Adult KTx Research Articles

Improvement in right heart function following kidney transplantation in esrd patients: insights from speckle tracking echocardiography analysis.

Chronic kidney disease (CKD) is commonly associated with unfavorable cardiovascular outcomes and remains the leading cause of mortality in individuals with end-stage renal disease (ESRD). Despite substantial knowledge about the impact of CKD on the left heart, the right heart, which holds significant clinical relevance, has often been overlooked and inadequately assessed in ESRD patients who have undergone kidney transplant (KTx). This study aimed to evaluate the effects of KTx on the right heart chambers in ESRD patients. 57 adult KTx candidates were enrolled in this prospective longitudinal study, while 49 of them were included in the final assessment. Patients underwent a comprehensive cardiac assessment, including conventional echocardiography, speckle tracking echocardiography, and three-dimensional heart modeling both before and after surgery. Echocardiographic assessments showed significant increases in right ventricular (RV) ejection fraction, RV fractional area change (RVFAC), tricuspid annular plain systolic excursion, RV fractional shortening, right atrial (RA) reservoir, conduit, and booster strains, and RV global longitudinal strain (RVGLS). Moreover, significant reductions in RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume, RV end-diastolic diameter (RVEDD) in mid-cavity view, systolic pulmonary artery pressure was observed (all P values < 0.05). However, no significant difference was found in S velocity, as well as RVEDD in basal and apex-to-annulus view. Moreover, pre-KTx measurements of RVGLS, RVEDD (apex-to-annulus diameter), RV fractional shortening, and S velocity were predictors of RVGLS after KTx. RA conduit strain was also identified as a predictor of RA conduit strain after KTx. Additionally, age, RVEDV, RVESV, RVFAC, and RA reservoir strain before KTx were identified as independent predictors of RA reservoir strain after KTx. The findings of this study demonstrate a significant improvement in right heart function following KTx. Furthermore, strain analysis can provide valuable insights for predicting right heart function after KTx.

Cellular immunity against cytomegalovirus and risk of infection after kidney transplantation.

Cytomegalovirus (CMV) infection remains a challenge following kidney transplantation (KTx). Currently, CMV-IgG serostatus at transplantation is used to individualize CMV preventive strategies. We assessed the clinical utility of CMV-IGRA for predicting CMV infection following KTx. We performed a nationwide prospective cohort study from August 2016 until December 2022. Data from all adult KTx recipients in Norway, n=1,546 (R+; n=1,157, D+/R-; n=260, D-/R-; 129), were included with a total of 3,556 CMV-IGRA analyses (1,375 at KTx, 1,188 at eight weeks, 993 one-year after KTx) and 35,782 CMV DNAemia analyses. In R+ recipients CMV-IGRA status, measured at any of the time-points, could not identify any differential risk of later CMV infection. D+/R- recipients remaining CMV-IGRA negative 1-year after transplantation (regardless of positive CMV DNAemia and/or CMV IgG status at that time) had increased risk of developing later CMV infection compared to D+/R- recipients who had become CMV-IGRA positive (14% vs. 2%, p=0.01). Knowledge of pre-transplant CMV-IGRA status did not provide additional information to CMV-IgG serostatus that could improve current post-transplant CMV treatment algorithms. However, D+/R- recipients with a persisting negative CMV-IGRA one-year after transplantation remained at increased risk of experiencing later CMV infection. Therefore we advocate post-transplant CMV-IGRA monitoring in these patients.

243.2: Pediatric Kidney Transplantation in Argentina: Is Delayed Graft Function a Problem? Results of a Multicenter Study

Introduction: Delayed graft function (DGF) is a manifestation of acute kidney injury occurring after kidney transplantation (KTx). Incidence of DGF in pediatric KTx recipients is variable (10% to 25%) due to different definitions of DGF and different subgroups of kidney donors. It is associated with an increased risk of graft loss in adult KTx. Several factors related to donor, recipient, and organ procurement/transplantation procedures may increase the risk of DGF. The aim of our study was to evaluate the cumulative incidence of DGF in a children who received a kidney graft from a brain-dead donor, its impact on patient and graft survival, and to identify predictive risk factors of DGF. Methods: A retrospective multicenter study was conducted including recipients under 18 years of age who underwent KTx from a brain-dead donor between January 1, 2015 and December 31, 2017. DGF was defined as the need for dialysis within the first week after KTx. Data were obtained from the clinical records of the patients and from the Registry and Management System of Argentina (SINTRA) and were analyzed using MedCalc® Statistical Software version 20.014; 2021. Results: We analyzed 239 KTx performed at 17 centers. Of the recipients 54.4% were male, median age at Tx was 13.7 yr (r: 2.8 -17.9), weight 30 kg (r: 7 - 82), BMI 17 Kg/m2 (r: 11 - 36). Etiology of ESRD: CAKUT 30%, glomerular diseases with risk of recurrence 24.3%, typical HUS 3.8%, others 29.7%, and unknown 12.2%. Pre-emptive KTx was performed in 18.8% of patients, 39.7% were receiving hemodialysis, and 41.5% peritoneal dialysis. Median of time on dialysis was 2.62 yr (r: 0.12 - 9.8). Of the donors 70.7% were male, median age was 17.6 yr (r: 2.8 - 55), BMI 23 Kg/m2 (r: 17 - 35), BMI ratio donor/recipient 1.35, and pre-ablation serum creatinine 0.82 mg/dl (r: 0.6 - 2.6). Cause of death was trauma in 57%, vascular in 24%, and others in 19%. Cold ischemia time was 16.6 hours (r: 4.2 - 42), HLA mismatches ≼ 3: 54% and > 3: 46 %. Multiple-organ donor in 84.5%. Overall, 59 patients (24.7%) developed DGF. Patients without DGF had better graft survival at 1 (96% vs 78%) and 3 yrs of follow-up (89% vs 73%) p= 0.001. There were no significant differences in patient survival between both groups at the 3-year follow-up (95% vs 91%). Incidence of early AR (90 days post Tx) was higher in patients with DGF (34.5% vs 10.6%) p= 0.0001. In univariate analysis risk factors for DGF were: age at Tx > 13.7 yr, male gender, glomerular disease with risk of recurrence, hemodialysis as prior to KTx, and time on dialysis > 1 yr. In multivariate analysis independent risk factors for DGF were: time on dialysis > 1 yr (OR 9.2 - 95% CI 2.1 - 39) and age at KTx > 13.7 yr (OR 1.09 - 95% CI 1.01 - 1.18). Conclusion: In our cohort, cumulative incidence of DGF was higher than that reported by other authors. Patients with DGF had worse graft survival than those without DGF. Shortening the time on dialysis seems to be a modifiable factor to reduce DGF.

The impact of a student pharmacist‐led inpatient medication counseling initiative on medication safety in kidney transplant recipients

AbstractIntroductionEngaging student pharmacists as pharmacist extenders to facilitate medication education may represent a unique pathway for preventing medication safety issues and mitigating downstream consequences in the high‐risk kidney transplant (KTX) population. The aim of this study was to describe the implementation and impact of a student pharmacist‐led counseling initiative designed to promote patient and caregiver understanding of transplant medications.MethodsThis is a single‐center, retrospective quality improvement initiative comparing adult KTX recipients who received interventional student pharmacist‐led education vs a historical cohort. Data on clinical outcomes, including the incidence of medication errors (MEs), adverse drug events (ADEs), and readmissions, was extracted from the patient's electronic medical record. In the intervention cohort, attendee satisfaction was assessed based on responses obtained from surveys distributed to patients and caregivers on the day they attended the student pharmacist‐led class.ResultsA total of 311 KTX recipients were included in this analysis; 149 in the intervention cohort and 162 in the historical cohort. Patients in the intervention cohort experienced more MEs than those in the historical cohort (31 vs 11; P &lt; .001). Rates of ADEs within the first 30 days post‐transplant were comparable across cohorts (56 vs 52; P = .406). No significant difference in readmissions at days 7, 14, and 30 was observed between groups. Attendee satisfaction was high across all survey response fields.ConclusionThe results of this study demonstrate that KTX recipients who participated in student‐pharmacist led medication counseling had comparable rates of ADEs and readmissions to those who did not, but were more likely to experience MEs. Future research is needed to explore the role of structured medication counseling and the utility of student pharmacists in the clinical setting.

Temporal trends and current use of de novo belatacept in kidney transplant recipients in the United States.

The adoption of de novo belatacept in kidney transplant (kTx) recipients was hampered by an increased risk of acute cellular rejection (ACR) with variation in adopted belatacept based immunosuppressive therapies across centers. We used data from the Scientific Registry of Transplant Recipients (SRTR) to evaluate the temporal trends in belatacept use and describe the associated induction and maintenance regimens in US adult kTx recipients transplanted between June 2011 and December 2018. The number of patients receiving de novo-belatacept based immunosuppressive therapy increased from .74% in 2011 to 3.11% in 2016. In 2016, 66/207 centers used de novo belatacept-based regimen with 3.03% using it in over 50% of their patients. The use of T-cell depleting agents increased with time. Since 2012, the rate of calcineurin inhibitor (CNI) use in combination with belatacept remained stable around 50% and ∼30% remained under belatacept/CNI combination at 1-year post-transplantation. The adoption of belatacept as de novo immunosuppressive regimen has been slow and its use remains low in the United States. Various regimens have been used to modulate the risk of ACR. Further studies evaluating the long-term outcomes of these regimens and assessing their safety especially with regard to the risk of infection are needed.

Regional Citrate Anticoagulation during Double-Filtration Plasmapheresis in Kidney Transplant Recipients: A Single-Center Retrospective Cohort Study

Introduction: Double-filtration plasmapheresis (DFPP) may be used for immunomodulation in kidney transplant (KTx). While DFPP reduces plasma product exposure, risk of circuit clotting merits adequate anticoagulation. Regional citrate anticoagulation (RCA) avoids the risks of systemic anticoagulation, but a protocol for RCA-DFPP is not previously widely described. Methods: We conducted a single-center retrospective cohort study involving adult (≥21 years old) KTx recipients who underwent RCA-DFPP from 2018 to 2020 to investigate efficacy and safety for an RCA protocol during DFPP in KTx recipients. Results: Fifty-one (85%) of 60 RCA-DFPP sessions in 17 patients completed without circuit clotting. Circuit clotting was associated with high post-filter ionized calcium (28 vs. 3.7%, odds ratio 10.1, 95% CI 1.1–89.4, p = 0.037). Hypo- and hypercalcemia developed in 5 (8.3%) and 8 (13.3%) sessions, respectively, but no adverse effects were noted despite severe hypocalcemia in one. There was no significant change in pre- and post-RCA-DFPP sodium, bicarbonate, albumin, and platelet levels. With regards DFPP procedure, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) was observed following 38 (64.4%) and 12 (20.3%) sessions, respectively. Severely prolonged (>1.5 × upper limit normal) PT and aPTT were recorded in 2 sessions each. Expectedly, hypofibrinogenemia developed after 31 (51.7%) sessions: including 4 (6.7%) severe hypofibrinogenemia (<0.5 g/L). Two patients developed bleeding requiring blood product transfusion. The median total volume of fluids administered per session was 1.495 (1.373–1.612) L; post-RCA-DFPP significant weight gain of 0.5 (0–1.25) kg was noted. Diuretic was commenced or dose increased following 20 (33.3%) sessions for fluid balance management. Discussion/Conclusion: Protocol-based RCA for DFPP is feasible and safe in KTx recipients. However, DFPP-related coagulopathy can develop consequent to treatment; caution should be exercised for patients with bleeding risk. Close monitoring and management of the patients’ electrolytes, especially hypocalcemia and hypomagnesemia, and fluid status is recommended.

MO976GENDER AND AGE DISPARITY IN INFECTIOUS COMPLICATIONS AFTER KIDNEY TRANSPLANTATION

Abstract Background and Aims Number of older patients with end stage kidney disease has been increasing, therefore there are increased number of older kidney transplant recipients. Potent immunosuppression (IS) used in patients after kidney transplantation (KTx) lowered the incidence of acute kidney rejection but increased the risk of post-transplant infection and sepsis as the most common non-cardiac cause of death. Older adults are at high risk of infections due to functional impairment and multiple comorbidities leading to poor outcome after KTx. Nowadays, no change in IS or prophylactic therapy is recommended based on the age of an adult KTx recipient. Female gender may be risk factor for infection after KTx due immunomodulatory effect of sex hormones such as estradiol. Methods The aim of our analysis was to find whether there are sex differences in the incidence of single and repeat infection and whether there is increased incidence of single and recurrent infectious complications in older kidney transplant recipients. Results Our analysis consisted of 100 patients after KTx (66 males, 34 females), average age 47,5 ± 12,6 years, treated with anti-thymocyte globulin as an induction IS. Male gender was a protective factor for the incidence of following infections in the 1st month after KTx: infection in general (P = 0.0054), recurrent infection (P = 0.0239), bacterial (P = 0.0125) and mycotic infection (P = 0.0103), recurrent bacterial infection (P = 0.0258). From the 1st to 6th month after KTx, female gender was identified as a risk factor for the incidence of infection in general (P = 0.0218), bacterial (P = 0.0186) and mycotic infection (P = 0.0318), repeat infection (P = 0.0216), recurrent bacterial infection (P = 0.0368). From 6th to 12th month after KTx, female gender was found as a risk factor for the incidence of bacterial infection (P = 0.0144), single infection (P = 0.0355), recurrent infection (P = 0.0007), single bacterial infection (P = 0.0309). Age &amp;gt; 60 years was not found as a risk factor for the incidence of single, repeat infection regarding its etiology. In our analysis we did not found correlation between gender and the incidence of single or recurrent infection of any etiology, we did not find significant differences in the severity of infections reflected by need for hospitalization, intensive care unit or use of vasopressors neither in gender, nor in older patients. In our study we did not confirm gender or age as a risk factor for the acute kidney rejection. Conclusion In our analysis, we found significant sex differences in the incidence of bacterial, viral, mycotic, single and repeat infection in different time intervals after kidney transplantation, while we did not confirmed age &amp;gt; 60 years is a risk factor for the infectious complications after KTx.

Prophylactic antithrombotic management in adult and pediatric kidney transplantation: A systematic review and meta-analysis.

RGT is a major cause for early graft loss after KTx. Although evidence-based recommendations are lacking, aP is often used to prevent RGT. This systematic review aimed to determine the effectiveness and safety of aP in adult and pediatric KTx recipients. MEDLINE, EMBASE, Cochrane Controlled Trials Register, conference proceedings, and electronic databases for trial registries were searched for eligible studies using search terms relevant to this review (April 21, 2020). The systematic review was carried out following the recommendations of the Cochrane Collaboration and the Prefered Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. Twelve studies comprising 2370 patients (adult=1415, pediatric=955) were included, of which three were RCTs. The overall risk for developing RGT was lower in the group with aP compared with the control group (RR 0.24, 95% confidence interval 0.12-0.49). The antithrombotic drugs used were heparin (7/12), acetylsalicylic acid (2/12), a combination of both (2/12), and dipyridamole (1/12) with a high variability in timing, dosing, and mode of application. Adverse effects were reported rarely, with minor bleeding as the main complication. The non-randomized studies had significant risks of bias in the domains of patient selection, confounder, and measurement of outcomes. Based on pooled analysis, aP seems to reduce the risk of RGT in KTx. However, the reliability of these results is limited, as the quality of the available studies is poor and information on adverse effects associated with aP is scarce. Additional high-quality research is urgently needed to provide sufficient data supporting the use of aP in KTx.

Blood Pressure Treatment in Kidney Transplant Recipients-Can We Improve?

Background.Hypertension in kidney transplant (KTx) recipients is common, affecting both patient and graft survival. Annual data from the Norwegian Renal Registry reveal that <50% of adult (>18 y) KTx recipients reach target blood pressure (BP) ≤130/80 mm Hg. The aim of this study was to identify the determinants of failure to achieve BP control.Methods.In conjunction with the 2018 annual data reporting, additional questions were added for recipients with BP >130/80 mm Hg (treating physician´s target BP for each patient, reasons for not achieving target, method of measurement).Results.Annual forms were received from 98% (3407 of 3486) of KTx recipients, with 1787 (52%) reporting a BP >130/80 mm Hg (“above-target” group). These recipients were older, mostly male, with higher body mass index and serum creatinine levels (P < 0.05) compared with patients with controlled hypertension (“on-target” group). Valid survey answers were available for 84% of the “above-target” group (Survresp) with no significant demographic differences versus nonresponders (Survnonresp). Among Survresp, 32% were under antihypertensive dose titration, whereas dose-limiting side effects were reported in 7%. Target BP was confirmed to 130/80 mm Hg for 60% of Survresp. In recipients for whom the treating physician set target BP >130/80 mm Hg, 51% did not reach these individual targets. The number of antihypertensive drugs was significantly higher in the “above-target” group versus “on-target” group (mean 2.1 ± 1.2 versus 1.8 ± 1.3) and 36% versus 25% used ≥3 antihypertensive drugs (P < 0.05). Automatic attended BP measurement was utilized by 51%.Conclusions.In KTx recipients, a higher BP target achievement seems possible, potentially in the range of 75%-80%.

Predicting the outcome of COVID-19 infection in kidney transplant recipients

BackgroundWe aimed to present the demographic characteristics, clinical presentation, and outcomes of our multicenter cohort of adult KTx recipients with COVID-19.MethodsWe conducted a multicenter, retrospective study using data of patients hospitalized for COVID-19 collected from 34 centers in Turkey. Demographic characteristics, clinical findings, laboratory parameters (hemogram, CRP, AST, ALT, LDH, and ferritin) at admission and follow-up, and treatment strategies were reviewed. Predictors of poor clinical outcomes were analyzed. The primary outcomes were in-hospital mortality and the need for ICU admission. The secondary outcome was composite in-hospital mortality and/or ICU admission.ResultsOne hundred nine patients (male/female: 63/46, mean age: 48.4 ± 12.4 years) were included in the study. Acute kidney injury (AKI) developed in 46 (42.2%) patients, and 4 (3.7%) of the patients required renal replacement therapy (RRT). A total of 22 (20.2%) patients were admitted in the ICU, and 19 (17.4%) patients required invasive mechanical ventilation. 14 (12.8%) of the patients died. Patients who were admitted in the ICU were significantly older (age over 60 years) (38.1% vs 14.9%, p = 0.016). 23 (21.1%) patients reached to composite outcome and these patients were significantly older (age over 60 years) (39.1% vs. 13.9%; p = 0.004), and had lower serum albumin (3.4 g/dl [2.9–3.8] vs. 3.8 g/dl [3.5–4.1], p = 0.002), higher serum ferritin (679 μg/L [184–2260] vs. 331 μg/L [128–839], p = 0.048), and lower lymphocyte counts (700/μl [460–950] vs. 860 /μl [545–1385], p = 0.018). Multivariable analysis identified presence of ischemic heart disease and initial serum creatinine levels as independent risk factors for mortality, whereas age over 60 years and initial serum creatinine levels were independently associated with ICU admission. On analysis for predicting secondary outcome, age above 60 and initial lymphocyte count were found to be independent variables in multivariable analysis.ConclusionOver the age of 60, ischemic heart disease, lymphopenia, poor graft function were independent risk factors for severe COVID-19 in this patient group. Whereas presence of ischemic heart disease and poor graft function were independently associated with mortality.

Competing Risk Analysis in Renal Allograft Survival: A New Perspective to an Old Problem.

Graft survival after kidney transplant (KTX) is often estimated by the Kaplan-Meier (KM) method censoring for competing endpoints, primarily death. This method overestimates the incidence of graft loss. In 3157 adult KTX recipients followed for a mean of 79.2 months, we compared kidney and patient survival probabilities by KM versus competing risk analysis (CRA). These methods are extended to comparing different regression methods. Compared with CRA, the probabilities of death and graft loss (censored for the other outcome) were substantially higher by KM. These differences increased with increasing follow-up time. Importantly, differences in graft losses were magnified in subgroups with greater probabilities of death. Among recipients with diabetes, the probabilities of graft loss at 20 years were 57% by KM and 32% by CRA, while for non-diabetes mellitus corresponding values were 44% and 35%. Similar results are noted when comparing older versus younger recipients. Finally, we find that the Fine-Gray method assumptions are violated when using age and gender as covariates and that the alternative method of Aalen-Johansen may be more appropriate. CRA provides more accurate estimates of long-term graft survival and death, particularly in subgroups of recipients with higher rates of the competing event. Overestimation of risk by KM leads to both quantitative and qualitative misinterpretations of long-term KTX outcomes. When using regression analyses, care should be taken to check assumptions to guide the choice of appropriate method.

Safety and effectiveness of everolimus in maintenance kidney transplant patients in the real-world setting: results from a 2-year post-marketing surveillance study in Japan

BackgroundData on real-world use of everolimus (EVR) in Japanese maintenance kidney transplant (KTx) patients are limited. This post-marketing surveillance study was conducted to assess the safety and effectiveness of EVR, and identify factors affecting renal impairment.MethodsAdult maintenance KTx patients were enrolled within 14 days of initiating EVR. Patient medical data were collected using electronic data capture case report forms at 6 months, 1, and 2 years after initiating EVR, or at discontinuation.ResultsAll patients receiving EVR in Japan during the surveillance period were enrolled (N = 263). Mean time from transplantation to EVR initiation was 75.7 months. Decreased renal function (31.56%) was the primary reason for initiating EVR. In combination with EVR, the mean daily dose of tacrolimus and cyclosporine could be reduced to ~ 79 and ~ 64%, by 2 years, respectively. Incidences of serious adverse events and adverse drug reactions were 15.97 and 49.43%, respectively. Two-year graft survival rate was 95.82% and low in patients with baseline estimated glomerular filtration rate (eGFR; modification of diet in renal disease) < 30 mL/min/1.73 m2 (69.57%; P < 0.0001) and urinary protein/creatinine ratio (UPCR) ≥ 0.55 g/gCr (84.21%; P = 0.0206). Throughout the survey, mean eGFR values were stable (> 55 mL/min/1.73 m2). Renal impairment was influenced by patient and donor age, eGFR, and UPCR at baseline.ConclusionsNo new safety concerns for the use of EVR in adult maintenance KTx patients were identified. Early EVR initiation may be considered in these patients before renal function deterioration occurs.

Treatment of C3 Glomerulopathy in Adult Kidney Transplant Recipients: A Systematic Review.

Background: C3 glomerulopathy (C3G), a rare glomerular disease mediated by alternative complement pathway dysregulation, is associated with a high rate of recurrence and graft loss after kidney transplantation (KTx). We aimed to assess the efficacy of different treatments for C3G recurrence after KTx. Methods: Databases (MEDLINE, EMBASE, and Cochrane Database) were searched from inception through 3 May, 2019. Studies were included that reported outcomes of adult KTx recipients with C3G. Effect estimates from individual studies were combined using the random-effects, generic inverse variance method of DerSimonian and Laird., The protocol for this meta-analysis is registered with PROSPERO (no. CRD42019125718). Results: Twelve studies (7 cohort studies and 5 case series) consisting of 122 KTx patients with C3G (73 C3 glomerulonephritis (C3GN) and 49 dense deposit disease (DDD)) were included. The pooled estimated rates of allograft loss among KTx patients with C3G were 33% (95% CI: 12–57%) after eculizumab, 42% (95% CI: 2–89%) after therapeutic plasma exchange (TPE), and 81% (95% CI: 50–100%) after rituximab. Subgroup analysis based on type of C3G was performed. Pooled estimated rates of allograft loss in C3GN KTx patients were 22% (95% CI: 5–46%) after eculizumab, 56% (95% CI: 6–100%) after TPE, and 70% (95% CI: 24–100%) after rituximab. Pooled estimated rates of allograft loss in DDD KTx patients were 53% (95% CI: 0–100%) after eculizumab. Data on allograft loss in DDD after TPE (1 case series, 0/2 (0%) allograft loss at 6 months) and rituximab (1 cohort, 3/3 (100%) allograft loss) were limited. Among 66 patients (38 C3GN, 28 DDD) who received no treatment (due to stable allograft function at presentation and/or clinical judgment of physicians), pooled estimated rates of allograft loss were 32% (95% CI: 7–64%) and 53% (95% CI: 28–77%) for C3GN and DDD, respectively. Among treated C3G patients, data on soluble membrane attack complex of complement (sMAC) were limited to patients treated with eculizumab (N = 7). 80% of patients with elevated sMAC before eculizumab responded to treatment. In addition, all patients who responded to eculizumab had normal sMAC levels after post-eculizumab. Conclusions: Our study suggests that the lowest incidence of allograft loss (33%) among KTX patients with C3G are those treated with eculizumab. Among those who received no treatment for C3G due to stable allograft function, there is a high incidence of allograft loss of 32% in C3GN and 53% in DDD. sMAC level may help to select good responders to eculizumab.

A Systematic Review of COVID-19 Infection in Kidney Transplant Recipients: A Universal Effort to Preserve Patients' Lives and Allografts.

The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to physicians and healthcare systems worldwide. Evidence about kidney transplant (KTx) recipients is still limited. A systematic literature review was performed. We included 63 articles published from 1 January until 7 July 2020, reporting on 420 adult KTx recipients with confirmed COVID-19. The mean age of patients was 55 ± 15 years. There was a male predominance (67%). The majority (74%) were deceased donor recipients, and 23% were recently transplanted (<1 year). Most patients (88%) had at least one comorbidity, 29% had two, and 18% three. Ninety-three percent of cases were hospitalized. Among them, 30% were admitted to the intensive care unit, 45% developed acute respiratory distress syndrome, and 44% had acute kidney injury with 23% needing renal replacement therapy. From the hospitalized patients a total of 22% died, 59% were discharged, and 19% were still in hospital at the time of publication. Immunosuppression was reduced in 27%, discontinued in 31%, and remained unchanged in 5%. Hydroxychloroquine was administered to 78% of patients, antibiotics to 73%, and antivirals to 30% while 25% received corticosteroid boluses, 28% received anti-interleukin agents, and 8% were given immunoglobulin. The main finding of our analysis was that the incidence of COVID-19 among kidney transplant patients is not particularly high, but when they do get infected, this is related to significant morbidity and mortality.

Analysis of Susceptibility to Selected Antibiotics in Klebsiella pneumoniae, Escherichia coli, Enterococcus faecalis and Enterococcus faecium Causing Urinary Tract Infections in Kidney Transplant Recipients over 8 Years: Single-Center Study.

Background: Urinary tract infections (UTIs) are the most common bacterial infections among kidney transplant (KTX) recipients. The purpose of this study was to analyze antimicrobial resistance (AMR) in four most common pathogens responsible for UTIs in KTX recipients and determine risk factors (RF) for resistance in the same group. Methods: Analyzed antibiograms were based on urine samples positive for bacterial growth of 105 colony-forming units (CFU)/mL obtained from hospitalized adult KTX recipients presenting with UTI symptoms upon admission to the center in years 2011–2018. Results: In total, 783 antibiograms were analyzed for Klebsiella pneumoniae (258 samples, 33.0%), Escherichia coli (212, 27.0%), Enterococcus faecalis (128, 24.0%), and Enterococcus faecium (125, 16.0%). The decrease in susceptibility of E. coli to amoxicillin/clavulanic acid (62.9% vs. 40.0%) and ciprofloxacin (100% to 40.0%) was observed. Susceptibility to gentamicin increased from 33.3% to 92.9% in E. faecium. Susceptibility to tigecycline remained 100% through all years in case of E. faecalis and E. faecium. Male gender was a RF for resistance to amoxicillin/clavulanic acid (p = 0.008), ciprofloxacin (p = 0.0003), trimethoprim/sulfamethoxazole (p = 0.00009), ceftriaxone (p = 0.0001), and cefuroxime axetil (p = 0.00038) in K. pneumoniae and against gentamicin in E. faecalis (p = 0.015). Higher resistance to ampicillin in E. faecalis (p = 0.012) and to ciprofloxacin (p = 0.0003), trimethoprim/sulfamethoxazole (p = 0.007), piperacillin/tazobactam (p = 0.003), ceftriaxone (p = 0.001), and cefuroxime axetil (p = 0.013) in K. pneumoniae was observed in higher age groups of patients. Diabetes as a cause of kidney insufficiency (p = 0.026) and kidney-pancreas transplantation (p = 0.014) was RF for resistance to ceftriaxone in K. pneumoniae. Conclusions: AMR in uropathogens from KTX recipients fluctuated. There were identifiable RFs for resistance in the examined bacteria–antibiotic combinations. We recommend continuous mapping of site-specific microorganisms as etiology and susceptibility may vary between institutions and over time.

Impacts of center and clinical factors in antihypertensive medication use after kidney transplantation.

Hypertension guidelines recommend calcium channel blockers (CCBs), thiazide diuretics, and angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) as first-line agents to treat hypertension. Hypertension is common among kidney transplant (KTx) recipients, but data are limited regarding patterns of antihypertensive medication (AHM) use in this population. We examined a novel database that links national registry data for adult KTx recipients (age>18years) with AHM fill records from a pharmaceutical claims warehouse (2007-2016) to describe use and correlates of AHM use during months 7-12 post-transplant. For patients filling AHMs, individual agents used included: dihydropyridine (DHP) CCBs, 55.6%; beta-blockers (BBs), 52.8%; diuretics, 30.0%; ACEi/ARBs, 21.1%; non-DHP CCBs, 3.0%; and others, 20.1%. Both BB and ACEi/ARB use were significantly lower in the time period following the 2014 Eighth Joint National Committee (JNC-8) guidelines (2014-2016), compared with an earlier period (2007-2013). The median odds ratios generated from case-factor adjusted models supported variation in use of ACEi/ARBs (1.51) and BBs (1.55) across transplant centers. Contrary to hypertension guidelines for the general population, KTx recipients are prescribed relatively more BBs and fewer ACEi/ARBs. The clinical impact of this AHM prescribing pattern warrants further study.

Development and outcomes of de novo donor-specific antibodies in low, moderate, and high immunological risk kidney transplant recipients.

De novo donor-specific antibodies (dnDSA) play an important role in antibody-mediated rejection (ABMR) and graft failure, yet their development in kidney transplant recipients (KTx) of higher immunological risk has not been characterized. We prospectively determined the incidence of dnDSA at 3 and 12months posttransplant and assessed their associations with outcomes in recipients stratified by low, moderate, and high immunological risk. Adult KTx were screened for DSA pretransplant, months 3 and 12 posttransplant, and when clinically indicated. Outcomes included incidence of dnDSA, death-censored graft survival (DCGS), and ABMR. Of 371 recipients, 154 (42%) were transplanted across a pretransplant DSA that became undetectable by 12months posttransplant in 78% of cases. dnDSA were detected in 16% (95% confidence interval [CI]: 12-20%) by 3months and 23% (95% CI: 18-29%) by 12months posttransplant. Incidence at 12months was higher in the moderate (30%) and high-risk groups (29%) compared to the low-risk group (16%). dnDSA were associated with an increased risk of ABMR (hazard ratio [HR] 2.2; 95% CI: 1.1-4.4; P=.04) but were not an independent risk factor for DCGS. In conclusion, dnDSA were more frequent in transplant recipients of higher immune risk and associated with an increased risk of ABMR.

Higher rates of rejection in HIV-infected kidney transplant recipients on ritonavir-boosted protease inhibitors: 3-year follow-up study.

Rejection rates in HIV-infected kidney transplant (KTx) recipients are higher than HIV-negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug-drug interactions, likely influencing outcomes. This is an IRB-approved, single-center, retrospective study of adult HIV-infected KTx patients between 5/2009 and 12/2014 with 3-year follow-up, excluding antibody-depleting induction. A total of 42 patients were included; median age was 52years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian. The most common renal failure etiology was hypertensive nephrosclerosis (50%) with 5.8 median years of pre-transplant dialysis. All patients received IL-2 receptor antagonist, were maintained on tacrolimus (76%) or cyclosporine (17%), and 40% received ritonavir-boosted PI-based HAART (rtv+) regimen. Patient and graft survival at 3years were 93% and 90%. At 1-, 2-, and 3-year time points, median serum creatinine was 1.49, 1.35, and 1.67; treated biopsy-proven rejection was 38%, 38%, and 40.5%; and 92% of episodes were acute rejection. At these time points, rejection rates were significantly higher with boosted PI HAART regimens compared to other HAART regimens, 59% vs 24% (P=0.029), 59% vs 24% (P=0.029), and 68% vs 24% (P=0.01). Despite higher rejection rates, HIV-infected KTx recipients have reasonable outcomes. Given significantly higher rejection rates using rtv+ regimens, alternative HAART regimens should be considered prior to transplantation.

Characterization of Potentially Unsafe Ambulatory Antibiotic Use and Associated Outcomes in an Adult Kidney Transplant Population.

Antibiotics are frequently prescribed to kidney transplant (KTX) recipients in the outpatient setting, but there are limited data assessing the safety and outcomes associated with this practice. The primary objective of this study was to describe ambulatory antibiotic prescribing in a large cohort of adult KTX recipients. The secondary objective was to assess the outcomes associated with potentially unsafe antibiotic use in this population. National Veterans Health Administration data compiled between 2001 and 2010 were used to conduct a pharmacovigilance assessment of antibiotic prescribing, excluding intravenous agents, antifungals, antivirals, and prophylactic regimens. Multivariable Cox proportional hazard regression was used to determine the impact of safe and potentially unsafe antibiotic use on time to event for graft loss. Among 5130 KTX recipients and 30 127 patient-years of follow-up, 14 259 antibiotic courses were prescribed at a rate of 0.47 courses per patient-year. Transplant or nephrology providers prescribed 24.8% of courses. Overall, 608 courses (4.3%) in 311 patients (6.1%) were considered potentially unsafe for dosages in disagreement with recommended adjustments for renal function, interaction with immunosuppressive regimens, and other pertinent safety concerns. After adjusting for baseline characteristics, unsafe antibiotic use was associated with a 40% higher risk of graft loss (adjusted hazard ratio = 1.40; 95% CI = 1.03-1.89; P = 0.030) compared with safe use. Although unsafe antibiotic prescribing was uncommon, it was associated with increased risk of graft loss. Prospective research is needed to elucidate whether the driver of poor outcomes is the safety of the antibiotic prescription or fragmented care.

Long-term Patient and Graft Survival of Kidney Transplant Recipients With Hepatitis C Virus Infection in the United States.

Hepatitis C virus (HCV) infection is common among kidney transplant (KTx) recipients. However, the impact of HCV infection on long-term graft and recipient survival after KTx from large-scale data remains to be determined. We used the Organ Procurement and Transplantation Network database to identify all adults undergoing KTx in 2004 to 2006 in the United States. A propensity score was created to match each HCV-positive recipient with an HCV-negative control for unbiased comparisons. Survival analysis was conducted to evaluate recipient and death-censored graft survival. Out of 33 357 adult primary KTx recipients, 1470 (4.4%) were HCV-positive: 1364 HCV-positive and -negative pairs were selected by propensity score matching. Based on multivariable regression models, HCV is associated with a higher risk of death (hazard ratio [HR], 1.50; 95% confidence interval [95% CI], 1.28-1.75) and graft failure (HR, 1.26; 95% CI, 1.08-1.47). Infection was a more common cause of death in HCV-positive patients than in HCV-negative recipients (HR, 1.64; 95% CI, 1.12-2.42). The incidence of death due to liver failure was 0.23% per year among HCV-positive recipients, whereas no HCV-negative recipients died from liver failure. Graft failure due to recurrent disease was higher in HCV-positive than in HCV-negative recipients (HR, 2.00; 95% CI, 1.06-3.78). HCV infection is associated with decreased long-term recipient and graft survival. Future studies are needed to examine whether recently available, safe, and effective antiviral therapy improves the long-term clinical outcome in these patients.