Late renal allograft torsion in a pediatric transplant recipient.

2021

e14210

2021 Dec 15

1399-3046

<p><strong>BACKGROUND: </strong>Kidney allograft torsion is a rare complication of kidney transplant that can lead to allograft loss from prolonged ischemia if not quickly corrected with detorsion and nephropexy. We report a case of late intraperitoneal renal allograft torsion in a pediatric transplant recipient.</p>

<p><strong>CASE REPORT: </strong>The patient is a 7-year-old male with a history of end-stage renal disease secondary to renal dysplasia in the setting of bilateral high-grade vesicoureteral reflux. He underwent bilateral native nephrectomies for recurrent pyelonephritis and right ureteral kink with urinary tract obstruction. Torsion occurred 3&nbsp;years after transplant in the setting of one day of emesis, loose stool, severe abdominal pain, and decreased urine output. Diagnosis of transplant torsion was suspected on non-contrast CT scan done after transplant Doppler ultrasound showed no flow to the allograft. The CT scan showed that the kidney had been medialized and renal hilum was flipped from the expected orientation. The patient required a transplant nephrectomy.</p>

<p><strong>CONCLUSIONS: </strong>Renal transplant torsion is a rare event but should be suspected in any renal transplant recipient with acute onset of abdominal pain, acute kidney injury, and decreased urine output, regardless of length of time from transplantation. Patients suspected to have renal torsion should be evaluated emergently with a transplant ultrasound Doppler.</p>

10.1111/petr.14210

Pediatr Transplant

34907635

Patient-Reported Outcomes in Children With Chronic Kidney Disease.

2021

476-484

2021 Sep

1558-4488

<p>Patient-reported outcomes (PROs) are quantitative assessments of a patient's perspective on their health and are derived directly from the patient, as opposed to clinician interpretation. PROs can serve as unique tools to improve health care providers' understanding of the patient's daily lived experience and highlight salient domains that are specific to children with chronic kidney disease (CKD). As such, PROs fill an important gap in achieving optimal health and well-being for children with CKD. However, several knowledge gaps remain in the implementation of PROs within both the clinical and research realms. This review provides a broad overview of PRO development, implementation for children with CKD, and highlights future directions and challenges.</p>

10.1016/j.semnephrol.2021.09.010

Semin Nephrol

34916009

Design and Methods of the Validating Injury to the Renal Transplant Using Urinary Signatures (VIRTUUS) Study in Children.

2021

e791

2021 Dec

2373-8731

<p>Lack of noninvasive diagnostic and prognostic biomarkers to reliably detect early allograft injury poses a major hindrance to long-term allograft survival in pediatric kidney transplant recipients.</p>

<p><strong>Methods: </strong>Validating Injury to the Renal Transplant Using Urinary Signatures Children's Study, a North American multicenter prospective cohort study of pediatric kidney transplant recipients, aims to validate urinary cell mRNA and metabolite profiles that were diagnostic and prognostic of acute cellular rejection (ACR) and BK virus nephropathy (BKVN) in adult kidney transplant recipients in Clinical Trials in Organ Transplantation-4. Specifically, we are investigating: (1) whether a urinary cell mRNA 3-gene signature (-normalized mRNA, and ribosomal RNA) discriminates biopsies with versus without ACR, (2) whether a combined metabolite profile with the 3-gene signature increases sensitivity and specificity of diagnosis and prognostication of ACR, and (3) whether mRNA levels in urinary cells are diagnostic of BKVN and prognostic for allograft failure.</p>

<p><strong>Results: </strong>To date, 204 subjects are enrolled, with 1405 urine samples, including 144 biopsy-associated samples. Among 424 urine samples processed for mRNA, the median A260:280 ratio (RNA purity) was 1.91, comparable with Clinical Trials in Organ Transplantation-4 (median 1.82). The quality control failure rate was 10%. Preliminary results from urine supernatant showed that our metabolomics platform successfully captured a broad array of metabolites. Clustering of pool samples and overlay of samples from various batches demonstrated platform robustness. No study site effect was noted.</p>

<p><strong>Conclusions: </strong>Multicenter efforts to ascertain urinary biomarkers in pediatric kidney transplant recipients are feasible with high-quality control. Further study will inform whether these signatures are discriminatory and predictive for rejection and infection.</p>

10.1097/TXD.0000000000001244

Transplant Direct

34805493

Real-World Treatment Escalation from Metformin Monotherapy in Youth-Onset Type 2 Diabetes Mellitus: A Retrospective Cohort Study.

2021

2021 May 12

1399-5448

<p><strong>BACKGROUND: </strong>Due to high rates of comorbidities and rapid progression, youth with type 2 diabetes may benefit from early and aggressive treatment. However, until 2019, the only approved medications for this population were metformin and insulin.</p>

<p><strong>OBJECTIVE: </strong>To investigate patterns and predictors of treatment escalation within 5 years of metformin monotherapy initiation for youth with type 2 diabetes in clinical practice.</p>

<p><strong>SUBJECTS: </strong>Commercially-insured patients with incident youth-onset (10-18 years) type 2 diabetes initially treated with metformin only. METHODS: Retrospective cohort study using a patient-level medical claims database with data from 2000 - 2020. Frequency and order of treatment escalation to insulin and non-insulin antihyperglycemics were determined and categorized by age at diagnosis. Cox proportional hazards regression was used to evaluate potential predictors of treatment escalation, including age, sex, race/ethnicity, comorbidities, complications, and metformin adherence (medication possession ratio ≥0.8).</p>

<p><strong>RESULTS: </strong>The cohort included 829 (66% female; median age at diagnosis 15 years; 19% Hispanic, 17% Black) patients, with median 2.9-year follow-up after metformin initiation. One-quarter underwent treatment escalation (n=207; 88 to insulin, 164 to non-insulin antihyperglycemic). Younger patients were more likely to have insulin prescribed prior to other antihyperglycemics. Age at diagnosis (HR 1.14, 95% CI 1.07-1.21), medication adherence (HR 4.10, 95% CI 2.96-5.67), Hispanic ethnicity (HR 1.83, 95% CI 1.28-2.61), and diabetes-related complications (HR 1.78, 95% CI 1.15-2.74) were positively associated with treatment escalation.</p>

<p><strong>CONCLUSIONS: </strong>In clinical practice, treatment escalation for pediatric type 2 diabetes differs with age. Off-label use of non-insulin antihyperglycemics occurs, most commonly among older adolescents. This article is protected by copyright. All rights reserved.</p>

10.1111/pedi.13232

Pediatr Diabetes

33978986

Early Detection of SARS-CoV-2 and other Infections in Solid Organ Transplant Recipients and Household Members using Wearable Devices.

2021

2021 Mar 18

1432-2277

<p>The increasing global prevalence of SARS-CoV-2 and the resulting COVID-19 disease pandemic pose significant concerns for clinical management of solid organ transplant recipients (SOTR). Wearable devices that can measure physiologic changes in biometrics including heart rate, heart rate variability, body temperature, respiratory, activity (such as steps taken per day) and sleep patterns and blood oxygen saturation, show utility for the early detection of infection before clinical presentation of symptoms. Recent algorithms developed using preliminary wearable datasets show that SARS-CoV-2 is detectable before clinical symptoms in &gt;80% of adults. Early detection of SARS-CoV-2, influenza, and other pathogens in SOTR, and their household members, could facilitate early interventions such as self-isolation and early clinical management of relevant infection(s). Ongoing studies testing the utility of wearable devices such as smartwatches for early detection of SARS-CoV-2 and other infections in the general population are reviewed here, along with the practical challenges to implementing these processes at scale in pediatric and adult SOTR, and their household members. The resources and logistics, including transplant specific analyses pipelines to account for confounders such as polypharmacy and comorbidities, required in studies of pediatric and adult SOTR for the robust early detection of SARS-CoV-2 and other infections are also reviewed.</p>

10.1111/tri.13860

Transpl Int

33735480

Effect of Kidney Function on Relationships between Lifestyle Behaviors and Mortality or Cardiovascular Outcomes: A Pooled Cohort Analysis.

2021

663-675

2021 Mar

1533-3450

<p><strong>BACKGROUND: </strong>Adherence to healthy behaviors reduces risks of cardiovascular disease and death in the general population. However, among people with kidney disease, a group at higher risk for cardiovascular disease, such benefits have not been established.</p>

<p><strong>METHODS: </strong>We pooled data from three cohort studies with a total of 27,271 participants. Kidney function was categorized on the basis of eGFR (≥60, 45 to &lt;60, and &lt;45 ml/min per 1.73 m). We used proportional hazard frailty models to estimate associations between healthy behaviors (not smoking, at recommended body mass index [BMI], physical activity, healthy diet, and moderate to no alcohol intake) and outcomes (all-cause death, major coronary events, ischemic stroke, and heart failure events).</p>

<p><strong>RESULTS: </strong>All recommended lifestyle behaviors were significantly associated with lower risks of death, regardless of eGFR. Not smoking (versus current) and any moderate to vigorous physical activity (versus none) was significantly associated with reduced risks of major coronary and heart failure events, regardless of eGFR. Any (versus no) moderate or vigorous physical activity significantly associated with decreased risk of ischemic stroke events only among those with eGFR ≥60. Moderate to no daily alcohol intake (versus excessive) was significantly associated with an increased risk of major coronary events, regardless of eGFR. For heart failure events, a BMI of 18.5 to 30 associated with decreased risk, regardless of eGFR. Across all eGFR categories, the magnitude of risk reduction for death and all cardiovascular outcomes increased with greater numbers of recommended lifestyle behaviors.</p>

<p><strong>CONCLUSIONS: </strong>Recommended lifestyle behaviors are associated with lower risk of death and cardiovascular disease events among individuals with or without reduced kidney function, supporting lifestyle behaviors as potentially modifiable risk factors for people with kidney disease.</p>

10.1681/ASN.2020040394

J Am Soc Nephrol

33547215

The current outcomes and future challenges in pediatric vascularized composite allotransplantation.

2020

576-583

2020 Dec

1531-7013

<p><strong>PURPOSE OF REVIEW: </strong>We review the outcomes and future challenges associated with pediatric vascularized composite allotransplantation, including follow-up data from our bilateral pediatric hand-forearm transplantation.</p>

<p><strong>RECENT FINDINGS: </strong>In 2015, the first heterologous pediatric upper extremity hand-forearm transplant was performed at the Children's Hospital of Philadelphia, and in 2019, the first pediatric neck reconstructive transplantation was performed in Poland. The 5-year follow-up of the pediatric upper extremity recipient demonstrates similar growth rates bilaterally, an increase in bone age parallel to chronologic age, and perhaps similar overall growth to nontransplant norms. The pediatric upper extremity recipient continues to make gains in functional independence. He excels academically and participates in various extracurricular activities. Future challenges unique to the pediatric population include ethical issues of informed consent, psychosocial implications, limited donor pool, posttransplant compliance issues, and greater life expectancy and therefore time to inherit the many complications of immunosuppression.</p>

<p><strong>SUMMARY: </strong>Currently, we recommend pediatric vascularized composite allotransplantation (VCA) for bilateral upper extremity amputees, preferably on immunosuppression already, and those patients who would have the most potential gain not available through standard reconstructive techniques while being able to comply with postoperative immunosuppression protocols, surveillance, rehabilitation, and follow-up.</p>

10.1097/MOT.0000000000000809

Curr Opin Organ Transplant

33044345

Empowering patients to adhere to their treatment regimens: A multifaceted approach.

2020

e13849

2020 Oct 18

1399-3046

<p>It is well-recognized that adolescence and early adulthood are a high-risk period for non-adherence with treatment regimens in solid organ transplant recipients, leading to high rates of rejection and graft loss (Transplantation, 92, 2011, 1237; Pediatr Transplant, 9, 2005, 381; Transplantation, 77, 2004, 769). Preventing medication non-adherence is the holy grail of transplant adolescent care. If we can determine how best to support our patients in taking their daily medications as prescribed, we can improve long-term health, reduce need for re-transplantation, and reduce healthcare costs. In the last few years, several studies have provided us with additional insights into potentially effective interventions and have highlighted existing gaps in knowledge. This article reviews recent literature published over the last 5&nbsp;years on the topic of adherence in transplant recipients, highlighting insights and opportunities to promote adherence at the individual patient level, family level, healthcare system level, and community level. Above all, the recent work that is highlighted suggests that adherence interventions for prevention and treatment must be multifaceted, individualized, and longitudinal to be effective.</p>

10.1111/petr.13849

Pediatr Transplant

33073474

Trends in Living Donation by Race and Ethnicity Among Children With End-stage Renal Disease in the United States, 1995-2015.

2020

e570

2020 Jul

2373-8731

<p><strong>Background: </strong>Living donor kidney transplants have declined among adults with end-stage renal disease (ESRD), with increases in racial/ethnic disparities over time. Secular trends in racial/ethnic disparities in living donor kidney transplantation have not been well studied in children.</p>

<p><strong>Methods: </strong>Using multivariable Cox modeling, we examined changes in living donor kidney transplant rates over time and probability of receiving living donor kidney transplantation within 2 years of incident ESRD by race/ethnicity among 19 772 children in the US Renal Data System, 1995-2015. We also examined racial/ethnic concordance between donors and recipients.</p>

<p><strong>Results: </strong>Overall, living donor kidney transplant rates declined by 3% annually since 1995 for all racial/ethnic groups except Asians for whom living donor kidney transplant rates remained stable; however, disparities persist. Compared with non-Hispanic white children, Hispanics were 42% less likely (adjusted hazard ratio: 0.58; 95% confidence interval: 0.49-0.67), Asians 39% less likely (0.61; 0.47-0.79), and blacks 66% less likely (0.34; 0.28-0.42) to receive living kidney donor transplantation within 2 years, even when accounting for deceased donor transplantation as a competing risk. Additionally, while 95% of non-Hispanic white children had non-Hispanic white donors, only 56% of Asian recipients had Asian donors ( &lt; 0.001). Asian recipients were more likely to have nonrelated donors ( &lt; 0.001).</p>

<p><strong>Conclusions: </strong>There are ongoing declines in living donation for children with ESRD for uncertain reasons, and minority populations experience significantly reduced access to timely living donor transplant, even when accounting for changes in deceased donation and donor-recipient relationships.</p>

10.1097/TXD.0000000000001008

Transplant Direct

32766425

Secular Trends in Survival Outcomes of Kidney Transplantation for Children: Is the Future Bright Enough?

2020

308-310

2020 03 06

1555-905X

10.2215/CJN.00370120

Clin J Am Soc Nephrol

32096764