First name
Michelle
Last name
Denburg

Title

Long-term kidney and cardiovascular complications in pediatric cancer survivors.

Year of Publication

2022

Date Published

11/2022

ISSN Number

1097-6833

Abstract

OBJECTIVE: To describe the burden of adverse kidney and cardiovascular outcomes in patients evaluated by pediatric nephrology in a multidisciplinary survivorship clinic.

STUDY DESIGN: Retrospective chart review of all patients followed by nephrology in our multidisciplinary survivorship clinic from 8/2013-6/2021. Data included clinic blood pressure (BP), longitudinal ambulatory blood pressure monitoring (ABPM), echocardiography, serum creatinine, and first-morning urine protein/creatinine ratios. For patients with multiple ABPMs, results of initial and most recent ABPMs were compared.

RESULTS: Of 422 patients followed in the multidisciplinary cancer survivorship clinic, 130 were seen by nephrology. Median time after therapy completion to first nephrology visit was 8 years. The most common diagnoses were leukemia/myelodysplastic syndrome (27%), neuroblastoma (24%), and Wilms tumor (15%). At last follow-up, 68% had impaired kidney function, 38% had a clinical diagnosis of hypertension, and 12% had proteinuria. There were 91 ABPMs performed in 55 (42%) patients. Patients with multiple ABPMs (n=21) had statistically significant reductions in overall median BP loads: systolic initial load 37% vs. most recent 10% (p=0.005) and diastolic load 36% vs. 14% (p=0.017). Patients with impaired kidney function were more likely to have received ifosfamide. Patients with hypertension were more likely to have received total body irradiation or allogeneic stem cell transplant.

CONCLUSIONS: History of leukemia/myelodysplastic syndrome, neuroblastoma, and Wilms tumor were frequent among survivors seen by nephrology. There was significant improvement in cardiovascular measures with increased recognition of hypertension and subsequent treatment.

DOI

10.1016/j.jpeds.2022.10.029

Alternate Title

J Pediatr

PMID

36336006

Title

Late effects in survivors of high-risk neuroblastoma following stem cell transplant with and without total body irradiation.

Year of Publication

2021

Number of Pages

e29537

Date Published

2021 Dec 31

ISSN Number

1545-5017

Abstract

<p><strong>BACKGROUND: </strong>Neuroblastoma is the most common extracranial solid tumor in children. Those with high-risk disease are treated with multimodal therapy, including high-dose chemotherapy, stem cell transplant, radiation, and immunotherapy that have led to multiple long-term complications in survivors. In the late 1990s, consolidation therapy involved myeloablative conditioning including total body irradiation (TBI) with autologous stem cell rescue. Recognizing the significant long-term toxicities of exposure to TBI, more contemporary treatment protocols have removed this from conditioning regimens. This study examines an expanded cohort of 48 high-risk neuroblastoma patients to identify differences in the late effect profiles for those treated with TBI and those treated without TBI.</p>

<p><strong>PROCEDURE: </strong>Data on the study cohort were collected from clinic charts, provider documentation in the electronic medical record of visits to survivorship clinic, including all subspecialists, and ancillary reports of laboratory and diagnostic tests done as part of risk-based screening at each visit.</p>

<p><strong>RESULTS: </strong>All 48 survivors of BMT for high-risk neuroblastoma had numerous late effects of therapy, with 73% having between five and 10 late effects. TBI impacted some late effects significantly, including growth hormone deficiency (GHD), bone outcomes, and cataracts.</p>

<p><strong>CONCLUSION: </strong>Although high-risk neuroblastoma survivors treated with TBI have significant late effects, those treated without TBI also continue to have significant morbidity related to high-dose chemotherapy and local radiation. A multidisciplinary care team assists in providing comprehensive care to those survivors who are at highest risk for significant late effects.</p>

DOI

10.1002/pbc.29537

Alternate Title

Pediatr Blood Cancer

PMID

34971017

Title

Urine Biomarkers of Kidney Tubule Health, Injury, and Inflammation are Associated with Progression of CKD in Children.

Year of Publication

2021

Date Published

2021 Sep 20

ISSN Number

1533-3450

Abstract

<p><strong>BACKGROUND: </strong>Novel urine biomarkers may improve identification of children at greater risk of rapid kidney function decline, and elucidate the pathophysiology of CKD progression.</p>

<p><strong>METHODS: </strong>We investigated the relationship between urine biomarkers of kidney tubular health (EGF and -1 microglobulin), tubular injury (kidney injury molecule-1; KIM-1), and inflammation (monocyte chemoattractant protein-1 [MCP-1] and YKL-40) and CKD progression. The prospective CKD in Children Study enrolled children aged 6 months to 16 years with an eGFR of 30-90ml/min per 1.73m. Urine biomarkers were assayed a median of 5 months [IQR: 4-7] after study enrollment. We indexed the biomarker to urine creatinine by dividing the urine biomarker concentration by the urine creatinine concentration to account for the concentration of the urine. The primary outcome was CKD progression (a composite of a 50% decline in eGFR or kidney failure) during the follow-up period.</p>

<p><strong>RESULTS: </strong>Overall, 252 of 665 children (38%) reached the composite outcome over a median follow-up of 6.5 years. After adjustment for covariates, children with urine EGF concentrations in the lowest quartile were at a seven-fold higher risk of CKD progression versus those with concentrations in the highest quartile (fully adjusted hazard ratio [aHR], 7.1; 95% confidence interval [95% CI], 3.9 to 20.0). Children with urine KIM-1, MCP-1, and -1 microglobulin concentrations in the highest quartile were also at significantly higher risk of CKD progression versus those with biomarker concentrations in the lowest quartile. Addition of the five biomarkers to a clinical model increased the discrimination and reclassification for CKD progression.</p>

<p><strong>CONCLUSIONS: </strong>After multivariable adjustment, a lower urine EGF concentration and higher urine KIM-1, MCP-1, and -1 microglobulin concentrations were each associated with CKD progression in children.</p>

DOI

10.1681/ASN.2021010094

Alternate Title

J Am Soc Nephrol

PMID

34544821

Title

Race and Ethnicity Predict Bone Markers and Fracture in Pediatric Patients With Chronic Kidney Disease.

Year of Publication

2021

Number of Pages

298-304

Date Published

2021 02

ISSN Number

1523-4681

Abstract

<p>Studies in healthy children have shown racial-ethnic differences in bone markers and bone outcomes including fractures. At present, limited studies have evaluated the impact of race and ethnicity on bone markers and fractures within the pediatric chronic kidney disease (CKD) population. In a cohort study of 762 children between the ages of 1.5 years and 18 years, with CKD stages 1 to 4 from the CKD in children (CKiD) cohort, the relationship between racial-ethnic group and bone markers (parathyroid hormone [PTH], 25-hydroxyvitamin D [25-OHD], 1,25-dihydroxyvitamin D [1,25(OH) D], and C-terminal fibroblast growth factor [FGF23]) was determined using linear mixed models. Additionally, logistic regression was used to evaluate racial-ethnic differences in prevalent fracture upon study entry. Black race was associated with 23% higher PTH levels (confidence interval [CI], 2.5% to 47.7%; p = .03), 33.1% lower 25-OHD levels (CI, -39.7% to -25.7%; p &lt; .0001), and no difference in C-terminal FGF23 or 1,25(OH) D levels when compared to whites. Hispanic ethnicity was associated with 15.9% lower C-terminal FGF23 levels (CI, -28.3% to -1.5%; p = .03) and 13.8% lower 25-OHD levels (CI, -22.2% to -4.5%; p = .005) when compared to whites. Black and Hispanic children had 74% (odds ratio [OR] 0.26; CI, 0.14 to 0.49; p = .001) and 66% (OR 0.34; CI, 0.17 to 0.65; p &lt; .0001) lower odds of any fracture than white children at study entry, respectively. Race and ethnicity are associated with differences in bone markers and despite lower 25-OHD levels, both black and Hispanic children with CKD reported a lower prevalent fracture history than white children. The current findings in the CKD population are similar to racial-ethnic differences described in healthy children. Additional studies are needed to better understand how these differences might impact the management of pediatric CKD-MBD. © 2020 American Society for Bone and Mineral Research (ASBMR).</p>

DOI

10.1002/jbmr.4182

Alternate Title

J Bone Miner Res

PMID

32960469

Title

Bone mineral density in adolescent urinary stone formers: is sex important?

Year of Publication

2020

Number of Pages

329-335

Date Published

2020 Aug

ISSN Number

2194-7236

Abstract

<p>Urinary stone disease (USD) is affecting a greater number of children and low bone mineral density (BMD) and increased skeletal fractures have been demonstrated in stone patients; however, the mechanism(s) driving bone disease remain unclear. This pilot study was undertaken to assess an adolescent kidney stone cohort's BMD and evaluate for an inverse correlation between BMD and urine concentration of lithogenic minerals and/or inflammatory levels. Prospective case-control study was carried out at a large pediatric center. 15 participants with USD (12-18&nbsp;years of age, 8 female) were matched by age, sex, and body mass index to 15 controls. Lumbar and total body BMD z-score did not differ between groups. When stone formers were separated by sex, there was a significant difference between male stone formers vs. controls total body BMD z-score (Fig. 1). BMD z-score did not significantly correlate with urine calcium, oxalate, citrate or magnesium. Higher urine IL-13 did significantly correlate with higher total body BMD z-score (r = 0.677, p = 0.018). Total body BMD z-score did significantly correlate with body mass index (BMI) as expected for the control group (r = 0.6321, p = 0.0133). However, this relationship was not present in the USD group (r = -&nbsp;0.1629, p = 0.5619). This is a small but hypothesis-generating study which demonstrates novel evidence of male-specific low BMD in adolescent stone formers. Furthermore, we demonstrated a positive association between urine IL-13 and total body BMD z-score USD patients as well as a lack of a positive BMD and BMI correlations in stone formers.</p>

DOI

10.1007/s00240-020-01183-w

Alternate Title

Urolithiasis

PMID

32236650

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