Patient-Reported Outcomes Over 24 Months in Pediatric CKD: Findings From the MyKidneyHealth Cohort Study.

2023

03/2023

1523-6838

RATIONALE AND OBJECTIVE: The lived experience of children with chronic kidney disease (CKD) is poorly characterized. We examined the associations between patient-reported outcomes (PROs) measuring children's fatigue, sleep health, psychological distress, family relationships, and global health with clinical outcomes over time in children with CKD and investigated how PROs of children with CKD compare with those of other children.

STUDY DESIGN: Prospective cohort study.

SETTING AND PARTICIPANTS: 212 children 8-21 years-old with CKD and their parents recruited from 16 nephrology programs across North America.

PREDICTORS: CKD stage, disease etiology, sociodemographic and clinical variables.

OUTCOMES: PROs over 2 years.

ANALYTICAL APPROACH: We compared PROs in the CKD sample with a nationally representative general pediatric population. Change of PROs over time and association of sociodemographic and clinical variables with PROs were assessed using multivariable regression models.

RESULTS: 84% parents and 77% children completed PROs at all time points. Baseline PRO scores for children with CKD revealed higher burden of fatigue, sleep-related impairment, psychological distress, impaired global health, and poorer family relationships compared with the general pediatric population, with median score differences ≥ one standard deviation for fatigue and global health. Baseline PRO scores did not differ by CKD stage or glomerular vs. non-glomerular etiology. Over two years, PROs were stable with < 1-point annual change on average on each measure and intraclass correlation coefficients ranging 0.53 to 0.79, indicating high stability. Hospitalization and parent-reported sleep problems were associated with worse fatigue, psychological health and global health scores (all p<0.04).

LIMITATIONS: Unable to assess responsiveness to change with dialysis or transplant.

CONCLUSIONS: Children with CKD experience high, yet stable burden of impairment across numerous PRO measures, especially fatigue and global health, independent of disease severity. These findings underscore the importance of assessing PRO, including fatigue and sleep measures, in this vulnerable population.

10.1053/j.ajkd.2022.12.014

Am J Kidney Dis

36889426

Use of renin angiotensin aldosterone system inhibitors in children with lupus and time to glucocorticoid discontinuation.

2022

395-404

05/2022

1523-1755

There is little data to inform use of renin angiotensin aldosterone system (RAAS) inhibitors in pediatric patients with systemic lupus erythematosus (SLE). Here, we sought to characterize RAAS inhibitor use in pediatric SLE and determine whether early RAAS inhibitor initiation among children with incident lupus nephritis is associated with decreased duration of chronic glucocorticoid exposure. A retrospective cohort study was performed of children (ages 5-18) with SLE and/or lupus nephritis in the Truven MarketScan™ Medicaid and Commercial databases (2013-2018) and estimated RAAS inhibitor use. Among incident nephritis cases, we used competing risk hazard models with inverse probability of treatment weighting to estimate the association between RAAS inhibitor initiation less than 180 days after diagnosis and time to glucocorticoid discontinuation with kidney failure as a competing event. Among 592 children with nephritis and 1407 children with non-kidney SLE, 67% and 15% ever received RAAS inhibitors, respectively. Median duration of RAAS inhibitor use among 323 incident users was 14 and 9 months in children with and without nephritis, respectively. Medicaid enrollment was independently associated with greater likelihood of RAAS inhibitor use, irrespective of nephritis. Among 158 incident nephritis cases, early RAAS inhibitor initiation was significantly associated with a faster rate of glucocorticoid discontinuation (adjusted sub-distribution hazard ratio 1.81, 95% confidence interval [1.09 - 3.00]). Thus, early initiation of RAAS inhibitors may have a role in children newly diagnosed with lupus nephritis; not only those with refractory proteinuria after induction therapy. Hence, integrated health systems data could be leveraged to confirm these findings and optimize adjunctive therapies in pediatric lupus.

10.1016/j.kint.2022.04.023

Kidney Int

35618096

Vitamin D supplementation in children and young adults with persistent proteinuria secondary to glomerular disease.

2022

07/2022

1432-198X

BACKGROUND: Vitamin D deficiency is common in glomerular disease. Supplementation may be ineffective due to ongoing urinary losses of vitamin D binding protein. We sought to determine if daily cholecalciferol supplementation would increase vitamin D concentrations in children with glomerular disease and persistent proteinuria, without adverse effects.

METHODS: Eighteen participants at least 5 years of age with primary glomerular disease and urine protein:creatinine ratio ≥ 0.5 were enrolled from four pediatric nephrology practices to receive cholecalciferol supplementation: 4,000 IU or 2,000 IU per day for serum 25 hydroxyvitamin vitamin D (25OHD) concentrations < 20 ng/mL and 20 ng/mL to < 30 ng/mL, respectively. Measures of vitamin D and mineral metabolism were obtained at baseline and weeks 6 and 12. Multivariable generalized estimating equation (GEE) regression estimated mean percent changes in serum 25OHD concentration.

RESULTS: Median baseline 25OHD was 12.8 ng/mL (IQR 9.3, 18.9) and increased to 27.8 ng/mL (20.5, 36.0) at week 6 (p < 0.001) without further significant increase at week 12. A total of 31% of participants had a level ≥ 30 ng/mL at week 12. Supplementation was stopped in two participants at week 6 for mildly elevated calcium and phosphorus, respectively, with subsequent declines in 25OHD of > 20 ng/mL. In the adjusted GEE model, 25OHD was 102% (95% CI: 64, 141) and 96% (95% CI: 51, 140) higher versus baseline at weeks 6 and 12, respectively (p < 0.001).

CONCLUSION: Cholecalciferol supplementation in vitamin D deficient children with glomerular disease and persistent proteinuria safely increases 25OHD concentration. Ideal dosing to fully replete 25OHD concentrations in this population remains unknown.

CLINICAL TRIAL: NCT01835639. A higher resolution version of the Graphical abstract is available as Supplementary information.

10.1007/s00467-022-05660-9

Pediatr Nephrol

35852656

Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus Nephritis: Development and Validation of Computable Phenotypes.

2021

2021 Nov 03

1555-905X

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Performing adequately powered clinical trials in pediatric diseases, such as SLE, is challenging. Improved recruitment strategies are needed for identifying patients.</p>

<p><strong>DESIGN, SETTING, PARTICIPANTS, &amp; MEASUREMENTS: </strong>Electronic health record algorithms were developed and tested to identify children with SLE both with and without lupus nephritis. We used single-center electronic health record data to develop computable phenotypes composed of diagnosis, medication, procedure, and utilization codes. These were evaluated iteratively against a manually assembled database of patients with SLE. The highest-performing phenotypes were then evaluated across institutions in PEDSnet, a national health care systems network of &gt;6.7 million children. Reviewers blinded to case status used standardized forms to review random samples of cases (=350) and noncases (=350).</p>

<p><strong>RESULTS: </strong>Final algorithms consisted of both utilization and diagnostic criteria. For both, utilization criteria included two or more in-person visits with nephrology or rheumatology and ≥60 days follow-up. SLE diagnostic criteria included absence of neonatal lupus, one or more hydroxychloroquine exposures, and either three or more qualifying diagnosis codes separated by ≥30 days or one or more diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 100% (95% confidence interval [95% CI], 99 to 100), specificity was 92% (95% CI, 88 to 94), positive predictive value was 91% (95% CI, 87 to 94), and negative predictive value was 100% (95% CI, 99 to 100). Lupus nephritis diagnostic criteria included either three or more qualifying lupus nephritis diagnosis codes (or SLE codes on the same day as glomerular/kidney codes) separated by ≥30 days or one or more SLE diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 90% (95% CI, 85 to 94), specificity was 93% (95% CI, 89 to 97), positive predictive value was 94% (95% CI, 89 to 97), and negative predictive value was 90% (95% CI, 84 to 94). Algorithms identified 1508 children with SLE at PEDSnet institutions (537 with lupus nephritis), 809 of whom were seen in the past 12 months.</p>

<p><strong>CONCLUSIONS: </strong>Electronic health record-based algorithms for SLE and lupus nephritis demonstrated excellent classification accuracy across PEDSnet institutions.</p>

10.2215/CJN.07810621

Clin J Am Soc Nephrol

34732529

Changes in Hepcidin and Hemoglobin After Anti-TNF-alpha Therapy in Children and Adolescents With Crohn Disease.

2018

90-94

2018 01

1536-4801

<p><strong>OBJECTIVES: </strong>Anemia is the most common systemic complication of inflammatory bowel disease, is more common in affected children than in adults, and is mediated in large part by chronic inflammation. Inflammation increases levels of the iron-regulatory protein hepcidin, which have been elevated in adults with Crohn disease.</p>

<p><strong>METHODS: </strong>We measured serum hepcidin-25 and hemoglobin (Hgb) in 40 children and adolescents with Crohn disease at baseline and 10 weeks after initiation of anti-tumor necrosis factor (TNF)-α therapy. Measures of disease activity, inflammatory markers, and cytokines were obtained in all subjects. Anemia was defined by World Health Organization criteria.</p>

<p><strong>RESULTS: </strong>At baseline hepcidin and C-reactive protein levels were correlated, and 95% of subjects were anemic. After anti-TNF-α therapy, median (interquartile range) hepcidin concentrations decreased significantly and the distribution narrowed (27.9 [16.2, 52.9] vs 23.2 [11.1, 37.7] ng/mL, P = 0.01). Mean (standard deviation) Hgb also increased significantly (10.6 ± 1.2 to 10.9 ± 1.1 g/dL, P = 0.02), and the increase was sustained at 12 months, although 90% of participants continued to meet anemia criteria at 10 weeks. Disease activity and markers of inflammation also decreased and albumin levels increased. In generalized estimating equation analyses, higher TNF-α, interleukin 6, erythrocyte sedimentation rate, and C-reactive protein were associated with higher hepcidin concentrations (P = 0.04, P = 0.03, P = 0.003, and P &lt; 0.001, respectively), and increased levels of disease activity were associated with higher hepcidin.</p>

<p><strong>CONCLUSIONS: </strong>In children with Crohn disease, anti-TNF-α therapy is associated with decreased levels of hepcidin and increased Hgb 10 weeks after induction. Improvement in anemia may be a secondary benefit for children who receive this therapy.</p>

10.1097/MPG.0000000000001650

J. Pediatr. Gastroenterol. Nutr.

28604512