Changes in estimated glomerular filtration rate over the first year following repeat heart transplant in children and young adults.

BACKGROUND: Renal function is reduced in patients undergoing heart transplant due to hemodynamic compromise, cardiorenal syndrome, and nephrotoxin exposure. No current studies evaluate renal function in retransplants. METHODS: We reviewed all heart transplants at our center from 1995 to 2021 and matched first-time heart transplants with retransplants, based on age at transplant, sex, and race. Estimated glomerular filtration rate (eGFR) was derived from CKiD-U25 calculator using creatinine and measured prior to transplant, 1-week post-transplant, 1-3, 6, and 12 months post-transplant, and recent follow-up. Changes in eGFR were measured within and between patients using a piecewise linear mixed effect model with matching. Exploratory univariate analysis was performed to evaluate pre-transplant risk factors for decreased eGFR. RESULTS: The unmatched cohort included 393 heart transplant recipients, with 47 being retransplants. Thirty-eight patients in both groups with at least 1 year of follow-up underwent matching. Both retransplants and first-time transplants had an initial decline in eGFR. eGFR rebounded to baseline or above baseline at 1-3 months post-transplant, but eGFR in retransplants remained significantly lower. At 1-year post-transplant, the average eGFR was 67.8 ± 4.3 mL/min/1.73 m2 versus 104.7 ± 4.3 mL/min/1.73 m2 (p < .001) in the retransplants and first-time transplants group, respectively. CONCLUSION: This study provides data on anticipated renal trajectory following retransplantation.

Prenatally Diagnosed Posterior Urethral Valves: Ethical Dilemmas of Fetal Intervention.

Although anhydramnios due to in utero renal failure has traditionally been considered lethal, in utero interventions offer the potential for pulmonary survival. As fetal interventions become more common, questions arise about how to identify and counsel eligible candidates.  In this report we describe the presentation and management of a 17-year-old pregnant female who presented from out-of-state with severe lower urinary tract obstruction (LUTO) with associated anhydramnios, focusing on the ethical questions that this case raised.

Outcomes of dialysis in neonates with anuric end-stage renal disease at birth: ethical considerations.

INTRODUCTION: We present a case series of neonates with anuric ESRD undergoing renal replacement therapy (RRT) and discuss the associated ethical implications of RRT in this population. METHODS: We reviewed patients who initiated RRT within 1 week of life due to anuric ESRD from 2009-2019 at a single tertiary center. Primary outcomes were receipt of renal transplant (RT), one-year survival, and overall survival. RESULTS: Five patients met the inclusion criteria. Two patients received an RT. One-year survival was 80%, while overall survival was 60% with a median follow-up of 18 months. In the 2 still-living patients who have not undergone RT, they are ineligible, one due to recent malignancy and the other from acquired cardiovascular comorbidities. CONCLUSION: Patients with anuric ESRD requiring RRT undergo multiple treatment challenges with low RT and survival rates. These findings should be shared with families considering intervention for cases of severe renal disease diagnosed prenatally.

Management of dyslipidemia in pediatric renal transplant recipients.

Dyslipidemia after kidney transplantation is a common complication that has historically been underappreciated, especially in pediatric recipients. It is also a major modifiable risk factor for cardiovascular disease, a top cause of morbidity and mortality of transplant patients. While most knowledge about post-transplant dyslipidemia has been generated in adults, recommendations and treatment strategies also exist for children and are presented in this review. Awareness of these applicable guidelines and approaches is required, but not sufficient, for the reliable management of dyslipidemia in our patients, and additional needs and opportunities for comprehensive care in this area (e.g., quality improvement) are outlined.

Utility of thrombophilia screening in pediatric renal transplant recipients.

Thrombosis after kidney transplantation may result in catastrophic outcomes, including graft loss. Thrombophilia has been implicated in post-transplant thrombosis; data, however, are inconclusive on the impact of acquired and inherited thrombophilia and resultant thrombosis in renal graft recipients. We aimed to evaluate whether identifying children with thrombophilia during the pretransplant evaluation predicted post-transplant outcomes. We reviewed 100 kidney transplants performed in 100 children, aged 1-18 years, in a single-center retrospective study. Routine pretransplant comprehensive thrombophilia evaluation was completed. Thrombophilia was demonstrated in 36% patients (N = 36). TEs occurred in 11 patients before kidney transplant. Low PS and antithrombin were found in 9/86 (10.5%) and 2/89 (2.2%) children, respectively. Heterozygosity for FLV and PGM were found in 5/81 (6.2%) and 1/93(1.1%) children, respectively. A post-transplant thrombotic event occurred in 10 children (10%); six involved the renal transplant. The association between a history of a pretransplant thrombotic event and post-operative renal graft thrombosis approached, but did not reach significance (P = 0.071). There was no association between preoperative screening abnormalities and post-operative TEs. Graft loss due to a thrombotic event occurred in two patients; none had underlying thrombophilia. Our data suggest that the utility of universal, comprehensive preoperative thrombophilia testing is not beneficial in determining risk of post-operative graft thrombosis. Thrombophilia testing may be considered in a select population with a history of pretransplant thrombotic event.

Pediatric kidney transplantation.

Since first performed in 1954, kidney transplantation has evolved as the preferred long-term treatment of children with end stage renal disease (ESRD). The etiology of chronic kidney disease (CKD) and ESRD in children is broad and can be quite complicated, necessitating a multidisciplinary team to adequately care for these patients and their myriad needs. Precise surgical techniques and modern protocols for immunosuppression provide excellent long-term patient and graft survival. This article reviews the many etiologies of renal failure in the pediatric population focusing on those most commonly leading to the need for kidney transplantation. The processes of evaluation, kidney transplantation, short-term and long-term complications, as well as long-term outcomes are also reviewed.

Serum soluble urokinase-type plasminogen activator receptor levels and idiopathic FSGS in children: a single-center report.

BACKGROUND AND OBJECTIVES: FSGS is the primary cause of childhood nephrotic syndrome leading to ESRD. Permeability factors, including circulating serum soluble urokinase-type plasminogen activator receptor (suPAR), have been postulated as putative causes in adults with primary FSGS. Similar results have yet to be proven in children. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This cross-sectional single-center study assessed the association of serum suPAR in children with FSGS or other glomerular and nonglomerular kidney diseases. RESULTS: This study examined 110 samples retrieved from 99 individuals (between January 2011 and April 2012), aged 1-21 years; of these individuals, 20 had primary FSGS, 24 had non-FSGS glomerular disease, 26 had nonglomerular kidney disease, and 29 were healthy controls. suPAR levels were not significantly different in children with FSGS, non-FSGS glomerular disease, and healthy controls (P>0.05). However, suPAR levels (median [25%-75%]) were higher in children with nonglomerular kidney disease (3385 pg/ml [2695-4392]) versus FSGS (2487 pg/ml [2191-3351]; P<0.05). Female patients with nephrotic-range proteinuria (U-Pr/Cr >2) had lower suPAR levels than those without proteinuria (2380 pg/ml [2116-2571] versus 3125 pg/ml [2516-4198], respectively; P<0.001). This trend was not seen among male participants; suPAR levels in all female participants were lower than in male participants (P=0.03). Thirty-four patients studied were kidney transplant recipients; transplant status was not associated with suPAR levels in patients with FSGS or non-FSGS diagnoses, independent of proteinuria, race, or sex (P>0.05). CONCLUSIONS: On the basis of these results, circulating suPAR is unlikely the leading cause for childhood idiopathic FSGS.

Treatment of childhood nephrotic syndrome with long-term, low-dose tacrolimus.

AIM: Children with steroidresistant (SR) and steroid-dependent (SD) nephrotic syndrome (NS) pose a treatment challenge. Literature on the use of tacrolimus (TAC), a calcineurin inhibitor, for maintenance treatment of NS is sparse. We aimed to evaluate the efficacy and safety of low-dose, long-term TAC for inducing and sustaining remission in children with SD/SR NS. METHODS: Data from patients treated at our center from 1999 to 2009 were analyzed. RESULTS: 40 patients with NS were treated with TAC for 3 - 80-month periods (median 25.2 months). Diagnoses included focal segmental glomerulosclerosis (FSGS) (60%), IgM nephropathy (15%), minimal change disease (20%) and membrano-proliferative glomerulonephritis (MPGN) (5%). 58% of patients had been previously treated with alternate agents. After 1, 2, and 3 years on TAC, complete remission was achieved in 26%, 48%, and 29% of patients; complete or partial remission was achieved in 85%, 100%, and 86%, respectively (p < 0.05). Median time to remission was 41 days (range: 10 - 270 days). FSGS and SR diseases were associated with lower likelihood of remission (p < 0.05). Remission was equally likely in both treatment naïve patients and those who had received prior second-line agents. CONCLUSION: Our results demonstrate that TAC treatment for children with SR/SD NS is associated with high rates of sustained remission, even when prior second-line agents failed.