Monitoring of alphatorquevirus DNA levels for the prediction of immunosuppression‐related complications after kidney transplantation

The replication kinetics of nonpathogenic anelloviruses belonging to the Alphatorquevirus genus (such as torque teno virus) might reflect the overall state of posttransplant immunosuppression. We analyzed 221 kidney transplant (KT) recipients in whom plasma alphatorquevirus DNA load was quantified by real‐time polymerase chain reaction at baseline and regularly through the first 12 posttransplant months. Study outcomes included posttransplant infection and a composite of opportunistic infection and/or de novo malignancy (immunosuppression‐related adverse event [iRAE]). Alphatorquevirus DNA loads at month 1 were higher among patients who subsequently developed posttransplant infection (P  = .023) or iRAE (P  = .009). Likewise, those with iRAE beyond months 3 and 6 also exhibited higher peak viral loads over the preceding periods. Areas under the curve for log₁₀ alphatorquevirus DNAemia estimated by months 1 or 6 were significantly higher in patients experiencing study outcomes. Alphatorquevirus DNA loads above 3.15 and 4.56 log₁₀ copies/mL at month 1 predicted the occurrence of posttransplant infection (adjusted hazard ratio [aHR]: 2.88; 95% confidence interval [CI]: 1.13‐7.36; P  = .027) and iRAE (aHR: 5.17; 95% CI: 2.01‐13.33; P  = .001). In conclusion, posttransplant monitoring of plasma alphatorquevirus DNA kinetics may be useful to identify KT recipients at increased risk of immunosuppression‐related complications.     

Parvovirus B19 infection in kidney transplant recipients: A prospective study in a teaching hospital in Shanghai,China

BackgroundThere is a lack of epidemiological studies on the course and clinical characteristics of Parvovirus B19 (B19V) infections in kidney transplant (KT) recipients. This study was undertaken to provide recommendations for clinical B19V infection diagnosis and treatment.MethodsSerum samples of KT recipients were regularly collected and tested for B19V-DNA copies, B19V-IgG/IgM levels, as well as hematological parameters and functions of kidney and liver. The course of B19V infection was described according to the results of serology and DNA testing, and the clinical and epidemiological data were combined for analysis.Results75% B19V infections occurred within 2 weeks after KT(n = 9). The infection rate of B19V in KT recipients was high, namely 10.17% (n = 12). The number of 10 patients IgM antibodies against B19V (IgM+) and the DNA B19V (DNA+), whereas 2 patients were IgM negative (IgM-) but DNA+. The B19V infected KT patients showed several symptoms, including anemia (100%), reduction of platelets (8.33%), and damage to liver (75%) and kidney function (16.67%) Patients with progressive anemia in the first two weeks after KT, which combined with the decrease of reticulocytes, are more likely to have B19V infection. Associations of four main therapeutic risk factors for B19V infections in KT patients have been analyzed. B19V infection was associated with use of basiliximab (OR = 1.19; 95%- CI: 1.08–1.32; P = 0.003) and use of thymoglobulins (OR = 0.84; 95%-CI: 0.76–0.93; P = 0.003).ConclusionsDoctors should be alert to B19V infection, especially in the immunodeficient patients within the first two weeks after transplantation.     

Torque teno virus for risk stratification of graft rejection and infection in kidney transplant recipients—A prospective observational trial

The nonpathogenic and ubiquitous torque teno virus (TTV) is associated with immunosuppression in solid organ transplant recipients. Studies in kidney transplant patients proposed TTV quantification for risk stratification of graft rejection and infection. In this prospective trial (DRKS00012335) 386 consecutive kidney transplant recipients were subjected to longitudinal per‐protocol monitoring of plasma TTV load by polymerase chain reaction for 12 months posttransplant. TTV load peaked at the end of month 3 posttransplant and reached steady state thereafter. TTV load after the end of month 3 was analyzed in the context of subsequent rejection diagnosed by indication biopsy and infection within the first year posttransplant, respectively. Each log increase in TTV load decreased the odds for rejection by 22% (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.62‐0.97; P = .027) and increased the odds for infection by 11% (OR 1.11, 95% CI 1.06‐1.15; P < .001). TTV was quantified at a median of 14 days before rejection was diagnosed and 27 days before onset of infection, respectively. We defined a TTV load between 1 × 10⁶ and 1 × 10⁸ copies/mL as optimal range to minimize the risk for rejection and infection. These data support the initiation of an interventional trial assessing the efficacy of TTV‐guided immunosuppression to reduce infection and graft rejection in kidney transplant recipients.     

Association studies of cytochrome P450, family 2, subfamily E,polypeptide 1 (CYP2E1) gene polymorphisms with acute rejection in kidney transplantation recipients

Recent studies have shown that single‐nucleotide polymorphisms (SNPs) are associated with allograft rejection in kidney transplantation recipients. We evaluated the possible association between SNPs of the cytochrome P450, family 2, subfamily E, polypeptide 1 (CYP2E1) gene, and acute rejection (AR) among renal transplant patients in a Korean population. We conducted a case–control association study in 63 AR and 284 non‐AR kidney transplant recipients. The SNPs of CYP2E1 were genotyped by direct sequencing. Recipient sex (p = 0.023) and the use of tacrolimus (p = 0.017) were significantly different between the two groups. The use of mycophenolate mofetil (MMF) and antibody induction therapy was significantly lower in the AR group. Multiple logistic regression models (codominant, dominant, recessive, and log‐additive models) adjusted by sex and type of immunosuppressive regimens were applied to determine the odds ratios (ORs), 95% confidence intervals (CIs), and p‐values. The rs2515641 of CYP2E1 showed significant differences between the AR patient group and non‐AR group (p = 0.003, OR = 2.55, 95% CI = 1.37–4.75 in the codominant 1 model; p = 0.002, OR = 2.61, 95% CI = 1.43–4.77 in the dominant model; p = 0.0035, OR = 2.13, 95% CI = 1.29–3.50 in the log‐additive model). The allele of the rs2515641 SNP also showed a significant association (p = 0.004, OR = 1.99, 95% CI = 1.24–3.21). This study suggests that the CYP2E1 polymorphism may be related to the development of AR in Korean kidney transplantation recipients.     

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case–Control Study

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case–control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09–90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08–10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04–339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63–456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.     

Risk factors associated with Hepatitis E virus infection in kidney transplant recipients in a single tertiary Center in the United States

BackgroundHepatitis E virus (HEV), the causative agent of hepatitis E, is a common but self-limiting disease. However, in immunosuppressed kidney transplant 47 recipients (KTRs), HEV infection can become chronic. We investigated risk factors associated with HEV infection among 271 KTRs at the Johns Hopkins Hospital transplanted between 1988 and 2012.MethodsHEV infection was defined as having positive anti-HEV IgM, anti-HEV IgG, or HEV RNA. The risk factors included: age at transplant, sex, hemodialysis/peritoneal dialysis, plasmapheresis, transfusions, community urbanization, and other socioeconomic factors. Logistic regression was used to determine independent risk factors associated with HEV infection.ResultsOut of 271 KTRs, 43 (16%) had HEV infection though not active disease. HEV infection in KTRs was associated with older age (≥45 years; OR = 4.04; 95% CI = 1.81–57 10.03; p = 0.001) and living in communities with low proportions of minorities (OR = 0.22; 95% 58 CI = 0.04–0.90; p = 0.046).ConclusionKTRs who had HEV infection may be at an increased risk of developing chronic HEV.     

Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry

SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July–December) than in the first one (March–June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.     

The Association of Race/Ethnicity and Total Knee Arthroplasty Outcomes in a Universally Insured Population

BackgroundPrior studies have documented racial/ethnic disparities in the United States for total knee arthroplasty (TKA) outcomes. One factor cited as a potential mediator is unequal access to care. We sought to assess whether racial/ethnic disparities persist in a universally insured TKA population.MethodsA US integrated health system’s total joint replacement registry was used to identify elective primary TKA (2000-2016). Racial/ethnic differences in revision and 90-day postoperative events (readmission, emergency department [ED] visit, infection, venous thromboembolism, and mortality) were analyzed using Cox proportional hazard and logistic regression with adjustment for confounders.ResultsOf 129,402 TKA, 68.8% were white, 16.2% were Hispanic, 8.4% were black, and 6.6% were Asian. Compared to white patients, Hispanic patients had lower risks of septic revision (hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.57-0.83) and infection (odds ratio [OR] = 0.42, 95% CI = 0.30-0.59), but a higher likelihood of ED visit (OR = 1.28, 95% CI = 1.22-1.34). Black patients had higher risks of aseptic revision (HR = 1.61, 95% CI = 1.42-1.83), readmission (OR = 1.13, 95% CI = 1.02-1.24), and ED visit (OR = 1.31, 95% CI = 1.23-1.39). Asian patients had lower risks of aseptic revision (HR = 0.67, 95% CI = 0.54-0.83), septic revision (HR = 0.78, 95% CI = 0.60-0.99), readmission (OR = 0.89, 95% CI = 0.79-1.00), and venous thromboembolism (OR = 0.59, 95% CI = 0.45-0.78).ConclusionWe observed differences in TKA outcome, even within a universally insured population. While lower risks in some outcomes were observed for Asian and Hispanic patients, the higher risks of aseptic revision and readmission for black patients and ED visit for black and Hispanic patients warrant further research to determine reasons for these findings to mitigate disparities.Level of EvidenceLevel III.     

Prevalence of frailty among kidney transplant candidates and recipients in the United States: Estimates from a National Registry and Multicenter Cohort Study

Frailty, a measure of physiologic reserve, is associated with poor outcomes and mortality among kidney transplant (KT) candidates and recipients. There are no national estimates of frailty in this population, which may help patient counseling and resource allocation at transplant centers. We studied 4616 KT candidates and 1763 recipients in our multicenter prospective cohort of frailty from 2008‐2018 with Fried frailty measurements. Using Scientific Registry of Transplant Recipients (SRTR) data (KT candidates = 560 143 and recipients = 243 508), we projected the national prevalence of frailty (for KT candidates and recipients separately) using standardization through inverse probability weighting, accounting for candidate/recipient, donor, and transplant factors. In our multicenter cohort, 13.3% of KT candidates were frail at evaluation; 8.2% of LDKT recipients and 17.8% of DDKT recipients were frail at transplantation. Projected nationally, our modeling strategy estimated 91 738 KT candidates or 16.4% (95% confidence interval [CI] 14.4%‐18.4%) of all KT candidates during the study period were frail, and that 34 822 KT recipients or 14.3% (95% CI 12.3%‐16.3%) of all KT recipients were frail (LDKT = 8.2%; DDKT = 17.8%). Given the estimated national prevalence of frailty, transplant programs should consider assessing the condition during KT evaluation to improve patient counseling and resource allocation along with identification of recipients at risk for poor outcomes.     

Does Regional Anesthesia Reduce Complications Following Total Hip and Knee Replacement Compared With General Anesthesia? An Analysis From the National Joint Registry for England,Wales, Northern Ireland and the Isle of Man

BackgroundRegional anesthesia is increasingly used in enhanced recovery programs following total hip replacement (THR) and total knee replacement (TKR). However, debate remains about its potential benefit over general anesthesia given that complications following surgery are rare. We assessed the risk of complications in THR and TKR patients receiving regional anesthesia compared with general anesthesia using the world’s largest joint replacement registry.MethodsWe studied the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man linked to English hospital inpatient episodes for 779,491 patients undergoing THR and TKR. Patients received either regional anesthesia (n = 544,620, 70%) or general anesthesia (n = 234,871, 30%). Outcomes assessed at 90 days included length of stay, readmissions, and complications. Regression models were adjusted for patient and surgical factors to determine the effect of anesthesia on outcomes.ResultsLength of stay was reduced with regional anesthesia compared with general anesthesia (THR = −0.49 days, 95% confidence interval [CI] = −0.51 to −0.47 days, P < .001; TKR = −0.47 days, CI = −0.49 to −0.45 days, P < .001). Regional anesthesia also had a reduced risk of readmission (THR odds ratio [OR] = 0.93, CI = 0.90-0.96; TKA OR = 0.91, CI = 0.89-0.93), any complication (THR OR = 0.88, CI = 0.85-0.91; TKA OR = 0.90, CI = 0.87-0.93), urinary tract infection (THR OR = 0.85, CI = 0.77-0.94; TKR OR = 0.87, CI = 0.79-0.96), and surgical site infection (THR OR = 0.87, CI = 0.80-0.95; TKR OR = 0.84, CI = 0.78-0.89). Anesthesia type did not affect the risk of revision surgery or mortality.ConclusionRegional anesthesia was associated with reduced length of stay, readmissions, and complications following THR and TKR when compared with general anesthesia. We recommend regional anesthesia should be considered the reference standard for patients undergoing THR and TKR.     

Impact of Protease Inhibitor–Based Anti‐Retroviral Therapy on Outcomes for HIV+ Kidney Transplant Recipients

Excellent outcomes have been demonstrated among select HIV‐positive kidney transplant (KT) recipients with well‐controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01–10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre‐ and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non–PI‐based ART (88 PI vs. 244 non‐PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI‐based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p = 0.02) than those on non‐PI regimens. On adjusted analyses, PI‐based regimens were associated with a 1.8‐fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22–2.77, p = 0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75–11.48, p = 0.002), and a 1.9‐fold increased risk of death as compared to non‐PI regimens (aHR 1.91, 95% CI 1.02–3.59, p = 0.05). These results suggest that whenever possible, recipients should be converted to a non‐PI regimen prior to kidney transplantation.     

Monitoring of CMV‐specific cell‐mediated immunity with a commercial ELISA‐based interferon‐γ release assay in kidney transplant recipients treated with antithymocyte globulin

Monitoring for cytomegalovirus (CMV)‐specific cell‐mediated immunity (CMV‐CMI) may be useful for individualizing valganciclovir (VGCV) prophylaxis after kidney transplantation (KT). We performed a commercial ELISA‐based interferon (IFN)‐γ release assay (QTF‐CMV) from posttransplant months 2‐5 (362 points) in 120 CMV‐seropositive KT recipients that received antithymocyte globulin as induction therapy and VGCV prophylaxis (median of 92 days). Forty‐seven patients (39.3%) had CMV infection after discontinuation of prophylaxis. The QTF‐CMV assay was reactive, nonreactive, and indeterminate in 264 (72.9%), 90 (24.9%), and 8 points (2.2%). The QTF‐CMV assay at prophylaxis discontinuation exhibited suboptimal accuracy for predicting protective CMV‐CMI (sensitivity: 77.4%; specificity: 34.3%; positive predictive value [PPV]: 64.1%; negative predictive value [NPV]: 50.0%), with no differences in 1‐year CMV infection rates between patients with negative (nonreactive or indeterminate) or reactive results (45.8% vs 36.1%; P = .244). Specificity and PPV to predict protective CMV‐CMI improved by elevating the IFN‐γ cutoff value to 1.13 IU/mL (65.7% and 71.4%) and 7.0 IU/mL (85.7% and 76.2%), although NPVs decreased. The QTF‐CMV assay as per manufacturer's interpretative criteria performed poorly to predict protection from CMV infection following discontinuation of VGCV prophylaxis among ATG‐treated CMV‐seropositive KT recipients. This performance is slightly improved by modifying the IFN‐γ positivity threshold.     

Risk Factors for Mortality in Liver Transplant Recipients With ESKAPE Infection

BackgroundAlthough infections caused by the pathogens Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) have recently been identified as serious emerging problems in solid organ transplant, no information in liver transplant (LT) recipients is available. We sought to investigate the risk factors for associated mortality in LT recipients with ESKAPE infections.MethodsA retrospective analysis of infection after LT was reviewed. Risk factors for mortality caused by ESKAPE infection were identified.ResultsFifty-three episodes of infections caused by ESKAPE were documented in 51 LT recipients. The main sites of infection were the bloodstream (49.0%), the lungs (33.3%), and the intra-abdominal/biliary tract (17.6%). The risk factors for mortality independently associated with ESKAPE infection were female sex (odds ratio [OR] = 6.6, 95% confidence interval [CI] = 1.1–40.8, P = .042), septic shock (OR = 30.1, 95% CI = 3.7–244.8, P = .001), and lymphocyte counts <300/mm³ (OR = 20.2, 95% CI = 2.9–142.2, P = .003).ConclusionsTo improve the results of LT, more effective therapeutic treatments are of paramount importance when female LT recipients with ESKAPE infection present with septic shock and decreased lymphocyte counts.     

Quantifying infection risks in incompatible living donor kidney transplant recipients

Desensitization has enabled incompatible living donor kidney transplantation (ILDKT) across HLA/ABO barriers, but added immunomodulation might put patients at increased risk of infections. We studied 475 recipients from our center from 2010 to 2015, categorized by desensitization intensity: none/compatible (n = 260), low (0-4 plasmaphereses, n = 47), moderate (5-9, n = 74), and high (≥10, n = 94). The 1-year cumulative incidence of infection was 50.1%, 49.8%, 66.0%, and 73.5% for recipients who received none, low, moderate, and high-intensity desensitization (P < .001). The most common infections were UTI (33.5% of ILDKT vs. 21.5% compatible), opportunistic (21.9% vs. 10.8%), and bloodstream (19.1% vs. 5.4%) (P < .001). In weighted models, a trend toward increased risk was seen in low (wIRR = _0.771.40_2.56,P = .3) and moderately (wIRR = _0.881.35_2.06,P = .2) desensitized recipients, with a statistically significant 2.22-fold (wIRR = _1.332.22_3.72,P = .002) increased risk in highly desensitized recipients. Recipients with ≥4 infections were at higher risk of prolonged hospitalization (wIRR = _2.623.57_4.88, P < .001) and death-censored graft loss (wHR = _1.154.01_13.95,P = .03). Post–KT infections are more common in desensitized ILDKT recipients. A subset of highly desensitized patients is at ultra-high risk for infections. Strategies should be designed to protect patients from the morbidity of recurrent infections, and to extend the survival benefit of ILDKT across the spectrum of recipients.     

Influence of epidemiology,immunosuppressive regimens,clinical presentation,and treatment on kidney transplant outcomes of patients diagnosed with tuberculosis: A retrospective cohort analysis

Tuberculosis (TB) mortality is high among kidney transplant (KT) recipients. Although local epidemiology is an important factor, diagnostic/therapeutic challenges and immunosuppressive therapy (ISS) may influence outcomes. We analyzed the cumulative incidence (CumI) of TB in KT recipients receiving a variety of ISS with long‐term follow‐up. Our retrospective single‐center cohort study included all KT procedures performed between January 1, 1998, and August 31, 2014, with follow‐up until August 31, 2014. Induction therapy was based on perceived immunological risk; maintenance ISS included prednisone and calcineurin inhibitor (CNI) plus azathioprine (AZA), and mycophenolic acid (MPA) or mechanistic target of rapamycin inhibitor (mTORi). Thirty‐four patients received belatacept/MPA. KT was performed on 11 453 patients and followed for 1989 (IQR 932 to 3632) days. Among these, 152 patients were diagnosed with TB (CumI 1.32%). Median time from KT to TB was 18.8 (IQR 7.2 to 60) months, with 59% of patients diagnosed after the first year. Unadjusted analysis revealed an increasing confidence interval (CI) of TB (0.94% CNI/AZA vs 1.6% CNI/MPA [HR = 1.62, 95% CI = 1.13 to 2.34, P = .009] vs 2.85% CNI/mTORi [HR = 2.45, 95% CI = 1.49 to 4.32, P < .001] vs 14.7% belatacept/MPA [HR = 13.14, 95% CI = 5.27 to 32.79, P < .001]). Thirty‐seven (24%) patients died, and 39 (25.6%) patients experienced graft loss. Cytomegalovirus infection (P = .02) and definitive ISS discontinuation (P < .001) were associated with death. Rejection (P = .018) and ISS discontinuation (P = .005) occurred with graft loss. TB occurred at any time after KT and was influenced by ISS.     

Pretransplant Psoas Muscle Cross-Sectional Area and Postkidney Transplant Outcomes

BackgroundSarcopenia is associated with adverse outcomes in end-stage kidney disease. We evaluated if pretransplant sarcopenia affects posttransplant outcomes in kidney transplant (KT) recipients.MethodsIn this single-center retrospective study of adult patients with end-stage kidney disease, we analyzed the association between pre-KT psoas muscle cross-sectional area and critical posttransplant outcomes of decline in estimated glomerular filtration rate (eGFR), graft loss, rehospitalization, and mortality using Cox proportional hazard model adjusted for age, sex, and race.ResultsPre-KT abdomen and pelvic computed tomography scans performed during evaluation for KT eligibility were available for 573 KT recipients. Of these, 465 KT recipients received kidney alone transplant, 71 received simultaneous liver kidney transplant (SLK), and 37 received simultaneous pancreas kidney transplant (SPK). Patients were 49 (SD, 13) years old, 16% Black, and 60% men. For kidney alone transplant recipients, a higher psoas muscle cross-sectional area was associated with a shorter length of hospitalization (β coefficient = ?0.003; 95% CI, ?0.005 to ?0.0007). Conversely, pre-KT psoas muscle cross-sectional area did not predict decline in eGFR, graft loss, mortality, or early rehospitalization. For SLK recipients, psoas muscle cross-sectional area did not predict any of the priori outcomes. For SPK recipients, higher pretransplant psoas muscle cross-sectional area predicted a longer length of hospitalization (β coefficient = 0.03; 95% CI, 0.01-0.05). There was no association between psoas muscle cross-sectional area and other outcomes assessed.ConclusionsPretransplant psoas muscle cross-sectional areas are not predictive of post-transplant decline in eGFR, graft loss, rehospitalization or mortality in kidney alone, SPK, or SLK transplants.     

Comparing outcomes of third and fourth kidney transplantation in older and younger patients

Performing third or fourth kidney transplantation (3KT and 4KT) in older patients is rare due to surgical and immunologic challenges. We aimed to analyze and compare the outcomes of younger (18–64 years) and older (≥65 years) recipients of 3KT and 4KT. Between 1990 and 2016, we identified 5816 recipients of 3KTs (153 were older) and 886 recipients of 4KTs (18 were older). The incidences of delayed graft function (24.3% vs. 24.8%, p = .89), primary non-function (3.2% vs. 1.3%, p = .21), 1-year acute rejection (18.6% vs. 14.8%, p = .24), and 5-year death censored graft failure (DCGF) (24.8% vs. 17.9%, p = .06) were not different between younger and older recipients of 3KT. However, 5-year mortality was higher in older recipients (14.0% vs. 33.8%, p < .001) which remained significant after adjustment (aHR = 3.21, 95% CI: 2.59–3.99). Similar patterns were noted in the 4KT cohort. When compared with waitlisted patients, 3KT and 4KT are associated with a lower risk of mortality; aHR = 0.37, 95% CI: 0.33–0.41 and aHR = 0.31, 95% CI: 0.24–0.41, respectively. This survival benefit did not differ by recipient age (younger vs. older, p for interaction = 3KT: .49 and 4KT: .58). In the largest cohort described to date, we report that there is a survival benefit of 3KT and 4KT even among older patients. Although a highly selected cohort, our results support improving access to 3KT and 4KT.     

Characteristics of Antibiotic Prophylaxis and Risk of Surgical Site Infections in Primary Total Hip and Knee Arthroplasty

BackgroundDespite numerous antibiotic prophylaxis options for total hip arthroplasty (THA) and total knee arthroplasty (TKA), an assessment of practice patterns and comparative effectiveness is lacking. We aimed to characterize antibiotic utilization patterns and associations with infection risk and hypothesized differences in infection risk based on regimen.MethodsA retrospective cohort study was performed using data from 436,724 THA and 862,918 TKA (Premier Healthcare Database; 2006-2016). Main exposures were antibiotic type and duration: day of surgery only (day 0) or through postoperative day 1 (day 1). The primary outcome was surgical site infection (SSI) <30 days postoperation. Mixed-effect models measured associations between prophylaxis regimen and SSI as odds ratios (ORs) with 95% confidence intervals (CIs).ResultsSSI prevalence was 0.21% (n = 914) for THA and 0.22% (n = 1914) for TKA. Among THA procedures, the most commonly used antibiotics were cefazolin (74.1%), vancomycin (8.4%), “other” antibiotic combinations (7.1%), vancomycin + cefazolin (5.1%), and clindamycin (3.3%). Here, 51.8% received prophylaxis on day 0 only, whereas 48.2% received prophylaxis through day 1. Similar patterns existed for TKA. Relative to cefazolin, higher SSI odds were seen with vancomycin (OR = 1.36; CI 1.09-1.71) in THA and with vancomycin (OR = 1.29; CI = 1.10-1.52), vancomycin + cefazolin (OR = 1.35; CI = 1.12-1.64), clindamycin (OR = 1.38; CI = 1.11-1.71), and “other” antibiotic combinations (OR = 1.28; CI = 1.07-1.53) in TKA. Prophylaxis duration did not alter SSI odds. Results were corroborated in sensitivity analyses.ConclusionAntibiotic prophylaxis regimens other than cefazolin were associated with increased SSI risk among THA/TKA patients. These findings emphasize a modifiable intervention to mitigate infection risk.     

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case–control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17–83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03–1.36), and therapy with renin–angiotensin–aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47–34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline.     

Impact of MBL2 gene polymorphisms on the risk of infection in solid organ transplant recipients: A systematic review and meta‐analysis

Mannose‐binding lectin (MBL) is a soluble pattern recognition molecule involved in complement activation. Single nucleotide polymorphisms (SNPs) in the MBL2 gene have been associated with susceptibility to infection, although data in solid organ transplant recipients remains inconclusive. This meta‐analysis was primarily aimed at investigating the association between posttransplant bacterial and fungal infection and variant alleles of MBL2 gene SNPs in the promoter/5’ untranslated region and exon 1. Cytomegalovirus (CMV) infection and/or disease were considered secondary outcomes. PubMed, EMBASE, and Web of Knowledge were searched for relevant articles up to August 2018. Eleven studies (comprising 1858 patients) were included, with liver transplant (LT) recipients accounting for 80.4% of the pooled population. As compared to high‐MBL expression haplotypes (YA/YA, YA/XA), any MBL‐deficient haplotype was associated with an increased risk of posttransplant bacterial and fungal infections (risk ratio [RR]: 1.30; P = .04). Low/null‐MBL expression haplotypes (XA/O, O/O) also increased the risk of primary outcome (RR: 1.51; P = .008) and CMV events (RR: 1.50; P = .006). No effect was observed for individual promoter SNPs. In conclusion, MBL‐deficient haplotypes are associated with a significant, albeit moderate, increase in the risk of posttransplant infection, with this association being mainly restricted to LT recipients.