Acute Kidney Injury Requiring Dialysis After Pediatric Heart Transplant.

BACKGROUND: Acute kidney injury (AKI) is a common complication of pediatric heart transplant, with a subset of patients developing severe AKI requiring dialysis (AKI-D). We aimed to identify the epidemiology, risk factors, and outcomes of postoperative AKI-D in pediatric heart transplant recipients. METHODS: We retrospectively identified all pediatric first-time, single-organ heart transplants at our institution from 2014 to 2022. Postoperative AKI was defined as AKI within 2 weeks of transplant. Unadjusted and adjusted logistic regression were used to identify characteristics associated with AKI-D, and unadjusted time-to-event analyses were used to determine the association between AKI-D and survival free of kidney failure. RESULTS: Among 177 patients included, 116 (66%) developed postoperative AKI of any stage, including 13 (7%) who developed AKI-D with median time from transplant to dialysis initiation of 6 days (IQR 3-13). In adjusted models, increased cardiopulmonary bypass time (OR 1.19, 95% CI 1.04-1.37, per 15 min increase in bypass time) and higher weight at transplant were associated with higher odds of AKI-D, whereas patient demographics and pretransplant kidney function were not associated with AKI-D. AKI-D was associated with greater mortality during initial hospitalization (46% vs. 1%, p < 0.001) and a lower rate of survival free of kidney failure. CONCLUSIONS: The incidence of AKI-D after pediatric heart transplant was 7%, with extended cardiopulmonary bypass time associated with postoperative AKI-D even in adjusted models. Further research is needed to improve the prediction and management of AKI-D in this population.

Clinical and genetic characterization of CACNA1A-related disease.

Pathogenic variants in the CACNA1A gene have been associated with episodic ataxia type 2, familial hemiplegic migraine, and spinocerebellar ataxia 6. With increasing use of clinical genetic testing, associations have expanded to include developmental delay, epilepsy, paroxysmal dystonia, and neuropsychiatric disorders. We report 47 individuals with 33 unique likely pathogenic or pathogenic CACNA1A variants. A machine learning method, funNCion, was used to predict loss-of-function (LoF)/gain-of-function (GoF) impact of genetic variants, and a heuristic severity score was designed to analyze genotype/phenotype correlations. Commonly reported phenotypes include developmental delay/intellectual disability (96%), hemiplegic migraines (36%), episodic ataxia type 2 (32%), epilepsy (55%), autism spectrum disorder (23%), and paroxysmal tonic upward gaze (36%). Severity score was significantly higher for predicted GoF variants, variants in the S5/S6 helices, and the recurrent p.Val1392Met variant. Seizures/status epilepticus were correlated with GoF and were more frequent in those with the p.Val1392Met variant. Our findings demonstrate a breadth of disease severity in CACNA1A-related disease and suggest that the clinical phenotypic heterogeneity likely reflects diverse molecular phenotypes. A better understanding of the natural history of CACNA1A-related disease and genotype/phenotype correlations will help inform prognosis and prepare for future clinical trials.