Background
We report follow-up data from an ongoing prospective cohort study of COVID-19 in pediatric kidney transplantation through the Improving Renal Outcomes Collaborative (IROC).
Methods
...Patient-level data from the IROC registry were combined with testing, indication, and outcomes data collected to describe the epidemiology of COVID testing, treatment, and clinical outcomes; determine the incidence of a positive COVID-19 test; describe rates of COVID-19 testing; and assess for clinical predictors of a positive COVID-19 test.
Results
From September 2020 to February 2021, 21 centers that care for 2690 patients submitted data from 648 COVID-19 tests on 465 patients. Most patients required supportive care only and were treated as outpatients, 16% experienced inpatient care, and 5% experienced intensive care. Allograft complications were rare, with acute kidney injury most common (7%). There was 1 case of respiratory failure and 1 death attributed to COVID-19. Twelve centers that care for 1730 patients submitted complete testing data on 351 patients. The incidence of COVID-19 among patients at these centers was 4%, whereas the incidence among tested patients was 19%. Risk factors to predict a positive COVID-19 test included age > 12 years, symptoms consistent with COVID-19, and close contact with a confirmed case of COVID-19.
Conclusions
Despite the increase in testing and positive tests over this study period, the incidence of allograft loss or death related to COVID-19 remained extremely low, with allograft loss or death each occurring in < 1% of COVID-19-positive patients and in less than < 0.1% of all transplant patients within the IROC cohort.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Background
Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in ...reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence.
Methods
We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation.
Discussion
Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment.
Clinical trial registration
https://clinicaltrials.gov/ct2/show/NCT03763643
, identifier NCT03763643.
Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). ...Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (
= < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (
= 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology (
= 0.035), being from a center that enrolled >10 cases (
= 0.049) and baseline serum ferritin level (
= 0.017). Increasing serum ferritin after conversion to PVA is concerning. This increase is not associated with serum hematocrit trends. Future studies should investigate the correlation of serum transferrin saturation and ferritin levels in pediatric HD patients.
Kidney transplantation is the preferred treatment for end-stage renal disease (ESRD) in children and confers improved survival, skeletal growth, heath-related quality of life, and neuropsychological ...development compared with dialysis. Kidney transplantation in children with ESRD results in 10-year patient survival exceeding 90%. Therefore, the long-term management of these patients is focused on maintaining quality of life and minimizing long-term side effects of immunosuppression. Optimal management of pediatric kidney transplant recipients includes preventing rejection and infection, identifying and reducing the cardiovascular and metabolic effects of long-term immunosuppressive therapy, supporting normal growth and development, and managing a smooth transition into adulthood.
The development of new-onset diabetes after kidney transplantation (NODAT) is associated with reduced graft function, increased cardiovascular morbidity and lower patient survival among adult ...recipients. In the pediatric population, however, the few studies examining NODAT have yielded inconsistent results. Therefore, the true incidence of NODAT in the pediatric population has been difficult to establish. The identification of children and adolescents at risk for NODAT requires appropriate screening questions and tests pre- and post-kidney transplant. Several risk factors have been implicated in the pathogenesis of NODAT and post-transplant glucose intolerance, including African American race, obesity, family history of diabetes and the type of immunosuppressant regimen. Moreover, uremia per se results in a state of insulin resistance that increases the risk of developing diabetes post-transplant. When an individual becomes glucose intolerant, early lifestyle modification and antihyperglycemic measures with tailoring of the immunosuppressant regimen should be implemented to prevent the development of NODAT. For the child or adolescent with NODAT, antihyperglycemic therapy should be prescribed in order to achieve optimal glycemic control, ultimately reducing complications and improving overall allograft and patient survival. In this article, we review the risk factors, screening methods, diagnosis, management and outcome of children and adolescents with NODAT and post-kidney transplant glucose intolerance.
Abstract
Background and Aims
Rejection remains the first cause of allograft loss in pediatric kidney transplant (pkTx) recipients. Detection of rejection currently relies on kTx biopsies performed ...either because of allograft dysfunction with the risk of late diagnosis or per surveillance protocols allowing early detection of subclinical rejection but resulting in many unnecessary biopsies. Dd-cfDNA was reported as a new non-invasive biomarker with the potential to improve rejection detection and guide biopsy indications. We aim to assess the association of dd-cfDNA levels with biopsy results in a large cohort of pediatric kTx recipients.
Method
All pediatric kTx patients with at least one dd-cfDNA assessment at the time of a biopsy at a single pediatric transplant center were included. Clinical, biological and histological data were collected from medical reports. Dd-cfDNA were retrospectively measured from plasma samples biobanked at the time of allograft biopsy between 2015 and 2020 or collected in patients who received regular dd-cfDNA testing as part as clinical care between 2021 and 2022.
Results
170 cfDNA measurements in 132 pkTx recipients were available at the time of a biopsy, including 100 performed for surveillance. Mean age at biopsy was 16 years with a median time from kTx of 21 11;38 months. Median eGFR was 62 48;83 mL/min/1.73 m2, median UPCR 0,21 0,14;0,36 g/g, and 20% had DSA at the time of the biopsy. Biopsy findings included: 109 normal, 30 borderline, 15 TCMR, 11 AMR and 5 mixed rejections. Median cfDNA level was 0,64 0,31;1,80 %. We found a strong association between cfDNA levels and active tubule-interstitial and microvascular Banff lesions (Figure 1). cfDNA levels were significantly increased in cases with rejection (Figure 2). Using the proposed cut-off of 0.5%, performances of the test to detect rejection were Se 84%, Spe 51%, PPV 33%, NPV 92%. Among the borderline cases, 17 (57%) had cfDNA>0.5%.
Conclusion
We confirm in the largest pediatric kTx cohort to date, the association of dd-cfDNA levels with allograft rejection and its potential interest as a non-invasive biomarker in children. Further studies are needed to assess the added value of dd-cfDNA monitoring to the current standard of care and its ability to reduce unnecessary surveillance biopsies and improve outcomes.
Abstract
Background and Aims
Belatacept is a co-stimulation blocker associated with better long-term outcomes in adult patients compared to CNI based regimens. Data on its use in older children and ...young adults are lacking. We are the 1st to report outcomes for 45 pediatric kidney transplant recipients converted to belatacept.
Method
45 patients were included from 4 centers (USA and France) between 05/2018 and 12/2021. Patients received an induction with basiliximab (n = 39) or ATG (n = 6). Maintenance immunosuppression included CNI, MMF +/− steroids. Patients’ viral status (EBV, CMV) were monitored monthly and allograft biopsies were performed prior and ∼6 months after starting belatacept. The first 5 belatacept injections were administered at 5 mg/kg/dose (10 mg/kg/dose if early conversion) every 2 weeks, then monthly. CNI were progressively reduced and stopped. MMF doses were also increased at CNI withdrawal.
Results
Median age at conversion was 17.7 y (range 10.3-20.6). 7/45 patients received an early conversion (median: 1 month post-transplant, IQR 0.5-1.2): 6 patients because of delayed graft function and 1 to avoid CNI toxicity (post-transplant diabetes). 38/45 patients were converted after a median of 4.1 years post-transplant (IQR 1.7-6.0). Conversion indication was based on the need for long term CNI avoidance: either because of toxicity (histology, post-transplant diabetes, tremors; n = 13) or sub-optimal creatinine (n = 12) or to improve adherence (e.g. monthly IV-treatment, n = 13). CNI were withdrawn in 42/45 patients by a median of 2.4 months (IQR 1.4-6.0). GFR was stable or improved over a median follow-up time of 1.6 years (IQR 1.1-2.4), Fig 1 A. Rejection episodes were observed in 10/45 patients (22%) after a median of 10.2 months (IQR 6.1-15.8) and included 7 TCMR, 2 ABMR and 1 mixed rejection. None of these patients were converted early (<3 m), 5 had been converted for non-adherence, 4 had pre-existing DSA and 4 had prior history of rejection. Evolution of GFR in rejectors is shown in Fig 1 B. CNI were reintroduced for 6/10 and belatacept stopped for 3/10. Regarding viral complications, 1 severe BKv nephropathy required the discontinuation of belatacept. All patients were EBV+ at conversion (4 were EBV- at the time of transplant). No EBV replication was observed.
Conclusion
Selected pediatric kidney recipients benefit from long-term CNI toxicity avoidance, but selection criteria need to be refined to avoid rejection under costimulation blockade.
In this review, we describe the multidisciplinary, multidimensional care required to optimize outcomes for pediatric transplant recipients with rare genetic kidney diseases. Transplant success, ...recipient survival, and improvement in quality of life depend on collaboration between patients, families, and a team of specialists with medical, as well as nonmedical expertise. A multidisciplinary transplant team composed of experts from medicine, surgery, nursing, nutrition, social services, transplant coordination, psychology, and pharmacology, is now standard in most transplant centers and is critical to the success of a transplant. In addition to these professionals, other specialists, such as cardiologists, urologists, geneticists, metabolic disease specialists, occupational therapists, case management, child life, chaplain, and palliative care services, have a crucial role to play in the preparation, surgery, and follow‐up care, especially when a pediatric patient has a rare genetic disorder leading to renal involvement, and the need for transplantation. In order to describe this multidisciplinary care, we divide the genetic renal diseases into five subgroups—metabolic and tubular disorders, glomerular diseases, congenital anomalies of the kidney and urinary tract, ciliopathies including cystic diseases, and miscellaneous renal conditions; and describe for each, the need for care beyond that provided by the standard transplant team members.
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