Nephrectomy improves both antihypertensive requirement and left ventricular mass for pediatric renal hypertension.

BACKGROUND: Renal hypertension causes left ventricular (LV) hypertrophy leading to cardiomyopathy. Nephrectomy has been utilized to improve blood pressure and prepare for kidney transplantation in the pediatric population. We sought to investigate antihypertensive medication (AHM) requirement and LV mass in patients undergoing nephrectomy with renal hypertension. METHODS: We performed a single institution retrospective review from 2009 to 2021 of children who have undergone nephrectomy for hypertension. Primary outcome was decrease in number of AHM. Secondary outcomes included change in LV mass and elimination of AHM. LV mass was measured using echocardiogram area-length and linear measurements. Non-parametric analyses were utilized to assess significance. RESULTS: Thirty-one patients underwent nephrectomy. Median age was 12.5 years (0.8-19 years). Median of 3 AHM (range 1-5 medications) were used pre-operatively and patients had been managed for median 2.5 years. Twenty-nine had preoperative echocardiogram. Forty-eight percent of patients had LVH at nephrectomy. Median AHM after surgery was 1 (range 0-4 medications) at 30 days and 12 months, (p < 0.001). By 12 months after nephrectomy, 79.2% of patients had decreased the number of AHM. Eight (26%) patients were on no AHM 30 days after surgery, and 13 (43%) at 12 months. Systemic vascular disease and multicystic dysplastic kidney were the only factors associated with lack of improvement in AHM (p = 0.040). Fourteen patients had pre- and post-operative echocardiogram and 11 (79%) had improvement in LV mass (p = 0.016, 0.035). CONCLUSIONS: Nephrectomy is effective in improving LV mass and reducing AHM for children with renal hypertension. Improvement is less likely in patients with systemic vascular disease and multicystic dysplastic kidneys. A higher resolution version of the Graphical abstract is available as Supplementary information.

Organ transplantation using COVID-19-positive deceased donors.

The COVID-19 pandemic has influenced organ transplantation decision making. Opinions regarding the utilization of coronavirus disease-2019 (COVID-19) donors are mixed. We hypothesize that COVID-19 infection of deceased solid organ transplant donors does not affect recipient survival. All deceased solid organ transplant donors with COVID-19 testing results from March 15, 2020 to September 30, 2021 were identified in the OPTN database. Donors were matched to recipients and stratified by the COVID-19 test result. Outcomes were assessed between groups. COVID-19 test results were available for 17 694 donors; 150 were positive. A total of 269 organs were transplanted from these donors, including 187 kidneys, 57 livers, 18 hearts, 5 kidney-pancreases, and 2 lungs. The median time from COVID-19 testing to organ recovery was 4 days for positive and 3 days for negative donors. Of these, there were 8 graft failures (3.0%) and 5 deaths (1.9%). Survival of patients receiving grafts from COVID-19-positive donors is equivalent to those receiving grafts from COVID-19-negative donors (30-day patient survival = 99.2% COVID-19 positive; 98.6% COVID-19 negative). Solid organ transplantation using deceased donors with positive COVID-19 results does not negatively affect early patient survival, though little information regarding donor COVID-19 organ involvement is known. While transplantation is feasible, more information regarding COVID-19-positive donor selection is needed.

Rapid Whole Genome Sequencing Has Clinical Utility in Children in the PICU.

OBJECTIVES: Genetic disorders are a leading contributor to mortality in the neonatal ICU and PICU in the United States. Although individually rare, there are over 6,200 single-gene diseases, which may preclude a genetic diagnosis prior to ICU admission. Rapid whole genome sequencing is an emerging method of diagnosing genetic conditions in time to affect ICU management of neonates; however, its clinical utility has yet to be adequately demonstrated in critically ill children. This study evaluates next-generation sequencing in pediatric critical care. DESIGN: Retrospective cohort study. SETTING: Single-center PICU in a tertiary children's hospital. PATIENTS: Children 4 months to 18 years admitted to the PICU who were nominated between July 2016 and May 2018. INTERVENTIONS: Rapid whole genome sequencing with targeted phenotype-driven analysis was performed on patients and their parents, when parental samples were available. MEASUREMENTS AND MAIN RESULTS: A molecular diagnosis was made by rapid whole genome sequencing in 17 of 38 children (45%). In four of the 17 patients (24%), the genetic diagnoses led to a change in management while in the PICU, including genome-informed changes in pharmacotherapy and transition to palliative care. Nine of the 17 diagnosed children (53%) had no dysmorphic features or developmental delay. Eighty-two percent of diagnoses affected the clinical management of the patient and/or family after PICU discharge, including avoidance of biopsy, administration of factor replacement, and surveillance for disorder-related sequelae. CONCLUSIONS: This study demonstrates a retrospective evaluation for undiagnosed genetic disease in the PICU and clinical utility of rapid whole genome sequencing in a portion of critically ill children. Further studies are needed to identify PICU patients who will benefit from rapid whole genome sequencing early in PICU admission when the underlying etiology is unclear.

Growth in children with chronic kidney disease: role of nutrition, growth hormone, dialysis, and steroids.

PURPOSE OF REVIEW: Children with chronic kidney disease (CKD) have impaired growth that leads to short stature in adulthood. The problem persists even with successful transplantation and steroid withdrawal protocols. The aim of this review is to provide an overview of the pressing issues related to growth failure in children with CKD both before and after transplantation. RECENT FINDINGS: Although great strides have been made in dialysis and transplantation, the incidence of abnormal adult height in children growing up with CKD remains as high as 45-60%. The lack of catch-up growth and resultant short stature is a critical issue for self-esteem and quality of life in many children with CKD. Aggressive daily dialysis, improved nutrition, treatment of metabolic bone disease, and the use of recombinant human growth hormone provide some hope for catch-up growth in select patients. SUMMARY: The causes of growth failure in the setting of CKD are multifactorial. Attention to all the details by optimizing nutritional, bone and mineral metabolism, correcting metabolic acidosis and anemia, achieving excellent blood pressure control, reversing cardiovascular complications such as left ventricular hypertrophy, and minimizing the use of corticosteroids is the current standard of care. Aggressive daily dialysis can reverse many of the uremic derangements. For patients not yet on dialysis or for those after renal transplant, early institution of recombinant human growth hormone can promote growth. Improved understanding of the mechanisms of hormone resistance may offer novel targets or measurements of treatment effectiveness.

Renal Transplants Due to Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) Have Better Graft Survival Than Non-CAKUT Controls: Analysis of Over 10,000 Patients.

OBJECTIVE: To determine whether graft survival for patients with congenital anomalies of the kidney and urinary tract (CAKUT) is impaired compared to non-CAKUT counterparts. METHODS: The United States Renal Data System (USRDS) is a national data system that has collected information about end stage renal disease (ESRD) and renal transplantation since 1995. We identified 10,635 first-time renal transplant patients with ESRD attributed to a CAKUT diagnosis transplanted between 1995 and 2018, with follow-up of 7.9 ± 5.8 years. We matched 1:1 with non-CAKUT transplant recipients, using age at transplant, sex, race, year of transplant, and donor-type. We compared renal transplant death-censored graft survival between CAKUT vs non-CAKUT controls, with further stratification for age at transplant and lower urinary tract malformations (LUTM) vs upper urinary tract malformations (UUTM). RESULTS: Graft survival was better in CAKUT patients with a 5-year survival of 83.3% vs 79.3% (P< .001), and CAKUT status infers a hazard ratio of 0.878 for graft failure on multivariable analysis with Cox regression. Favorability of CAKUT status persisted when stratifying for both pediatric (80.3 vs 77.6% P< .001) and adult (84.5 vs 81.4% P< .001) age groups. Looking within the CAKUT population: comparison of LUTM to UUTM yielded no difference, implying that LUTM is not a risk factor for graft failure. Examining pediatric LUTM alone, graft survival was not better than matched non-CAKUT counterparts with 5-year graft survival of 69%-75% for LUTM adolescents. CONCLUSION: Renal transplant graft survival is better overall in CAKUT patients as opposed to non-CAKUT counterparts. Pediatric LUTM patients have similar graft survival to controls.

Cost Efficacy of Rapid Whole Genome Sequencing in the Pediatric Intensive Care Unit.

The diagnostic and clinical utility of rapid whole genome sequencing (rWGS) for critically ill children in the intensive care unit (ICU) has been substantiated by multiple studies, but comprehensive cost-effectiveness evaluation of rWGS in the ICU outside of the neonatal age group is lacking. In this study, we examined cost data retrospectively for a cohort of 38 children in a regional pediatric ICU (PICU) who received rWGS. We identified seven of 17 patients who received molecular diagnoses by rWGS and had resultant changes in clinical management with sufficient clarity to permit cost and quality adjusted life years (QALY) modeling. Cost of PICU care was estimated to be reduced by $184,846 and a total of 12.1 QALYs were gained among these seven patients. The total cost of rWGS for patients and families for the entire cohort (38 probands) was $239,400. Thus, the net cost of rWGS was $54,554, representing $4,509 per QALY gained. This quantitative, retrospective examination of healthcare utilization associated with rWGS-informed medicine interventions in the PICU revealed approximately one-third of a QALY gained per patient tested at a cost per QALY that was approximately one-tenth of that typically sought for cost-effective new medical interventions. This evidence suggests that performance of rWGS as a first-tier test in selected PICU children with diseases of unknown etiology is associated with acceptable cost-per-QALY gained.

Levetiracetam induced interstitial nephritis and renal failure.

A 17-year-old girl who had started on levetiracetam because of new onset partial complex seizures developed acute renal failure and biopsy-confirmed interstitial nephritis 10 days after starting the drug. She made a complete and rapid recovery after discontinuation of levetiracetam and administration of oral corticosteroids. Levetiracetam, known to be predominantly excreted by the kidneys, has not previously been reported to cause significant renal complications in children. Children taking levetiracetam who present with abdominal pain, malaise, vomiting, oliguria, rash, or urticaria may require screening laboratory evaluation for potential renal adverse effects.

The adjuvant effects of Mycobacterium tuberculosis heat shock protein 70 result from the rapid and prolonged activation of antigen-specific CD8+ T cells in vivo.

Heat shock protein 70 (hsp70) is a potent adjuvant that links innate and adaptive immune responses. To study how hsp70 activates naive CD8(+) T cells in vivo, we tracked Ag-specific CD8(+) T cells in mice immunized with a fusion protein containing chicken OVA linked to hsp70 derived from Mycobacterium tuberculosis (OVA.TBhsp70). On a molar basis, OVA.TBhsp70 was several hundred times more effective than OVA peptide plus CFA in eliciting specific CD8(+) T cell responses. Immunization with OVA.TBhsp70 activated >90% of detectable OVA-specific CD8(+) T cells within 3 days and led to the persistence of cytotoxic effectors for at least 17 days. These studies demonstrate that the potent adjuvant effect of M. tuberculosis hsp70 results from the relatively complete, rapid, and durable activation of Ag-specific CD8(+) T cells.