Special Considerations in Pediatric Kidney Transplantation

Hebert, Sean A.; Swinford, Rita D.; Hall, David R.; Au, Jason; Bynon, John S.

doi:10.1053/j.ackd.2017.09.009

Cited by 38 publications

(38 citation statements)

References 49 publications

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“…Previous reports suggested superior results for infant/juvenile allografts transplanted onto pediatric recipients. The benefits of kidney transplantation in terms of somatic growth, psychosocial rehabilitation, and long‐term dialysis free periods 40‐42 should further prioritize pediatric recipients for suitable allografts from pediatric donors. Additional rules should also prioritize “young‐to‐young” kidney allocations to provide more children with ESRD access to transplantation.…”

Section: Discussionmentioning

confidence: 99%

Kidney transplantation with allografts from infant donors—Small organs, big value

Hoyer

Dittmann

Büscher

et al. 2020

Pediatric Transplantation

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Section: Discussionmentioning

confidence: 99%

Kidney transplantation with allografts from infant donors—Small organs, big value

Hoyer

Dittmann

Büscher

et al. 2020

Pediatric Transplantation

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“…Detecting and treating rejection episodes remain one of the greatest challenges in pediatric kidney transplantation. While current immunosuppressive protocols follow those used in adult kidney transplantation, the pediatric recipient has a unique immunological environment and varied immunosuppression metabolism with age‐dependent pharmacokinetics, making attention to dosing and trough levels of paramount importance to combat higher rates of rejection 3 . This can be the case in very young children, while older children and adolescents are also at higher risk of rejection typically due to issues with adherence and the challenges of transitioning to adult care.…”

Section: Introductionmentioning

confidence: 99%

Donor‐derived cell‐free DNA (dd‐cfDNA) for detection of allograft rejection in pediatric kidney transplants

Puliyanda

Swinford

Pizzo

et al. 2020

Pediatric Transplantation

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In pediatric transplantation, acute rejection is a major contributor of graft failure. Current approaches include kidney biopsy in response to graft dysfunction and/or the emergence of donor‐specific HLA antibodies (DSA). However, biopsy is associated with potential complications. Thus, there is a need for non‐invasive diagnostics. Detection of donor‐derived cell‐free DNA (dd‐cfDNA, AlloSure) > 1% is associated with rejection in adult kidney transplants. Here, we evaluate the utility of dd‐cfDNA for identifying allograft rejection in pediatric patients. Between 10/2017 and 10/2019, 67 patients, who underwent initial testing with dd‐cfDNA as part of routine monitoring or in response to clinical suspicion for rejection, were included. Biopsies were performed when dd‐cfDNA > 1.0% or where clinical suspicion was high. Demographics, dd‐cfDNA, antibody status, and biopsies were collected prospectively. Data were analyzed to determine predictive value of dd‐cfDNA for identifying grafts at risk for rejection. 19 of 67 patients had dd‐cfDNA testing as part of routine monitoring with a median dd‐cfDNA score of 0.37 (IQR: 0.19‐1.10). 48 of 67 patients who had clinical suspicion of rejection had median dd‐cfDNA score of 0.47 (0.24‐2.15). DSA‐positive recipients had higher dd‐cfDNA scores than those who were negative or had AT1R positivity alone (P = .003). There was no association between dd‐cfDNA score and strength of DSA positivity. 7 of 48 recipients had a biopsy with a dd‐cfDNA score <1%; two showed evidence of rejection. Neither DSA nor AT1R positivity was statistically associated with biopsy‐proven rejection. However, dd‐cfDNA >1% was diagnostic of rejection with sensitivity of 86% and specificity of 100% (AUC: 0.996, 0.98‐1.00; P = .002). dd‐cfDNA represents a non‐invasive method for early detection of rejection in pediatric renal transplants. Our study shows dd‐cfDNA to be highly predictive of histological rejection and superior to other indicators such as graft dysfunction or antibody positivity alone. Further studies are necessary to refine these initial observations.

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“…Coordination of urologic and medical management was paramount to the successful outcomes in these complex patients. Prenatal interventions occurred in a discrete number of the current birth cohort; but this is not a primary focus of the current report (27, 28). Importantly, early post-natal management in each subject included relief of obstruction and establishment of free urine flow.…”

Section: Methodsmentioning

confidence: 99%

“…Subsequent surgeries were predicated on the need to establish constant urine flow, avoid infection and establish long-term urinary and bladder drainage. Preparation for transplantation included bladder augmentation when indicated and establishment of adequate long-term urinary drainage for the renal allograft (27, 28).…”

Section: Methodsmentioning

confidence: 99%

“…This included the use of non-radioactive imaging for improved safety and to allow for early prognostic-based planning. Vascular imaging with computed tomography (CT)-angiography and magnetic resonance (MR) urography and angiography allowed for pre-surgical planning, including urologic reconstruction and vascular anatomical planning for renal transplantation (28, 29). The use of specialized contrast agents such as or ferumoxytol (Feraheme®) for MR angiography to avoid gadolinium associated nephrogenic systemic fibrosis in ESRD patients should also be considered if resources are available (29, 30).…”

Section: Methodsmentioning

confidence: 99%

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Risk Assessment of Severe Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): A Birth Cohort

et al. 2019

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Recent advances in the early diagnosis of fetal CAKUT with an increase in fetal surgical interventions have led to a growing number of neonatal survivors born with severe renal dysfunction. This, in turn, has required the development of multi-disciplinary treatment paradigms in the individualized management of these infants with advanced stage kidney disease from birth. Early multi-modal management includes neonatal surgical interventions directed toward establishing adequate urine flow, respiratory support with the assessment of pulmonary hypoplasia, and establishing metabolic control to avoid the need for dialysis intervention. The development of specialized imaging to assess for residual renal mass with non-invasive 3-dimensional techniques are rapidly evolving. The use of non-radioactive imaging offers improved safety and allows for early prognostic-based planning including anticipatory guidance for progression to end stage renal disease (ESRD). The trajectory of kidney function during the neonatal period as determined by peak and nadir serum creatinine (SCr) and cystatin C (CysC) during the first months of life provides a guide toward individualized prospective management. This is a single center experience based on a birth cohort of 42 subjects followed prospectively from birth for an average of 6.1 ± 2.8 years at the University of Miami/Holtz Children's Hospital during the past decade. There was an 8:1 male: female ratio. The birth cohort was divided into 3 subgroups according to CKD Stages at the current age: CKD 1–2 (Group 1) (eGFR ≥ 60 ml/min/1.73 m 2 ) ( N = 15), CKD stage 3–5 (Group 2) (eGFR ≤ 59 ml/min/1.73 m 2 ) ( N = 12), and ESRD—Dialysis and/or Transplantation (Group 3) ( N = 15). A neonatal CysC >3.0 mg/L predicted progression to ESRD while a nadir SCr >0.6 mg/dL predicted progression to CKD 3–5 with the highest specificity and sensitivity by ROC-AUC analysis ( P < 0.0001). Medical management was directed toward nutritional support with novel formula designs, early introduction of growth hormone and strict control of mineral bone disorder. One of the central aspects of the management was to avoid dialysis for as long as feasible with a primary goal toward pre-emptive transplantation.

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Special Considerations in Pediatric Kidney Transplantation

Cited by 38 publications

References 49 publications

Kidney transplantation with allografts from infant donors—Small organs, big value

Kidney transplantation with allografts from infant donors—Small organs, big value

Donor‐derived cell‐free DNA (dd‐cfDNA) for detection of allograft rejection in pediatric kidney transplants

Risk Assessment of Severe Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): A Birth Cohort

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