Kidney volume normative values in Central European children aged 0-19 years: a multicenter study.

BACKGROUND AND OBJECITVES: The currently available kidney volume normative values in children are restricted to small populations from single-centre studies not assessing kidney function and including none or only a small number of adolescents. This study aimed to obtain ultrasound-based kidney volume normative values derived from a large European White/Caucasian paediatric population with normal kidney function. METHODS: After recruitment of 1427 children aged 0-19 years, 1396 individuals with no history of kidney disease and normal estimated glomerular filtration rate were selected for the sonographic evaluation of kidney volume. Kidney volume was correlated with age, height, weight, body surface area and body mass index. Kidney volume curves and tables related to anthropometric parameters were generated using the LMS method. Kidney volume predictors were evaluated using multivariate regression analysis with collinearity checks. RESULTS: No clinically significant differences in kidney volume in relation to height were found between males and females, between supine and prone position and between left and right kidneys. Males had, however, larger age-related kidney volumes than females in most age categories. For the prediction of kidney volume, the highest coefficient correlation was observed for body surface area (r = 0.94), followed by weight (r = 0.92), height (r = 0.91), age (r = 0.91), and body mass index (r = 0.67; p < 0.001 for all). CONCLUSIONS: This study presents LMS-percentile curves and tables for kidney volume which can be used as reference values for children aged 0-19 years.

Mitigating the Denosumab-Induced Rebound Phenomenon with Alternating Short- and Long-Acting Anti-resorptive Therapy in a Young Boy with Severe OI Type VI.

Osteogenesis imperfecta (OI) type VI, a recessively inherited form of OI caused by mutations in SERPINF1, is a severe form distinguished by osteomalacia on bone histomorphometry. We describe a boy with severe OI type VI who was initially treated with intravenous (IV) zoledronic acid (ZA) at 1.4 years of age; however, a year later he transitioned to denosumab 1 mg/kg sub-cutaneously every three months in an effort to decrease fracture rates. After two years on denosumab, he presented with symptomatic hypercalcemia due to the denosumab-induced, hyper-resorptive rebound phenomenon. Laboratory parameters at the time of the rebound were as follows: elevated serum ionized calcium (1.62 mmol/L, N 1.16-1.36), elevated serum creatinine due to hypercalcemia-induced muscle catabolism (83 µmol/L, N 9-55), and suppressed parathyroid hormone (PTH) (< 0.7 pmol/L, N 1.3-5.8). The hypercalcemia was responsive to low-dose IV pamidronate, with a rapid decline in serum ionized calcium, and otherwise normalization of the aforementioned parameters within 10 days. To benefit from the powerful, albeit short-term, anti-resorptive effect of denosumab without further rebound episodes, he was treated thereafter with denosumab 1 mg/kg alternating every three months with IV ZA 0.025 mg/kg. Five years later, he remained on dual alternating anti-resorptive therapy without further rebound episodes, and an overall improvement in his clinical status. This novel pharmacological approach of alternating short- and long-term anti-resorptive therapy every three months has not previously been described. Our report suggests this strategy may be an effective method for prevention of the rebound phenomenon in select children for whom denosumab may be beneficial.

Hypertension in pediatric kidney transplantation.

Arterial hypertension (HTN) in children after kidney transplantation is an important risk factor not only for graft loss but also for cardiovascular morbidity and mortality. The prevalence of posttransplant HTN ranges between 60% and 90%. The etiology of posttransplant HTN is multifactorial and includes residual chronic native kidney disease, immunosuppressive therapy, and chronic allograft dysfunction among other causes. Clinic blood pressure (BP) should be measured at each outpatient visit. However, ambulatory blood pressure monitoring (ABPM) is the gold standard method for BP evaluation in children after kidney transplantation, as it often reveals masked and nocturnal HTN; given this, it should be regularly performed in each transplanted child. All classes of antihypertensive drugs are used in the treatment of posttransplant HTN because it has never been proven that one class is better than another. However, in several retrospective studies, the use of calcium channel blockers is associated with better graft function. The optimal target BP for transplanted children is still a matter of debate; it is recommended to target the same BP as for healthy children, that is, <95th percentile. Control of HTN in transplanted children remains poor - only 20%-50% of treated children have normal BP. There is a great potential for improvement of antihypertensive treatment that could potentially result in improvement of both graft and patient survival in children after kidney transplantation.

Kidney length normative values - new percentiles by age and body surface area in Central European children and adolescents.

BACKGROUND: Kidney size evaluation is an essential examination in pediatric nephrology. While body length/height is the best predictor of kidney length, age-based and body surface area (BSA)-based normative values may be useful in clinical practice or research. This study aimed to establish ultrasound-based kidney length lambda-mu-sigma (LMS) percentiles by age and BSA in healthy children. METHODS: In 1758 Polish and Lithuanian children (868 boys, 49%) aged 0-19 years, kidney length was measured using ultrasonography. In all participants, anthropometric measurements were taken and kidney function was evaluated based on serum creatinine concentration. Participants with chronic or kidney diseases, abnormal kidney function, or pathologies in sonographic examination were excluded from the analysis. RESULTS: Kidney length (median kidney length) increased progressively from infancy to the age of 18 years, from 60.1 to 114.2 mm in males, and from 57.3 to 105.2 mm in females. A gradual increase of kidney length (50th percentile) in relation to BSA (from 46.1 mm in infants with a BSA of 0-1.2 m2 to 118.3 mm in adolescents with a BSA of 2.6-2.8 m2) was also observed. LMS percentiles by age (stratified by sex) and BSA were determined and presented as graphs and tables of percentiles and LMS parameters by 1-year age intervals and 0.2 m2 of BSA, respectively. CONCLUSIONS: We present the first age- and BSA-based kidney length LMS normative values based on the largest pediatric cohort to date, which can be used in both clinical practice and research studies. A higher resolution version of the Graphical abstract is available as Supplementary information.

Blood pressure variability in children with obesity and sleep-disordered breathing following positive airway pressure treatment.

Obese youth with sleep-disordered breathing are treated with positive airway pressure to improve sleep and cardiovascular status. While improvements in sleep parameters have been confirmed, a study by Katz et al. showed no major improvement in ambulatory blood pressure. The aim of this ancillary study was to analyze short-term blood pressure variability, following positive airway pressure treatment, as a more sensitive marker of cardiovascular health. We analyzed 24-h blood pressure variability data in 17 children, taken at baseline and after 12 months of treatment. These data were derived from an already published prospective, multicenter cohort study conducted in 27 youth (8-16 years) with obesity who were prescribed 1-year of positive airway pressure for moderate-severe sleep-disordered breathing. Significant decreases were found in 24 h systolic blood pressure (p = 0.040) and nighttime diastolic blood pressure (p = 0.041) average real variability, and diastolic blood pressure (p = 0.035) weighted standard deviation. Significant decreases were noted in nighttime diastolic blood pressure time rate variability (p = 0.007). Positive airway pressure treatment resulted in a significant decrease in blood pressure variability, suggesting a clinically significant improvement of sympathetic nerve activity in youth with obesity and sleep-disordered breathing. IMPACT: Cardiovascular variability, as measured by blood pressure variability, is improved in children following positive airway pressure treatment. Our novel findings of improved blood pressure time rate variability are the first described in the pediatric literature. Future studies aimed at analyzing target organ damage in this patient population will allow for a better understanding as to whether alterations in blood pressure variability translate to decreasing target organ damage in children, as seen in adults.

Kidney length normative values in children aged 0-19 years - a multicenter study.

BACKGROUND: Currently used pediatric kidney length normative values are based on small single-center studies, do not include kidney function assessment, and focus mostly on newborns and infants. We aimed to develop ultrasound-based kidney length normative values derived from a large group of European Caucasian children with normal kidney function. METHODS: Out of 1,782 children aged 0-19 years, 1,758 individuals with no present or past kidney disease and normal estimated glomerular filtration rate had sonographic assessment of kidney length. The results were correlated with anthropometric parameters and estimated glomerular filtration rate. Kidney length was correlated with age, height, body surface area, and body mass index. Height-related kidney length curves and table were generated using the LMS method. Multivariate regression analysis with collinearity checks was used to evaluate kidney length predictors. RESULTS: There was no significant difference in kidney size in relation to height between boys and girls. We found significant (p < 0.001), but clinically unimportant (Cohen's D effect size = 0.04 and 0.06) differences between prone vs. supine position (mean paired difference = 0.64 mm, 95% CI = 0.49-0.77) and left vs. right kidneys (mean paired difference = 1.03 mm, 95% CI = 0.83-1.21), respectively. For kidney length prediction, the highest coefficient correlation was observed with height (adjusted R2 = 0.87, p < 0.0001). CONCLUSIONS: We present height-related LMS-percentile curves and tables of kidney length which may serve as normative values for kidney length in children from birth to 19 years of age. The most significant predictor of kidney length was statural height.

Should ACE inhibitors or calcium channel blockers be used for post-transplant hypertension?

Arterial hypertension in renal transplant recipients warrants antihypertensive treatment. The preferable choice of antihypertensives that should be used in patients after kidney transplantation remains a matter of debate; however, calcium channel blockers (CCB) and angiotensin-converting enzyme inhibitors (ACEI) are currently the most commonly used antihypertensives. This educational review summarizes the current evidence about the effects of these two classes of medications in transplant recipients. Several studies have demonstrated that both classes of drugs can reduce blood pressure (BP) to similar extents. Meta-analyses of adult randomized controlled trials have shown that graft survival is improved in patients treated with ACEIs and CCBs, and that CCBs increase, yet ACEIs decrease, graft function. Proteinuria is usually decreased by ACEIs but remains unchanged with CCBs. In children, no randomized controlled study has ever been performed to compare BP or graft survival between CCBs and ACEIs. Post-transplant proteinuria could be reduced in children along with BP by ACEIs. The results of the most current meta-analyses recommend that due to their positive effects on graft function and survival, along with their lack of negative effects on serum potassium, CCBs could be the preferred first-line antihypertensive agent in renal transplant recipients. However, antihypertensive therapy should be individually tailored based on other factors, such as time after transplantation, presence of proteinuria/albuminuria, or hyperkalemia. Furthermore, due to the difficulty in controlling hypertension, combination therapy containing both CCBs and ACEIs could be a reasonable first-step therapy in treating children with severe post-transplantation hypertension.

Evolution of isolated systolic hypertension with normal central blood pressure in adolescents-prospective study.

BACKGROUND: The clinical significance of isolated systolic hypertension with normal central blood pressure known as spurious hypertension (sHT) in adolescents and its evolution over time is not known. METHODS: The aim of this study was to analyze changes in office, ambulatory blood pressure (ABPM), central systolic blood pressure (cSBP), hemodynamic parameters, and target organ damage (TOD) over a 1-year follow-up in a group of non-obese children with sHT. RESULTS: Of 294 patients referred for primary hypertension, 138 patients (31 girls; 22%) had hypertension confirmed by ABPM. 48/138 (35%) patients (7 girls; 15%) were diagnosed with sHT (elevated office and ambulatory systolic BP, but normal cSBP); 43 of them (6 girls; 14%) were followed for 12 ± 3 months during non-pharmacological therapy. At baseline 7 (16%) patients had borderline values of cIMT or LVMi indicating mild TOD. After 12 months, 10/43 (3 girls; 23%) patients developed sustained HT (elevated office, ambulatory BP and cSBP), 11/43 (1 girl; 26%) maintained sHT, and 22/43 (2 girls; 51%) evolved to white coat hypertension or normotension. The cSBP values increased in 27 patients (4 girls; 63%), but the group average remained in the normal range. Prevalence of TOD did not change during observation. The multivariate regression analysis showed that the only predictor of cSBP change over time was a change in serum uric acid level. CONCLUSIONS: In conclusion, after 1 year of non-pharmacological treatment, 23% of adolescents with sHT developed sustained hypertension, with the main predictor of cSBP change being the change in serum uric acid.

Unattended automated office blood pressure measurement in children.

PURPOSE: We studied the performance of unattended automated office blood pressure (uAOBP) measurement in children, in relation to oscillometric office BP (OBP) and ambulatory blood pressure monitoring (ABPM). MATERIALS AND METHODS: One hundred and eleven stable treated and untreated outpatients investigated for hypertension underwent uAOBP measurements (seated unattended in a quiet room separate from the renal clinic room, six times after a 5 min rest with the BpTRU device), and immediately before using the oscillometric device. Ambulatory 24 h blood pressure monitoring (ABPM) was performed on the same day in a subgroup of 42 children. RESULTS: UAOBP measurements were successful in 106 children (95%), 5 pre-school children did not tolerate to be alone in the room. The mean ± SD systolic/diastolic uAOBP, OBP and daytime ABP were 109.1 ± 14.0/70.8 ± 10.7 mmHg, 121.6 ± 16.5/77.6 ± 10.5 mmHg and 123.5 ± 11.3/73.7 ± 6.8 mmHg, respectively. Systolic/diastolic uAOBP was significantly lower than OBP by 13.6/7.6 mmHg (p < 0.0001) and lower than daytime ABP by 14.4 ± 0.5/2.9 ± 0.3 mmHg (p < 0.0001). The heart rate was not significantly different during uAOBP than during OBP measurements. On Bland Altman analysis the uAOBP underestimated OBP by a mean of 15.6 mmHg for systolic BP and by 8.6 mmHg for diastolic BP. In all 9 children with white-coat systolic hypertension uAOBP was within the normal range (<95th pc for OBP), in six of nine children with white-coat diastolic hypertension uAOBP was within the normal range however, in three of them it was elevated despite normal ABP. CONCLUSION: uAOBP measurement is feasible in school-aged children, its values are considerably lower than OBP as well as daytime ABP and it could help with detection of white-coat systolic hypertension. The clinical applicability of uAOBP in children should be confirmed in further studies.

Obstructive sleep apnea and hypertension in pediatric chronic kidney disease.

BACKGROUND: Children with chronic kidney disease (CKD) are at risk for obstructive sleep apnea (OSA) and hypertension. The objectives of this study were to explore associations between OSA severity using the apnea-hypopnea-index(AHI) and obstructive apnea-hypopnea-index(OAHI) on polysomnography (PSG), OSA symptoms, and measures of hypertension in children with CKD. METHODS: One-night in-laboratory PSGs and 24-h ambulatory blood pressure monitoring (ABPM) were performed on children with CKD stages 2-5 (non-dialysis dependent). Sleep questionnaires, including the modified Epworth Sleepiness Scale (ESS) and the Pediatric Sleep Questionnaire (PSQ), were administered during the sleep study. RESULTS: Nineteen children and adolescents completed a PSG and questionnaires and thirteen completed ABPMs. Mean (standard deviation) age at the time of the sleep study was 14.1 (3.2) years. Eleven (58%) participants had CKD stage two, and eight (42%) had stage 3-4. None of the participants were found to have OSA on PSG. One participant had a positive ESS score (≥ 11) and five participants had positive PSQ scores (≥  eight). Night systolic and diastolic pressures were strongly correlated with the OAHI (r = 0.67 and r = 0.69, respectively, p < 0.05), while the AHI was not correlated with any blood pressure measures. CONCLUSIONS: Our study did not find OSA on PSG in children with predominantly mild to moderate CKD. The OAHI was found to be strongly correlated with nighttime blood pressures. Future prospective studies with a larger sample size are needed to monitor for potential progression of symptoms and findings on PSG in pediatric patients as they evolve across the spectrum of CKD.

Blood pressure (BP) assessment-from BP level to BP variability.

The assessment of blood pressure (BP) can be challenging in children, especially in very young individuals, due to their variable body size and lack of cooperation. In the absence of data relating BP with cardiovascular outcomes in children, there is a need to convert absolute BP values (in mmHg) into age-, gender- and height appropriate BP percentiles or Z-scores in order to compare a patient's BP with the BP of healthy children of the same age, but also of children of different ages. Traditionally, the interpretation of BP has been based mainly on the assessment of the BP level obtained by office, home or 24-h BP monitoring. Recent studies suggest that it is not only BP level (i.e. average BP) but also BP variability that is clinically important for the development of target organ damage, including the progression of chronic kidney disease. In this review we describe current methods to evaluate of BP level, outline available methods for BP variability assessment and discuss the clinical consequences of BP variability, including its potential role in the management of hypertension.

Primary hypertension is a disease of premature vascular aging associated with neuro-immuno-metabolic abnormalities.

There is an increasing amount of data indicating that primary hypertension (PH) is not only a hemodynamic phenomenon but also a complex syndrome involving abnormal fat tissue distribution, over-activity of the sympathetic nervous system (SNS), metabolic abnormalities, and activation of the immune system. In children, PH usually presents with a typical phenotype of disturbed body composition, accelerated biological maturity, and subtle immunological and metabolic abnormalities. This stage of the disease is potentially reversible. However, long-lasting over-activity of the SNS and immuno-metabolic alterations usually lead to an irreversible stage of cardiovascular disease. We describe an intermediate phenotype of children with PH, showing that PH is associated with accelerated development, i.e., early premature aging of the immune, metabolic, and vascular systems. The associations and determinants of hypertensive organ damage, the principles of treatment, and the possibility of rejuvenation of the cardiovascular system are discussed.

Eculizumab hepatotoxicity in pediatric aHUS.

BACKGROUND: Eculizumab is a humanized anti-C5 antibody approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use is increasing in children following reports of its safety and efficacy. METHODS: We reviewed biochemical and clinical data related to possible drug-induced liver injury in 11 children treated with eculizumab for aHUS in a single center. RESULTS: Elevated aminotransferases were observed in 7 children aged 6 to 11 years following eculizumab treatment for aHUS. Internationally accepted liver enzyme thresholds for drug-induced liver injury were exceeded in 5 cases. In all cases, liver injury was classified as mixed hepatocellular and cholestatic. Infectious and other causes were excluded in each case. One patient with no pre-existing liver disease developed tender hepatomegaly and liver enzyme derangement exceeding 20 times the upper limit of normal following initiation of eculizumab. Recurrent liver injury following re-challenge with eculizumab necessitated its discontinuation and transition to plasma therapy. CONCLUSIONS: Hepatotoxicity in association with eculizumab is a potentially important yet previously unreported adverse event. We recommend monitoring liver enzymes in all patients receiving eculizumab. Further research is required to clarify the impact of this adverse event, to characterize the mechanism of potential hepatotoxicity, and to identify which patients are most at risk.

Canadian Society of Nephrology commentary on the 2012 KDIGO clinical practice guideline for the management of blood pressure in CKD.

The KDIGO (Kidney Disease: Improving Global Outcomes) 2012 clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) provides the structural and evidence base for the Canadian Society of Nephrology (CSN) commentary on this guideline's relevancy and application to the Canadian health care system. While in general agreement, we provide commentary on 13 of the 21 KDIGO guideline statements. Specifically, we agreed that nonpharmacological interventions should play a significant role in the management of hypertension in patients with CKD. We also agreed that the approach to the management of hypertension in elderly patients with CKD should be individualized and take into account comorbid conditions to avoid adverse outcomes from excessive BP lowering. In contrast to KDIGO, the CSN Work Group believes there is insufficient evidence to target a lower BP for nondiabetic CKD patients based on the presence and severity of albuminuria. The CSN Work Group concurs with the Canadian Hypertension Education Program (CHEP) recommendation of a target BP for all non-dialysis-dependent CKD patients without diabetes of ≤140 mm Hg systolic and ≤90 mm Hg diastolic. Similarly, it is our position that in diabetic patients with CKD and normal urinary albumin excretion, raising the threshold for treatment from <130 mm Hg systolic BP to <140 mm Hg systolic BP could increase stroke risk and the risk of worsening kidney disease. The CSN Work Group concurs with the CHEP and the Canadian Diabetic Association recommendation for diabetic patients with CKD with or without albuminuria to continue to be treated to a BP target similar to that of the overall diabetes population, aiming for BP levels < 130/80 mm Hg. Consistent with this, the CSN Work Group endorses a BP target of <130/80 mm Hg for diabetic patients with a kidney transplant. Finally, in the absence of evidence for a lower BP target, the CSN Work Group concurs with the CHEP recommendation to target BP<140/90 mm Hg for nondiabetic patients with a kidney transplant.

Autonomic nervous system dysregulation in pediatric hypertension.

Historically, primary hypertension (HTN) has been prevalent typically in adults. Recent data however, suggests an increasing number of children diagnosed with primary HTN, mainly in the setting of obesity. One of the factors considered in the etiology of HTN is the autonomous nervous system, namely its dysregulation. In the past, the sympathetic nervous system (SNS) was regarded as a system engaged mostly in buffering major acute changes in blood pressure (BP), in response to physical and emotional stressors. Recent evidence suggests that the SNS plays a much broader role in the regulation of BP, including the development and maintenance of sustained HTN by a chronically elevated central sympathetic tone in adults and children with central/visceral obesity. Consequently, attempts have been made to reduce the SNS hyperactivity, in order to intervene early in the course of the disease and prevent HTN-related complications later in life.

Diagnostic accuracy of carotid plaque instability by noninvasive imaging: a systematic review and meta-analysis.

AIMS: There is increasing evidence that plaque instability in the extracranial carotid artery may lead to an increased stroke risk independently of the degree of stenosis. We aimed to determine diagnostic accuracy of vulnerable and stable plaque using noninvasive imaging modalities when compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis. METHODS AND RESULTS: Medline Ovid, Embase, Cochrane Library, and Web of Science were searched for diagnostic accuracy of noninvasive imaging modalities (CT, MRI, US) in the detection of 1) vulnerable/stable plaque, and 2) vulnerable/stable plaque characteristics, compared to histology. The quality of included studies was assessed by QUADAS-2 and univariate and bivariate random-effect meta-analyses were performed. We included 36 vulnerable and 5 stable plaque studies in the meta-analysis, and out of 211 plaque characteristics from remaining studies, we classified 169 as vulnerable and 42 as stable characteristics (28 CT, 120 MRI, 104 US characteristics). We found that MRI had high accuracy [90% (95% CI: 82-95%)] in the detection of vulnerable plaque, similar to CT [86% (95% CI: 76-92%); P > 0.05], whereas US showed less accuracy [80% (95% CI: 75-84%); P = 0.013]. CT showed high diagnostic accuracy in visualizing characteristics of vulnerable or stable plaques (89% and 90%) similar to MRI (86% and 89%; P > 0.05); however, US had lower accuracy (77%, P < 0.001 and 82%, P > 0.05). CONCLUSION: CT and MRI have a similar, high performance in detecting vulnerable carotid plaques, whereas US showed significantly less diagnostic accuracy. Moreover, MRI visualized all vulnerable plaque characteristics allowing for a better stroke risk assessment. REGISTRATION: PROSPERO ID CRD42022329690.

Screening for hypertension in adults: protocol for evidence reviews to inform a Canadian Task Force on Preventive Health Care guideline update.

PURPOSE: To inform updated recommendations by the Canadian Task Force on Preventive Health Care on screening in a primary care setting for hypertension in adults aged 18 years and older. This protocol outlines the scope and methods for a series of systematic reviews and one overview of reviews. METHODS: To evaluate the benefits and harms of screening for hypertension, the Task Force will rely on the relevant key questions from the 2021 United States Preventive Services Task Force systematic review. In addition, a series of reviews will be conducted to identify, appraise, and synthesize the evidence on (1) the association of blood pressure measurement methods and future cardiovascular (CVD)-related outcomes, (2) thresholds for discussions of treatment initiation, and (3) patient acceptability of hypertension screening methods. For the review of blood pressure measurement methods and future CVD-related outcomes, we will perform a de novo review and search MEDLINE, Embase, CENTRAL, and APA PsycInfo for randomized controlled trials, prospective or retrospective cohort studies, nested case-control studies, and within-arm analyses of intervention studies. For the thresholds for discussions of treatment initiation review, we will perform an overview of reviews and update results from a relevant 2019 UK NICE review. We will search MEDLINE, Embase, APA PsycInfo, and Epistemonikos for systematic reviews. For the acceptability review, we will perform a de novo systematic review and search MEDLINE, Embase, and APA PsycInfo for randomized controlled trials, controlled clinical trials, and observational studies with comparison groups. Websites of relevant organizations, gray literature sources, and the reference lists of included studies and reviews will be hand-searched. Title and abstract screening will be completed by two independent reviewers. Full-text screening, data extraction, risk-of-bias assessment, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers. Results from included studies will be synthesized narratively and pooled via meta-analysis when appropriate. The GRADE approach will be used to assess the certainty of evidence for outcomes. DISCUSSION: The results of the evidence reviews will be used to inform Canadian recommendations on screening for hypertension in adults aged 18 years and older. SYSTEMATIC REVIEW REGISTRATION: This protocol is registered on PROSPERO and is available on the Open Science Framework (osf.io/8w4tz).

Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.

PURPOSE: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome. METHODS: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4). RESULTS: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001). CONCLUSION: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity.