Chronic kidney disease after liver, cardiac, lung, heart–lung, and hematopoietic stem cell transplant

Patient survival after cardiac, liver, and hematopoietic stem cell transplant (HSCT) is improving; however, this survival is limited by substantial pretransplant and treatment-related toxicities. A major cause of morbidity and mortality after transplant is chronic kidney disease (CKD). Although the majority of CKD after transplant is attributed to the use of calcineurin inhibitors, various other conditions such as thrombotic microangiopathy, nephrotic syndrome, and focal segmental glomerulosclerosis have been described. Though the immunosuppression used for each of the transplant types, cardiac, liver and HSCT is similar, the risk factors for developing CKD and the CKD severity described in patients after transplant vary. As the indications for transplant and the long-term survival improves for these children, so will the burden of CKD. Nephrologists should be involved early in the pretransplant workup of these patients. Transplant physicians and nephrologists will need to work together to identify those patients at risk of developing CKD early to prevent its development and progression to end-stage renal disease

Using machine learning to predict five-year transplant-free survival among infants with hypoplastic left heart syndrome

Abstract Hypoplastic left heart syndrome (HLHS) is a congenital malformation commonly treated with palliative surgery and is associated with significant morbidity and mortality. Risk stratification models have often relied upon traditional survival analyses or outcomes data failing to extend beyond infancy. Individualized prediction of transplant-free survival (TFS) employing machine learning (ML) based analyses of outcomes beyond infancy may provide further valuable insight for families and healthcare providers along the course of a staged palliation. Data from both the Pediatric Heart Network (PHN) Single Ventricle Reconstruction (SVR) trial and Extension study (SVR II), which extended cohort follow up for five years was used to develop ML-driven models predicting TFS. Models incrementally incorporated features corresponding to successive phases of care, from pre-Stage 1 palliation (S1P) through the stage 2 palliation (S2P) hospitalization. Models trained with features from Pre-S1P, S1P operation, and S1P hospitalization all demonstrated time-dependent area under the curves (td-AUC) beyond 0.70 through 5 years following S1P, with a model incorporating features through S1P hospitalization demonstrating particularly robust performance (td-AUC 0.838 (95% CI 0.836–0.840)). Machine learning may offer a clinically useful alternative means of providing individualized survival probability predictions, years following the staged surgical palliation of hypoplastic left heart syndrome

Heart Cells with Regenerative Potential from Pediatric Patients with End Stage Heart Failure: A Translatable Method to Enrich and Propagate

Background. Human cardiac-derived progenitor cells (hCPCs) have shown promise in treating heart failure (HF) in adults. The purpose of this study was to describe derivation of hCPCs from pediatric patients with end-stage HF. Methods. At surgery, discarded right atrial tissues (hAA) were obtained from HF patients (n=25; hAA-CHF). Minced tissues were suspended in complete (serum-containing) DMEM. Cells were selected for their tissue migration and expression of stem cell factor receptor (hc-kit). Characterization of hc-kitpositive cells included immunohistochemical screening with a panel of monoclonal antibodies. Results. Cells, including phase-bright cells identified as hc-kitpositive, spontaneously emigrated from hAA-CHF in suspended explant cultures (SEC) after Day 7. When cocultured with tissue, emigrated hc-kitpositive cells proliferated, first as loosely attached clones and later as multicellular clusters. At Day 21~5% of cells were hc-kitpositive. Between Days 14 and 28 hc-kitpositive cells exhibited mesodermal commitment (GATA-4positive and NKX2.5positive); then after Day 28 cardiac lineages (flk-1positive, smooth muscle actinpositive, troponin-Ipositive, and myosin light chainpositive). Conclusions. C-kitpositive hCPCs can be derived from atrial tissue of pediatric patients with end-stage HF. SEC is a novel culture method for derivation of migratory hc-kitpositive cells that favors clinical translation by reducing the need for exogenously added factors to expand hCPCs in vitro

Long-Term Survivors Following Pediatric Heart Transplantation: A PHTS Database Analysis

Short-term outcomes following pediatric heart transplantation have improved over time with 1-year survival of over 90%, but comparable improvements in longer-term survival continues to have important barriers. We sought to investigate long-term outcomes following pediatric heart transplantation and to identify favorable factors associated with long-term survival. The Pediatric Heart Transplant Society (PHTS) database was queried for pediatric heart transplant recipients from 1993-2010. Patients with graft survival ≥10 years were compared to the general cohort and to patients with follow up ≥3 but <10 years. Kaplan-Meier analysis was used to evaluate overall survival and 3-year conditional survival. Factors associated with graft loss after 3-year conditional survival were identified using Cox proportional hazard modeling. 3,436 patients were transplanted between 1993-2010, of whom 1355 (39.4%) had ≥10 years of follow up (median 13.7 years (range 10.0-27.5)). Of those surviving to 10 years post-transplant, 84.4% and 74.3% survived to 15 and 20 years, respectively. Of the complete PHTS cohort, overall survival at 15 years was 53.3%. Patients <1 year at transplant who survived to 10 years had improved survival compared to other age groups (Figure). In 10-year survivors, the leading cause of subsequent mortality was cardiac allograft vasculopathy (CAV). Risk factors for graft loss after 3 years post-transplant were age, female gender, African American race, use of steroids at 2 years, rejection (particularly with hemodynamic compromise) and CAV (p-value for all <0.05). Use of mTORi was not associated with long-term survival. Heart transplantation remains an effective therapy in pediatric patients with a growing number of long-term survivors. Of modifiable risk factors, cessation of steroids may provide long-term survival benefit. Additional studies on social determinants of health are warranted to address increased mortality among African Americans

Eighteen years of paediatric extracorporeal membrane oxygenation and ventricular assist devices: insight regarding late outcomes

We reviewed all patients who were supported with extracorporeal membrane oxygenation and/or ventricular assist device at our institution in order to describe diagnostic characteristics and assess mortality. A retrospective cohort study was performed including all patients supported with extracorporeal membrane oxygenation and/or ventricular assist device from our first case (8 October, 1998) through 25 July, 2016. The primary outcome of interest was mortality, which was modelled by the Kaplan-Meier method. A total of 223 patients underwent 241 extracorporeal membrane oxygenation runs. Median support time was 4.0 days, ranging from 0.04 to 55.8 days, with a mean of 6.4±7.0 days. Mean (±SD) age at initiation was 727.4 days (±146.9 days). Indications for extracorporeal membrane oxygenation were stratified by primary indication: cardiac extracorporeal membrane oxygenation (n=175; 72.6%) or respiratory extracorporeal membrane oxygenation (n=66; 27.4%). The most frequent diagnosis for cardiac extracorporeal membrane oxygenation patients was hypoplastic left heart syndrome or hypoplastic left heart syndrome-related malformation (n=55 patients with HLHS who underwent 64 extracorporeal membrane oxygenation runs). For respiratory extracorporeal membrane oxygenation, the most frequent diagnosis was congenital diaphragmatic hernia (n=22). A total of 24 patients underwent 26 ventricular assist device runs. Median support time was 7 days, ranging from 0 to 75 days, with a mean of 15.3±18.8 days. Mean age at initiation of ventricular assist device was 2530.8±660.2 days (6.93±1.81 years). Cardiomyopathy/myocarditis was the most frequent indication for ventricular assist device placement (n=14; 53.8%). Survival to discharge was 42.2% for extracorporeal membrane oxygenation patients and 54.2% for ventricular assist device patients. Kaplan-Meier 1-year survival was as follows: all patients, 41.0%; extracorporeal membrane oxygenation patients, 41.0%; and ventricular assist device patients, 43.2%. Kaplan-Meier 5-year survival was as follows: all patients, 39.7%; extracorporeal membrane oxygenation patients, 39.7%; and ventricular assist device patients, 43.2%. This single-institutional 18-year review documents the differential probability of survival for various sub-groups of patients who require support with extracorporeal membrane oxygenation or ventricular assist device. The indication for mechanical circulatory support, underlying diagnosis, age, and setting in which cannulation occurs may affect survival after extracorporeal membrane oxygenation and ventricular assist device. The Kaplan-Meier analyses in this study demonstrate that patients who survive to hospital discharge have an excellent chance of longer-term survival