Post-transplant Acute Kidney Injury Research Articles

Changes in Microbiome in Patients with Kidney Injury after Allogeneic Hematopoietic Stem Cell Transplantation.

Acute kidney injury (AKI) is a common complication of allogeneic hematopoietic cell transplantation (allo-HCT) that increases the risk of mortality. In contrast, higher diversity of intestinal microbiota at the time of neutrophil engraftment has been associated with lower mortality. We aimed to better understand kidney outcomes in relation to changes in gut diversity in this patient population, hypothesizing that patients with lower microbiome diversity at baseline and at engraftment were at higher risk of developing kidney complications. We performed a single-center retrospective study of 419 hematopoietic cell transplant recipients from 2014-2017 at our institution whose gut microbiota were analyzed. We defined AKI and CKD based on KDIGO criteria and estimated glomerular filtration rate (GFR) using the CKD Epidemiology Collaboration equation. We defined gut microbiome diversity using Shannon and Simpson reciprocal diversity indices, with higher levels indicating more diverse microbiota. Simpson reciprocal DI and Shannon DI were 21.8 (IQR: 13.7, 35.2; range: 1.6, 102.5) and 3.7 (IQR: 3.2, 4.2; range: 0.7,5.2) in our cohort at baseline and 6.3 (IQR: 3.7, 10.4) and 2.3 (IQR: 1.7, 2.8) at peri-engraftment. Of the 419, 263 patients (63%) developed any grade AKI in 100 days post-HCT, and 114 (27%) developed Grade 2+ AKI. There were no significant differences in microbiome diversity at baseline or peri-engraftment in patients who developed post-transplant AKI or CKD, respectively, in comparison to those who did not develop kidney complications. Our findings do not support the existence of a link between baseline or peri-engraftment gut diversity and the risk for development of AKI or CKD in patients undergoing allo-HCT. This study highlights the complex and multifactorial etiology of AKI in allo-HCT recipients and the need for additional prospective and mechanistic studies.

Are there any benefits of prolonged hypothermic oxygenated perfusion? - Results from a national retrospective study.

Dual hypothermic oxygenated perfusion (DHOPE) is increasingly being used to extend liver preservation to improve transplant logistics. However, little is known about its benefits in high-risk liver grafts. This study aimed to investigate whether prolonged DHOPE provides benefits other than improved logistics in all liver types. We performed a national retrospective cohort study of 177 liver transplants from 12 Italian centers preserved with DHOPE for ≥4h between 2015 and 2022. A control group of 177 DHOPEs of <4h during the same period was created using 1:1 propensity score matching. The impact of risk profiles and preservation times on the outcomes was assessed using univariable and multivariable regression models. No significant differences in post-transplant outcomes were found between prolonged and short DHOPEs. However, the prolonged group had a significantly lower incidence of post-transplant acute kidney injury (AKI) compared to the short group (30.5% vs. 44.6%, p=0.008). Among prolonged DHOPEs, no differences in transplant outcomes were observed according to donor risk index (DRI), Eurotransplant definition for marginal grafts, and balance of risk (BAR) score. DHOPE duration was associated with a lower risk of AKI in multivariable models adjusted for DRI, Eutrotransplant marginal grafts, and BAR score. Prolonged HOPE confirmed its protective effect against AKI in a multivariable model adjusted for donor and recipient risk factors [OR: 0.412, 95%CI: 0.200-0.850, p=0.016]. Prolonged DHOPE is widely used to improve transplant logistics, provides good results with high-risk grafts, and appears to be associated with a lower risk of post-transplant AKI. These results provide further insight into the important role of DHOPE in preventing post-transplant complications.

Postoperative Fluid Accumulation is Associated With Underestimation of AKI Severity in Lung Transplant Recipients.

Post-lung transplantation (LTx) fluid accumulation can lead to dilution of serum creatinine (SCr). We hypothesized that fluid accumulation might impact the diagnosis, staging, and outcome of posttransplant acute kidney injury (AKI). In this retrospective study, we analyzed data from 131 adult LTx patients at a single German lung center between 2005 and 2018. We assessed the occurrence of AKI within 7 days posttransplant, both before and after SCr-adjustment for fluid balance (FB), and investigated its impact on all-cause mortality. Transient and persistent AKIs were defined as return to baseline kidney function or continuation of AKI beyond 72h of onset, respectively. AKI was diagnosed in 58.8% of patients according to crude SCr values. When considering FB-adjusted SCr values, AKI severity was underestimated in 20.6% of patients, that is, AKI was detected in an additional 6.9% of patients and led to AKI upstaging in 23.4% of cases. Patients initially underestimated but detected with AKI only after FB adjustment had higher mortality compared to those who did not meet AKI criteria (hazard ratio [HR] 2.98; 95% confidence interval [CI] 1.06, 8.36; p=0.038). Persistent AKI was associated with higher mortality than transient AKI, regardless of using crude or adjusted SCr values (p < 0.05). Persistent AKI emerged as an independent risk factor for mortality (HR 2.35; 95% CI 1.29, 4.30; p=0.005). Adjusting for FB and evaluating renal recovery patterns post-AKI may enhance the sensitivity of AKI detection. This approach could help identify patients with poor prognosis and potentially improve outcomes in lung transplant recipients. ClinicalTrials.gov identifier: NCT03039959, NCT03046277.

Leveraging Electronic Health Records to Predict the Risk of Acute Kidney Injury after Allogeneic Hematopoietic Cell Transplantation.

The objective of this study is to assess the electronic health records (EHRs), which are potential risk factors for acute kidney injury (AKI) after allogenic hematopoietic cell transplantation (allo-HCT), and to propose a basic dataset and score for the calculation of HCT-acute kidney injury risk (HCT-AKIR). We undertook a retrospective analysis of the EHRs of 312 patients. Pre- and post-transplant factors were assessed, recognizing the following structured entries: laboratory data, encounters, medication, imaging studies, diagnoses, and procedures. Composite variables were used to create patient groups by combining two or more multivariate significant risk factors for AKI. The EHRs dataset and HCT-AKIR score were created based on the multivariate analysis of the composite variables. A multivariate analysis showed that previous CKD and once-impaired pre-transplant kidney function, sepsis, imaging procedures with contrast media, and cumulative length of intensive care unit stay after transplantation were significant risk factors. A new unit-weighted composite score based on the combination of significant risk factors contained in common EHR resources was proposed. Using our novel HCT-AKIR score calculated from the basic EHR dataset could be an easy way to increase awareness of post-transplant AKI and provide risk stratification.

Acute Kidney Injury After Liver Transplantation: Incidence, Risk Factors, and Outcomes

Introduction: Although numerous risk factors for acute kidney injury (AKI) have been identified, their cumulative impact remains unclear. This study aimed to identify perioperative risk factors for early post-transplant AKI on patients and outcomes and to predict AKI using clinical variables.&#x0D; Material and Methods: A single-center, retrospective cohort study involving 34 pediatric patients and 31 adults who underwent LT between 2015 and 2017.&#x0D; Results: AKI occurred in 16 (47%) pediatric patients during the first-week post-LT with stage 1, stage 2, and stage 3 AKI frequencies of 43.8, 50, and 6.3%, respectively. Renal replacement therapy (RRT) was initiated in 18.8% of pediatric LT patients. Preoperative liver enzymes and the etiology of liver failure are the most critical factors affecting AKI in pediatric LT patients. AKI occurred in 15 (48%) adult patients during the first-week post-LT with stage 1, stage 2, and stage 3 AKI frequencies of 43%, 21%, and 21%, respectively. The requirement for RRT was seen in 43% of adult LT patients. There were also statistical differences between the two groups regarding the number of patients with preoperative kidney dysfunction (20-80%, p=.047) and mortality rates (6-31 %, p=.047). In adult patients who developed post-LT AKI compared with those who did not develop post-LT AKI, they had significantly higher levels of serum creatinine (sCr) (1.9±1.9 mg/dL vs. 0.7±0.1 mg/dL, p=.013), were given lower amounts of crystalloids (73±32 mL/kg vs. 106±33 mL/kg, p=.018) and had lower urine output (UO) intraoperatively (11±9 mL/kg vs. 20±9 mL/kg, p=.047). There was a higher mortality rate in adult patients with post-LT AKI (89 vs. 11%, p=.003).&#x0D; Conclusion: The results of our study contribute to raising awareness of the potential risk factors associated with preoperative evaluation, intraoperative and postoperative close follow-up, careful anesthesia management, and early onset of post-LT AKI.

Risk factors for acute kidney injury in pediatric patients after hematopoietic stem cell transplantation: a systematic review and meta-analysis.

Risk factors for acute kidney injury (AKI) in pediatric patients after hematopoietic stem cell transplantation (HSCT) remain controversial. This study aimed to identify risk factors for AKI following HSCT in the pediatric population. PubMed, Embase, Web of Science, Cochrane Library, and Scopus databases were searched from inception to February 8, 2023. Studies meeting the following criteria were included: (1) The study was a case-control, cohort study, or cross-sectional design, (2) the study was performed among pediatric and young patients aged 21 years or younger undergoing HSCT, (3) the study measured at least one related factor for AKI after pediatric HSCT, (4) the study included a sample of at least ten patients, and (5) original articles published in English in peer-reviewed scientific journals. Children who were undergoing pediatric HSCT. We assessed the quality of the included studies and analyzed them with a random-effect model. Fifteen studies with a total of 2,093 patients were included. All were cohort studies of high quality. The overall pooled incidence of AKI was 47.4% (95%CI 0.35, 0.60). We found significant associations between post-transplant AKI in pediatric patients and unrelated donor [odds ratio (OR) = 1.74, 95% confidence interval (CI) 1.09-2.79], cord blood stem cell transplantation (OR = 3.14, 95%CI 2.14-4.60), and veno-occlusive disease (VOD)/sinusoidal obstruction syndrome (SOS) (OR = 6.02, 95%CI 1.40-25.88). Other controversial factors such as myeloablative conditioning (MAC), acute graft vs. host disease (aGVHD), and the use of calcineurin inhibitors (CNI) were not found to be related to AKI after pediatric HSCT. Results were limited mainly by heterogeneity in the characteristics of patients and transplantation. Posttransplant AKI in children is a common complication. Unrelated donors, cord blood stem cell transplantation, and VOD/SOS might be risk factors for AKI after pediatric HSCT. Further large-scale studies are still needed to draw firm conclusions. CRD42022382361 A higher resolution version of the Graphical abstract is available as Supplementary information.

401.4: Combined Genome Wide and Single Nuclei Transcriptomics in Posttransplant Acute Kidney Injury Identifies Early Proinflammatory/Profibrogenic Cell Origin

401.4: Combined Genome Wide and Single Nuclei Transcriptomics in Posttransplant Acute Kidney Injury Identifies Early Proinflammatory/Profibrogenic Cell Origin

Identification of Multiple Hub Genes in Acute Kidney Injury after Kidney Transplantation by Bioinformatics Analysis.

Background and Objectives: The molecular mechanisms of the development of acute kidney injury (AKI) after kidney transplantation are not yet clear. The aim of this study was to confirm the genes and mechanisms related to AKI after transplantation. Materials and Methods: To investigate potential genetic targets for AKI, an analysis of the gene expression omnibus database was used to identify key genes and pathways. After identification of differentially expressed genes, Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses were performed. We identified the hub genes and established the protein–protein interaction network. Results: Finally, we identified 137 differentially expressed genes (59 upregulated genes and 16 downregulated genes). AKAP12, AMOT, C3AR1, LY96, PIK3AP1, PLCD4, PLCG2, TENM2, TLR2, and TSPAN5 were filtrated by the hub genes related to the development of post-transplant AKI from the Protein–Protein Interaction (PPI) network. Conclusions: This may provide important evidence of the diagnostic and therapeutic biomarker of AKI.

Intraoperative risk factors of acute kidney injury after liver transplantation.

Acute kidney injury (AKI) is one of the most common complications of liver transplantation (LT). We examined the impact of intraoperative management on risk for AKI following LT. In this retrospective observational study, we linked data from the electronic health record with standardized transplant outcomes. Our primary outcome was stage 2 or 3 AKI as defined by Kidney Disease Improving Global Outcomes guidelines within the first 7 days of LT. We used logistic regression models to test the hypothesis that the addition of intraoperative variables, including inotropic/vasopressor administration, transfusion requirements, and hemodynamic markers improves our ability to predict AKI following LT. We also examined the impact of postoperative AKI on mortality. Of the 598 adult primary LT recipients included in our study, 43% (n = 255) were diagnosed with AKI within the first 7 postoperative days. Several preoperative and intraoperative variables including (1) electrolyte/acid‐base balance disorder (International Classification of Diseases, Ninth Revision codes 253.6 or 276.x and International Classification of Diseases, Tenth Revision codes E22.2 or E87.x, where x is any digit; adjusted odds ratio [aOR], 1.917, 95% confidence interval [CI], 1.280–2.869; p = 0.002); (2) preoperative anemia (aOR, 2.612; 95% CI, 1.405–4.854; p = 0.002); (3) low serum albumin (aOR, 0.576; 95% CI, 0.410–0.808; p = 0.001), increased potassium value during reperfusion (aOR, 1.513; 95% CI, 1.103–2.077; p = 0.01), and lactate during reperfusion (aOR, 1.081; 95% CI, 1.003–1.166; p = 0.04) were associated with posttransplant AKI. New dialysis requirement within the first 7 days postoperatively predicted the posttransplant mortality. Our study identified significant association between several potentially modifiable variables with posttransplant AKI. The addition of intraoperative data did not improve overall model discrimination.

Association between gut colonization of vancomycin-resistant enterococci and liver transplant outcomes.

Vancomycin-resistant enterococci (VRE) colonization is common in liver transplant recipients and has been associated with worse posttransplant outcomes. We conducted a retrospective cohort study at the University of Alberta Hospital including patients who underwent a liver transplant between September 2014 and December 2017. Of 343 patients, 68 (19.8%) had pretransplant VRE colonization and 27 (27/275, 9.8%) acquired VRE posttransplant, 67% were males and the median age was 56.5 years. VRE colonized patients at baseline had higher MELD scores and required longer posttransplant hospitalization. VRE colonization was associated with increased risk of early acute kidney injury (AKI) (64%vs. 52%, p=.044), clinically significant bacterial/fungal infection (29%vs. 17%, p=.012) and invasive VRE infection (5%vs. 1%, p=.017). Mortality at 2 years was 13% in VRE-colonized versus 7% in noncolonized (p=.085). On multivariate analysis, VRE colonization increased the risk of posttransplant AKI (HR 1.504, 95% CI: 1.077-2.100, p=.017) and clinically significant bacterial or fungal infection at 6months (HR 2.038, 95% CI: 1.222-3.399, p=.006), and was associated with nonsignificant trend toward increased risk of mortality at 2 years posttransplant (HR 1.974 95% CI 0.890-4.378; p=.094). VRE colonization in liver transplant patients is associated with increased risk of early AKI, clinically significant infections, and a trend toward increased mortality at 2 years.

Acute Kidney Injury After Liver Transplant: Incidence, Risk Factors, and Impact on Patient Outcomes.

Acute kidney injury is a frequent complication of liver transplant. Here, we assessed the rate and contributing factors of acute kidney injury and need for renal replacement therapy in patients undergoing liver transplant at a transplant center in Tehran, Iran. We identified all patients who underwent liver transplant at the Imam Khomeini Hospital Complex from March 2018 to March 2019 and who were followed for 3 months after transplant. Acute kidney injury was defined based on the Acute Kidney Injury Network criteria. We collected demographic and pretransplant, intraoperative, and posttransplant data. Univariable and multivariable models were applied to explore independent risk factors for acute kidney injury incidence and need for renal replacement therapy. Our study included 173 deceased donor liver transplant recipients. Rates of incidence of acute kidney injury and need for renal replacement therapy were 68.2% and 14.5%, respectively. The 3-month mortality rate among those with severe and mild or moderate acute kidney injury was 44.0% (14/25) and 9.7% (9/ 93), respectively (P < .001). Multivariable analyses indicated that serum albumin (relative risk of 0.55; 95% confidence interval, 0.34-0.87; P = .021), baseline serum creatinine (relative risk of 2.11; 95% confidence interval, 1.56-2.90; P = .037), and intraoperative mean arterial pressure (relative risk of 0.76; 95% confidence interval, 0.63-0.82; P = .008) were independent factors for predicting posttransplant acute kidney injury. Independent risk factors for requiring renal replacement therapy were pretransplant serum creatinine (relative risk of 1.99; 95% confidence interval, 1.89-4.47; P = .044) and intraoperative vasopressor infusion (relative risk of 1.41; 95% confidence interval, 1.38-2.00; P = .021). We found a high incidence of acute kidney injury among liver transplant recipients in our center. There was a significant association between severity of acute kidney injury and 3-month and in-hospital mortality.

Cardiac Outcomes in Isolated Heart and Simultaneous Kidney and Heart Transplants in the United States

IntroductionKidney dysfunction is not uncommon in patients with advanced heart failure. Simultaneous kidney and heart transplants (SKHTs) have gained acceptance as a treatment for patients with end-stage heart failure and severe kidney dysfunction. United States saw a rise of 650% in SKHT from 2000 to 2019. Despite increasing number of SKHT, the selection criteria remain poorly defined and vary across transplant centers.MethodsWe evaluated patient and cardiac allograft survival for SKHT and heart transplant alone (HTA) using the United Network for Organ Sharing (UNOS) database. We then performed a subgroup analysis in recipients with post-transplant acute kidney injury requiring renal replacement therapy (RRT) and compared outcomes between SKHT and HTA recipients.ResultsAlthough patient survival was comparable between SKHT and HTA groups (12.4 vs. 11.3 years), patients dependent on dialysis pretransplant derived greater survival advantage from SKHT as compared with HTA (12.4 vs. 9.9 years). Cardiac graft survival was better in SKHT (12.5 vs. 11.2 years). Among patients who developed acute kidney injury requiring RRT postoperatively, SKHT recipients had a significantly better survival (11.9 vs. 2.7 years).ConclusionOur data support consideration of SKHT in dialysis-dependent heart transplant candidates and suggest that patients who are at increased risk of requiring RRT after heart transplant may benefit from SKHT.

Initial piggyback technique facilitates late liver retransplantation - a retrospective monocentric study.

Optimal management of inferior vena cava (IVC) is crucial to ensure safety in late liver retransplantation (ReLT). The aim of this study was to evaluate different surgical strategies with regard to IVC in late ReLT. All consecutive late ReLT (≥90days from the previous transplant) from 2013 to 2018 in a single center was reviewed (n=66). Of them, 46 (69.7%) were performed without venovenous bypass (VVB) including 29 with caval preservation (CP) and 17 with caval replacement (CR). The remaining 20 cases (30.3%) required the use of VVB. Among ReLT without VVB, CP was associated with a lower number of packed red blood cells (median 4 vs. 7; P=0.016) and a lower incidence of post-transplant acute kidney injury (6.9% vs. 47.1%; P=0.003). The feasibility of CP was 95% (14/15) in patients with previous 3-vein piggyback caval anastomosis versus 48.3% (15/31) after other techniques (P=0.003). Indirect signs of portal hypertension (PHT) before retransplantation were predictive of VVB requirement. Early and long-term outcomes were similar across the three groups (CP without VVB, CR without VVB, and VVB). Preserving the IVC in late ReLT is associated with better postoperative renal function and is facilitated by a previous 3-vein piggyback. Routine CR is not justified in late ReLT.

The Prevalence, Risk Factors, and Prognosis of Acute Kidney Injury After Lung Transplantation: A Single-Center Cohort Study in China

PurposeThe aim of this study is to evaluate the incidence, risk factors, and prognosis of acute kidney injury (AKI) after lung transplantation (LTx). MethodsRecords of patients who underwent LTx in a single center were retrospectively reviewed. The prevalence of post-transplant AKI, the use of continuous renal replacement therapy (CRRT), and the risk factors for AKI were investigated. The effects of AKI and CRRT on short-term outcomes and long-term survival were measured. ResultsThis study included 148 patients, 67 of which developed postoperative AKI. Of these, 31 patients underwent CRRT; the percentage of cases with no AKI was 6.2%, and the percentage of cases with stage 1, 2, and 3 who used CRRT was 0%, 10%, and 86.2%, respectively. Patients with AKI had significantly higher intensive care unit mortality and in-hospital mortality. The 1-year post-LTx survival rate of patients with AKI was 47.8%, significantly lower than those without AKI (74.1%). There was no difference in 1-year survival rate of those with stage 1 and stage 2 AKI, but patients with stage 3 AKI showed the worst survival. Patients who underwent CRRT had an inferior survival outcome (9.7% vs 76.1%, P < .05). We found that higher acute physiologic assessment and chronic health evaluation (APACHE) II scores (odds ratio [OR] 1.082, P = .009) and higher intraoperative fluid balance (OR 1.001, P = .012) were independent risk factors, and female sex (OR 2.539) and pulmonary hypertension (OR 2.869) were potential risk factors for post-LTx AKI. A prediction model integration of the above factors showed a good concordance with actual risks and had a concordance index (C-index) of 0.76 (95% confidence interval [CI], 0.66-0.87). ConclusionSevere AKI requiring CRRT had a negative impact on the short-term and long-term outcomes of patients.

The Impact of Anti-Microbial Drug-Drug Interactions on Acute Kidney Injury after Allogeneic Hematopoietic Cell Transplantation

Introduction: Acute kidney injury (AKI) is one of the major complications after allogeneic hematopoietic cell transplantation (allo-HCT), and several studies have demonstrated a relationship between poor outcome and the concomitant AKI in the early phase after allo-HCT. Among various post-transplant factors, usage of antimicrobial agents, especially in cases where multiple agents are combined, may be one of the major causes of post-transplant AKI, due the potential nephrotoxicity of each agent and drug-drug interactions. An association between the combination of vancomycin (VCM) with piperacillin/tazobactam (PIPC/TAZ) and increased risk of developing AKI after allo-HCT has been reported; however, no reports have demonstrated the impact of other combinations on post-transplant AKI. Herein, we performed a retrospective analysis to compare the incidence of AKI according to selected antimicrobial agents, using a database with information covering the time-dependent administrative status of all the agents involved. Methods: We included patients with hematological malignancies who received allo-HCT between 2006 and 2018 in Kyoto University, Kyoto, Japan to evaluate the incidence and risk factors of AKI early after transplantation (before Day100). The incidence of AKI was defined according to Acute Kidney Injury Network (AKIN) classification and evaluated, considering early death as a competing risk. Administrative status of each antimicrobial agent was treated as a time-dependent covariate, and the synergetic effects on AKI by multiple agents in combination were evaluated as p for interaction. Results: In total, 465 transplant cases (416 patients) were included. The median age at HCT was 49 years old (range, 17-70). Among these, 104 cases received a related-donor transplant (64 patients received bone marrow and 40 peripheral-blood stem cell grafts), 207 received a transplant from unrelated donors, and 154 received a single-unit cord-blood transplant. The median value for pre-transplant serum creatinine (sCr) was 0.6 (range, 0.20-1.68). The cumulative incidence of AKI at Day100 was 40.0%, and overall survival (OS) at 3 years after HCT was 43.5% in patients with AKI while 70.9% in those without AKI (hazard ratio [HR] = 2.63, 95% confidence interval = 1.95-3.55, p &amp;lt; 0.01). Being male and having a higher pre-transplant sCr were significant risk factors for AKI (HR = 1.53, p &amp;lt; 0.01 and HR = 4.21, p &amp;lt; 0.01, respectively). After HCT, 34 types of oral or intravenous antimicrobial agents (17 antibiotics, 6 antivirals, and 11 antifungals) were utilized across the entire cohort. A higher incidence of AKI was significantly associated with the use of intravenous ciprofloxacin, foscarnet (FCN), ganciclovir (GCV), liposomal amphotericin B (L-AMB), meropenem (MEPM), PIPC/TAZ, and VCM (p &amp;lt; 0.05). Next, we investigated the synergistic impacts of using anti-pseudomonal antibiotics and anti-methicillin resistant staphylococcus aureus (MRSA) agents, because empiric treatment of febrile neutropenia after HCT often relies on this combination, i.e. CFPM, PIPC/TAZ, or MEPM in combination with VCM or teicoplanin (TEIC). As a result, sole administration of VCM was associated with a higher incidence of AKI; this effect was enhanced when VCM was used in combination with PIPC/TAZ (HR = 3.03, p &amp;lt; 0.01 for VCM without PIPC/TAZ; HR = 4.38, p &amp;lt; 0.01 for VCM with PIPC/TAZ), indicating the existence of interaction between VCM and PIPC/TAZ. However, for the concomitant use of VCM plus CFPM or MEPM, no synergistic interaction was observed with regard to the increased incidence of AKI. In addition, administration of TEIC alone and any combination used with TEIC were not associated with an increased risk of AKI. An increased risk of AKI was also confirmed for the combination of MEPM plus GCV or FCN, and GCV plus L-AMB. Conclusions: AKI was significantly associated with poorer OS, and specific antimicrobial combinations were suggested to increase the risk of AKI. Avoidance of such combinations should be considered to preserve renal function and to reduce AKI-related morbidity and mortality. Disclosures No relevant conflicts of interest to declare.

Stable renal function in children and adolescents with sickle cell disease after nonmyeloablative hematopoietic stem cell transplantation.

Sickle cell disease (SCD) is associated with renal complications starting as early as infancy. Allogeneic hematopoietic stem cell transplant (HSCT) treatments using newer nonmyeloablative (NMA) conditioning regimens show promising results in treating SCD in the pediatric population, but renal outcome parameters after transplantation have not been described. To describe baseline renal parameters as well as short- and long-term renal outcomes in pediatric patients with SCD who underwent NMA-HSCT. A retrospective chart review of pediatric patients who received NMA-HSCT in Alberta, Canada. Short-term renal outcomes evaluated were: (1) acute kidney injury (AKI), (2) fluid overload (FO), and (3) hypertension. Long-term outcomes evaluated were: (1) estimated glomerular filtration rate (eGFR) development and at last follow-up with hyperfiltration defined as eGFR≥150mL/min/1.73 m2 , (2) proteinuria, and (3) hypertension. The mean follow-up time was 128.6weeks (standard deviations, 69.3). No posttransplant AKI events or FO were observed. eGFR remained>90mL/min/1.73 m2 at last follow-up in all patients, whereas hyperfiltration was present in eight (44.4%) and four (22.2%) patients pre- and post-HSCT, respectively, which are significantly different (P<0.0001). Consequently, median GFR was significantly higher pre-HSCT compared with 24 months HSCT (P<0.009). Long-term hypertension post-HSCT was present in six patients (33.3%). This study describes stable kidney function in children with SCD after NMA-HSCT without evidence of AKI or FO episodes. Rates of hyperfiltration decreased post-HSCT, which signifies that NMA-HSCT could potentially preserve long-term renal function in this population at risk of progressive chronic kidney disease. Further prospective studies are needed to confirm these novel findings.

The impact of severe acute kidney injury requiring renal replacement therapy on survival and renal function of heart transplant recipients - a UK cohort study.

Severe acute kidney injury (AKI), defined as requiring renal replacement therapy (RRT), is associated with higher mortality postheart transplantation, but its long-term renal consequences are not known. Anonymized data of 3365 patients, who underwent heart transplantation between 1995 and 2017, were retrieved from the UK Transplant Registry. Multivariable binary logistic regression was performed to identify risk factors for severe AKI requiring RRT, Kaplan-Meier analysis to compare survival and renal function deterioration of the RRT and non-RRT groups, and multivariable Cox regression model to identify predicting factors of mortality and end-stage renal disease (ESRD). 26.0% of heart recipients received RRT post-transplant. The RRT group has lower survival rates at all time points, especially in the immediate post-transplant period. However, conditional on 3months survival, older age, diabetes and coronary heart disease, but not post-transplant RRT, were the risk factors for long-term survival. The predicting factors for ESRD were insulin-dependent diabetes, renal function at transplantation, eGFR decline in the first 3months post-transplant, post-transplant severe AKI and transplantation era. Severe AKI requiring RRT post-transplant is associated with worse short-term survival, but has no impact on long-term mortality. It also accelerates recipients' renal function deterioration in the long term.

New trends in the study of post-transplant acute kidney injury after liver transplantation

Acute kidney injury (AKI) after liver transplantation (LT) is a pressing issue and remains the focus of many researchers. The etiology of AKI is multifactorial, but the main one is ischemia-reperfusion injury to the liver transplant. Numerous preoperative, intraoperative and postoperative risk factors contribute to the development of AKI. The use of standard classifications, such as AKIN, RIFLE and KDIGO, has improved post-transplant AKI diagnosis. However, determination of creatinine levels in the blood enables AKI diagnosis only in the later stages of this syndrome. Therefore, studies are currently underway to find ways of early diagnosis of AKI using biomarkers. Transition to a molecular level not only improves accuracy but also facilitates early diagnosis of AKI. Currently, the diagnostic capabilities of neutrophil gelatinase-associated lipocalin (NGAL) are the most investigated. To date, there are no known measures of preventing post-transplant AKI. Moreover, treatment of this condition cannot be considered satisfactory. Even a mild post-transplant AKI can be fatal. In severe AKI, where renal replacement therapy is used, there is a risk of death in the intensive care unit. More than half of AKI patients develop chronic kidney disease requiring chronic hemodialysis.

Risk Factors for Acute Kidney Injury and Chronic Kidney Disease following Allogeneic Hematopoietic Stem Cell Transplantation for Hematopoietic Malignancies

Background: Acute kidney injury (AKI) and chronic kidney disease (CKD) are considered common complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Objectives and Method: In this study, 114 patients who had undergone allo-HSCT were retrospectively analyzed to investigate the risk factors for onset of posttransplant AKI and CKD as defined by the new Kidney Disease Improving Global Outcomes criteria. Results: Seventy-four patients (64.9%) developed AKI and 25 (21.9%) developed CKD. The multivariate analysis showed that the risk factors for developing stage 1 or higher AKI were age ≥46 years at the time of transplant (p = 0.001) and use of ≥3 nephrotoxic drugs (p = 0.036). For CKD, the associated risk factors were disease status other than complete remission at the time of transplantation (p = 0.018) and onset of AKI after transplant (p = 0.035). The 5-year overall survival (OS) was significantly reduced by development of AKI (p < 0.001), but not CKD. Posttransplant AKI significantly increased the 5-year nonrelapse mortality (p < 0.001), whereas posttransplant CKD showed an increasing tendency, but the difference was not significant. Conclusions: Posttransplant AKI impacts OS, significantly increases the risk of CKD, and is significantly associated with disseminated intravascular coagulation and use of ˃3 nephrotoxic drugs.

The Role of Secretory Leukocyte Proteinase Inhibitor During Transplantation

Old and new players of the innate immune response have been studied in the context of transplantation. Nonetheless, little interest has been focused toward the immune regulatory feedback in transplantation. Here, we revised the role of secretory leukocyte proteinase inhibitor (SLPI), which limits the activity of serine proteases, in solid organ transplantation. Ischemia-reperfusion injury increases SLPI gene expression. Furthermore, post-transplant acute kidney injury increases the expression of SLPI transcript and protein. Several studies have shown that SLPI exerts direct, indirect, and locally mediated beneficial effects in multiple ischemia-reperfusion models. Moreover, the addition of SLPI in the preservation solution improved cardiac performance in a cardiac transplantation model. Diverse factors present at the time of transplantation facilitate the production and secretion of SLPI, which in turn acts as a feedback mechanism to control graft injury. The pleiotropic activity of SLPI as a tolerogenic factor, as well as microbicidal and wound healing agent, should motivate the exploration of its utility as an adjuvant therapeutic tool in transplanted patients. Further studies are also required to analyze the utility of SLPI as a biomarker of graft quality and injury.