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Maternal and fetal determinants on kidney size in early childhood: insights from a New York City cohort
Ling, Rui; Seok, Eunsil; Encarnacion, Sarai; Kapoor, Vasuda; Liu, Mengling; Afanasyeva, Yelena; Lala, Shailee; Vokshi, Fjolla Hyseni; Liu, Jie; Malaga-Dieguez, Laura; Trasande, Leonardo
BACKGROUND:The role of maternal and fetal characteristics in determining kidney size in early childhood remains largely unexplored. This study aims to evaluate the association between birth weight and kidney size in children aged one to six years and explore other children and maternal determinants in a United States cohort. METHODS:We analyzed data from 892 mother-child pairs enrolled in the New York University Children's Health and Environment Study (CHES). Renal sonographic measurements were taken from one to six years of age. Kidney size outcomes included average kidney length, width, depth, total kidney volume (TKV), adjusted kidney length (kidney length/body length), and adjusted TKV (TKV/body surface area). Maternal determinants include age, demographic characteristics, pre-pregnancy BMI, lifestyle, pregnancy complications, and diet during pregnancy. Fetal determinants included sex, birth weight for gestational age z-score, and gestational age at delivery. Anthropometric z change and breastfeeding duration were also considered. Associations were examined using crude and covariate-adjusted linear mixed models. RESULTS:Birth weight z-score and anthropometric z change were observed positively associated with all measures except adjusted kidney length. Female children had smaller average kidney length and TKV, and breastfeeding duration was negatively associated with average kidney depth and TKV. Children of non-Hispanic Black mothers and parous mothers had smaller kidney measures. CONCLUSION/CONCLUSIONS:In NYU CHES, we found that early childhood kidney size measures were consistently influenced by birth weight z-scores and changes in postnatal weight gain z-scores. Additionally, we observed racial differences and the influence of breastfeeding duration on kidney size. TRIAL REGISTRATION/BACKGROUND:Not applicable.
PMID: 41981395
ISSN: 1471-2369
CID: 6027752
Pediatric Kidney Transplant Outcomes After Kidney Donor Profile Index-Based Organ Prioritization
Husain, Syed Ali; Stewart, Darren; Orandi, Babak J; Lipton, Marissa; Malaga-Dieguez, Laura; Bae, Sunjae; Levan, Macey L; Gentry, Sommer E; Segev, Dorry L; Massie, Allan B
INTRODUCTION/BACKGROUND:Following implementation of the U.S. Kidney Allocation System (KAS) in 2014, deceased donor kidneys with a kidney donor profile index (KDPI) < 35% are prioritized for allocation to pediatric candidates. Early post-KAS data suggested this prioritization may have led to more frequent delayed graft function compared to pre-KAS, when pediatric allocation priority was based on donor age < 35 years. We sought to understand the impact of this allocation change on longer-term pediatric kidney transplant outcomes. METHODS:We used SRTR data to identify all deceased donor kidney transplants with pediatric recipients during two eras: "Pre-KAS" (12/1/2009-11/30/2014) and "KAS" (12/1/2015-11/30/2020). We used Cox proportional hazards models to calculate the association between study era and all-cause graft failure (graft failure or death) after adjusting for recipient characteristics. RESULTS:, p = 0.001). Results were similar in sensitivity analyses limited to recipients < 10 years old and recipients alive with a functioning graft 90 days post-transplant. CONCLUSIONS:KDPI-based prioritization of kidneys for pediatric allocation was associated with a lower risk of graft failure compared to donor age-based prioritization. Further refining donor risk scores may enable additional improvements in graft survival.
PMID: 41603235
ISSN: 1399-3046
CID: 6003462
Beyond genetics: how environmental stressors drive pediatric hypertension risk
Manuel, Robbie S J; Malaga-Dieguez, Laura; Trasande, Leonardo
Pediatric hypertension is increasing in prevalence and is associated with cardiovascular and kidney outcomes in adulthood. Beyond traditional contributors such as obesity and kidney disease, a growing body of evidence implicates environmental exposures in the early disruption of blood pressure regulation. This review aims to evaluate and synthesize current evidence on key exposure routes, including airborne pollutants, heavy metals, and endocrine-disrupting chemicals, and their impact on pediatric blood pressure regulation through biological pathways involving vascular integrity, kidney sodium handling, neurohormonal signaling, and epigenetic programming. Mechanistic studies support roles for oxidative stress, endothelial dysfunction, hormonal dysregulation, and persistent transcriptional changes in mediating exposure-related blood pressure elevations. Although pediatric data remain limited and often are derived from observational studies, the plausibility of these pathways and the developmental sensitivity of the cardiovascular system underscore the urgency for longitudinal research. Clinical and public health strategies should incorporate environmental risk assessment to better identify modifiable exposures contributing to hypertension in children.
PMID: 41575522
ISSN: 1432-198x
CID: 5988782
Severe Striae Distensae in the Setting of Pediatric Nephrotic Syndrome [Case Report]
Cohen, Koral; Oza, Vikash; Malaga-Dieguez, Laura
Striae distensae, or stretch marks, are common dermal scars resulting from skin overstretching. This case series documents the occurrence of severe striae in three pediatric patients with nephrotic syndrome. This report details the clinical manifestations, including widespread and edematous striae, and explores potential etiological factors such as rapid skin stretching from edema and high-dose corticosteroid use underlying this association.
PMID: 40785667
ISSN: 1525-1470
CID: 5906812
Changes in plasma suPAR levels across pregnancy and in relation to hypertensive disorders [Letter]
Cowell, Whitney; Limaye, Meghana; Brubaker, Sara G; Kahn, Linda G; Reiser, Jochen; Silverstein, Jenna; Malaga-Dieguez, Laura; Mehta-Lee, Shilpi S; Trasande, Leonardo
OBJECTIVE:, suggesting that elevated suPAR levels may reflect a heightened inflammatory response in preeclamptic pregnancies rather than serving as a pre-clinical indicator. No data currently exist on the trajectory of suPAR across pregnancy. In the present study, we investigated if and how plasma suPAR levels change across gestation and examined whether this change and the levels in each trimester varied between women with and without HDP. STUDY DESIGN/METHODS:Participants included pregnant individuals enrolled in the [study name removed for blinding], a prospective birth cohort designed to study an array of exposures and conditions relevant to maternal and child health. Maternal blood was collected at up to three time points during pregnancy and plasma suPAR levels were analyzed by enzyme-linked immunosorbent assay. Information on maternal HDP was abstracted from electronic medical records. Study participants with suPAR data in any trimester and information about HDP were eligible for inclusion (n=393); 64 non-HDP participants who had chronic hypertension (n=5), gestational diabetes mellitus (n=55), lupus (n=1), type 1 diabetes (n=1) or type 2 diabetes (n=2) were excluded, resulting in a final analytic sample of 329. The study was approved by the Institutional Review Board of the [institution removed for blinding] and all participants provided written informed consent. We first regressed suPAR levels on gestational age at the time of sample collection to assess change over the course of pregnancy. We did this for the sample overall and stratified by HDP status. Among the subset of participants with repeated measures, we used paired Wilcoxon signed-rank tests to assess the within-person change in suPAR across trimesters in both groups. Finally, we used Wilcoxon signed-rank tests to assess whether suPAR levels in each trimester and averaged over pregnancy were different among participants with and without HDP. RESULTS:and ranged from 16.8-50.1; 44% of the sample was overweight or obese defined by a BMI ≥ 25. The majority had at least a high school degree (90.1%) and reported never smoking cigarettes (92.9%). Participants with HDP (n=44) were older and had higher BMI; other participant characteristics did not significantly vary by HDP status. suPAR levels did not significantly differ between those with and without HDP at any gestational timepoint (Table 1), although the association was marginal when considering the third trimester such that those with HDP had higher suPAR levels (2.43 ng/mL vs. 2.12 ng/mL, p=0.11). In the sample overall, suPAR levels decreased by 1.1% per week of advancing gestation (p-value< 0.001); however, when stratified by HDP status, suPAR levels only significantly decreased among those without HDP (1.2% per week, p<0.001), while remaining more stable among the cases (0.8% per week, p=0.17) (Figure 1). This finding was also apparent when examining the subset of participants with repeated measures. Among those with paired samples that did not have HDP, the median suPAR level in early gestation (2.79 ng/mL) was significantly higher than late gestation (2.30 ng/mL) with a p-value <0.001 and large effect size r=0.634. In contrast, among those with paired samples and HDP, the median suPAR level in early gestation (2.37 ng/mL) was not significantly different than late gestation (2.45 ng/mL) with a p-value=0.578 and small effect size r=0.256. It is notable however that the sample size of participants with repeated measures and HDP was small (n=7) and the timing of HDP onset was variable across participants. CONCLUSIONS:Although HDP is a primary cause of morbidity and mortality in pregnancy, predictive biomarkers are lacking. suPAR levels decrease with advancing gestation among healthy women, but remain stable in women with HDP, which may reflect a heightened inflammatory state. Additional research is needed to understand how suPAR correlates with other biomarkers of HDP and whether stable suPAR levels can predict HDP accurately in clinical practice.
PMID: 36775198
ISSN: 2589-9333
CID: 5448002
Elevated Levels of Urinary Biomarkers TIMP-2 and IGFBP-7 Predict Acute Kidney Injury in Neonates after Congenital Heart Surgery
RamÃrez, Michelle; Chakravarti, Sujata; Busovsky-McNeal, Melissa; McKinstry, Jaclyn; Al-Qaqaa, Yasir; Sahulee, Raj; Kumar, T K Susheel; Li, Xiaochun; Goldberg, Judith D; Gefen, Ashley M; Malaga-Dieguez, Laura
PMCID:9208843
PMID: 35734207
ISSN: 2146-4618
CID: 5282022
Catheter-Directed Thrombolysis for Neonatal IVC and Bilateral Renal Vein Thrombosis: A Case Report
Guichet, Phillip L; Jasinski, Sylwia; Malaga-Dieguez, Laura; De Los Reyes, Francis A; Ahuja, Tania; Bride, Karen L; Patel, Amish
Renal vein thrombosis is the most common non-catheter-associated venous thromboembolism event in neonates, accounting for up to 20% of cases. Although mortality rates are lower than a variety of other forms of pediatric thrombosis, renal vein thrombi are associated with significant short-term and long-term sequelae. This report presents the case of a full-term neonate presenting with bilateral renal vein thrombosis with inferior vena cava involvement treated with catheter-directed thrombolysis. This case report intends to highlight the value of a multidisciplinary approach to pediatric venous thromboembolism and to outline relevant procedural details and current laboratory and imaging monitoring of catheter-directed thrombolysis.
PMID: 32569035
ISSN: 1536-3678
CID: 4492822
Pulmonary Manifestations of Renal Disorders in Children
Malaga-Dieguez, Laura; Trachtman, Howard; Giusti, Robert
The causes of kidney disease in pediatric patients are evenly divided between congenital abnormalities of the kidney and urinary tract and acquired disorders. Nearly 10% to 15% of adults in the United States have chronic kidney disease (CKD); there are no comparable data in children. Regardless of patient age, CKD is a systemic problem that affects every organ system, including the lung. We review the tests used to diagnose and evaluate kidney disease and the main clinical syndromes that are likely to be encountered to aid the pulmonology consultant who is asked to evaluate patients with kidney disease.
PMID: 33228933
ISSN: 1557-8240
CID: 4680392
Center Volume and Kidney Transplant Outcomes in Pediatric Patients
Contento, Marissa N; Vercillo, Rachel N; Malaga-Dieguez, Laura; Pehrson, Laura Jane; Wang, Yuyan; Liu, Mengling; Stewart, Zoe; Montgomery, Robert; Trachtman, Howard
Rationale & Objectives/UNASSIGNED:Recent data demonstrate that center volume is not a factor in the outcomes of adult kidney transplant recipients. This study assessed whether center volume affects graft survival in pediatric patients who received a kidney transplant. Study Design/UNASSIGNED:Case-cohort study. Setting & Participants/UNASSIGNED:Kidney transplantation centers, recipients younger than 18 years. Results/UNASSIGNED:Â = 0.02. Although outcomes for deceased donor kidney recipients were similar in the 3 volume categories, outcomes in patients who received a living kidney donation were better in the high-volume centers. Low household income was associated with poorer outcomes. However, 3-year graft survival was similar in the 3 center volume categories in high and low mean household income states. Limitations/UNASSIGNED:Lack of information for complications and individual family household income of recipients. Conclusions/UNASSIGNED:Transplantation outcomes are worse in pediatric patients treated at lower-volume centers. The difference was more pronounced for patients receiving living versus deceased donor kidneys. The distribution of household income in pediatric transplant recipients may also be a factor that contributes to lower 3-year graft survival in low-volume centers.
PMCID:7380383
PMID: 32734249
ISSN: 2590-0595
CID: 4540722
The Psychosocial Impact of a Diagnosis of Hypertension in Pediatric Patients
Bieber, Amy Kalowitz; Pehrson, Laura Jane; Vento, Suzanne; Malaga-Dieguez, Laura; Spruill, Tanya M; Trachtman, Howard
PMCID:7000847
PMID: 32043037
ISSN: 2468-0249
CID: 4303892