Early interstitial macrophage infiltration with mild dysfunction is associated with subsequent kidney graft loss

Macrophage infiltration is associated with unfavorable kidney graft outcome in protocol biopsies, but few studies have evaluated its impact on clinical practice. We therefore prospectively evaluated 37 kidney transplant recipients (KTRs) who underwent kidney biopsy due to slight increases in serum creatinine, or mild proteinuria (>0.3 g/24 hr), in the first post‐transplant year. Banff score, CD68⁺ count (score 0‐3) by immunohistochemistry, and 1‐year DSA were assessed. DGF was reported in 10 (27%) patients, 6 (16%) had normal biopsy, 7 (19%) borderline lesions, 13 (35%) IFTA, and 11 (30%) other lesions. Fifteen KTRs had grade 3 CD68⁺ infiltration, and 47% developed de novo DSA. During a 6.2 ± 2.7 year follow‐up, four patients (11%) suffered from biopsy‐proven T‐cell rejection, 17 KTRs (46%) lost their graft (12 in the grade 3 CD68⁺ group). Graft survival was lower in KTRs with grade 3 CD68⁺ infiltration (P = 0.0074; log‐rank test). Grade 3 CD68⁺ infiltrate was an independent predictor of graft loss (HR 5.41, 95% CI 1.74‐16.8; P = 0.003), together with more severe graft dysfunction at biopsy (HR 6.41, 95% CI 2.57‐16; P < 0.001). We conclude that grade 3 CD68⁺ interstitial infiltration is associated with increased risk of subsequent graft loss independent of other factors.     

Different risk factor profiles distinguish early‐onset from late‐onset BKV‐replication

Two of three reactivations of latent BKV‐infection occur within the first 6 months after renal transplantation. However, a clear differentiation between early‐onset and late‐onset BKV‐replication is lacking. Here, we studied all kidney transplant recipients (KTRs) at our single transplant center between 2004 and 2012. A total of 103 of 862 KTRs were diagnosed with BK viremia (11.9%), among which 24 KTRs (2.8%) showed progression to BKV‐associated nephropathy (BKVN). Sixty‐seven KTRs with early‐onset BKV‐replication (65%) and 36 KTRs with late‐onset BKV‐replication (35%) were identified. A control group of 598 KTRs without BKV‐replication was used for comparison. Lymphocyte‐depleting induction, CMV‐reactivation, and acute rejection increased the risk of early‐onset BKV‐replication (P < 0.05). Presensitized KTRs undergoing renal retransplantation were those at increased risk of late‐onset BKV‐replication (P < 0.05). Among KTRs with BK viremia, higher doses of mycophenolate increased the risk of progression to BKVN (P = 0.004). KTRs with progression to BKVN showed inferior allograft function (P < 0.05). KTRs with late‐onset BK viremia were more likely not to recover to baseline creatinine after BKV‐replication (P = 0.018). Our data suggest different risk factors in the pathogenesis of early‐onset and late‐onset BKV‐reactivation. While a more intensified immunosuppression is associated with early‐onset BKV‐replication, a chronic inflammatory state in presensitized KTRs may contribute to late‐onset BKV‐replication.     

Kidney transplant graft outcomes in 379 257 recipients on 3 continents

Kidney transplant outcomes that vary by program or geopolitical unit may result from variability in practice patterns or health care delivery systems. In this collaborative study, we compared kidney graft outcomes among 4 countries (United States, United Kingdom, Australia, and New Zealand) on 3 continents. We analyzed transplant and follow‐up registry data from 1988‐2014 for 379 257 recipients of first kidney‐only transplants using Cox regression. Compared to the United States, 1‐year adjusted graft failure risk was significantly higher in the United Kingdom (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.18‐1.26, P < .001) and New Zealand (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.14‐1.46, P < .001), but lower in Australia (HR 0.90, 95% CI 0.84‐0.96, P = .001). In contrast, long‐term adjusted graft failure risk (conditional on 1‐year function) was significantly higher in the United States compared to Australia, New Zealand, and the United Kingdom (HR 0.74, 0.75, and 0.74, respectively; each P < .001). Thus long‐term kidney graft outcomes are approximately 25% worse in the United States than in 3 other countries with well‐developed kidney transplant systems. Case mix differences and residual confounding from unmeasured factors were found to be unlikely explanations. These findings suggest that identification of potentially modifiable country‐specific differences in care delivery and/or practice patterns should be sought.     

Epidemiology of invasive fungal infections in lung transplant recipients on long‐term azole antifungal prophylaxis

Lung transplant recipients (LTR) at our institution receive prolonged and mostly lifelong azole antifungal (AF) prophylaxis. The impact of this prophylactic strategy on the epidemiology and outcome of invasive fungal infections (IFI) is unknown. This was a single‐center, retrospective cohort study. We reviewed the medical records of all adult LTR from January 2002 to December 2011. Overall, 16.5% (15 of 91) of patients who underwent lung transplantation during this time period developed IFI. Nineteen IFI episodes were identified (eight proven, 11 probable), 89% (17 of 19) of which developed during AF prophylaxis. LTR with idiopathic pulmonary fibrosis were more likely to develop IFI (HR: 4.29; 95% CI: 1.15–15.91; p = 0.03). A higher hazard of mortality was observed among those who developed IFI, although this was not statistically significant (hazard ratio [HR]: 1.71; 95% confidence interval [CI] [0.58–4.05]; p = 0.27). Aspergillus fumigatus was the most common cause of IFI (45%), with pulmonary parenchyma being the most common site of infection. None of our patients developed disseminated invasive aspergillosis, cryptococcal or endemic fungal infections. IFI continue to occur in LTR, and the eradication of IFI appears to be challenging even with prolonged prophylaxis. Azole resistance is uncommon despite prolonged AF exposure.     

Donor‐Derived Fungal Infections in Organ Transplant Recipients: Guidelines of the American Society of Transplantation,Infectious Diseases Community of Practice†

Donor‐derived fungal infections can be associated with serious complications in transplant recipients. Most cases of donor‐derived candidiasis have occurred in kidney transplant recipients in whom contaminated preservation fluid is a commonly proposed source. Donors with cryptococcal disease, including those with unrecognized cryptococcal meningoencephalitis may transmit the infection with the allograft. Active histoplasmosis or undiagnosed and presumably asymptomatic infection in the donor that had not resolved by the time of death can result in donor‐derived histoplasmosis in the recipient. Potential donors from an endemic area with either active or occult infection can also transmit coccidioidomycosis. Rare instances of aspergillosis and other mycoses, including agents of mucormycosis may also be transmitted from infected donors. Appropriate diagnostic evaluation and prompt initiation of appropriate antifungal therapy are warranted if donor‐derived fungal infections are a consideration. This document discusses the characteristics, evaluation and approach to the management of donor‐derived fungal infections in organ transplant recipients.     

Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma,Aspergillus Colonization,Invasive Aspergillosis and Death in Lung Transplant Recipients

Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all‐cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04–2.88; p = 0.03), with each additional 30‐day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02–1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34–0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all‐cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13–0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient‐specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients.     

Increased risk of rejection after basiliximab induction in sensitized kidney transplant recipients without pre‐existing donor‐specific antibodies – a retrospective study

Depleting induction therapy is recommended in sensitized kidney transplant recipients (KTRs), though the detrimental effect of nondonor‐specific anti‐HLA antibodies is not undeniable. We compared the efficacy and safety of basiliximab and rabbit anti‐thymocyte globulin (rATG) in sensitized KTRs without pre‐existing donor‐specific antibodies (DSAs). This monocentric retrospective study involved all sensitized KTR adults without pre‐existing DSAs (n = 218) who underwent transplantation after June 2007. Patients with basiliximab and rATG therapy were compared for risk of biopsy‐proven acute rejection (BPAR) and a composite endpoint (BPAR, graft loss and death) by univariate and multivariate analysis. Patients with basiliximab (n = 60) had lower mean calculated panel reactive antibody than those with rATG (n = 158; 23.7 ± 24.2 vs. 63.8 ± 32.3, P < 0.0001) and more often received a first graft (88% vs. 54%, P < 0.0001) and a transplant from a living donor (13% vs. 2%, P = 0.002). Risks of BPAR and of reaching the composite endpoint were greater with basiliximab than rATG [HR = 3.63 (1.70–7.77), P = 0.0009 and HR = 1.60 (0.99–2.59), P = 0.050, respectively]. Several adjustments did not change those risks [BPAR: 3.36 (1.23–9.16), P = 0.018; composite endpoint: 1.83 (0.99–3.39), P = 0.053]. Infections and malignancies were similar in both groups. rATG remains the first‐line treatment in sensitized KTR, even in the absence of pre‐existing DSAs.     

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 12 months 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 12 months posttransplant in 78% of cases. dnDSA were detected in 16% (95% confidence interval [CI]: 12‐20%) by 3 months and 23% (95% CI: 18‐29%) by 12 months posttransplant. Incidence at 12 months 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.     

Risk factors for multidrug‐resistant organisms among deceased organ donors

Donor infection or colonization with a multidrug‐resistant organism (MDRO) affects organ utilization and recipient antibiotic management. Approaches to identifying donors at risk of carrying MDROs are unknown. We sought to determine the risk factors for MDROs among transplant donors. A multicenter retrospective cohort study was conducted at four transplant centers between 2015 and 2016. All deceased donors who donated at least one organ were included. Cultures obtained during the donor's terminal hospitalization and organ procurement were evaluated. The primary outcome was isolation of an MDRO on culture. Multivariable Cox regression was used to determine risk factors associated with time to donor MDRO. Of 440 total donors, 64 (15%) donors grew an MDRO on culture. Predictors of an MDRO on donor culture included hepatitis C viremia (hazard ratio [HR] 4.09, 95% confidence interval [CI] 1.71‐9.78, P = .002), need for dialysis (HR 4.59, 95% CI 1.09‐19.21, P = .037), prior hematopoietic cell transplant (HR 7.57, 95% CI 1.03‐55.75, P = .047), and exposure to antibiotics with a narrow gram‐negative spectrum (HR 1.13, 95% CI 1.00‐1.27, P = .045). This is the first study to determine risk factors for MDROs among deceased donors and will be important for risk stratifying potential donors and informing transplant recipient prophylaxis.     

Organ donor management and delayed graft function in kidney transplant recipients: A multicenter retrospective cohort study

Meeting donor management goals (DMGs) has been reported to decrease the incidence of delayed graft function (DGF) after kidney transplant, but whether this relationship is independent of cold machine perfusion is unclear. We aimed to determine whether meeting DMGs is associated with a reduced incidence of DGF, independent of the use of machine perfusion. We collected data on consecutive brain‐dead donors and their KT recipients (KTRs) between June 2013 and December 2016 in 5 adult transplant centers. We evaluated whether DMGs were met at donor neurologic death (DND) and later time points. We defined a priori meeting optimal DMG as achieving ≥7 DMGs. Generalized estimating equations were used to predict DGF. Among 122 donors, 34% were extended‐criteria donors (ECDs). The number of DMGs met increased over time (5.6 ± 1.4 at DND and 6.1 ± 1.3 at organ procurement [P < .001]). DGF occurred in 23% of 214 KTRs, and 55% received organs placed on machine perfusion. In multivariate analysis, ECD (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.13‐4.45), use of machine perfusion (OR 0.45, 95% CI 0.22‐0.94), and optimal DMG at DND (OR 0.39, 95% CI 0.16‐0.99) were associated with DGF. Early achievement of DMGs was associated with a reduced risk of the development of DGF, independent of the use of machine perfusion.     

Early inhibition of the renin‐angiotensin system improves the long‐term graft survival of single pediatric donor kidneys transplanted in adult recipients

Transplanting single pediatric donor kidneys into adult recipients has an increased risk of hyperfiltration injury and graft loss. It is unknown if renin‐angiotensin system (RAS) blockers are beneficial in this setting. We retrospectively analyzed 94 adults who received single kidneys from donors <10 years old during 1996–2009. The recipients were divided into group 1 with RAS blockers (n = 40) and group 2 without RAS blockers (n = 54) in the first year of transplant. There was no significant difference in any donor/recipient demographic between the two groups. Graft function, incidence of delayed graft function, acute rejection, and persistent proteinuria were not statistically different either. Kaplan–Meier estimated death‐censored graft survivals were significantly better in group 1 than in group 2: 95 vs. 81.2%, 82.4 vs. 61.2%, 72.6 vs. 58.5%, and 68.5 vs. 47.2% at 1, 3, 5, and 7 years, respectively (log rank P = 0.043). Multivariable analysis found persistent proteinuria was a risk factor for graft loss (OR 2.70, 95% CI 1.33–5.49, P = 0.006), while RAS blockers reduced the risk of graft loss (OR 0.38, 95% CI 0.18–0.79, P = 0.009). Early RAS blockade therapy in the first year of transplant is associated with superior long‐term graft survival among adults transplanted with single pediatric donor kidneys.     

Hospital readmissions following HLA‐incompatible live donor kidney transplantation: A multi‐center study

Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. Those with donor‐specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22‐center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant‐matched controls and to waitlist‐only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed‐effects Poisson regression. In the first month, ILDKTs had a 1.28‐fold higher readmission risk than compatible controls (95% confidence interval [CI] 1.13‐1.46; P < .001). Risk peaked at 6‐12 months (relative risk [RR] 1.67, 95% CI 1.49‐1.87; P < .001), attenuating by 24‐36 months (RR 1.24, 95% CI 1.10‐1.40; P < .001). ILDKTs had a 5.86‐fold higher readmission risk (95% CI 4.96‐6.92; P < .001) in the first month compared to waitlist‐only controls. At 12‐24 (RR 0.85, 95% CI 0.77‐0.95; P = .002) and 24‐36 months (RR 0.74, 95% CI 0.66‐0.84; P < .001), ILDKTs had a lower risk than waitlist‐only controls. These findings of ILDKTs having a higher readmission risk than compatible controls, but a lower readmission risk after the first year than waitlist‐only controls should be considered in regulatory/payment schemas and planning clinical care.     

Clostridium difficile infection is associated with graft loss in solid organ transplant recipients

Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case‐control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty‐eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38‐0.58), with the highest rate in lung (1.48, 95% CI 0.93‐2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29‐6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03‐10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15‐4.37; P = .02). These findings may help to improve the management of SOT recipients.     

Delayed kidney graft function in simultaneous pancreas‐kidney transplant recipients is associated with early pancreas allograft failure

Delayed graft function (DGF) is a common complication associated with significant untoward effects in kidney‐alone transplantation. The incidence and outcomes following kidney delayed graft function (K‐DGF) among patients undergoing simultaneous pancreas‐kidney (SPK) transplantation are less certain. We analyzed SPK recipients transplanted at our center between January 1994 and December 2017. A total of 632 recipients fulfilled the selection criteria, including 69 (11%) with K‐DGF and 563 without. The incidence of K‐DGF was significantly higher in recipients of organs from older donors and donation after circulatory death (DCD). The presence of K‐DGF was significantly associated with an increased risk of pancreas graft failure during the first 90 days (n = 9, incidence rate [IR] 2.45/100 person‐months), but not with late pancreas failure (n = 32, IR 0.84/100 person‐months), kidney graft failure, or patient death. Although DCD was associated with K‐DGF, it was not associated with either pancreas (hazard ratio [HR] 0.91, 95% CI 0.58‐1.44, P = .69) or kidney (HR 1.09, 95% CI 0.66‐1.82, P = .74) graft failure after adjustment for potential confounders. We found K‐DGF to be a significant risk factor for pancreas graft failure but not kidney graft failure, with the major risk period being early (<90 days) posttransplant, and the major donor risk factor being older donor age.     

Prognostic Significance of 1‐Year Serum Albumin Levels Within the Normal Range After Kidney Transplantation

Hypoalbuminemia is associated with poor outcomes in kidney transplantation (KT). However, what level is optimal in serum albumin is not clear for the long‐term prognosis. To determine whether the long‐term outcomes are different even between the normal ranges of serum albumin after KT, we analyzed data from 404 renal allograft recipients whose 1‐year post‐transplant serum albumin levels were within the normal limits (3.5–5.5 g/dL). During a follow‐up of 122 ± 56 months, 97 graft losses, 20 patient deaths, and 50 cardiovascular (CV) events occurred. Based on 1‐year serum albumin levels, the patients were divided into high normal (≥4.6 g/dL, n = 209) and low normal (<4.6 g/dL, n = 195) groups. Kaplan–Meier analyses revealed that the low normal group had poorer allograft survival (P = 0.01), patient survival (P < 0.001), and CV event‐free survival (P < 0.001) than the high normal group. Cox regression analysis confirmed that 1‐year serum albumin was inversely associated with the risk of graft loss (hazard ratio [HR] 0.414, 95% confidence interval [CI] 0.200–0.856), patient death (HR 0.097, 95% CI 0.019–0.484), and CV events (HR 0.228, 95% CI 0.074–0.702). In conclusion, a relatively low 1‐year post‐transplant serum albumin level within the normal limits (<4.6 g/dL) significantly predicts poor long‐term outcomes.     

Renal resistance thresholds during hypothermic machine perfusion and transplantation outcomes – a retrospective cohort study

Renal resistance (RR), of allografts undergoing hypothermic machine perfusion (HMP), is considered a measure of organ quality. We conducted a retrospective cohort study of adult deceased donor kidney transplant (KT) recipients whose grafts underwent HMP. Our aim was to evaluate whether RR is predictive of death‐censored graft failure (DCGF). Of 274 KT eligible for analysis, 59% were from expanded criteria donor. RR was modeled as a categorical variable, using a previously identified terminal threshold of 0.4, and 0.2 mmHg/ml/min (median in our cohort). Hazard ratios (HR) of DCGF were 3.23 [95% confidence interval (CI): 1.12–9.34, P = 0.03] and 2.67 [95% CI: 1.14–6.31, P = 0.02] in univariable models, and 2.67 [95% CI: 0.91–7.86, P = 0.07] and 2.42 [95% CI: 1.02–5.72, P = 0.04] in multivariable models, when RR threshold was 0.4 and 0.2, respectively. Increasing risk of DCGF was observed when RR over the course of HMP was modeled using mixed linear regression models: HR of 1.31 [95% CI: 1.07–1.59, P < 0.01] and 1.25 [95% CI: 1.00–1.55, P = 0.05], in univariable and multivariable models, respectively. This suggests that RR during HMP is a predictor of long‐term KT outcomes. Prospective studies are needed to assess the survival benefit of patients receiving KT with higher RR in comparison with staying wait‐listed.     

Graft and patient outcomes of zero‐human leucocyte‐antigen‐mismatched deceased and live donor kidney transplant recipients

Greater compatibility of human leucocyte antigen (HLA) alleles between kidney donors and recipients may lead to improved graft outcomes. This study aimed to compare the incidence of acute rejection and graft failure in zero‐HLA‐mismatched recipients of living‐related (LD) and deceased donor (DD) kidney transplants. Using data from the Australia and New Zealand Dialysis and Transplant Registry, we compared the risk of any acute rejection and biopsy‐proven acute rejection (BPAR) and graft failure in recipients of zero‐HLA‐mismatched kidneys between LD and DD using logistic and Cox regression models. Of the 931 zero‐HLA‐mismatched recipients transplanted between 1990 and 2012, 19 (2.0%) received kidneys from monozygotic/dizygotic twins (twin), 500 (53.7%) from nontwin LD and 412 (44.3%) from DD. Twin kidney transplant recipients did not experience rejection. Compared to DD transplant recipients, the risk of any acute rejection (adjusted odds ratio 0.52, 95%CI 0.34–0.79, P = 0.002) and overall graft failure (adjusted hazard ratio 0.55, 95%CI 0.41–0.73, P < 0.001) was significantly lower in LD recipients independent of initial immunosuppression, but not for BPAR (adjusted odds ratio 0.52, 95%CI 0.16–1.64, P = 0.263). Zero‐HLA‐mismatched DD kidney transplant recipients have a significantly higher risk of any acute rejection episodes and graft loss compared to zero‐HLA‐mismatched LD kidney transplant recipients. A cautious and careful approach in reducing immunosuppression appears to be warranted in this group of transplant recipients.     

The effect of liver transplantation on patient‐centred outcomes: a propensity‐score matched analysis

It is unclear whether liver transplantation confers an increase in health‐related quality of life (HR‐QoL) across all dimensions of health. This study aimed to estimate the effect of liver transplantation on HR‐QoL. Pre‐ and post‐transplantation patients attending an outpatient clinic were invited to complete the condition‐specific ‘Short form of liver disease QOL’ questionnaire. Mixed‐effect linear regression and propensity‐score matching (PSM) on pretransplantation characteristics were used to estimate the difference in overall HR‐QoL associated with transplantation. Of 454/609 (74.5%) eligible patients who were included in the analysis, 102 (22.5%) patients fall under pretransplantation category, and 352 (77.5%) were under post‐transplantation category. Overall HR‐QoL post‐transplantation significantly increased in patients without hepatocellular carcinoma (HCC) (β = 16.84, 95% CI: 13.33 to 20.35, P < 0.001), but not with HCC (β = 1.25, 95% CI: ?5.09 to 7.60, P = 0.704). Donation after circulatory death (DCD) organ recipients had a significantly lower HR‐QoL (β = ?4.61, 95% CI: ?8.95 to ?0.24, P = 0.043). Following PSM, transplantation was associated with a significant increase in overall HR‐QoL (average treatment effect: 6.3, 95% CI: 2.1–10.9). There is a significant improvement in HR‐QoL attributable to transplantation in this cohort. Post‐transplantation HR‐QoL was affected by several factors, including HCC status and DCD transplantation, which has important implications for counselling prior to liver transplantation.     

Idiopathic pulmonary fibrosis lung transplant recipients are at increased risk for EBV‐associated posttransplant lymphoproliferative disorder and worse survival

Epstein‐Barr virus (EBV)–associated posttransplant lymphoproliferative disorder (EBV‐PTLD) is a serious complication in lung transplant recipients (LTRs) associated with significant mortality. We performed a single‐center retrospective study to evaluate the risks for PTLD in LTRs over a 7‐year period. Of 611 evaluable LTRs, we identified 28 cases of PTLD, with an incidence of 4.6%. Kaplan‐Meier analysis showed a decreased freedom from PTLD in idiopathic pulmonary fibrosis (IPF)‐LTRs (P < .02). Using a multivariable Cox proportional hazards model, we found IPF (hazard ratio [HR] 3.51, 95% confidence interval [CI] 1.33‐8.21, P = .01) and alemtuzumab induction therapy (HR 2.73, 95% CI 1.10‐6.74, P = .03) as risk factors for PTLD, compared to EBV mismatch (HR: 34.43, 95% CI 15.57‐76.09, P < .0001). Early PTLD (first year) was associated with alemtuzumab use (P = .04), whereas IPF was a predictor for late PTLD (after first year) (P = .002), after controlling for age and sex. Kaplan‐Meier analysis revealed a shorter time to death from PTLD in IPF LTRs compared to other patients (P = .04). The use of alemtuzumab in EBV mismatch was found to particularly increase PTLD risk. Together, our findings identify IPF LTRs as a susceptible population for PTLD. Further studies are required to understand the mechanisms driving PTLD in IPF LTRs and develop strategies to mitigate risk.     

Hospitalizations for fungal infections after initiation of chronic dialysis in the United States.

AIMS: Hospitalized fungal infections are reported frequently in renal transplant recipients and peritoneal dialysis patients, but the frequency of hospitalized fungal infections in dialysis patients has not been studied in a national population. METHODS: 327,993 dialysis patients in the United States Renal Data System initiated from January 1, 1992 to June 30, 1997 were analyzed in a retrospective registry study of fungal infections (based on ICD9 Coding). RESULTS: Dialysis patients had an age-adjusted incidence ratio for fungal infections of 9.80 (95% confidence interval (CI) 6.34-15.25)) compared to the general population in 1996 (the National Hospital Discharge Survey). Candidiasis accounted for 79% of all fungal infections, followed by cryptococcosis (6.0%) and coccidioidomycosis (4.1%). In multivariate analysis, fungal infections were associated with earlier year of dialysis, diabetes, female gender, decreased weight and serum creatinine at initiation of dialysis, chronic obstructive lung disease and AIDS. In Cox regression analysis the hazard ratio for mortality of fungal infections was 1.35 (95% CI 1.28-1.42). CONCLUSIONS: Dialysis patients were at increased risk for fungal infections compared to the general population, which substantially decreased patient survival. Female and diabetic patients were at increased risk for fungal infections. Although candidiasis was the dominant etiology of fungal infections, the frequency of cryptococcosis and coccidioidomycosis were higher than previously reported.