Non-renal Solid Organ Transplant Research Articles

Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort.

Chronic kidney disease is common after non-renal solid organ transplantation, mainly secondary to calcineurin inhibitors toxicity. Uterus transplantation (UTx) is an innovative treatment for women with absolute uterine factor infertility. UTx is exclusive because it is transient with the absence of lifelong immunosuppression and is performed in young healthy participants. Therefore, UTx provides a unique setting for evaluating the effect of time-limited calcineurin inhibitors treatment on recipients' kidney function. In the first UTx cohort worldwide, we studied kidney function using estimated glomerular filtration rate (eGFR) in 7 women over a median follow-up of 121 (119-126) mo. Median eGFR (mL/min/1.73 m2) of the cohort was 113 at UTx, which declined to 74 during month 3, 71 at months 10-12, 76 at hysterectomy (HE), and 83 at last follow-up. Median duration of tacrolimus exposure was 52 (22-83) mo, and median trough levels (µg/L) were 10 during month 3 and 5.8 at HE. Between UTx and month 3, decline in kidney function was observed in all 7 participants with a median eGFR slope for the whole cohort of -24 mL/min/1.73 m2, which declined further by -4 mL/min/1.73 m2 until months 10-12. Thereafter, eGFR slope improved in 3 participants, remained stable in 3, and worsened in 1 until HE/tacrolimus discontinuation, after which it improved in 2. Eventually, between UTx and last follow-up, 4 of 7 participants had a decline in their eGFR, the median annual eGFR slope being negative at -1.9 mL/min/1.73 m2/y for the whole group. Kidney function declined in all recipients early after UTx followed by a persistent long-term decrease in majority, despite transplantectomy and discontinuation of immunosuppression. Thus, UTx may incur an increased risk of chronic kidney disease even in this young and healthy population, highlighting the importance of close surveillance of kidney function and minimization of tacrolimus exposure.

Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation.

Antibody mediated rejection (ABMR) is a major factor limiting outcome after organ transplantation. Anti-HLA donor-specific antibodies (DSA) of the IgG isotype are mainly responsible for ABMR. Recently DSA of the IgE isotype were demonstrated in murine models as well as in a small cohort of sensitized transplant recipients. In the present study, we aimed to determine the frequency of pre-existing and de novo anti-HLA IgE antibodies in a cohort of 105 solid organ transplant recipients. We prospectively measured anti-HLA IgE antibodies in a cohort of kidney (n=60), liver, heart and lung (n=15 each) transplant recipients before and within one-year after transplantation, employing a single-antigen bead assay for HLA class I and class II antigens. Functional activity of anti-HLA IgE antibodies was assessed by an in vitro mediator release assay. Antibodies of the IgG1-4 subclasses and Th1 and Th2 cytokines were measured in anti-HLA IgE positive patients. Pre-existing anti-HLA IgE antibodies were detected in 10% of renal recipients (including 3.3% IgE-DSA) and in 4.4% of non-renal solid organ transplant recipients (heart, liver and lung cohort). Anti-HLA IgE occurred only in patients that were positive for anti-HLA IgG, and most IgE positive patients had had a previous transplant. Only a small fraction of patients developed de novo anti-HLA IgE antibodies (1.7% of kidney recipients and 4.4% of non-renal recipients), whereas no de novo IgE-DSA was detected. IgG subclass antibodies showed a distinct pattern in patients who were positive for anti-HLA IgE. Moreover, patients with anti-HLA IgE showed elevated Th2 and also Th1 cytokine levels. Serum from IgE positive recipients led to degranulation of basophils in vitro, demonstrating functionality of anti-HLA IgE. These data demonstrate that anti-HLA IgE antibodies occur at low frequency in kidney, liver, heart and lung transplant recipients. Anti-HLA IgE development is associated with sensitization at the IgG level, in particular through previous transplants and distinct IgG subclasses. Taken together, HLA specific IgE sensitization is a new phenomenon in solid organ transplant recipients whose potential relevance for allograft injury requires further investigation.

Does therapeutic drug monitoring (TDM) of trough concentrations suffice for optimizing preemptive therapy with ganciclovir of cytomegalovirus infections in non-renal solid organ transplant recipients?

The aim of this study is to explore the relationship between ganciclovir exposure and clinical efficacy and/or safety in non-renal solid organ transplant (SOT) recipients receiving preemptive therapy with ganciclovir/valganciclovir and undergoing therapeutic drug monitoring (TDM)-guided dosing optimization. Non-renal SOT recipients admitted to IRCCS Azienda Ospedaliero-Universitaria of Bologna receiving preemptive therapy with ganciclovir or valganciclovir for active cytomegalovirus (CMV) infection and who underwent at least one TDM were included. Desired ganciclovir Cmin range was set at 1-3mg/L, and average ganciclovir trough concentrations (Cmin ) were calculated for each patient. Reduced CMV viral load below the lower limit of quantification (LLQ) at 30 days and occurrence of myelotoxicity were selected as the primary outcome. Univariate analysis was performed by comparing patients with average Cmin below or above 1 or 3mg/L. Receiver operating characteristic (ROC) curve analysis was performed to identify the average ganciclovir Cmin cut-off predictive for clinical efficacy or toxicity. Twenty-nine out of 89 retrieved patients met the inclusion criteria, with a median (interquartile [IQR]) baseline CMV viral load of 27,163 copies/mL (IQR 13159.75-151340.25 copies/mL). Reduced CMV viral load below the LLQ at 30 days was found in 17 patients (58.6%). No difference was found in the primary outcome between patients showing average Cmin below or above 1mg/L (100.0%vs. 53.8%; p= .25) and/or 3mg/L (65.2%vs. 33.3%; p = .20). ROC analysis did not allow to identify an average Cmin cut-off predictive of clinical efficacy or toxicity. No clear relationship between ganciclovir Cmin and neither CMV eradication nor safety issues was identified.

BK DNAemia and native kidney polyomavirus nephropathy following lung transplantation.

BK virus DNAemia (BKPyV) and nephropathy are common after kidney transplant; however, there are limited data on BK infections in nonrenal solid organ transplant recipients. We examined the frequency, clinical and pathologic features, and kidney and lung outcomes of BKPyV and BK virus native kidney nephropathy (BKVN) in lung transplant recipients at our center. Among 878 recipients transplanted from 2003 to 2019, 56 (6%) developed BKPyV at a median of 30.1 months after transplant (range, 0.6-213) and 11 (1.3%) developed BKVN at a median of 46 months after transplant (range, 9-213). The incidence of end-stage kidney disease was significantly higher in patients with peak viral load ≥10 000 copies/mL (39% vs 8%, P < .001). All cases of BKVN were in patients with peak viral load of ≥10 000 copies/mL, and 55% of these patients developed end-stage kidney disease. Despite the reduction of immunosuppression to treat BKVN, only 1 patient developed acute rejection, and lung function was stable >1 year. BKPyV and nephropathy are more common after lung transplantation than previously reported. Routine screening for BKPyV should be considered in all lung transplant recipients.

The Role of Peritoneal Dialysis in Different Phases of Kidney Transplantation.

The utilization of peritoneal dialysis (PD) has been increasing in the past decade owing to various government initiatives and recognition of benefits such as better preservation of residual renal function, quality of life, and lower cost. The Advancing American Kidney Health initiative aims to increase the utilization of home therapies such as PD and kidney transplantation to treat end stage kidney disease (ESKD). A natural consequence of this development is that more patients will receive PD, and many will eventually undergo kidney transplantation. Therefore, it is important to understand the effect of pretransplant PD on posttransplant outcomes such as delayed graft function (DGF), rejection, thrombosis, graft, and patient survival. Furthermore, some of these patients may develop DGF, which raises the question of the utility of PD during DGF and its risks. Although transplant is the best renal replacement therapy option, it is not everlasting, and many transplant recipients must go on dialysis after allograft failure. Can PD be a good option for these patients? This is another critical question. Furthermore, a significant proportion of nonrenal solid organ transplant recipients develop ESKD. Is PD feasible in this group? In this review, we try to address all of these questions in the light of available evidence.

Immunogenicity of the BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis Is Associated with Medical Conditions

Background and Objectives: Patients undergoing maintenance hemodialysis have an attenuated immune response to vaccination. The aim of our study was to determine the predictive factors for humoral response to vaccination with the BNT162b2 mRNA vaccine (Pfizer-BioNTech) in patients on maintenance hemodialysis. Design, Setting, Participants, and Measurements: In this retrospective, single-center study, we included patients on maintenance hemodialysis already vaccinated with two doses of the BNT162b2 vaccine (Pfizer-BioNTech) and with a post-vaccination serological follow-up. Results: 252 patients were included for study with a mean age of 71.9 (±14.4) years. Twelve patients (4.7%) were under immunosuppressive therapy (calcineurin inhibitors: n = 4; chemotherapy for myeloma: n = 3; last infusion of rituximab over the previous 4 years: n = 2; abatacept: n = 2; adalimumab n = 1). Three of these patients were under immunosuppressive therapy for nonrenal solid organ transplantation. Multivariate analysis identified immunosuppressive therapy (OR 4.73 [1.38–16.17], p = 0.013) and lower baseline albumin levels (OR 1.23 [1.09–1.38], p < 0.001) as independent predictive factors of nonresponse to vaccination. Older age (β = −0.59 ± 0.21, p = 0.006) and immunosuppressive therapy (β = 40.33 ± 13.33, p = 0.003) were significantly associated with lower humoral response to vaccination. Conclusions: Approximately 90% of patients under maintenance hemodialysis developed specific antibodies to the BNT162b2 mRNA vaccine. Immunosuppressive therapy, malnutrition, and older age were associated with a higher risk of nonseroconversion or lower humoral response to mRNA-based vaccination against SARS-CoV-2. We strongly recommend serological monitoring after vaccination to determine booster timing, especially for patients with malnutrition or on immunosuppressive therapy.

Native BK virus nephropathy in lung transplant: a case report and literature review.

ABSTRACTClassically described in renal allografts, BK virus nephropathy is increasingly recognized in native kidneys of other non-renal solid organ transplants. We discuss a 68-year-old woman with a history of bilateral lung transplant referred for worsening renal function, confirmed to have BK virus nephropathy by biopsy with a serum BK virus polymerase chain reaction of over 59 million copies/mL. She was managed with a reduction in immunosuppression and intravenous cidofovir with no improvement in her clinical parameters. The seven prior reported cases of polyoma virus nephropathy in lung transplant recipients are reviewed, and the challenges of screening and management are discussed.

Outcomes for Atypical Hemolytic Uremic Syndrome (aHUS) Treated with Eculizumab: A Single Center Analysis

INTRODUCTIONAHUS is a rare thrombotic microangiopathy (TMA), classically defined as microangiopathic hemolytic anemia, thrombocytopenia, and end-organ damage caused by alternative complement pathway abnormalities. Complement amplifying conditions (CACs) have been demonstrated to provoke or be associated with the emergence of aHUS manifestations, but their presence has also been associated with longer time to treatment initiation despite similar clinical presentation. (Cunningham et al. ASH 2016) Prior to effective therapy, more than half of patients progressed to death or end-stage renal disease within one year. (Noris et al. CJASN 2010) Eculizumab (ECU), a monoclonal C5 inhibitor, was approved for the treatment of aHUS in 2011. (Legendre et al. NEJM 2013) Here we report the results of the largest retrospective, single center series in the literature to date of 52 patients diagnosed with aHUS treated with ECU. METHODSWe performed a retrospective chart review of all patients diagnosed with aHUS who received at least one dose of ECU between December 2011 and February 2017 at MedStar Georgetown University Hospital. RESULTSFifty three patients received at least one dose of ECU for the treatment of aHUS between December 2011 and February 2017. One patient received a single dose of ECU, but was later found to have an ADAMTS13 level <5% and was removed from further analysis.CACs were identified in 71% of the 52 patients and 29% had de novo aHUS. Ninety percent of patients received ≥1 month of ECU and 40% remain on chronic ECU therapy through 15 February 2017. Of the 21 patients on chronic therapy, 67% had CACs and 33% did not. Of the 31 patients not currently known to be on therapy, 81% discontinued therapy or died and the treatment status was unknown in 19%. Six patients (12%) are deceased.Forty three patients were diagnosed while inpatients. Patients with CAC-associated aHUS had more pre-treatment days in the hospital than patients with de novo aHUS (35.73 and 12.92 days, respectively, p = 0.02). The lengths of hospital stays after ECU initiation were similar: 33.1 and 27.5 days, respectively. Presenting organ system involvement and laboratory data, including hemoglobin, platelet count and creatinine, were similar. (Table 1.) When adjusted for other variables, mean hemoglobin at presentation was lower in patients with CACs (p = 0.049). (Table 2.) After ECU initiation, similar trends in improvement of hemoglobin, platelet count, and creatinine were observed. (Figure 1)Hemodialysis (HD) rates prior to ECU initiation were similar regardless of CAC status. (Table 1.) Thirty five percent were started on HD either prior to or on the day of ECU initiation. Seventeen patients remained on HD one month post ECU, 14 of whom received ≥1 month of ECU. Eleven patients remained on HD ≥ 3 months post ECU, 6 /11 received ≥ 3 months of ECU, 3/11 received ≤ 3 months of ECU, and 2/11 were lost to follow-up. Three patients were on HD ≥1 month but ≤ 3 months; 1 remained on ECU through the 3 month time-point and two discontinued ECU after 4 and 5 weeks of therapy. Three patients on HD at 1 month were subsequently lost to follow-up.Six patient deaths (12%) were observed during the period of follow-up: 5 of 37 patients with CACs (14%) and 1 of 15 (6%) with de novo aHUS. CACs observed in the patients who died were non-renal solid organ transplant in 2 patients, renal transplant, rheumatoid arthritis, and ulcerative colitis. These patients had documented TMA involvement of between 2-5 organ systems. Survival after ECU initiation ranged from 2 to 24 weeks in the CAC associated group. The single patient death in the de novo aHUS group occurred at 20 weeks of follow-up. Four of the 6 patients remained on ECU through the date of death, including the single observed death in the de novo aHUS group, and 2 patients discontinued ECU after 4 and 9 weeks. CONCLUSIONIn a single center non clinical trial setting both CAC associated and de novo aHUS can be effectively treated with ECU. CAC status did not affect presentation characteristics. CAC status did not correlate with hematologic or creatinine response to ECU therapy. Our results suggest a higher rate of death among the CAC-associated aHUS patient population perhaps reflecting a longer time to diagnosis. Most patients remain on long-term therapy, regardless of CAC status at the time of diagnosis. [Display omitted] DisclosuresCunningham:TrueNorth therapeutics: Honoraria. Broome:TrueNorth Therapuetics: Honoraria; Alexion Pharmaceuticals: Honoraria.

MO195ATYPICAL HEMOLYTIC UREMIC SYNDROME IN LUNG TRANSPLANTATION: TREATMENT WITH ECULIZUMAB, OUR EXPERIENCE

Abstract Background and Aims Atypical haemolytic uremic syndrome (aHUS) is a clinical entity characterized by acute kidney injury, thrombocytopenia and microangiopathic hemolytic anemia. There are several cases of AHUS in non-renal solid organ transplants described in the literature, included lung transplant. Kidney and patient survival are compromised by this complication because of the lack of an effective treatment. Eculizumab is C5 complement factor specific blocker already administered in another kind of secondary aHUS with encouraging results Method We analys six lung transplants in a retrospective single-center study between 2018-2020 who developed an aHUS and were treated with eculizumab. Clinical and analytical data were collected along the follow-up. Principal outcome was to explore haematologycal and renal response after treatment with eculizumab. Results We included a total of six patients (83% were female) with a median age of 57 years at the time of transplantation. Aetiologies of lung transplantation were chronic obstructive pulmonary disease in 2 patients, interstitial lung disease in another 2, and cystic fibrosis in the remaining two. Induction and maintenance immunosuppressive therapy were based on tacrolimus, mycophenolate and prednisone in all cases. Baseline serum creatinine after lung transplantation was 1.1 mg/dl (0.9-2.4). Two patients developed an aHUS in the immediate post-transplant, one of them died because of surgical complications. Another four patients developed an aHUS 59 months (33-95) after transplantation. Previously of thrombotic microangiopathy, three patients were on treatment with everolimus instead of mycophenolate and two lung transplants have cytomegalovirus reactivation. At the aHUS onset, median serum creatinine was 4mg/dl (2.4-5-7) and acute dialysis was performed in 50% of patients. Median hemoglobin was 7.2g/dl (6.9-7.7), platelet count was 32x1000/µL (17-58), and DHL was 1343 U/L (581-1597) at the start of eculizumab despite having treated the trigger. After a median of 6 doses of eculizumab, the five surviving patients had haematologycal and renal response. No patients underwent chronic dialysis. Serum creatinine was 2.2 mg/dl (1.7-2.3), hemoglobin 9.8 g/dl and platelet count 159x1000/µL at the end of follow-up. Conclusion AHUS is a critical complication in lung transplantation, shortly related with immunosuppressive therapy. Patients are at risk of end stage renal disease. Eculizumab treatment appears promising.

The UNCX Polymorphism is Associated with the Development of Renal Dysfunction after Lung Transplantation

<h3>Purpose</h3> Renal dysfunction is a well-known long-term complication which could increase mortality after non-renal solid organ transplantation. Recently, the UNCX variant (rs10277115), which encodes a paired-type homeobox transcription factor and has essential roles in skeleton formation and kidney development, has been shown to be associated with increased risk for chronic kidney disease in east Asian populations. However, the association between the UNCX variant and renal dysfunction after lung transplantation (LT) has not yet been elucidated. In the present study, we evaluated the association between the UNCX variant and the postoperative change of renal function after LT. <h3>Methods</h3> A total of 99 recipients of LT more than 18 years were genotyped for the functional polymorphism of the UNCX gene (rs10277115) and divided into two groups: the wild-type allele (AA) group and the heterozygous and homozygous mutant allele (AT/TT) group. The results of renal function tests were compared between the two groups. Delta creatinine (ΔCr) and delta eGFR (ΔeGFR) were defined as the difference between the postoperative level and the preoperative baseline level. <h3>Results</h3> The clinical characteristics of the patients were similar between the two groups. There were no significant differences in the previously described risk factors for renal function, including age, diabetes mellitus, hypertension and dyslipidemia. The postoperative change of ΔCr was significantly higher in the AA group than the AT/TT group after LT (Figure 1(a)). Moreover, the postoperative change of ΔeGFR was significantly lower in the AA group than the AT/TT group after LT (Figure 1(b)). The multivariate analysis revealed that the UNCX variant was independently associated with the levels of ΔCr and ΔeGFR. <h3>Conclusion</h3> The UNCX variant was associated with significant differences in Cr and eGFR in the long term and the development of renal dysfunction after LT.

BK virus nephropathy in non-renal solid organ transplant recipients: Are we looking hard enough?

We retrospectively examined the clinical characteristics, pathological features, and outcomes of BK viremia and nephropathy in a population of non-renal solid organ transplant patients (NRSOT) referred for outpatient nephrology consultation over a period of 5years. In the entire cohort of liver, heart, and lung transplant recipients referred to this clinic, 14% percent were found to have BK viremia with a median peak serum BK viral load of 35500 copies/ml (range 250 to 21100000 copies/ml). BK viremia resolved in six of the seventeen patients (35%). Four out of five patients biopsied showed BK virus (BKV) nephropathy. Eleven out of seventeen patients with BK viremia developed advanced (stage 4 or 5) chronic kidney disease. Four patients developed rejection of their solid organ transplant within the first year post detection of BK viremia after immunosuppression reduction. We conclude that a multi-center study is required to evaluate whether implementation of a systematic BK screening program would be effective in early detection and management of this problem in the NRSOT population.

The Irish experience of kidney transplantation among recipients with prior non-renal solid organ transplants: A retrospective study on short- and long-term outcomes.

This study aims to evaluate allograft and patient outcomes among recipients of kidney transplants after non-renal solid organ transplants. We also aim to compare our findings with recipients of a repeat kidney transplant. We performed an analysis on kidney transplant recipients who underwent kidney transplantation after a non-renal solid organ transplant. Survival data were stratified into 2 groups: Group A (n=37) consisted of recipients of a kidney transplant after prior non-renal solid organ transplant, and Group B (n=330) consisted of recipients of a repeat kidney transplant. The 1-,5-, and 10-year graft survival (death-censored) for recipients of a kidney transplant post-non-renal solid organ transplant (Group A) were 97.3%, 91.5%, and 86.9%, compared with 97.9%, 90.2%, and 83.4% for recipients of a repeat kidney transplant (Group B) (p=.32). The 1-, 5-, and 10-year patient survival rates were 97.3%, 82.7%, and 79.1% in Group A compared to 97.9%, 90.2%, and 83.4% in Group B. Unadjusted overall patient survival was significantly lower for Group A (p=.017). Kidney transplant recipients who have undergone a previous non-renal solid organ transplant have similar allograft survival outcomes, but higher long-term mortality rates compared to repeat kidney transplant recipients.

Securing the future of kidney transplantation by addressing the challenges of transplant nephrology.

Kidney transplant is a life-changing procedure, and transplant nephrologists, as part of a larger transplant team, play an important role in the field by managing the complex medical needs of transplant patients. The subspecialty of transplant nephrology, however, faces structural challenges related to its workforce, reporting structures, compensation, research and innovation, and health care information technology. The position of transplant nephrology at the academic and operational intersection of medicine and surgery may limit its access to critical resources, hinder academic promotion, and contribute to physician burnout. The authors provide an overview of the subspecialty transplant nephrology and propose solutions. Collaborative efforts that fortify the subspecialty of transplant nephrology will ultimately improve the lives of patients suffering from kidney disease.

BK virus-associated nephropathy in a lung transplant patient: case report and literature review

BackgroundBK virus-associated nephropathy (BKVAN) is a relatively common cause of renal dysfunction in the first six months after renal transplantation. It arises from reactivation of the latent and usually harmless BK virus (BK virus) due to immunosuppression and other factors including some that are unique to renal transplantation such as allograft injury. BKVAN is much rarer in non-renal solid organ transplantation, where data regarding diagnosis and management are extremely limited.Case presentationWe report a case of a 58-year-old man found to have worsening renal dysfunction nine months after bilateral sequential lung transplantation for chronic obstructive pulmonary disease (COPD). He had required methylprednisolone for acute allograft rejection but achieved good graft function. Urine microscopy and culture and renal ultrasound were normal. BK virus PCR was positive at high levels in urine and blood. Renal biopsy subsequently confirmed BKVAN. The patient progressed to end-stage renal failure requiring haemodialysis despite reduction in immunosuppression, including switching mycophenolate for everolimus, and the administration of intravenous immunoglobulin (IVIG).ConclusionsThis very rare case highlights the challenges presented by BK virus in the non-renal solid organ transplant population. Diagnosis can be difficult, especially given the heterogeneity with which BKV disease has been reported to present in such patients, and the optimal approach to management is unknown. Balancing reduction in immunosuppression against prevention of allograft rejection is delicate. Improved therapeutic options are clearly required.

P1622GROWTH DIFFERENTIATION FACTOR 15: A BIOMARKER WITH HIGH CLINICAL POTENTIAL IN THE EVALUATION OF KIDNEY TRANSPLANT CANDIDATES

Abstract Background and Aims Kidney transplantation results a significant improvement in patient survival. Nevertheless, mortality the first years after transplant remains relatively high, being mostly related to cardiovascular (CV) events. The selection of patients for kidney transplantation includes a general assessment focused on CV status. In spite of that, due to the complexity and heterogeneity of mechanisms leading to vascular disease in this population (not exclusively related to traditional CV risk factors and pathogenesis), this evaluation remains insufficient and not particularly effective. During the last years different strategies have been studied to stratify potential receptors better and optimize organ allocation, including the development of clinical prognostic scores and novel biomarkers. Growth differentiation factor 15 (GDF-15) is a stress-responsive member of the TGF-β family. Although its mechanism of action is not completely understood, it acts as a cytokine with effects in regulation of inflammation, metabolism and senescence. In the recent years, interest has arisen regarding its use as a biomarker for diagnosis, prognosis and risk stratification in multiple scenarios. Encouraging results have shown its utility as a biomarker of mortality (all cause and CV), heart failure and acute coronary syndrome in different populations. The aim of this work is to assess the utility of GDF-15 to predict survival in kidney transplant candidates. Method 395 kidney transplant recipients between 2005 and 2015 were included. GDF-15 measurements were performed from stored serum samples obtained pretransplant. The concentration of GDF-15 was analyzed using an enzyme-linked immunosorbent assay (Quantikine, R&amp;D Systems). Results Patient characteristics are shown in Table 1. The median GDF-15 was 5331.3 (50.49-16242.3) pg/ml. After a mean of 90.6 ± 41.5 months of follow up 82 (20.8%) patients died. Patients were stratified in tertiles according to GDF-15 levels: low (GDF-15 ≤ 4612.1 pg/ml), medium (GDF-15 4612.1-6296.5 pg/ml) and high risk tertile (GDF-15 &amp;gt; 6296.5 pg/ml). Higher GDF-15 concentrations were significantly associated with mortality: HR 2.16 95%CI (1.14-1.44), p = 0.018 for medium tertile and HR 3.28 95%CI (1.79-6.1), p &amp;lt;0.001 for high risk tertile (Figure 1). After adjusting for age, diabetes, coronary artery disease, peripheral vascular disease, non-renal solid organ transplant and dialysis at the time of transplant, the relation between survival and GDF-15 was significant (HR 2.24 95%CI (1.2-4.16), p = 0.011 for high risk tertile). After adjusting by EPTS (Estimated Post Transplant Survival score) the association with GDF-15 remained significant: HR 3.24 95%CI (1.2-8.8), p = 0.021 for medium risk tertile and HR 4.3 95%CI (1.65-11.54), p = 0.003 for high risk tertile (calculated only in first renal transplants). Mortality at 3 years was 6.9% (27 patients) and it was only related to coronary artery disease and GDF-15 (OR 7.1 95%CI (1.6-32.1), p = 0.01 for high risk tertile) after adjustment. Conclusion In our cohort, higher GDF-15 levels were independently associated with mortality in kidney transplant candidates. This study suggests that GDF-15 may be useful in stratifying recipient risk, adding value to the prognostic tools already available in clinical practice. Further work is needed to confirm these findings and elucidate the mechanisms linking this protein with mortality and CV disease in patients with CKD.

Targeting Asymptomatic Bacteriuria in Antimicrobial Stewardship: the Role of the Microbiology Laboratory.

This minireview focuses on the microbiologic evaluation of patients with asymptomatic bacteriuria, as well as indications for antibiotic treatment. Asymptomatic bacteriuria is defined as two consecutive voided specimens (preferably within 2 weeks) with the same bacterial species, isolated in quantitative counts of ≥105 CFU/ml in women, including pregnant women; a single voided urine specimen with one bacterial species isolated in a quantitative count ≥105 CFU/ml in men; and a single catheterized urine specimen with one or more bacterial species isolated in a quantitative count of ≥105 CFU/ml in either women or men (or ≥102 CFU/ml of a single bacterial species from a single catheterized urine specimen). Any urine specimen with ≥104 CFU/ml group B Streptococcus is significant for asymptomatic bacteriuria in a pregnant woman. Asymptomatic bacteriuria occurs, irrespective of pyuria, in the absence of signs or symptoms of a urinary tract infection. The two groups with the best evidence of adverse outcomes in the setting of untreated asymptomatic bacteriuria include pregnant women and patients who undergo urologic procedures with risk of mucosal injury. Screening and treatment of asymptomatic bacteriuria is not recommended in the following patient populations: pediatric patients, healthy nonpregnant women, older patients in the inpatient or outpatient setting, diabetic patients, patients with an indwelling urethral catheter, patients with impaired voiding following spinal cord injury, patients undergoing nonurologic surgeries, and nonrenal solid-organ transplant recipients. Renal transplant recipients beyond 1 month posttransplant should not undergo screening and treatment for asymptomatic bacteriuria. There is insufficient evidence to recommend for or against screening of renal transplant recipients within 1 month, patients with high-risk neutropenia, or patients with indwelling catheters at the time of catheter removal. Unwarranted antibiotics place patients at increased risk of adverse effects (including Clostridioides difficile diarrhea) and contribute to antibiotic resistance. Methods to reduce unnecessary screening for and treatment of asymptomatic bacteriuria aid in antibiotic stewardship.

The Irish experience of kidney transplantation among recipients with prior nonrenal solid organ transplant and repeat kidney transplant

The Irish experience of kidney transplantation among recipients with prior nonrenal solid organ transplant and repeat kidney transplant

Mammalian target of rapamycin (mTOR) inhibitors and skin cancer risk in nonrenal solid organ transplant recipients: systematic review and meta-analysis.

Solid organ transplant recipients have an increased risk of malignancy compared with the general population. Mammalian target of rapamycin (mTOR) inhibitors have been used as immunosuppressants in transplant recipients. There remains a lack of evidence of this treatment in nonrenal solid organ transplantation. We aimed to perform a systematic review and meta-analysis to assess the effects of mTOR inhibitors on secondary nonmelanoma skin cancer(NMSC) malignancies in nonrenal transplant recipients. A systematic review and meta-analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies for the present systematic review and meta-analysis included those in which patient cohorts underwent heart, liver, lung, and pancreas (i.e. nonrenal solid organ) transplantation, with treatment group being those treated with an mTOR inhibitor such as sirolimus or everolimus, and control group being placebo, or alternative non-mTOR inhibitor treatment such as calcineurin inhibitors or as per standard treatment protocol. From the six included studies, we found no significant difference in the odds of either primary or secondary NMSC (OR 0.73, 95% CI 0.41-1.29, P=0.28). Pooled analysis of patients with secondary NMSC demonstrated a trend toward significant benefit with mTOR inhibitor treatment (OR 0.61, 95% CI 0.37-1.02, P=0.06) but no protective effect for primary NMSC (OR 0.53, 95% CI 0.03-9.96, P=0.67). Our results suggest that in nonrenal transplant recipients, mTOR inhibitors may have a protective effect against secondary NMSC but not primary NMSC posttransplantation. Extrapolating the findings of reduced NMSC in renal transplant populations to nonrenal transplant cases should be cautioned.

Symptomatic BK virus cystitis in non-renal transplant recipients.

BK virus is implicated most commonly in causing BK virus-associated nephropathy in renal transplant recipients. However, on rare occasions, it can also produce symptomatic cystitis in other solid organ transplant recipients. Retrospective review of 2,149 non-renal solid organ transplant recipients over a 6-year period to evaluate patients for cases of symptomatic BK virus cystitis. Three patients (two heart transplant recipients and one lung transplant recipient) are reported herein with symptomatic BK virus cystitis. These patients responded to reduced immunosuppressive medication with a reduction in viral load in two instances, and the third patient appeared to have an apparent response to prolonged levofloxacin treatment. A high index of suspicion should be exercised in non-renal solid organ transplant recipients (particularly heart and lung transplant recipients) who have symptoms consistent with cystitis but have a negative urine bacterial culture.

Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis

ABO-incompatible renal transplantation (ABOi-rTx) is increasingly used to overcome organ shortage. Evidence about its non-inferiority in comparison with ABO-compatible renal transplantation (ABOc-rTx) needs to be analysed at early and late timepoints. We aimed to investigate differences in outcome after ABOi-rTX and ABOc-rTX. We did a systematic review and meta-analysis of observational studies published up until Dec 31, 2017, that reported outcome data (≥1 year of follow-up) after ABOi-rTx and included an ABO-compatible control group, by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Embase Ovid, MEDLINE Ovid, and PubMed. Trials on recipients of ABOi-rTx were assessed, if an ABO-compatible control group was included and if outcome data on at least graft or recipient survival with 1 year or more of follow-up were available. Exclusion criteria included case reports, editorials, reviews and letters, animal studies, meeting papers, studies unable to extract data, non-renal solid organ and bone-marrow transplant studies, and deceased donor ABOc-rTx. Data were extracted from published reports. Primary endpoints were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation. In the meta-analysis, we used a fixed-effects model if the I2 value was 0, and both a fixed-effects and random-effects model if I2 was more than 0. This study is registered with PROSPERO, number CRD42018094550. 1264 studies were screened and 40 studies including 49 patient groups were identified. 65 063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx. Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year mortality (odds ratio [OR] 2·17 [95% CI 1·63-2·90], p<0·0001; I2=37%), 3 years (OR 1·89 [1·46-2·45], p<0·0001; I2=29%), and 5 years (OR 1·47 [1·08-2·00], p=0·010; I2=68%) following transplantation. Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year (OR 2·52 [1·80-3·54], p<0·0001; I2=61%) and 3 years (OR 1·59 [1·15-2·18], p=0·0040; I2=58%) only. Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years. No publication bias was detected and the results were robust to trial sequential analysis until 5 years after transplantation; thereafter, data became futile or inconclusive. Despite progress in desensitisation protocols and optimisation of ABOi-rTx procedures, excess mortality and loss of kidney grafts was found compared with ABOc-rTx within the first 3 years after transplantation. Only long-term outcomes after 5 years yielded equivalent survival rates and organ function. Awareness of the increased risks of infection, organ rejection, and bleeding could improve care of patients and promote efforts towards paired kidney exchange programmes. None.