Kidney Transplant Recipients Group Research Articles

Comparative Analysis of Real-World Efficacy and Safety of Hypoxia-Inducible Factor Prolyl-Hydroxylase Inhibitors in Kidney Transplant Recipients Versus Nontransplant Individuals: A Single-Center Study

ObjectivesTo compare the efficacy and safety of hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHis), a novel agent for management of anemia in chronic kidney disease (CKD), between transplant recipients and nontransplant individuals. MethodsA retrospective analysis was conducted on nondialysis-dependent CKD stage 3 to 5 patients treated with the HIF-PHi roxadustat or daprodustat at a single institution. Patients were categorized as kidney transplant recipients (KTRs) and non-KTRs. Efficacy outcomes (hemoglobin and creatinine levels) and safety profiles (rate of adverse events [AEs], descriptions, and discontinuations due to AEs) were assessed 3 months before and 6 months after HIF-PHi initiation within and then between the groups. ResultsThe study comprised 82 patients (KTR: 43, non-KTR: 39). Median ages significantly differed between the KTR (52.7 years) and non-KTR (82.9 years) groups (P < .001). Roxadustat was predominantly used in the KTR group (88.4%), while daprodustat was used in the non-KTR group (94.9%, P < .001). Both groups exhibited significant increases in Hb levels at 1, 3, and 6 months post-HIF-PHi initiation (P for trend, <.001), with a relative increase in Hb level at 6 months of 16% for KTRs and 13% for non-KTRs. Creatinine levels showed no significant changes over 6 months. Although no difference was observed in drug discontinuation due to AEs, the KTR group experienced a significantly higher rate of thrombotic events (18.6 vs 2.6%, P = .049). ConclusionsHIF-PHis demonstrate comparable efficacy for managing anemia in CKD, regardless of transplant status. However, heightened vigilance for thrombosis events is necessary during follow-up for KTRs.

Are There Differences in Skin Autofluorescence-Measured Advanced Glycation End-Product Levels between Chronic Kidney Disease and Kidney Transplant Recipients?

The aim of this cross-sectional study was to evaluate the differences in the levels of advanced glycation end products (AGE) between patients with chronic kidney disease (CKD) and kidney transplant recipients (KTRs) and to investigate the risk factors for the AGE levels in each group of these patients. There were 217 participants total, of which 99 (45.6%) were KTRs and 118 (54.4%) had CKD. Data on the levels of AGE, body mass composition, anthropometric parameters, central and peripheral blood pressure, and clinical and laboratory parameters were gathered for each study participant. The AGE values of the CKD and KTRs groups did not differ from one another. In both groups, a lower estimated glomerular filtration rate, male sex, and older age were positive predictors for increased AGE values. Furthermore, higher levels of AGE were linked to lower central systolic blood pressure (cSBP) in the CKD group, whilst, in the KTRs group, higher levels of AGE were linked to a shorter time since kidney transplantation (KTx), more years of dialysis prior to KTx, lower levels of trunk visceral fat, the presence of arterial hypertension, and the absence of prescriptions for the antihypertensive medications urapidil and angiotensin II receptor blockers. Further studies are needed to better understand the above associations. Consequently, a personalised multidisciplinary approach to assess the cardiovascular as well as dietary and lifestyle risk factors to reduce the AGE levels in both KTRs and CKD patients may be implemented.

Bridging the gap: assessing CMV DNAemia in kidney transplant recipients with previous solid organ transplants.

Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive regimens. The aim of this retrospective single-center study was to investigate the incidence and implications of CMV DNAemia in KTRs with prior SOTs. The study included 97 KTRs with prior SOTs and 154 KTRs with no prior transplants as a control group. In the study group, the most common SOT before the current kidney transplantation (KT), was a previous KT. Patients in the KTR group with prior SOTs were more sensitized than those in the control group [calculated panel-reactive antibody > 30%: 49 (50.5%) vs. 30 (19.45%) patients, p = 0.001]. There was a 39.2% incidence of CMV DNAemia in the previous SOT group compared to 48.7% in the control group [non-significant (NS)]. Patients with prior SOTs demonstrated a shorter post-transplant time to CMV DNAemia [median time 1.6 months (interquartile range, IQR 0.7-5.8) in the KTRs with prior SOTs vs. 2.6 months (IQR 1.5-8.1) in the control group (p = 0.001)]. Although the study highlights the need for tailored prophylaxis strategies and vigilant monitoring in KTRs with prior SOTs, its limitations, such as its retrospective nature and single-center design, call for further multicenter research to establish comprehensive guidelines for managing CMV DNAemia in this unique patient population. Despite these limitations, this study underscores the importance of recognizing the heightened risk of CMV infection or reactivation in KTRs overall and the potential benefits of proactive intervention to mitigate associated morbidity and mortality.

Sleep and quality of life in kidney transplant recipients with and without non-melanoma skin cancer: a comparative study.

Non-melanoma skin cancer (NMSC) is prevalent in kidney transplant recipients (KTR), related tothe immunosuppressive effects of anti-rejection therapy. Sleep disturbances can alterthe immune system and enhance oxidative stress, which may increase the risk of carcinogenesis. This study aimed to analyze the quality of life and sleep in KTR with and without NMSC. Participants answered a set of questionnaires, the WHOQOL-bref, thePittsburgh Sleep Quality Index (PSQI), theEpworth Sleepiness Scale (ESS), the Berlin Questionnaire and self-reported chronotype. The total sample was distributed in the following groups: KTR with NMSC (n = 42), KTR without NMSC (n = 43) and healthy controls (n = 41). The mean scores of the questionnaires were not statistically significant, except for 3 domains of PSQI (sleep quality, sleep latency and daily consequences of poor sleep). The KTR with NMSC and control group presented worse sleep quality. Worse sleep latency and more daytime consequences were found in KTR groups. All groups had a numerical predominance of low-quality sleep (PSQI) and greater sleepiness (EES). Higher risk of obstructive sleep apnea was not observed and the evening-type chronotype was most frequent. In the WHOQOL, compromised physical domain was observed in KTR. Significant results were reached in few aspects of quality of life and sleep comparing KTR and controls. All groups presented excessive daytime sleepiness and low-sleep quality.

BNT162b2 Elicited an Efficient Cell-Mediated Response against SARS-CoV-2 in Kidney Transplant Recipients and Common Variable Immunodeficiency Patients.

SARS-CoV-2 vaccination is the standard of care for the prevention of COVID-19 disease. Although vaccination triggers both humoral and cellular immune response, COVID-19 vaccination efficacy is currently evaluated by measuring antibodies only, whereas adaptative cellular immunity is unexplored. Our aim is to test humoral and cell-mediated response after three doses of BNT162b vaccine in two cohorts of fragile patients: Common Variable Immunodeficiency (CVID) patients and Kidney Transplant Recipients (KTR) patients compared to healthy donors. We enrolled 10 healthy controls (HCs), 19 CVID patients and 17 KTR patients. HC BNT162b third dose had successfully mounted humoral immune response. A positive correlation between Anti-Spike Trimeric IgG concentration and neutralizing antibody titer was also observed. CVID and KTR groups showed a lower humoral immune response compared to HCs. IFN-γ release induced by epitopes of the Spike protein in stimulated CD4+ and CD8+ T cells was similar among vaccinated HC, CVID and KTR. Patients vaccinated and infected showed a more efficient humoral and cell-mediated response compared to only vaccinated patients. In conclusion, CVID and KTR patients had an efficient cell-mediated but not humoral response to SARS-CoV-2 vaccine, suggesting that the evaluation of T cell responses could be a more sensitive marker of immunization in these subjects.

#5602 DEPRESSION AND ANXIETY IN FAMILY CAREGIVERS OF END STAGE KIDNEY DISEASE PATIENTS IN GREECE: A COMPARISON BETWEEN DIALYSIS AND KIDNEY TRANSPLANTATION

Abstract Background and Aims Chronic kidney disease (CKD) is considered a high-stress disease because of its chronicity, co-morbidity, and lifelong treatment. Family members are often the main caregivers of end stage kidney disease (ESKD) patients and they are involved in various roles. Caregivers of ESKD patients experience emotional stress, anxiety and depression as they support their family members throughout the disease and treatment. This cross-sectional study aimed to assess depression and anxiety in caregivers of ESKD patients and to compare these disorders between caregivers of hemodialysis (HD) patients’ and kidney transplant recipients (KTR), as well as to investigate potential social-demographic parameters associated with caregivers’ depression and anxiety. Method A total of 342 participants (171 couples of patients and caregivers) were recruited. Structured interviews and self-completed questionnaires were obtained from HD patients, KTR (138 HD patients and 33 KTR) and their caregivers. The Beck Depression Inventory and the Generalized Anxiety Disorder-2 scales were used as screening tools. Depression scores were classified into four levels based on the level of severity (low, mild, moderate, severe). The collected data were encoded and analyzed using ΙΒΜ SPSS version 25 and R Statistical Software. Results Mean age of caregivers was 58 years and the majority were females (67.2%). Total anxiety score was high (Mdn = 3) with a mildly increased score of depression (Mdn = 9.5). Caregivers’ anxiety and depressive symptoms were significantly associated with gender, duration of caregiving, educational level, financial status, and caregivers’ age (p&amp;lt;0.01 for all). Caregivers’ depression and anxiety were also, related to the type of patients’ treatment (Table 1). HD caregivers reported significantly higher anxiety scores (Mdn = 3(2-5)) in comparison to KTR caregivers (Mdn = 2(2-4)) (p = 0.048) (Table 2). Moreover, HD caregivers revealed higher (Mdn = 11(0-46)) levels of depression than the KTR group (Mdn = 6 (0-25)) (p = 0.049) (Table 3). Conclusion Based on the findings of this study, the type of ESKD treatment displayed an important role in caregivers’ anxiety and depression symptoms, with KTR caregivers having the best scores. In particular, KTR caregivers appeared to have lower levels of depression and anxiety than caregivers of HD patients.

#6369 RESULTS OF KIDNEY TRANSPLANTATION IN PATIENTS WITH LOW MFI PREFORMED DONOR SPECIFIC ANTIBODIES

Abstract Background and Aims Preformed DSA at transplantation, significantly increase risk of antibody-mediated rejection (ABMR). While pre-existing positive DSA with concomitant positive cross-match is a general contra-indication to kidney transplantation, DSA presence with negative crossmatch is still a controversial topic. The presence of DSA with Mean Fluorescence Index (MFI) up to 3.000 and a negative cross-match is not valued as a contraindication to transplantation and is widely accepted. In some transplant centers the chance of transplantation is also offered to DSA positive patients, with MFI up to 5.000. Aim of this study was to analyze graft and patient survival, acute cellular rejection, humoral rejection, renal function and side effects in kidney transplant recipients (KTR) with positive DSA (MFI up to 3.000) and negative cross-match. Method Nineteen pts (age 53+/-11) with chronic renal failure on chronic hemodialysis treatment (8+/-6 years) received a kidney transplant between May 2017 and December 2020. Median PRA was 66%; 100% pts had DSA with average MFI 2122 (min 1039, max 3779). As immunosuppressive therapies all pts received induction with Thymoglobuline plus Rituximab, followed by maintenance immunosuppression with Tacrolimus, MofetilMycoFenolate and Steroids. All patients were on periodic follow up in our Transplant Clinic. Mean follow up was 26.5+/-14.4 months. Results were compared to a concomitant KTR group DSA and crossmatch negative. Results After 2y follow-up, 17/19 pts are alive (89.5%), one patient died (1/19, 5.2%) after treatment for ABMR. Three patients returned to dialysis treatment (15.8%) during the first year post-tx, because of: PNF 1pt; irreversible ABMR rejection 2 pts. One other patient had reversible ABMR. Cumulative one year graft survival was 79% and the cumulative incidence of ABMR was 15.8%. Average 2 years follow-up creatinine was 1.46+/-0.88 mg/dl, median 2 year GFR was 51+/-25 ml/min. Comparing the matched control group (19 pts DSA and cross-match negative) 2 years patient survival, graft survival, GFR, acute rejection were not significantly different. Incidence of acute rejection was higher in the DSA positive group (16% vs 0%), as well as graft loss (21% vs 12%). Conclusion Our data suggest that low dose Thymoglobuline plus Rituximab induction allow kidney transplantation in recipient with high PRA (69%) and positive DSA with low MFI (&amp;lt; 3.000), with higher risk of acute rejection, and graft loss.

The results of SGLT-2 inhibitors use in kidney transplantation: 1-year experiences from two centers.

Sodium-glucose co-transporter-2 inhibitor (SGLT-2i) administration is associated with some concerns in regard to the increased risk of genital and urinary tract infections (UTI) in kidney transplant recipients (KTR). In this study, we present the results of SGLT-2i use in KTR, including the early post-transplant period. Participants were divided into two groups: SGLT-2i-free diabetic KTR (Group 1, n = 21) and diabetic KTR using SGLT-2i (Group 2, n = 36). Group 2 was further divided into two subgroups according to the posttransplant prescription day of SGLT-2i; < 3months (Group 2a) and ≥ 3months (Group 2b). Groups were compared for development of genital and urinary tract infections, glycated hemoglobin a1c (HgbA1c), estimated glomerular filtration rate (eGFR), proteinuria, weight change, and acute rejection rate during 12-month follow-up. Urinary tract infections prevalence was 21.1% and UTI-related hospitalization rate was 10.5% in our cohort. Prevalence of UTI and UTI-related hospitalization, eGFR, HgbA1c levels, and weight gain were similar between the SGLT-2i group and SGLT-2i-free group, at the 12-month follow-up. UTI prevalence was similar between groups 2a and 2b (p = 0.871). No case of genital infection was recorded. Significant proteinuria reduction was observed in Group 2 (p = 0.008). Acute rejection rate was higher in the SGLT-2i-free group (p = 0.040) and had an impact on 12-month follow-up eGFR (p = 0.003). SGLT-2i in KTR is not associated with an increased risk of genital infection and UTI in diabetic KTR, even in the early posttransplant period. The use of SGLT-2i reduces proteinuria in KTR and has no adverse effects on allograft function at the 12-month follow-up.

Decreased expression of ADAM10 on monocytes is associated with chronic allograft dysfunction in kidney transplant recipients.

Chronic allograft dysfunction (CAD) is a common cause of allograft loss in kidney transplant recipients (KTRs). Our previous study found that elevated serum soluble T cell immunoglobulin mucin-3 (sTim-3) was positively associated with the severity of CAD in KTRs. sTim-3 was reported to be generated from ADAM10/ADAM17-mediated ectodomain shedding of membrane Tim-3 (mTim-3) in humans. However, whether mTim-3 shedding-related molecules participate in the progression of CAD remains unknown. Here, we explored the relationships between different forms of Tim-3, including mTim-3 on different peripheral blood cell subsets, serum and urine sTim-3, and ADAM10/17 expression and active status to investigate their roles in CAD. 63 KTRs with stable grafts, 91 KTRs with CAD and 42 healthy controls (HCs) were enrolled. Total Tim-3, pADAM10/17 and mADAM10/17 proteins were semiquantified by western blot. Serum and urine sTim-3 concentrations were determined by ELISA. mTim-3 and ADAM10/17 expression on leukocyte subpopulations was determined by flow cytometry. The KTR groups displayed significantly higher levels of urine sTim-3pg/μmol creatinine than the HC group, while no difference was found between the two KTR groups. KTRs with CAD presented reduced nonactive pADAM10 protein but unaltered active mADAM10 when compared to the Stable group; no difference was found between the KTR groups regarding total Tim-3 and p/m ADAM17 protein levels. In addition, the CAD group showed lower mTim-3 expression on BDCA3+ DC than the Stable group; no other difference was observed in its expression on B, T, NK, NKT, monocyte subsets and other DC subsets among groups. With the deterioration of allograft function, ADAM10 expression densities on classical, intermediate, and non-classical monocytes were significantly decreased. Correlation analyses revealed that eGFR and serum sTim-3 exhibited weak to modest correlations with ADAM10 on monocyte and DC subsets. Our data indicated that ADAM10, especially its decreased expression on monocytes, may play an important role in the progression of CAD in KTRs. However, whether there is an interaction between ADAM10 and mTim-3 in the pathogenesis of CAD in KTRs needs to be further studied.

Standardization of neutrophil CD64 and monocyte HLA-DR measurement and its application in immune monitoring in kidney transplantation.

Infections cause high mortality in kidney transplant recipients (KTRs). The expressions of neutrophil CD64 (nCD64) and monocyte HLA-DR (mHLA-DR) provide direct evidence of immune status and can be used to evaluate the severity of infection. However, the intensities of nCD64 and mHLA-DR detected by flow cytometry (FCM) are commonly measured by mean fluorescence intensities (MFIs), which are relative values, thus limiting their application. We aimed to standardize nCD64 and mHLA-DR expression using molecules of equivalent soluble fluorochrome (MESF) and to explore their role in immune monitoring for KTRs with infection. The study included 50 KTRs diagnosed with infection, 65 immunologically stable KTRs and 26 healthy controls. The blood samples were collected and measured simultaneously by four FCM protocols at different flow cytometers. The MFIs of nCD64 and mHLA-DR were converted into MESF by Phycoerythrin (PE) Fluorescence Quantitation Kit. The intraclass correlation coefficients (ICCs) and the Bland-Altman plots were used to evaluate the reliability between the four FCM protocols. MESFs of nCD64 and mHLA-DR, nCD64 index and sepsis index (SI) with the TBNK panel were used to evaluate the immune status. Comparisons among multiple groups were performed with ANOVA one-way analysis. Receiver operating characteristics (ROC) curve analysis was performed to diagnose infection or sepsis. Univariate and multivariate logistic analysis examined associations of the immune status with infection. MESFs of nCD64 and mHLA-DR measured by four protocols had excellent reliability (ICCs 0.993 and 0.957, respectively). The nCD64, CD64 index and SI in infection group were significantly higher than those of stable KTRs group. Patients with sepsis had lower mHLA-DR but higher SI than non-sepsis patients. ROC analysis indicated that nCD64 had the highest area under the curve (AUC) for infection, and that mHLA-DR had the highest AUC for sepsis. Logistic analysis indicated that nCD64 > 3089 and B cells counts were independent risk factors for infection. The standardization of nCD64 and mHLA-DR made it available for widespread application. MESFs of nCD64 and mHLA-DR had good diagnostic performance on infection and sepsis, respectively, which could be promising indicators for immune status of KTRs and contributed to individualized treatment.

Altered Serum Bile Acid Profile Associated with Chronic Allograft Dysfunction in Kidney Transplant Recipients.

BACKGROUND Chronic allograft dysfunction (CAD) is the leading cause of graft loss among kidney transplant recipients (KTRs). Bile acids (BAs) play an important role in regulating inflammatory process, which is the major contributor to the development of CAD. The aim of this study was to evaluate the association between BAs metabolic dysregulation and CAD in KTRs. MATERIAL AND METHODS Fifteen serum BA species were determined in 43 healthy controls (HCs) and 131 KTRs by UPLC-MS/MS. KTRs were grouped into stable renal function (STA) and CAD1 and CAD2 groups based on eGFR levels. Circulating CYP7A1, CYP7B1, CYP27A1, and SLCO2B1 mRNA levels were determined by RT-PCR. RESULTS Total BA concentrations were comparable among the 4 groups. However, KTRs showed significantly different BAs profiling compared to HCs. KTRs with severe CAD (CAD2) had significantly lower unconjugated BAs and secondary BAs (SBAs) compared to the other 3 groups. KTRs had significantly lower SBAs/primary BAs (PBAs) ratios than HCs, which were comparable among the 3 KTR groups. Conjugated/unconjugated BAs ratios increased significantly with the deterioration of allograft function, which was further confirmed by correlation analysis. Differential correlation network analysis revealed that perturbations in intraclass and interclass BA coregulation existed during CAD progression. Moreover, relative gene expressions of CYP7B1 and CYP27A1 were positively correlated with eGFR. CONCLUSIONS BA species profiling, but not total BA concentrations, was significantly altered in KTRs with CAD. The shifts from unconjugated BAs toward conjugated BAs, SBAs toward PBAs, and distinct pairwise BAs coregulation patterns were the main characteristics of KTRs with CAD.

Immunogenicity and safety of double dosage of pneumococcal vaccines in adult kidney transplant recipients and waiting list patients: A non-blinded, randomized clinical trial

BackgroundPneumococcal prime-boost vaccination is recommended for solid organ transplant recipients, but is not thoroughly tested in this population. Furthermore, a pneumococcal vaccine dose effect has never been investigated, though observed in healthy adults. To assess whether a double dose of 13-valent pneumococcal conjugate vaccine (PCV13) and of 23-valent pneumococcal polysaccharide vaccine (PPV23) increases the immunogenicity of prime-boost vaccination in kidney transplant recipients (KTRs) and patients on the kidney transplant waiting list (WLPs), a phase 3, randomized, non-blinded trial was conducted. MethodsKTRs and WLPs were in parallel groups assigned either normal or double dosage of both vaccines 12 weeks apart. A ′protective response′ was an average geometric mean concentration ≥ 1 mg/L based on 12 vaccine shared serotype-specific IgG antibodies. Furthermore, number of antibodies with ≥ 2-fold rises and individual serotype-specific antibody concentrations were evaluated. Follow-up was 48 weeks. ResultsSeventy-four KTRs and 65 WLPs were enrolled. In WLPs, double dosage resulted in a significantly higher proportion of participants with a ′protective response′ (66.7%), 5 weeks after PPV23, compared to normal dosage (35.5%), p = 0.015. KTRs exhibited no dose effect. After PPV23, all four groups had increased their number of serotypes with ≥ 2-fold rises (p ≤ 0.05 for both WLPs groups; p ≤ 0.01 for both KTRs groups). Vaccines were safe, well tolerated and still immunogenic at week 48. ConclusionsData suggests that double dosage of pneumococcal vaccines used according to the prime-boost strategy might be recommendable for WLPs. Furthermore, our data supports PPV23́s additive effect to PCV13 in KTRs and WLPs. (EudraCT: 2016–004123-23)

A Comparison Study of Coronavirus Disease 2019 Outcomes in Hospitalized Kidney Transplant Recipients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect any human host, but kidney transplant recipients (KTR) are considered more susceptible on the basis of previous experience with other viral infections. We evaluated rates of hospital complications between SARS-CoV-2-positive KTR and comparator groups. We extracted data from the electronic health record on patients who were hospitalized with SARS-CoV-2, testing at six hospitals from March 4 through September 9, 2020. We compared outcomes between SARS-CoV-2-positive KTR and controls: SARS-CoV-2-positive non-KTR, SARS-CoV-2-negative KTR, and SARS-CoV-2-negative non-KTR. Of 31,540 inpatients, 3213 tested positive for SARS-CoV-2. There were 32 SARS-CoV-2-positive and 224 SARS-CoV-2-negative KTR. SARS-CoV-2-positive KTR had higher ferritin levels (1412; interquartile range, 748-1749 versus 553; interquartile range, 256-1035; P<0.01) compared with SARS-CoV-2-positive non-KTR. SARS-CoV-2-positive KTR had higher rates of ventilation (34% versus 14%, P<0.01; versus 9%, P<0.01; versus 5%, P<0.01), vasopressor use (41% versus 16%, P<0.01; versus 17%, P<0.01; versus 12%, P<0.01), and AKI (47% versus 15%, P<0.01; versus 23%, P<0.01; versus 10%, P<0.01) compared with SARS-CoV-2-positive non-KTR, SARS-CoV-2-negative KTR, and SARS-CoV-2-negative non-KTR, respectively. SARS-CoV-2-positive KTR continued to have increased odds of ventilation, vasopressor use, and AKI compared with SARS-CoV-2-positive non-KTR independent of Elixhauser score, Black race, and baseline eGFR. Mortality was not significantly different between SARS-CoV-2-positive KTR and non-KTR, but there was a notable trend toward higher mortality in SARS-CoV-2-positive KTR (25% versus 16%, P=0.15, respectively). Hospitalized SARS-CoV-2-positive KTR had a high rate of mortality and hospital complications, such as requiring ventilation, vasopressor use, and AKI. Additionally, they had higher odds of hospital complications compared with SARS-CoV-2-positive non-KTR after adjusting for Elixhauser score, Black race, and baseline eGFR. Future studies with larger sample size of KTR are needed to validate our findings. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/K360/2021_03_25_KID0005652020.mp3.

Is COVID-19 infection more severe in kidney transplant recipients?

There are no studies which have compared the risk of severe COVID‐19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID‐19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single‐center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID‐19 or mortality. Severe COVID‐19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30‐day cumulative incidence of severe COVID‐19 did not differ between KTR and nontransplant patients; however, 30‐day COVID‐19‐related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C‐reactive protein (CRP) were associated with severe COVID‐19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID‐19‐related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID‐19‐related mortality compared to nontransplant hospitalized patients.

Usefulness of BK virus-specific interferon-γ enzyme-linked immunospot assay for predicting the outcome of BK virus infection in kidney transplant recipients.

Background/AimsTo investigate if BK virus (BKV)-specific T cell immunity measured by an interferon-γ enzyme-linked immunospot (ELISPOT) assay can predict the outcome of BK virus infection in kidney transplant recipients (KTRs). MethodsWe included 68 KTRs with different viremia status (no viremia [n = 17], BK viremia [n = 27], and cleared viremia [n = 24]) and 44 healthy controls (HCs). The BK viremia group was divided into controller (< 3 months) and noncontroller (> 3 months) according to sustained duration of BKV infection. We compared BKV-ELISPOT results against five BKV peptides (large tumor antigen [LT], St, VP1-3). ResultsBKV-ELISPOT results were higher in three KTRs groups with different BKV infection status than the HCs group (p < 0.05). In KTR groups, they were higher in cleared viremia group than no viremia or BK viremia group. Within the BK viremia group, controller group had higher LT-ELISPOT results compared to noncontroller group (p = 0.032). Also, KTRs without BK virus-associated nephropathy (BKVN) had higher LT, St, VP1, and VP2-ELISPOT results than those with BKVN (p < 0.05). ConclusionsBKV-ELISPOT assay may be effective in predicting clinical outcomes of BKV infection in terms of clearance of BK virus and development of BKVN.

Higher mortality risk among kidney transplant recipients than among estimated glomerular filtration rate-matched patients with CKD-preliminary results.

Although kidney transplantation prolongs survival relative to dialysis, it is associated with a higher death rate than in the general population. The objective of the present study was to assess and compare the risk of mortality and frequency of non-lethal cardiovascular (CV) events in kidney transplant recipients (KTRs) beyond 1 year after successful transplantation versus patients with chronic kidney disease (CKD) using propensity score-matched analysis of estimated glomerular filtration rate (eGFR) and other parameters. After propensity score matching, we studied 340 KTRs from the French Données Informatisées et Validées en Transplantation cohort and 605 non-transplant patients with CKD (CKDps) from the French Chronic Kidney Disease-Renal Epidemiology and Information Network cohort. The mean ± standard deviation eGFR was 42 ± 13 and 41 ± 12 mL/min/ 1.73 m2, respectively (P = 0.649). Descriptive data were completed by a survival analysis with Cox regression models. After a median follow-up period of 2.8 years (KTRs 2.0 years, CKDp 2.9 years), 71 deaths were recorded (31 and 40 in the KTR and CKD groups, respectively). Univariate analysis showed that KTRs had a significantly greater risk of mortality than CKDps. In multivariable analysis, KTRs were found to have a 2.7-fold greater risk of mortality [hazard ratio 2.7 (95% confidence interval 1.6-4.7); P = 0.005]. There was no between-group difference concerning the risk of CV events (P = 0.448). CV death rates in KTRs (29.0%) approximated those of CKDps (22.5%), whereas death rates due to infections were higher in KTRs (19.4% versus 10.0%). Beyond 1 year after transplantation, KTRs, who possibly had a longer CKD history, had a significantly greater mortality risk than eGFR-matched CKDps. The excess risk was not associated with CV events.

The Risk of Stroke in Kidney Transplant Recipients with End-Stage Kidney Disease.

Background: The incidence of stroke after kidney transplantation is poorly understood. Our study aimed to determine the incidence and predictors of stroke as well as mortality from stroke in kidney transplant recipients (KTRs). Methods: This retrospective cohort study used the National Health Insurance Research Database in Taiwan to study KTRs (N = 4635), patients with end-stage renal disease (ESRD; N = 69,297), and patients from the general population who were chronic kidney disease (CKD)-free and matched by comorbidities (N = 69,297) for the years 2000 through 2010. The risk of stroke was analyzed using univariate and multivariate Cox regression models and compared between study cohorts. Findings: Compared with the ESRD subgroup, KTRs had a significantly lower risk of overall stroke (adjusted hazard ratio (aHR) = 0.37, 95% confidence interval (CI) = 0.31–0.44), ischemic stroke (aHR = 0.45, 95% CI = 0.37–0.55), and hemorrhagic stroke (aHR = 0.20, 95% CI = 0.14–0.29). The risk patterns for each type of stroke in the KTR group were not significantly different than those of the CKD-free control subgroup. The predictors of stroke were age and diabetes in KTRs. All forms of stroke after transplantation independently predicted an increased risk of subsequent mortality, and the strongest risk was related to hemorrhagic events. Interpretation: KTRs had a lower risk of stroke than ESRD patients, but this risk was not significantly different from that of the CKD-free comorbidities-matched general population group. Although stroke was relatively uncommon among cardiovascular events, it predicted unfavorable outcome in KTRs.

Clinical significance of the Kidney Donor Profile Index in deceased donors for prediction of post-transplant clinical outcomes: A multicenter cohort study.

BackgroundWe investigated whether the Kidney Donor Profile Index (KDPI) system is useful in predicting clinical outcomes in deceased donor kidney transplantation (DDKT).MethodsFour hundred sixty-nine kidney transplant recipients (KTRs) receiving kidneys from 359 deceased donors were included in this study, which involved three transplant centers. KTRs were divided into high and low KDPI KTR groups based on the median KDPI score of 67%. We compared clinical outcomes between the high KDPI and low KDPI groups.ResultsThere were no significant differences in the incidence of delayed graft function and acute rejection between high and low KDPI KTR groups. In comparison with histologic findings in allograft tissues obtained within three months from KT, the proportion of glomerulosclerosis was significantly higher in the high KDPI KTR group than in the low KDPI KTR group. With Kaplan-Meier analysis, the graft survival rate was significantly lower in the high KDPI KTR group than in the low KDPI KTR group (Log rank, P = 0.017), and multivariate analysis also demonstrated that a high KDPI score was a significant risk factor for death censored allograft failure (HR 2.62, 95% CI, 1.29–5.33, P = 0.008).ConclusionThe KDPI scoring system is useful in predicting allograft outcomes in a Korean DDKT cohort.

Nucleic Acid Tests for BK Polyomavirus Is Critical in Renal Transplant Recipients

This study evaluates the incidence of BK polyomavirus (BKV) and prognosis of BKV infection in kidney transplant recipients (KTRs) who received transplantation in our hospital before and after regular BKV nucleic acid test (NAT) was implemented. MethodsThe study included 74 KTRs who received a single kidney either from standard- or expanded-criteria deceased donor between March 2011 and March 2017. BKV NATs were regularly checked in 26 patients (group 1) in the first posttransplant year in accordance with current guidelines since NAT was implemented in our laboratory in 2014. We retrospectively compared 48 KTRs (group 2) who either received NAT when necessary in another laboratory or were not checked before 2014. ResultsThere was no significant difference in patient characteristics between groups. BKV viruria were confirmed in 8 of 26 (30.8%) group 1 patients, whereas only 2 of 48 (4.2%) BKV infections were confirmed in group 2. None of the BKV(+) KTRs in group 1 developed BK polyomavirus-associated nephropathy (BKVAN), whereas 2 BKV(+) patients (100%) of group 2 developed BKVAN, which indicates renal function deterioration and biopsy-validated nephropathy. There was no significant difference in graft survival and renal function between the 2 groups. ConclusionsThe risk of BKV infection is considerably higher in KTRs using NAT. Because there is no approval treatment, early diagnosis of BKV infection and early reduction of immunosuppression agents is critical for KTRs. Implementation of regular BKV NAT is mandatory before BKVAN and malignant neoplasms develop.

No Significant Influence of Reduced Initial Tacrolimus Dose on Risk of Underdosing and Early Graft Function in Older and Overweight Kidney Transplant Recipients

BackgroundNowadays, a reduced initial daily dose of tacrolimus (Tac) (0.1–0.15 mg/kg) is recommended for the majority of kidney transplant recipients (KTRs). The aim of the study was to analyze the safety of such a regimen, including the risk of first inadequately low Tac blood level, acute rejection (AR) occurrence, or early graft dysfunction. MethodsIn 2011, we introduced a modified (0.1–0.15 mg/kg/d) initial Tac dosing regimen in older (>55 years) and/or overweight KTRs. To assure the safety of this protocol, we monitored the risk of inadequately low blood Tac level (<6 ng/mL) and incidence of AR or delayed graft function (DGF). The historical cohort with the higher Tac dosing regimen (0.2 mg/kg/d, n = 208) served as a control group. ResultsThe mean Tac daily dose in 78 KTRs (group with reduced dosing) was 0.133 (95% confidence interval [CI], 0.130–0.136) mg/kg and was significantly lower than the standard, previously prescribed dose of 0.195 (95% CI, 0.194–0.197) mg/kg. Of note, induction therapy was employed twice more often in the reduced Tac dosing group. The dose reduction resulted in a slight, nonsignificant decrease in first Tac trough level. The percentages of patients with first Tac troughs <6 ng/mL (5.1% vs 4.8%), AR (6.4% vs 5.8%), and DGF (25.6% vs 31.2%) were similar in the reduced and standard dosing groups. ConclusionThe currently recommended reduction in Tac initial dosing does not increase the risk of inadequate immunosuppression and does not affect the early graft function. Regardless of Tac dose reduction, there is still a substantial risk of Tac overdosing in older or overweight KTRs.