Adult Kidney Transplant Recipients Research Articles

Efficacy and safety of bortezomib in the treatment of active antibody-mediated rejection in adult kidney-transplant recipients: A single-center retrospective study

Introduction: The management of active antibody-mediated rejection (ABMR) is evolving, and optimal treatment remains uncertain due to incomplete understanding of pathogenesis. Bortezomib is found to be useful in the treatment of active ABMR. We studied the efficacy and safety of bortezomib in renal-transplant recipients with active ABMR. Materials and Methods: We retrospectively included renal-transplant recipients with active ABMR, who received bortezomib as main management. Results: Eighteen live-related renal-transplant recipients of active ABMR were included. C4d was positive in 14 patients and negative in eight patients. Patients with active ABMR had a mean improvement in glomerular filtration rate (GFR) of 7, 10.5, and 15 ml/min/1.73 m2 at 3, 6, and 12 months, respectively, from baseline GFR. Improvement was significant at 3 (P = 0.009) and 6 months (P = 0.018) of follow-up. Conclusion: Bortezomib may be a safe and effective therapy in patients with active ABMR in patients.

Shear wave elastography and Doppler ultrasound in kidney transplant recipients.

ObjectiveTo evaluate the association between shear wave elastography parameters and arterial resistance in kidney transplant recipients.Materials and MethodsThis was a prospective cross-sectional study involving consecutive adult kidney transplant recipients. All patients underwent color Doppler to evaluate the resistive index (RI) and ultrasound shear wave elastography for the quantification of renal allograft stiffness.ResultsWe evaluated 55 patients, of whom 9 (16.4%) had an RI defined as abnormal (≥ 0.79) and 46 (83.6%) had an RI defined as normal (< 0.79). The mean age was higher in the abnormal RI group than in the normal RI group (68.0 ± 8.6 years vs. 42.6 ± 14.1 years; p < 0.001), as was the mean shear wave velocity (2.6 ± 0.4 m/s vs. 2.2 ± 0.4 m/s; p = 0.013). Multivariate analysis identified two independent predictors of arterial resistance: age (OR = 1.169; 95% CI: 1.056 to 1.294; p = 0.003) and shear wave velocity (OR = 17.1; 95% CI: 1.137 to 257.83; p = 0.040).ConclusionWe observed an association between rigidity in the cortex of the transplanted kidney, as evaluated by shear wave elastography, and arterial resistance, as evaluated by color Doppler, in kidney transplant recipients.

Proportion versus absolute counts of B cell populations in the assessment of immunological profiles of kidney transplant recipients

Immunophenotyping lymphocytes in kidney transplant recipients often raises questions as to whether proportions or absolute counts should be considered, especially for longitudinal assessment. Several studies conclude the pathophysiology of rejection based on proportions of naive and memory B cells. We compared the two analytical methods for B cells sampled from 82 clinically stable, adult kidney transplant recipients. Time post-transplant was analyzed both as a continuous variable and as tertiles (<1.5 years, 1.5–8 years, and > 8 years). B cells were stained for CD38 and IgD and were classified according to mature B cells (Bm) classification. The proportion of cells in the naive Bm2 compartment decreased by more than half in the late versus the early tertile, whereas the percentages of memory early Bm5 tripled and that of memory Bm5 cells doubled. In contrast, we observed a substantial reduction in naive B cell counts, but very stable memory B cell counts. Linear regressions showed that the absolute reduction in the Bm2 cell compartment was independent of age, sex, graft function, immunosuppression scheme, and rejection occurrence. In conclusion, the physiological reservoir of naive cells decreases over time post-transplant in kidney recipients, whereas that of memory B cells remains stable. Peripheral B subset percentages should be interpreted cautiously when analyzing pathophysiological processes.

A randomized crossover study comparing different tacrolimus formulations to reduce intrapatient variability in tacrolimus exposure in kidney transplant recipients.

A high intrapatient variability (IPV) in tacrolimus exposure is a risk factor for poor long‐term outcomes after kidney transplantation. The main objective of this trial was to investigate whether tacrolimus IPV decreases after switching patients from immediate‐release (IR)‐tacrolimus to either extended‐release (ER)‐tacrolimus or LifeCyclePharma (LCP)‐tacrolimus. In this randomized, prospective, open‐label, cross‐over trial, adult kidney transplant recipients on a stable immunosuppressive regimen, including IR‐tacrolimus, were randomized for conversion to ER‐tacrolimus or LCP‐tacrolimus, and for the order in which IR‐tacrolimus and the once‐daily formulations were taken. Patients were followed 6 months for each formulation, with monthly tacrolimus predose concentration assessments to calculate the IPV. The IPV was defined as the coefficient of variation (%) of dose corrected predose concentrations. Ninety‐two patients were included for analysis of the primary outcome. No significant differences between the IPV of IR‐tacrolimus (16.6%) and the combined once‐daily formulations (18.3%) were observed (% difference +1.7%, 95% confidence interval [CI] −1.1% to ‒4.5%, p = 0.24). The IPV of LCP‐tacrolimus (20.1%) was not significantly different from the IPV of ER‐tacrolimus (16.5%, % difference +3.6%, 95% CI −0.1% to 7.3%, p = 0.06). In conclusion, the IPV did not decrease after switching from IR‐tacrolimus to either ER‐tacrolimus or LCP‐tacrolimus. These results provide no arguments to switch kidney transplant recipients from twice‐daily (IR) tacrolimus formulations to once‐daily (modified‐release) tacrolimus formulations when the aim is to lower the IPV.

Clinical characteristics and outcomes of COVID-19 in kidney transplant recipients

Introduction. The pandemic caused by the SARS-CoV-2 coronavirus is characterized by significant morbidity and mortality. Kidney transplant recipients are at high risk of a more severe course of coronavirus infection due to ongoing immunosuppression, a high comorbidity index, and elder age.Aim. To investigate the features of the clinical course, the treatment applied and also the outcomes of the new coronavirus infection in patients after kidney transplantation.Material and methods. The retrospective study included 69 adult kidney transplant recipients continuously followed-up by our transplant nephrology service and who fell ill with COVID-19 from April 2020 till February 2021. The comparison study of the clinical pattern, laboratory and instrumental test results, treatment features and outcomes was made.Results. The most common clinical symptoms were hyperthermia (85.5%, n= 59), weakness (65.2%, n=45) and cough (52.2%, n=36), other symptoms were significantly less common. In 89.5% of cases (n=60), the virus ribonucleic acid was detected at least once by polymerase chain reaction; in 10.5% of cases (n=7), the polymerase chain reaction results were negative. According to CT, the extent of lung tissue lesion was identified as CT1 stage in 28 patients (46.7%), CT2 stage in 24 (40%); and only in 8 (13%) patients the lesion was assessed as CT3. Later on the number of patients with more than 50% lung damage increased to 16 (26.7%) and in 1 case the severity of lung tissue damage was consistent with CT4. Typical features for all patients were anemia and lymphopenia of varying severity, hypoproteinemia, increased serum creatinine and urea, C-reactive protein, ferritin, procalcitonin and D-dimer in the laboratory test results. The treatment included antiviral, antibacterial, anticoagulant therapy, corticosteroids, biological anti-cytokine drugs. In 95% of cases (n=66), the maintenance immunosuppressive therapy was changed up to complete withdrawal of the certain components. The patient survival rate with a functioning graft was 76.8% (n=53), the graft loss was observed in 4.3% of cases (n=3), and the lethal outcome was reported in 18.8% (n=13). The cause of death was a severe respiratory distress syndrome with multiple organ dysfunction complicated by sepsis and septic shock in 8 patients (61.5%). Invasive ventilation and hemodialysis were associated with 17.2 (p&lt;0.00001) and 21.5 (p&lt;0.0006) times higher risk of death, respectively.Conclusions. Severe lymphopenia is associated with a clinical worsening of the COVID-19 course. Predictors of fatal outcome were identified as follows: bacterial sepsis, invasive ventilation, the need for renal replacement therapy (p&lt;0.00001). Immunosuppression adjustment should be personalized considering the severity of infection, age, comorbidities, post-transplant timeframe, and the risk of rejection.&gt;&lt;0.00001). Immunosuppression adjustment should be personalized considering the severity of infection, age, comorbidities, post-transplant timeframe, and the risk of rejection.

Effect of Early Steroid Withdrawal on Posttransplant Diabetes Among Kidney Transplant Recipients Differs by Recipient Age.

Posttransplant diabetes (PTD), a major complication after kidney transplantation (KT), is often attributable to immunosuppression. The risk of PTD may increase with more potent steroid maintenance and older recipient age. Using United States Renal Data System data, we studied 12 488 adult first-time KT recipients (2010-2015) with no known pre-KT diabetes. We compared the risk of PTD among recipients who underwent early steroid withdrawal (ESW) versus continued steroid maintenance (CSM) using Cox regression with inverse probability weighting to adjust for confounding. We tested whether the risk of PTD resulting from ESW differed by recipient age (18-29, 30-54, and ≥55 y). Of 12 488, 28.3% recipients received ESW. The incidence rate for PTD was 13 per 100 person-y and lower among recipients who received ESW (11 per 100 person-y in ESW; 14 per 100 person-y in CSM). Overall, ESW was associated with lower risk of PTD compared with CSM (adjusted hazard ratio [aHR] = 0.720.790.86), but the risk differed by recipient age (P interaction = 0.09 for comparison between recipients aged 18-29 and those aged 30-54; P interaction = 0.01 for comparison between recipients aged 18-29 and those aged ≥55). ESW was associated with lower risk of PTD among recipients aged ≥55 (aHR = 0.620.710.81) and those aged 30-54 (aHR = 0.730.830.95), but not among recipients aged 18-29 (aHR = 0.811.181.72). Although recipients who received ESW had a higher risk of acute rejection across the age groups (adjusted odds ratio = 1.011.171.34), recipients with no PTD had a lower risk of mortality (aHR = 0.580.660.74). The beneficial association of ESW with decreased PTD was more pronounced among recipients aged ≥55, supporting an age-specific assessment of the risk-benefit balance regarding ESW.

1387. Impact of Cytomegalovirus Prophylaxis on Healthcare Resource Use and Costs among Kidney Transplant Recipients: A United States Renal Data System-Medicare Linked Database Study

BackgroundCytomegalovirus (CMV) management requires a balance between reducing the risk of CMV infection and avoiding anti-viral toxicities. Limited information is available on the impact of CMV prophylaxis on the healthcare resource use (HCRU) and costs among adult kidney transplant recipients (KTRs) in the United States. Therefore, we examined HCRU and cost associated with CMV prophylaxis stratified by the CMV risk categories among KTRs at 1-year post-KT. MethodsWe identified a cohort of 22,918 adults first-time KTRs during 2011–2017 using the US Renal Data System registry-linked Medicare data. Additional inclusion criteria were to have continuous coverage in Medicare Part A & B for ≥ 6-month pre- and ≥ 12-month post KT and Medicare Part D for ≥12-month post-KT. CMV prophylaxis was confirmed as ≥ 1 prescription fill for valacyclovir/(val)ganciclovir prophylaxis doses within 28 days post-KT. ResultsCMV prophylaxis was utilized in 86%, 82%, and 32% of high, intermediate, and low-risk KTRs with an average cost of prophylaxis per KTRs of &16,241, &9481, and &8,648, respectively. In no prophylaxis groups, valganciclovir was utilized in 52%, 34%, and 36% of KTRs (as either pre-emptive or deferred therapy) with an average cost of &6,719, &2,722, and &431 among high, intermediate, and low-risk KTRs, respectively. Among high-risk KTRs, CMV prophylaxis group had a significantly higher prescription drug cost (&26,060 vs. &13,433) but a lower average direct healthcare medical cost (&84,914 vs. &101,268), mainly due to lower all-cause hospitalization cost (&56,758 vs. &69,852) (Table 1). CMV prophylaxis group had lower rates of all-cause rehospitalization, and CMV-and opportunistic infection (OIs)-related hospitalization compared to no prophylaxis (Table 2). In high-risk KTRs, nearly 32% had myelosuppressive events-related hospitalization, and 15% filled granulocyte colony-stimulating factors with an average cost of &4,695 per treated KTR.ConclusionCMV prophylaxis had a higher cost of medications but had a lower medical cost with including all-cause and CMV-related hospitalizations. Myelosuppressive events were frequent and resource-intensive especially in high and intermediate-risk KTRs. Disclosures Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder)

1378. Impact of Cytomegalovirus Prophylaxis on Clinical Outcomes in Kidney Transplantation: A United States Renal Data System-Medicare Linked Database Study

BackgroundGuidelines recommends cytomegalovirus (CMV) prophylaxis by CMV serostatus/risk status, as the currently available antiviral agents may lead to myelosuppressive events in kidney transplant recipients (KTRs). Limited data exist for the United States (US) on the such clinical outcomes with CMV prophylaxis KTRs especially stratified by CMV risk strata. We examined the associations between clinical outcomes and CMV prophylaxis among adult KTRs stratified by CMV risk strata. MethodsWe employed a retrospective cohort design using the US Renal Data System registry-linked Medicare data (2011-2017). The cohort included 22,918 adult KTRs with continuous Medicare Part A & B coverage for ≥ 6-month pre and ≥ 12-month post KT and Part D coverage for ≥ 12-month post- KT. CMV prophylaxis was defined as ≥ 1 prescription fill or medical claim for valacyclovir or valganciclovir at prophylaxis doses within 28 days post-KT. ResultsCMV prophylaxis was utilized by 75% of the cohort. In no CMV prophylaxis group, 52.2% and 34.2% of high and intermediate risk KTRs received valganciclovir (as either pre-emptive or deferred therapy), respectively. Among high risk KTRs, CMV prophylaxis group had significantly lower proportions of KTRs with CMV infection, opportunistic infections (OIs) including bacterial, and fungal infections, and new onset of diabetes mellitus (NODAT) compared to no prophylaxis group. There were no differences in the rates of acute rejection or death; however, a trend towards lower rate of graft-failure at 12-month post-KT. Nearly 40% of high-risk KTRs had myelosuppressive events (leukopenia: 18%; neutropenia:15% thrombocytopenia :19%); however, their differences were non-significant except for thrombocytopenia by CMV prophylaxis status (Table 1). CMV infection and myelosuppressive event rates were higher in high-risk than intermediate/low risk KTRs irrespective of CMV prophylaxis status. ConclusionCMV prophylaxis was associated with lower rates of CMV infection, OIs, NODAT and graft failure compared to no prophylaxis, however, the burden of CMV infection, OIs and myelosuppression was greater in high-risk KTRs indicating further research is needed on factors associated with greater disease burden in high-risk KTRs. Table 1Disclosures Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder)

Less bleeding associated with apixaban versus other direct acting oral anticoagulation in solid organ transplant recipients.

The purpose of this study was to evaluate outcomes of bleeding and thrombosis resulting from the use of direct oral anticoagulants (DOACs) in a large cohort of solid organ transplant (SOT) recipients. This was a single center, retrospective cohort study of adult kidney, heart, lung, and liver transplant recipients transplanted between August 2009 and May 2018. Patients were stratified into two groups: those who received apixaban (apixaban group) or those patients receiving either rivaroxaban or dabigatran (non-apixaban group). The primary endpoint was the cumulative incidence of bleeding while receiving DOAC therapy. The secondary endpoints were incidence of major bleeding and thrombosis at any time while receiving DOAC therapy. A total of 106 patients were included; 70 patients received apixaban and 36patients received non-apixaban anticoagulation. Cumulative incidence of any bleeding was lower in the apixaban group compared to the non-apixaban group at both 90days (4.9% vs. 16.1%) and 180 days (11.4% vs. 24.9%, P=.034). Cumulative incidence of major bleeding (P=.686) and thrombosis (P=.515) were similar between groups. DOAC dosing congruent with the package insert(s) was associated with a lower risk of thrombosis. Apixaban-based anticoagulation was associated with a lower cumulative incidence of any bleeding compared to non-apixaban DOACs.

Time-Varying Proteinuria and the Risk of Cardiovascular Disease and Graft Failure in Kidney Transplant Recipients.

Introduction: Proteinuria is recognized as an independent risk factor for cardiovascular disease in kidney transplant recipients, but previous studies have not considered the impact of changes in urine protein over time. Research Question and Design: We used time-dependent, multivariable Cox proportional hazards models in this observational cohort study of adult kidney transplant recipients to evaluate whether proteinuria measured by dipstick on random spot urine samples starting from 1-month post-transplant was associated with the risk of major adverse cardiac events and graft loss. Results: A total of 144 major adverse cardiac events, defined as acute myocardial infarction, cerebrovascular accident, revascularization, or all-cause mortality, were observed in 1106 patients over 5728.7 person-years. Any level of proteinuria greater or equal to trace resulted in a two-fold increase in the risk of major adverse cardiac events (hazard ratio 2.00 [95% confidence interval 1.41, 2.84]). This relationship was not found to be dose-dependent (hazard ratios of 2.98, 1.76, 1.63, and 1.54 for trace, 1+, 2+, and 3+ urine protein, respectively). There was an increased risk of graft failure with greater urine protein concentration (hazard ratios 2.22, 2.85, 6.41, and 19.71 for trace, 1+, 2+, and 3+, respectively). Conclusion: Urine protein is associated with major adverse cardiac events and graft loss in kidney transplant recipients. The role of interventions to reduce proteinuria on decreasing the risk of adverse cardiovascular and graft outcomes in kidney transplant recipients requires further study.

Range and Consistency of Infection Outcomes Reported in Trials Conducted in Kidney Transplant Recipients: A Systematic Review.

Infection remains a leading cause of death in kidney transplant recipients. This study aimed to assess the scope and consistency of infection outcomes reported in contemporary trials conducted in kidney transplant recipients. A literature review of all randomized trials and trial protocols reporting infection outcomes in adult kidney transplant recipients was identified in the Cochrane Kidney and Transplant Specialized Register from January 2014 to July 2019. Characteristics and infection outcomes from the trials were analyzed. From 102 included trials, 772 outcome measures were extracted and categorized into 216 unique measures with a median of 3.2 outcome measures per trial (range: 1-9). Measures were further grouped into 32 outcomes based on site of infection (14 outcomes) and organism (18 outcomes). The most commonly reported site-specific outcome and organism-specific outcome were systemic infection (71% trials) and cytomegalovirus infection (62% trials), respectively. Outcome metric and methods of aggregation included mean, median, proportion, proportional change, and number of patients with at least 1 episode. Across all trials, measures were assessed at 55 different time points with a range of 1-11 time points per trial. Infection outcomes in kidney transplant recipients were frequently reported by site and organism but varied widely in terms of outcome, metrics, method of aggregation, and time point of measurement. Establishment of core outcomes for infection based on the shared priorities of patients/caregivers and health professionals may improve the consistency, comparability, and usefulness of trial evidence.

Belatacept in Kidney Transplant Recipients With Failed Allografts for the Prevention of Humoral Sensitization: A Pilot Randomized Controlled Trial.

Belatacept in Kidney Transplant Recipients With Failed Allografts for the Prevention of Humoral Sensitization: A Pilot Randomized Controlled Trial.

Transplant Prognosis in Kidney Transplant Recipients with Diabetes under Mycophenolic Acid-Focused Therapeutic Drug Monitoring.

Mycophenolate mofetil is a key immunosuppressant that is metabolized into mycophenolic acid (MPA). The prognostic impact of MPA-focused therapeutic drug monitoring on allograft prognosis has not been determined in kidney transplant recipients with diabetes. In this study, we assessed the pharmacokinetics of MPA and allograft prognosis in recipients with diabetes. This study retrospectively analyzed 64 adult kidney transplant recipients. MPA blood concentration data (e.g., the time to the maximum concentration (Tmax), and the area under the concentration–time curve from 0 to 12 h (AUC0–12)) were collected at 3 weeks and 3 months after kidney transplantation. Of the 64 recipients, 15 had pre-existing diabetes. At 3 months after kidney transplantation, the Tmax of MPA was significantly longer in recipients with diabetes (mean (standard deviation): 2.8 (2.1) h) than in recipients without diabetes (1.9 (1.1) h, p = 0.02). However, the allograft estimated glomerular filtration rate and acute rejection rate, including borderline change, did not differ according to the diabetes status in patients with adjusted AUC0–12 of MPA within the target range. In conclusion, a longer Tmax of MPA was observed in recipients with diabetes; however, acceptable allograft prognosis was observed in kidney transplant recipients with diabetes and a sufficient AUC0–12 of MPA.

Design and Methods of the Validating Injury to the Renal Transplant Using Urinary Signatures (VIRTUUS) Study in Children.

Background.Lack of noninvasive diagnostic and prognostic biomarkers to reliably detect early allograft injury poses a major hindrance to long-term allograft survival in pediatric kidney transplant recipients.Methods.Validating Injury to the Renal Transplant Using Urinary Signatures Children’s Study, a North American multicenter prospective cohort study of pediatric kidney transplant recipients, aims to validate urinary cell mRNA and metabolite profiles that were diagnostic and prognostic of acute cellular rejection (ACR) and BK virus nephropathy (BKVN) in adult kidney transplant recipients in Clinical Trials in Organ Transplantation-4. Specifically, we are investigating: (1) whether a urinary cell mRNA 3-gene signature (18S-normalized CD3ε, CXCL10 mRNA, and 18S ribosomal RNA) discriminates biopsies with versus without ACR, (2) whether a combined metabolite profile with the 3-gene signature increases sensitivity and specificity of diagnosis and prognostication of ACR, and (3) whether BKV-VP1 mRNA levels in urinary cells are diagnostic of BKVN and prognostic for allograft failure.Results.To date, 204 subjects are enrolled, with 1405 urine samples, including 144 biopsy-associated samples. Among 424 urine samples processed for mRNA, the median A260:280 ratio (RNA purity) was 1.91, comparable with Clinical Trials in Organ Transplantation-4 (median 1.82). The quality control failure rate was 10%. Preliminary results from urine supernatant showed that our metabolomics platform successfully captured a broad array of metabolites. Clustering of pool samples and overlay of samples from various batches demonstrated platform robustness. No study site effect was noted.Conclusions.Multicenter efforts to ascertain urinary biomarkers in pediatric kidney transplant recipients are feasible with high-quality control. Further study will inform whether these signatures are discriminatory and predictive for rejection and infection.

Comparison of free plasma versus saliva mycophenolic acid exposure following mycophenolate mofetil administration in adult kidney transplant recipients

Therapeutic monitoring (TDM) of mycophenolic acid (MPA) has the potential to improve drug inefficacy and toxicities in kidney transplantation. However, measurement of plasma MPA concentrations is laborious and invasive. This study examined the utility of saliva compared with plasma based TDM of MPA. Paired blood and saliva samples were collected from 47 adult kidney transplant recipients pre- and at 1-, 2-, and 4-hours post mycophenolate mofetil administration. No relationship was observed between saliva MPA concentrations and either total or free plasma MPA concentrations (p > 0.05). This suggests that saliva is a poor direct marker of plasma MPA concentrations and therefore should not be used for MPA TDM.

Kidney Transplant Recipient Behavior During the Early COVID-19 Pandemic: A National Survey Study in Norway

Rationale & ObjectiveStudies published from countries with a high prevalence of COVID-19 have found increased incidence and a more severe disease course of coronavirus disease 2019 (COVID-19) in kidney transplant recipients than in the general population. We investigated how the first wave of the COVID-19 pandemic affected the everyday life of kidney transplant recipients in a country with a low infection burden.Study DesignProspective case-control study.Setting & ParticipantsAll adult kidney transplant recipients in Norway with a functioning graft and listed in the public phone registry (n = 3,060) and a group of randomly recruited individuals >18 years from the general population (n = 20,000) were invited to participate in the study by an SMS text message. In parallel, all kidney transplant recipients in Norway were invited to measure severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG from mid-June to October 2020.PredictorsThe participants were asked to fill out a questionnaire focused on everyday life, travel history, exposure to known COVID-19 cases, and demographics.Analytical ApproachGroups were compared with independent tests using 2-sided 0.05 significance levels.ResultsA total of 1,007 kidney transplant recipients and 4,409 controls answered the questionnaire. The kidney transplant recipients reported being more concerned about SARS-CoV-2 infection (27%) than the control group (7%; P value < 0.001); ie, they behaved more carefully in their everyday life (not going to the grocery store, 5.9% vs 0.9%, P < 0.001; keeping at least 1 meter distance, 16.6% vs 5.8%, P < 0.001). Of the kidney transplant responders, 81% had a SARS-CoV-2 IgG taken; all were negative.LimitationsMortality data is not reliable because of the low number of SARS-CoV-2 infected kidney transplant recipients in Norway. The relatively low questionnaire response rate for kidney transplant recipients is not optimal.ConclusionsThe questionnaire shows that kidney transplant recipients have behaved more carefully compared with the general population with less social interaction and a very high degree of adherence to governmental advice.

Organ donor management goals and delayed graft function in adult kidney transplant recipients.

Delayed graft function (DGF) after kidney transplantation is a common occurrence and correlates with poor graft and patient outcomes. Donor characteristics and care are known to impact DGF. We attempted to show the relationship between achievement of specific donor management goals (DMG) and DGF. This is a retrospective case-control study using data from 14046 adult kidney donations after brain death from hospitals in 18 organ procurement organizations (OPOs) which were transplanted to adult recipients between 2012 and 2018. Data on DMG compliance and donor, recipient, and ischemia-related factors were used to create multivariable logistic regression models. The overall rate of DGF was 29.4%. Meeting DMGs for urine output and vasopressor use were associated with decreased risk of DGF. Sensitivity analyses performed with different imputation methods, omitting recipient factors, and analyzing multiple time points yielded largely consistent results. The development of DMGs continues to show promise in improving outcomes in the kidney transplant recipient population. Studies have already shown increased kidney utilization in smaller cohorts, as well as other organs, and shown decreased rates of DGF. Additional research and analysis are required to assess interactions between meeting DMGs and correlation versus causality in DMGs and DGF.

Blood transfusion and the risk for infections in kidney transplant patients.

Receipt of a red blood cell transfusion (RBCT) post-kidney transplantation may alter immunity which could predispose to subsequent infection. We carried out a single-center, retrospective cohort study of 1,258 adult kidney transplant recipients from 2002 to 2018 (mean age 52, 64% male). The receipt of RBCT post-transplant (468 participants transfused, total 2,373 RBCT) was analyzed as a time-varying, cumulative exposure. Adjusted cox proportional hazards models were used to calculate hazard ratios (HR) for outcomes of bacterial or viral (BK or CMV) infection. Over a median follow-up of 3.8 years, bacterial infection occurred in 34% of participants at a median of 409 days post-transplant and viral infection occurred in 25% at a median of 154 days post-transplant. Transfusion was associated with a step-wise higher risk of bacterial infection (HR 1.35, 95%CI 0.95-1.91; HR 1.29, 95%CI 0.92-1.82; HR 2.63, 95%CI 1.94-3.56; HR 3.38, 95%CI 2.30-4.95, for 1, 2, 3-5 and >5 RBCT respectively), but not viral infection. These findings were consistent in multiple additional analyses, including accounting for reverse causality. Blood transfusion after kidney transplant is associated with a higher risk for bacterial infection, emphasizing the need to use transfusions judiciously in this population already at risk for infections.

Risk of post-transplant cardiovascular events in kidney transplant recipients with preexisting aortoiliac stenosis.

Prediction of the risk of cardiovascular events (CVE's) is important to optimize outcomes after kidney transplantation. Aortoiliac stenosis is frequently observed during pre‐transplant screening. We hypothesized that these patients are at higher risk of post‐transplant CVE's due to the joint underlying atherosclerotic disease. Therefore, we aimed to assess whether aortoiliac stenosis was associated with post‐transplant CVE's. This retrospective, single‐center cohort study included adult kidney transplant recipients, transplanted between 2000 and 2016, with contrast‐enhanced imaging available. Aortoiliac stenosis was classified according to the Trans‐Atlantic Inter‐Society Consensus (TASC) II classification and was defined as significant in case of ≥50% lumen narrowing. The primary outcome was CVE‐free survival. Eighty‐nine of 367 patients had significant aortoiliac stenosis and were found to have worse CVE‐free survival (median CVE‐free survival: stenosis 4.5 years (95% confidence interval (CI) 2.8–6.2), controls 8.9 years (95% CI 6.8–11.0); log‐rank test P < .001). TASC II C and D lesions were independent risk factors for a post‐transplant CVE with a hazard ratio of 2.15 (95% CI 1.05–4.38) and 6.56 (95% CI 2.74–15.70), respectively. Thus, kidney transplant recipients with TASC II C and D aortoiliac stenosis require extensive cardiovascular risk management pre‐, peri,‐ and post‐transplantation.

Incidence of Mortality, Acute Kidney Injury and Graft Loss in Adult Kidney Transplant Recipients with Coronavirus Disease 2019: Systematic Review and Meta-Analysis.

The adverse impact of Coronavirus disease 2019 (COVID-19) on kidney function has been reported since the global pandemic. The burden of COVID-19 on kidney transplant recipients, however, has not been systematically analyzed. A systematic review and meta-analysis with a random-effect model was conducted to explore the rate of mortality, intensive care unit admission, invasive mechanical ventilation, acute kidney injury, kidney replacement therapy and graft loss in the adult kidney transplant population with COVID-19. Sensitivity analysis, subgroup analysis and meta-regression were also performed. Results: we demonstrated a pooled mortality rate of 21% (95% CI: 19−23%), an intensive care unit admission rate of 26% (95% CI: 22–31%), an invasive ventilation rate among those who required intensive care unit care of 72% (95% CI: 62–81%), an acute kidney injury rate of 44% (95% CI: 39–49%), a kidney replacement therapy rate of 12% (95% CI: 9–15%), and a graft loss rate of 8% (95% CI: 5–15%) in kidney transplant recipients with COVID-19. The meta-regression indicated that advancing age is associated with higher mortality; every increase in age by 10 years was associated with an increased mortality rate of 3.7%. Regional differences in outcome were also detected. Further studies focused on treatments and risk factor identification are needed.