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

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

2021

2021 Sep 20

1533-3450

<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>

10.1681/ASN.2021010094

J Am Soc Nephrol

34544821

Potential benefits of functional magnetic resonance urography (fMRU) over MAG3 renal scan in children with obstructive uropathy.

2021

2021 Jul 10

1873-4898

<p><strong>INTRODUCTION: </strong>Functional renal imaging, most commonly with MAG3 nuclear medicine renal scan, is recommended in the evaluation of children with urinary tract dilation (UTD) suspected of obstructive uropathy. Alternatively, renal function can be evaluated with functional Magnetic Resonance Urography (fMRU), which has superior anatomic detail. However, there are not enough data comparing both methods' equivalency. In this study, we compare the functional and obstruction parameters of fMRU and MAG3 in a pediatric cohort presenting with obstructive uropathy.</p>

<p><strong>STUDY DESIGN: </strong>This is an IRB-approved retrospective review of all children undergoing fMRU at a single, free-standing children's hospital between May 2008 and September 2017. Patients who also underwent a MAG3 renal scan within 6 months and who had no interval surgical intervention were included in the study. Bladder catheterization was performed prior to both imaging studies.</p>

<p><strong>RESULTS: </strong>735 children had 988 fMRU studies performed during the study period. 37 unique patients (13 girls and 24 boys) with median age of 6 months (range: 2 mo-19&nbsp;y) were included in the final sample. Median time interval between studies was 70 days (range 6-179 days). The majority of participants (26/37, 70.3%) presented with UTD P3 and had diagnosis of uretero-pelvic junction obstruction (UPJO) in 21/37. Differential renal function (DRF) was used to group 10 fMRU and 9 MAG3 patients as normal; 9 fMRU and 11 MAG3 as mild; 11 fMRU and 6 MAG3 as moderate; and 7 fMRU and 6 MAG3 as severe; Wilcoxon signed-rank test (p&nbsp;=&nbsp;0.5106). Results were similar for DRF among patients with and without duplex kidneys. In the analysis of obstruction, using reference standard T½ MAG3&nbsp;≥&nbsp;20&nbsp;min, a greater or equal than 6&nbsp;min renal transit time (RTT) from fMRU showed a specificity of 94%, a sensitivity of 62%, and an AUC of 0.827.</p>

<p><strong>DISCUSSION AND CONCLUSIONS: </strong>The differential renal function determined by MAG3 and fMRU in children was not statistically different, therefore we concluded that it was similar and potentially equivalent. Better correlation was shown in patients who had normal split kidney function. While the tests are clinically equivalent, the variability of DRF within each clinical category (i.e., normal, mild, moderate, severe) is not surprising, because MAG3 does not clearly differentiate the dilated collecting system from the functional parenchymal tissue, while fMRU does. Using MAG3 as the gold standard, fMRU was 94.74% specific and 5% more sensitive in detecting UPJO with a RTT of 6min vs. 8min.</p>

10.1016/j.jpurol.2021.07.005

J Pediatr Urol

34426090

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

2021

298-304

2021 02

1523-4681

<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>

10.1002/jbmr.4182

J Bone Miner Res

32960469

The association between diuretic class exposures and enteral electrolyte use in infants developing grade 2 or 3 bronchopulmonary dysplasia in United States children's hospitals.

2021

2021 Jan 28

1476-5543

<p><strong>OBJECTIVE: </strong>To evaluate the association between chronic diuretic exposures and enteral electrolyte use in infants developing severe bronchopulmonary dysplasia (sBPD).</p>

<p><strong>STUDY DESIGN: </strong>Retrospective longitudinal cohort study in infants admitted to United States children's hospitals. We identified diuretic exposures and measured enteral NaCl and KCl use during pre-defined exposure risk-interval days. We used mixed-effects logistic regression to model the association between diuretic exposures and electrolyte use.</p>

<p><strong>RESULTS: </strong>We identified 442,341 subject-days in 3252 infants. All common diuretic classes and class combinations were associated with increased NaCl and KCl use. Thiazide monotherapy was associated with greater electrolyte use than loop monotherapy. The addition of potassium-sparing diuretics was associated with a limited reduction in KCl use compared to thiazide monotherapy.</p>

<p><strong>CONCLUSIONS: </strong>Chronic diuretic exposures are associated with increased NaCl and KCl use. Presumptions about the relative impact of different diuretic classes on electrolyte derangements may be inaccurate and require further study.</p>

10.1038/s41372-021-00924-y

J Perinatol

33510422

State-of-the-Art Renal Imaging in Children.

2020

2020 Jan 08

1098-4275

<p>Imaging modalities for diagnosing kidney and urinary tract disorders in children have developed rapidly over the last decade largely because of advancement of modern technology. General pediatricians and neonatologists are often the front line in detecting renal anomalies. There is a lack of knowledge of the applicability, indications, and nephrotoxic risks of novel renal imaging modalities. Here we describe the clinical impact of congenital anomalies of the kidneys and urinary tract and describe pediatric-specific renal imaging techniques by providing a practical guideline for the diagnosis of kidney and urinary tract disorders.</p>

10.1542/peds.2019-0829

Pediatrics

31915193

Public health: Public investment in childhood health: worth the cost.

2017

2017 May 30

1759-507X

<p>A new study of mortality of children on renal replacement therapy in 32 European countries demonstrates that 67% of the variance between countries can be explained by disparities in public health expenditure. Investment in health care is critical and has demonstrable benefits for the most vulnerable populations.</p>

10.1038/nrneph.2017.66

Nat Rev Nephrol

28555648

Renal Parenchymal Area Growth Curves for Children 0 to 10 Months Old.

2016

1203-8

2016 Apr

1527-3792

<p><strong>PURPOSE: </strong>Low renal parenchymal area, which is the gross area of the kidney in maximal longitudinal length minus the area of the collecting system, has been associated with increased risk of end stage renal disease during childhood in boys with posterior urethral valves. To our knowledge normal values do not exist. We aimed to increase the clinical usefulness of this measure by defining normal renal parenchymal area during infancy.</p>

<p><strong>MATERIALS AND METHODS: </strong>In a cross-sectional study of children with prenatally detected mild unilateral hydronephrosis who were evaluated between 2000 and 2012 we measured the renal parenchymal area of normal kidney(s) opposite the kidney with mild hydronephrosis. Measurement was done with ultrasound from birth to post-gestational age 10 months. We used the LMS method to construct unilateral, bilateral, side and gender stratified normalized centile curves. We&nbsp;determined the z-score and the centile of a total renal parenchymal area of 12.4 cm(2) at post-gestational age 1 to 2 weeks, which has been associated with an&nbsp;increased risk of kidney failure before age 18 years in boys with posterior urethral valves.</p>

<p><strong>RESULTS: </strong>A total of 975 normal kidneys of children 0 to 10 months old were used to create renal parenchymal area centile curves. At the 97th centile for unilateral and single stratified curves the estimated margin of error was 4.4% to 8.8%. For&nbsp;bilateral and double stratified curves the estimated margin of error at the 97th centile was 6.6% to 13.2%. Total renal parenchymal area less than 12.4 cm(2) at post-gestational age 1 to 2 weeks had a z-score of -1.96 and fell at the 3rd percentile.</p>

<p><strong>CONCLUSIONS: </strong>These normal renal parenchymal area curves may be used to track kidney growth in infants and identify those at risk for chronic kidney disease progression.</p>

10.1016/j.juro.2015.08.097

J. Urol.

26926532

Longer interdialytic interval and cause-specific hospitalization in children receiving chronic dialysis.

2013

2628-36

2013 Oct

1460-2385

<p><strong>BACKGROUND: </strong>Previous studies have demonstrated a relationship between longer interdialytic intervals and hospitalization for cardiovascular causes in adults maintained on hemodialysis (HD). This association has not been previously demonstrated in children. We hypothesized that the risk of hospitalization for hypertension (HTN), fluid overload or electrolyte abnormalities would be increased on the days following a longer interdialytic interval in children.</p>

<p><strong>METHODS: </strong>We queried the Pediatric Hospital Information System for all admissions of patients with chronic kidney disease stage V or V-D who received dialysis during the hospitalization. Admissions were divided into two categories: admissions for HTN, fluid overload or electrolyte abnormalities and admissions for all other causes. We assumed that HD patients did not receive dialysis on weekends, and therefore any admission on Monday occurred following a longer interval from the last dialysis. We assumed that all peritoneal dialysis (PD) patients received dialysis on a daily basis. We used mixed effects logistic regression, clustering by patient within each hospital, to assess the increased odds for cause-specific admission on Monday versus other days of the week. We stratified the analysis by dialysis modality, HD or PD.</p>

<p><strong>RESULTS: </strong>Among HD patients, the odds ratio of admission for HTN, fluid overload or electrolyte abnormalities was 2.6 (95% CI = 1.4-4.7, P = 0.003) if the admission occurred on a Monday versus other days of the week. The odds of cause-specific admission among PD patients was not significantly different on Monday compared with other days of the week (95% CI =0.5-1.3, P = 0.8).</p>

<p><strong>CONCLUSION: </strong>Children receiving chronic HD are more likely to be hospitalized for HTN, fluid overload or electrolyte abnormalities following a longer interdialytic interval. Changes to the frequency of outpatient dialysis treatments may decrease admissions in this population and decrease resource utilization in this high-risk population.</p>

10.1093/ndt/gft276

Nephrol. Dial. Transplant.

23861468

Narrowing the focus: what we now know (and still don't know) about antibiotic prophylaxis for children with vesicoureteral reflux.

2015

214-6

02/2015

1523-6838

10.1053/j.ajkd.2014.09.004

Am. J. Kidney Dis.

25441431