women.

Improved understanding of differences in kidney disease epidemiology, management and outcomes in men and women could help nephrologists to better meet the needs of their patients from a sex- and gender-specific perspective. Evidence of sex differences in the risk and outcomes of acute kidney injury is mixed and dependent on aetiology. Women have a higher prevalence of chronic kidney disease (CKD) stages 3-5 than men, whereas men have a higher prevalence of albuminuria and hence CKD stages 1-2. Men show a faster decline in kidney function, progress more frequently to kidney failure and have higher mortality and risk of cardiovascular disease than women. However, the protective effect of female sex is reduced with CKD progression. Women are less likely than men to be aware of, screened for and diagnosed with CKD, started on antiproteinuric medication and referred to nephrologist care. They also consistently report a poorer health-related quality of life and a higher symptom burden than men. Women experience greater barriers than men to access the waiting list for kidney transplantation, particularly with respect to older age and obesity. However, women also have longer survival than men after transplantation, which may partly explain the comparable prevalence of transplantation between the sexes.

A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization.

Lesion scores on procurement donor biopsies are commonly used to guide organ utilization for deceased-donor kidneys. However, frozen sections present challenges for histological scoring, leading to inter- and intra-observer variability and inappropriate discard. Therefore, we constructed deep-learning based models to recognize kidney tissue compartments in hematoxylin & eosin-stained sections from procurement needle biopsies performed nationwide in years 2011-2020. To do this, we extracted whole-slide abnormality features from 2431 kidneys and correlated with pathologists' scores and transplant outcomes. A Kidney Donor Quality Score (KDQS) was derived and used in combination with recipient demographic and peri-transplant characteristics to predict graft loss or assist organ utilization. The performance on wedge biopsies was additionally evaluated. Our model identified 96% and 91% of normal/sclerotic glomeruli respectively; 94% of arteries/arterial intimal fibrosis; 90% of tubules. Whole-slide features of Sclerotic Glomeruli (GS)%, Arterial Intimal Fibrosis (AIF)%, and Interstitial Space Abnormality (ISA)% demonstrated strong correlations with corresponding pathologists' scores of all 2431 kidneys, but had superior associations with post-transplant estimated glomerular filtration rates in 2033 and graft loss in 1560 kidneys. The combination of KDQS and other factors predicted one- and four-year graft loss in a discovery set of 520 kidneys and a validation set of 1040 kidneys. By using the composite KDQS of 398 discarded kidneys due to "biopsy findings", we suggest that if transplanted, 110 discarded kidneys could have had similar survival to that of other transplanted kidneys. Thus, our composite KDQS and survival prediction models may facilitate risk stratification and organ utilization while potentially reducing unnecessary organ discard.

Belatacept with time-limited tacrolimus coimmunosuppression modifies the 3-year risk of eplet mismatch in kidney transplantation.

Solid organ transplant donor-recipient eplet mismatch has been correlated with donor-specific antibody (DSA) formation, antibody-mediated rejection, and overall rejection rates. However, studies have been predominantly in patients on tacrolimus-based immunosuppression regimens and have not fully explored differences in ethnically and racially diverse populations. Evidence indicates that patients on belatacept have lower rates of DSA formation, suggesting mediation of the immunogenicity of mismatched human leukocyte antigen polymorphisms. We performed a retrospective, single-center analysis of class II eplet disparity in a cohort of kidney transplant recipients treated using belatacept with tacrolimus induction (Bela/TacTL) or tacrolimus regimens between 2016 and 2019. Bela/TacTL (n = 294) and tacrolimus (n = 294) cohorts were propensity score-matched with standardized difference <0.15. Single-molecule eplet risk level was associated with immune event rates for both groups. In Cox regression analysis stratified by eplet risk level, Bela/TacTL immunosuppression was associated with a decreased rate of DSA (hazard ratio [HR] = 0.4), antibody-mediated rejection (HR = 0.2), and rejection (HR = 0.45). In the low-risk group, cumulative graft failure was lower for patients on Bela/TacTL (P < .02). Analysis of eplet mismatch burden may be a useful adjunct in identifying high-risk populations with increased immunosuppression requirements and should encourage the design of allocation rules to incentivize lower-risk pairings without negatively impacting equity in access.

Evaluating Cost-Effectiveness in Using High-Kidney Donor Profile Index Organs.

A more granular donor kidney grading scale, the kidney donor profile index (KDPI), has recently emerged in contradistinction to the standard criteria donor/expanded criteria donor framework. In this paper, we built a Markov decision process model to evaluate the survival, quality-adjusted life years (QALY), and cost advantages of using high-KDPI kidneys based on multiple KDPI strata over a 60-month time horizon as opposed to remaining on the waiting list waiting for a lower-KDPI kidney. Data for the model were gathered from the Scientific Registry of Transplant Recipients and the United States Renal Data System Medicare parts A, B, and D databases. Of the 129,024 phenotypes delineated in this model, 65% of them would experience a survival benefit, 81% would experience an increase in QALYs, 87% would see cost-savings, and 76% would experience cost-savings per QALY from accepting a high-KDPI kidney rather than remaining on the waiting list waiting for a kidney of lower-KDPI. Classification and regression tree analysis (CART) revealed the main drivers of increased survival in accepting high-KDPI kidneys were wait time ≥30 months, panel reactive antibody (PRA) <90, age ≥45 to 65, diagnosis leading to renal failure, and prior transplantation. The CART analysis showed the main drivers of increased QALYs in accepting high-kidneys were wait time ≥30 months, PRA <90, and age ≥55 to 65.

Renal cell carcinoma in kidney transplant recipients: incidence, trends, clinical management & outcomes.

OBJECTIVE: To describe the incidence, characteristics, clinical management, and outcomes of renal cell carcinoma (RCC) among a large, single-centre cohort of kidney transplant recipients (KTR). METHODS: We conducted an observational cohort study looking at KTR transplanted between January 2000-December 2017 (n = 2443) with ≥ 1 year of follow-up. Simultaneous kidney/pancreas transplants were excluded. The Kaplan-Meier product-limit method was used to determine the incidence of RCC. Characteristics and management of RCC were examined using descriptive statistics. Risk factors and clinical outcomes were analyzed using Cox regression models. RESULTS: The incidence of RCC among our cohort was 0.32 per 100 person-years, 2.1% of all KTRs. Almost half (47.1%) of cases occurred within 4 years post-transplant. The majority of cases were T1a (86.3%), clear-cell (45.1%), and in the native kidney (80.4%). KTR diagnosed with RCC had a twofold higher incidence of other malignancies versus KTR without RCC. Overall mortality, but not cancer-specific mortality, at 2- and 5-years post-transplant was threefold higher among KTR with RCC than those without. CONCLUSIONS: Incidence of RCC among our KTR was slightly higher than the general population; majority of cases occur in the native kidneys and are low stage, low grade. Indolent histologic variants were more common than the general population. KTR with RCC had a higher incidence of other malignancies. Overall, but not cancer-specific, mortality was higher among KTRs diagnosed with RCC.

Correctional health care and Australian prisoners as recipients of kidney transplants: Legal and ethical issues.

AIM: This research aims to examine the legal and ethical issues surrounding Australia prisoners as potential kidney transplant recipients. METHODS: Examination of relevant statutory and common law including human rights law, state and territory corrections legislation and negligence law. Ethical principles considered, particularly in regards to practical and logistical considerations including adequate delivery of transplantation medical care and implications on the broader organ donation program. Approaches in the United States of America and United Kingdom are compared with the Australian approach. RESULTS: Prisoners are more likely than non-incarcerated individuals to have chronic medical conditions. For most people with kidney failure, kidney transplantation improves both quality of life and life expectancy compared with dialysis therapy. Prisoners have a right to access reasonable medical care under state-based corrections legislation, which is underpinned by human rights law and ethical principles, primarily beneficence, transparency and justice. The right of prisoners to receive reasonable medical care likely extends to ensuring prisoners with kidney failure are considered for kidney transplantation and waitlisted if medically appropriate. Social factors and logistical factors can be relevant when considering eligibility for transplantation as they can relate to a person's ability to comply with medical therapy. Additionally, organ allocation decisions can be emotive, and a decision to offer a kidney transplant to a prisoner may generate significant negative publicity. CONCLUSION: Prisoners with kidney failure should be considered for kidney transplantation. Logistical barriers, such as guard availability, should be addressed by state departments responsible for prisoner health.

Cost-effectiveness of Kidney Transplantation From Donors at Increased Risk of Blood-borne Virus Infection Transmission.

BACKGROUND: Demand for donor kidneys outstrips supply. Using kidneys from selected donors with an increased risk of blood-borne virus (BBV) transmission (hepatitis B virus and hepatitis C virus [HCV], human immunodeficiency virus) may expand the donor pool, but cost-effectiveness of this strategy is uncertain. METHODS: A Markov model was developed using real-world evidence to compare healthcare costs and quality-adjusted life years (QALYs) of accepting kidneys from deceased donors with potential increased risk of BBV transmission, because of increased risk behaviors and/or history of HCV, versus declining these kidneys. Model simulations were run over a 20-y time horizon. Parameter uncertainty was assessed through deterministic and probabilistic sensitivity analyses. RESULTS: Accepting kidneys from donors at increased risk of BBVs (2% from donors with increased-risk behaviors and 5% from donors with active or past HCV infection) incurred total costs of 311 303 Australian dollars with a gain of 8.53 QALYs. Foregoing kidneys from these donors incurred total costs of $330 517 and a gain of 8.44 QALYs. A cost-saving of $19 214 and additional 0.09 QALYs (~33 d in full health) per person would be generated compared with declining these donors. Increasing the availability of kidneys with increased risk by 15% led to further cost-savings of $57 425 and additional 0.23 QALY gains (~84 d in full health). Probabilistic sensitivity analysis using 10 000 iterations showed accepting kidneys from donors at increased risk led to lower costs and higher QALY gains. CONCLUSIONS: Shifting clinical practice to accept increased BBV risk donors would likely produce lower costs and higher QALYs for health systems.

Value of conventional ultrasound and contrast-enhanced ultrasound for the assessment of renal allograft dysfunction and prognosis.

BACKGROUND: Ultrasound (US) is the primary imaging modality for the assessment of transplanted kidneys. This study aims to investigate the ability of conventional US and contrast-enhanced US (CEUS) in assessing renal allograft function and prognosis. METHODS: A total of 78 consecutive renal allograft recipients were enrolled. Patients were classified as normal allograft function (n = 41) and allograft dysfunction (n = 37) groups. All patients underwent US and parameters were measured. The independent-samples t-test or Mann-Whitney U test, logistic regression analysis, Kaplan-Meier survival plots, and Cox regression analysis were used. RESULTS: In multivariable analysis, cortical echo intensity (EI) and cortical peak intensity (PI) were determinant US parameters for renal allograft dysfunction (p = .024 and p = .003, respectively). The combination of cortical EI and PI showed an area under the receiver operating characteristic curve (AUROC) of .785 (p < .001). Of 78 patients (median follow-up: 20mo), 16 (20.5%) exhibited composite end points. Cortical PI had a general prediction accuracy with an AUROC of .691, sensitivity of 87.5%, and specificity of 46.8% at the threshold of 22.08 dB in predicting prognosis (p = .019). The combination of estimated-glomerular filtration rate (e-GFR) and PI in predicting prognosis showed an AUROC of .845 with a cut-off value of .836, sensitivity of 84.0%, and specificity of 67.3% (p < .001). CONCLUSION: This study indicates that cortical EI and PI are useful US parameters for evaluating renal allograft function and e-GFR combined with PI may provide a more accurate predictor of survival.

Deceased Donor Kidney Transplantation From Donors With Acute Kidney Injury: Realities and Costs.

OBJECTIVES: Transplant of kidneys from donors with acute kidney injury has shown favorable outcomes. We investigated the outcomes of kidney transplant recipients with deceased donors who developed acute kidney injury before organ procurement. MATERIALS AND METHODS: We retrospectively reviewed the medical records of recipients from January 2016 to December 2021 in a single center. Outcomes in recipients of kidney grafts from donors with and without acute kidney injury were compared. RESULTS: The mean follow-up time was 40 months. Our study included 129 (34%) kidneys transplanted from donors with acute kidney injury and 251 (66%) kidneys from donors without acute kidney injury. Delayed graft function rate in recipients was 33% in the acute kidney injury group and 25.5% in the group without acute kidney injury (P = .099). Readmission rate at 30 days was significantly higher among recipients of kidneys with acute kidney injury compared with recipients of kidneys without acute kidney injury (45% vs 33.5%; P = .02). The mean overall costs of transplant in the acute kidney injury group were comparable to the group without acute kidney injury ($253 865 vs $253 611; P = .97). The acute rejection rate was comparable between the 2 groups (4% in both groups; P = .96). Delayed graft function rate was increased with increased stage of acute kidney injury (18% stage 1, 45% stage 2, 36% stage 3; P = .03). However, the overall length of hospital stay and costs were comparable among recipients of different stages of acute kidney injury. CONCLUSIONS: Our study showed that kidney transplants from donors with acute kidney injury have early and late outcomes comparable to kidney transplants from donors without acute kidney injury. Allografts from donors with acute kidney injury can be used safely and can expand the donor pool in kidney transplant without increasing perioperative resource utilization.

Incidence, Risk Factors, and Management of Incisional Hernias After Kidney Transplant: A 20-Year Single Center Experience.

BACKGROUND: Incisional hernias (IH) constitute a complication after kidney transplant (KT). Patients may be particularly at risk because of comorbidities and immunosuppression. The study aim was to assess the incidence, risk factors, and treatment of IH in patients undergoing KT. METHODS: This retrospective cohort study included consecutive patients who underwent KT between January 1998 and December 2018. Patient demographics, comorbidities, perioperative parameters, and IH repair characteristics were assessed. Postoperative outcomes included morbidity, mortality, need for reoperation, and length of stay (LOS). Patients who developed IH were compared with those who did not develop one. RESULTS: Forty-seven patients (6.4%) developed an IH after a median delay of 14 months (IQR, 6-52 months) in 737 KTs. On uni- and multivariate analyses, body mass index (odds ratio [OR], 1.080; P = .020), pulmonary diseases (OR, 2.415; P = .012), postoperative lymphoceles (OR, 2.362; P = .018), and LOS (OR, 1.013; P = .044) were independent risk factors. Thirty-eight patients (81%) underwent operative IH repair, and 37 (97%) were treated with a mesh. The median LOS was 8 days (IQR, 6-11 days). Three patients (8%) developed surgical site infections, and 2 patients (5%) presented hematomas requiring surgical revision. After IH repair, 3 patients (8%) had a recurrence. CONCLUSIONS: The incidence of IH after KT seems rather low. Overweight, pulmonary comorbidities, lymphoceles, and LOS were identified as independent risk factors. Strategies focusing on the modifiable patient-related risk factors and early detection and treatment of lymphoceles may help to decrease the risk of IH formation after KT.

A Simple Molecular Tool for the Assessment of Kidney Transplant Biopsies.

BACKGROUND: The Banff Classification for Allograft Pathology recommendations for the diagnosis of kidney transplant rejection includes molecular assessment of the transplant biopsy. However, implementation of molecular tools in clinical practice is still limited, partly due to the required expertise and financial investment. The reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) assay is a simple, rapid, and inexpensive assay that permits simultaneous evaluation of a restricted gene panel using paraffin-embedded tissue blocks. The aim of this study was to develop and validate a RT-MLPA assay for diagnosis and classification of rejection. METHODS: A retrospective cohort of 220 kidney transplant biopsies from two centers, which included 52 antibody-mediated rejection, 51 T-cell-mediated rejection, and 117 no-rejection controls, was assessed. A 17-gene panel was identified on the basis of relevant pathophysiological pathways. A support vector machine classifier was developed. A subset of 109 biopsies was also assessed using the Nanostring Banff Human Organ Transplant panel to compare the two assays. RESULTS: The support vector machine classifier train and test accuracy scores were 0.84 and 0.83, respectively. In the test cohort, the F1 score for antibody-mediated rejection, T-cell-mediated rejection, and control were 0.88, 0.86, and 0.69, respectively. Using receiver-operating characteristic curves, the area under the curve for class predictions was 0.96, 0.89, and 0.91, respectively, with a weighted average at 0.94. Classifiers' performances were highest for antibody-mediated rejection diagnosis with 94% correct predictions, compared with 88% correct predictions for control biopsies and 60% for T-cell-mediated rejection biopsies. Gene expression levels assessed by RT-MLPA and Nanostring were correlated: r = 0.68, P < 0.001. Equivalent gene expression profiles were obtained with both assays in 81% of the samples. CONCLUSIONS: The 17-gene panel RT-MLPA assay, developed here for formalin-fixed paraffin-embedded kidney transplant biopsies, classified kidney transplant rejection with an overall accurate prediction ratio of 0.83. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_04_10_CJN10100822.mp3.

Age associations with tacrolimus and mycophenolic acid pharmacokinetics in stable Black and White kidney transplant recipients: Implications for health inequities.

Tacrolimus (TAC) and mycophenolic acid (MPA) provide maintenance immunosuppression and is dosed empirically in elderly kidney transplant recipients (KTRs) resulting in health inequities. Limited immunosuppressive pharmacokinetics are available comparing adult ages. This secondary analysis compared TAC and MPA pharmacokinetics and adverse effects (AEs) among young, middle-aged, and elderly Black and White KTRs. The 12-h TAC and MPA pharmacokinetics with AE evaluation were conducted in 67 stable KTRs greater than or equal to 6 months post-transplant. TAC regimens were adjusted to target troughs. MPA regimens were adjusted using clinical response. Participants were: young: less than or equal to 40 years; middle age: greater than 40 to 60 years, and elderly greater than 60 years. Noncompartmental pharmacokinetic analysis determined area under the concentration-time curve 0-12 h (AUC0-12h ), clearance (CL), and CL/body mass index (BMI) with 0-h troughs. MPA enterohepatic recirculation (EHR), MPA-AUC6-12h /MPA-AUC0-12h , and MPA glucuronide (MPAG)-AUC0-12h /MPA-AUC0-12h were determined. Univariate analysis of variance (ANOVA) was conducted using SAS version 9.4. No group differences were noted for estimated glomerular filtration rate, MPA, and TAC doses. EHR was reduced in elderly with decreased MPA-AUC6-12h /MPA-AUC0-12h (p = 0.049) and increased MPAG-AUC0-12h /MPA-AUC0-12h (p = 0.036). MPA troughs (p = 0.045) were reduced in the elderly. TAC CL/BMI (p = 0.043) was reduced in the elderly. For therapeutic MPA AUC0-12h : 30-60 mg·h/L, 34.3% KTRs achieved this target with 55.2% greater than the therapeutic range. 77.6% KTR were in the TAC AUC0-12h target: 100-190 ng·h/mL and 19.4% were below this range with no age relationship. In 44% young, 26% middle-age and 7.8% elderly subjects achieved target AUC0-12h for both medications (p = 0.036). Neurologic AEs were manifested in the elderly (p = 0.014). Immunosuppressive pharmacokinetics demonstrated age-related differences with reduced TAC CL/BMI and MPA EHR and increased neurologic AE in the elderly. This immunosuppressive regimen may require age-adjusted individualization to optimize allograft function.