Association of Fibroblast Growth Factor 23 with Blood Pressure in Primary Proteinuric Glomerulopathies.

INTRODUCTION: Fibroblast growth factor 23 (FGF23) has direct effects on the vasculature and myocardium, and high levels of FGF23 are a risk factor for cardiovascular disease (CVD); however, the impact of FGF23 on CVD in primary proteinuric glomerulopathies has not been addressed. METHODS: The associations of baseline plasma intact FGF23 levels with resting blood pressure (BP) and lipids over time among adults and children with proteinuric glomerulopathies enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were analyzed using generalized estimating equation regression analyses. Models were adjusted for age, sex, glomerular diagnosis, follow-up time, estimated glomerular filtration rate, urine protein/creatinine ratio, obesity, and serum phosphorous levels. RESULTS: Two hundred and four adults with median FGF23 77.5 (IQR 51.3-119.3) pg/mL and 93 children with median FGF23 62.3 (IQR 44.6-83.6) pg/mL were followed for a median of 42 (IQR 20.5-54) months. In adjusted models, each 1 µg/mL increase in FGF23 was associated with a 0.3 increase in systolic BP index at follow-up (p < 0.001). Greater baseline FGF23 was associated with greater odds of hypertensive BP (OR = 1.0003; 95% CI 1.001-1.006, p = 0.03) over time. Compared to tertile 1, tertile 2 (OR = 2.1; 95% CI 1.12-3.99, p = 0.02), and tertile 3 (OR = 3; 95% CI 1.08-8.08, p = 0.04), FGF23 levels were associated with greater odds of hypertensive BP over time. Tertile 2 was associated with greater triglycerides compared to tertile 1 (OR = 48.1; 95% CI 4.4-91.9, p = 0.03). CONCLUSION: Overall, higher baseline FGF23 was significantly associated with hypertensive BP over time in individuals with proteinuric glomerulopathies. Further study of FGF23 as a therapeutic target for reducing CVD in proteinuric glomerular disease is warranted.

Hypertension: An Important But Reversible Cause of Systolic Dysfunction in a Cohort of Pediatric Patients.

Cardiac dysfunction due to hypertension (CDHTN) in pediatrics is not well described. We aimed to describe the presentation and outcomes of pediatric CDHTN and identify clinical features associated with resolution of dysfunction. A single-center retrospective cohort study of patients ≤ 21 years with CDHTN from January 2005-September 2020 was performed. Patients with systolic dysfunction without another cause, blood pressure > 95th percentile, and physician judgment that dysfunction was secondary to hypertension were included. Demographics, clinical characteristics, echocardiographic findings, and outcomes were examined using Fisher's exact and Mann-Whitney U tests. Multiple correspondence analysis was used to explore the relationship of resolution of dysfunction to clinical features. Thirty-four patients were analyzed at a median age of 10.9 (IQR 0.3-16.9) years. Patients were divided into groups < 1 year (n = 12) and ≥ 1 year (n = 22). Causes of hypertension were varied by age, with renovascular disease most common in infants (42%) and medical renal disease most common in older patients (77%). Echocardiography demonstrated mild LV dilation (median LV end-diastolic z-score 2.6) and mild LV hypertrophy (median LV mass z-score 2.4). Most patients (81%) had resolution of dysfunction, particularly infants (92%). One patient died and one patient was listed for heart transplant. None required mechanical circulatory support (MCS). No clinical features were statistically associated with resolution of dysfunction. Hypertension is an important but reversible cause of systolic dysfunction in children. Patients are likely to recover with low mortality and low utilization of MCS or transplantation. Further studies are needed to confirm features associated with resolution of dysfunction.

Precision nephrology identified tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis.

The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns of injury on kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates of progression and response to therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used to identify molecular pathways which are shared by subgroups of patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Kidney tissue transcriptomic profile-based clustering identified three patient subgroups with shared molecular signatures across independent, North American, European, and African cohorts. One subgroup had significantly greater disease progression (Hazard Ratio 5.2) which persisted after adjusting for diagnosis and clinical measures (Hazard Ratio 3.8). Inclusion in this subgroup was retained even when clustering was limited to those with less than 25% interstitial fibrosis. The molecular profile of this subgroup was largely consistent with tumor necrosis factor (TNF) pathway activation. Two TNF pathway urine markers were identified, tissue inhibitor of metalloproteinases-1 (TIMP-1) and monocyte chemoattractant protein-1 (MCP-1), that could be used to predict an individual's TNF pathway activation score. Kidney organoids and single-nucleus RNA-sequencing of participant kidney biopsies, validated TNF-dependent increases in pathway activation score, transcript and protein levels of TIMP-1 and MCP-1, in resident kidney cells. Thus, molecular profiling identified a subgroup of patients with either MCD or FSGS who shared kidney TNF pathway activation and poor outcomes. A clinical trial testing targeted therapies in patients selected using urinary markers of TNF pathway activation is ongoing.

Sleep-related breathing disorders and cardiometabolic risk factors in pediatric kidney transplant recipients.

BACKGROUND: SRBDs have been shown to increase the risk of cardiovascular disease, which is a significant cause of mortality in kidney transplant recipients. Few studies have investigated the association between SRBDs and cardiometabolic risk factors in pediatric kidney transplant recipients. METHODS: This was a cross-sectional study of pediatric kidney transplant recipients using baseline cardiometabolic data from a previous clinical trial (NCT01007994). Parents/guardians of pediatric kidney transplant recipients filled out 22-item PSQ. A score greater than 33% was defined as a diagnosis of a SRBD. Fisher's exact test, Mann-Whitney U test, and regressions were used to determine associations. RESULTS: Among the 58 transplant recipients enrolled, 14.80% (n = 8) of participants identified as Black and 40.7% (n = 22) were male. The median age was 13 (IQR 8.25, 17) years and median number of years post-transplant for participants was 2 (IQR 1, 4). The prevalence of SRBDs was 26% (n = 14). The presence of a SRBD was associated with abnormalities in multiple cardiometabolic risk factors including total cholesterol level (ß = 23.63; 95% CI 3.58-43.67), LDL level (ß = 24.94; 95% CI 6.37-43.50), triglyceride level (ß = 54.62; 95% CI 8.74-100.50), and LVH (OR = 5.12; 95% CI 1.12-23.45) when adjusted for age, sex, and race. CONCLUSIONS: Similar to associations reported in the general pediatric and general CKD populations, SRBD is associated with increased cardiometabolic risk in pediatric kidney transplant recipients.

Kidney Outcomes and Hypertension in Survivors of Wilms Tumor: A Prospective Cohort Study.

OBJECTIVE: To assess the prevalence of therapy-related kidney outcomes in survivors of Wilms tumor (WT). STUDY DESIGN: This prospective cohort study included survivors of WT who were ≥5 years old and ≥1 year from completing therapy, excluding those with preexisting hypertension, prior dialysis, or kidney transplant. Participants completed 24-hour ambulatory blood pressure monitoring (ABPM). Abnormal blood pressure (BP) was defined as ≥90th percentile. Masked hypertension was defined as having normal office BP and abnormal ABPM findings. Urine was analyzed for kidney injury molecule-1, interleukin-18, epidermal growth factor, albumin, and creatinine. The estimated glomerular filtration rate (eGFR) was calculated using the bedside chronic kidney disease in children equation. Recent kidney ultrasound examinations and echocardiograms were reviewed for contralateral kidney size and left ventricular hypertrophy, respectively. Clinical follow-up data were collected for approximately 2 years after study enrollment. RESULTS: Thirty-two participants (median age, 13.6 years [IQR, 10.5-16.3 years]; 75% stage 3 or higher WT) were evaluated at a median of 8.7 years (IQR, 6.5-10.8 years) after therapy; 29 participants underwent unilateral radical nephrectomy, 2 bilateral partial nephrectomy, and 1 radical and contralateral partial nephrectomy. In this cohort, 72% received kidney radiotherapy and 75% received doxorubicin. Recent median eGFR was 95.6 mL/min/1.73 m2 (IQR, 84.6-114.0; 11 [34%] had an eGFR of <90 mL/min/1.73 m2). Abnormal ABPM results were found in 22 of 29 participants (76%), masked hypertension in 10 of 29 (34%), and microalbuminuria in 2 of 32 (6%). Of the 32 participants, 22 (69%) had abnormal epidermal growth factor; few had abnormal kidney injury molecule-1 or interleukin-18. Seven participants with previous unilateral nephrectomy lacked compensatory contralateral kidney hypertrophy. None had left ventricular hypertrophy. CONCLUSIONS: In survivors of WT, adverse kidney outcomes were common and should be closely monitored.

Hypertension in Children and Adolescents with Turner Syndrome (TS), Neurofibromatosis 1 (NF1), and Williams Syndrome (WS).

PURPOSE OF REVIEW: Turner syndrome (TS), neurofibromatosis type 1(NF1), and William Syndrome (WS) are 3 genetic conditions that are all associated with a substantial increase in risk of hypertension. In this review, we focus on factors leading to hypertension and on clinical manifestations and management of hypertension in children and adolescents with these genetic conditions RECENT FINDINGS: In most instances, hypertension is secondary. There is a high prevalence of masked hypertension in TS; however, the extent to which control of the BP helps reduce the risk of aortic dissection/aneurysm in TS is not yet fully elucidated. Vasculopathies are the least emphasized but most important manifestation of NF1. Of note, routine screening for pheochromocytoma in NFI is not recommended as it is not cost-effective. Cardiovascular complications are the major cause of death in patients with WBS. ABPM identifies patients without overt aortic or renovascular narrowing. Antihypertensive agents such as ARBs that have direct vascular wall effects and agents that inhibit oxidative stress (minoxidil) should be considered, even in those who do not exhibit overt hypertension. Elevated blood pressure in children and adolescence manifests early with end-organ changes and when left untreated, increases risk for premature onset of cardiovascular disease. Vigilant monitoring of the blood pressure is recommended. Accurate early diagnosis and management of hypertension will delay or prevent target organ damage and ensure a healthier transition to adulthood among children afflicted with these conditions.

APOL1 genotype-associated morphologic changes among patients with focal segmental glomerulosclerosis.

BACKGROUND: The G1 and G2 alleles of apolipoprotein L1 (APOL1) are common in the Black population and associated with increased risk of focal segmental glomerulosclerosis (FSGS). The molecular mechanisms linking APOL1 risk variants with FSGS are not clearly understood, and APOL1's natural absence in laboratory animals makes studying its pathobiology challenging. METHODS: In a cohort of 90 Black patients with either FSGS or minimal change disease (MCD) enrolled in the Nephrotic Syndrome Study Network (58% pediatric onset), we used kidney biopsy traits as an intermediate outcome to help illuminate tissue-based consequences of APOL1 risk variants and expression. We tested associations between APOL1 risk alleles or glomerular APOL1 mRNA expression and 83 light- or electron-microscopy traits measuring structural and cellular kidney changes. RESULTS: Under both recessive and dominant models in the FSGS patient subgroup (61%), APOL1 risk variants were significantly correlated (defined as FDR <0.1) with decreased global mesangial hypercellularity, decreased condensation of cytoskeleton, and increased tubular microcysts. No significant correlations were detected in MCD cohort. Independent of risk alleles, glomerular APOL1 expression in FSGS patients was not correlated with morphologic features. CONCLUSIONS: While APOL1-associated FSGS is associated with two risk alleles, both one and two risk alleles are associated with cellular/tissue changes in this study of FSGS patients. Our lack of discovery of a large group of tissue differences in FSGS and no significant difference in MCD may be due to the lack of power but also supports investigating whether machine learning methods may more sensitively detect APOL1-associated changes.

Validation of computed tomography angiography as a complementary test in the assessment of renal artery stenosis: a comparison with digital subtraction angiography.

BACKGROUND: Renal artery stenosis is an important cause of hypertension in children, accounting for 5-10% of cases. When suspected, noninvasive imaging options include ultrasound (US), computed tomography (CT) angiography and magnetic resonance (MR) angiography. However, digital subtraction angiography (DSA) remains the gold standard. OBJECTIVE: To investigate the accuracy and inter-reader reliability of CT angiography in children with suspected renal artery stenosis. MATERIALS AND METHODS: This is a retrospective study of patients suspected of having renal artery stenosis evaluated by both CT angiography and DSA between 2008 and 2019 at a tertiary pediatric hospital. Only children who underwent CT angiography within 6 months before DSA were included. CT angiography studies were individually reviewed by two pediatric radiologists, blinded to clinical data, other studies and each other's evaluation, to determine the presence of stenosis at the main renal artery and 2nd- and 3rd-order branches. The sensitivity, specificity and accuracy were calculated using DSA as the reference. The effective radiation dose for CT angiography and DSA was also calculated. Kappa statistics were used to assess inter-reader agreement. RESULTS: Seventy-four renal units were evaluated (18 girls, 19 boys). The patients' median age was 8 years (range: 1-21 years). Overall, CT angiography was effective in detecting renal artery stenosis with a sensitivity of 85.7%, specificity of 91.5% and accuracy of 88.9%. There was moderate inter-reader agreement at the main renal artery level (k=0.73) and almost perfect inter-reader agreement at the 2nd/3rd order (k=0.98). However, the sensitivity at the 2nd- and 3rd-order level was lower (14.3%). CT angiography provided excellent negative predictive value for evaluating renal artery stenosis at the main renal artery level (90.1%) and at the 2nd- or 3rd-order branches (82.7%). The median effective dose of CT angiography studies was 2.2 mSv (range: 0.6-6.3) while the effective dose of DSA was 13.7 mSv. CONCLUSION: CT angiography has high sensitivity and specificity at the main renal artery level with a lower radiation dose than previously assumed. Therefore, it can be used as a diagnostic tool in patients with low to medium risk of renal artery stenosis, and as a screening and treatment planning tool in patients at high risk.

Restoration of nocturnal blood pressure dip and reduction of nocturnal blood pressure with evening anti-hypertensive medication administration in pediatric kidney transplant recipients: A pilot randomized clinical trial.

Non-dipping and nocturnal hypertension are commonly found during ABPM in pediatric kidney transplant recipients. These entities are independently associated with increased cardiovascular disease risk in adults. Kidney transplant recipients aged 5-21 years with eGFR > 30 mL/min/1.73 m2 and ABPM demonstrating non-dipping status and normal daytime BP were randomized to intervention (short acting BP medication added in the evening) or control (no medication change) in this pilot, randomized, open-label, blinded end-point clinical trial. ABPM, echocardiography, and PWV were performed at baseline, 3 months, and 6 months. The trial included 17 intervention and 16 control participants. Conversion to dipper status occurred in 53.3% vs 7.7% (P = .01) at 6 months for intervention and controls, respectively. Systolic dip was greater in the intervention group compared to controls (10.9 ± 4.5 vs 4.2 ± 4.6, P = .001), and average systolic nighttime BP was significantly lower in the intervention group (106 ± 8.3 vs 114.9 ± 9.5 mm Hg, P = .01) at 6 months. There were no significant differences in LVMI, PWV, or eGFR between groups. Within-group changes in the intervention group demonstrated improvements in non-dippers, dipping, systolic nighttime BP and nighttime BP load. Restoration of nocturnal dip and improvement in nocturnal BP were observed in the population following chronotherapy. Future studies are needed with larger sample sizes over a longer period of time to delineate the long-term effect of improved nocturnal dip on target organ damage.

Echocardiographic strain analysis reflects impaired ventricular function in youth with pediatric-onset systemic lupus erythematosus.

BACKGROUND: Strain analysis with speckle-tracking echocardiography shows promise as a screening tool for silent myocardial dysfunction in pediatric-onset systemic lupus erythematosus (pSLE). We compared left ventricular (LV) systolic deformation (measured by strain) in children and adolescents with pSLE to controls, and assessed the relationship between strain, disease activity, and other noninvasive measures of cardiovascular health. METHODS: Twenty pSLE subjects ages 9-21 underwent comprehensive cardiovascular testing, including 2D speckle-tracking echocardiography, ambulatory blood pressure monitoring (ABPM), peripheral endothelial function testing, pulse wave velocity and analysis, and carotid ultrasound. Longitudinal apical-4 chamber (LSA4C ) and midpoint circumferential strain (CSmid ) were compared to that of 70 healthy controls using multivariable linear regression. Among pSLE subjects, Pearson correlation coefficients were calculated to evaluate relationships between global longitudinal or circumferential strain and other measures of cardiovascular health. RESULTS: Average SLE disease duration was 3.2 years (standard deviation [SD] 2.1). 2/20 pSLE subjects had persistent disease activity, and only one met criteria for hypertension by ABPM. LSA4C was significantly reduced in pSLE subjects compared to controls (mean -18.3 [SD 3.2] vs -21.8% [SD 2.2], P-value <.001). There was no significant difference in CSmid (-24.8 [SD 3.7] vs -25.7% [SD 3.4], P = .29). Among pSLE subjects, decreased nocturnal blood pressure dipping on ABPM was associated with reduced global circumferential strain (r -0.59, P = .01). CONCLUSIONS: Longitudinal myocardial deformation is impaired in pSLE patients despite clinical remission and may represent early myocardial damage. Strain analysis should be considered in addition to standard echocardiographic assessment during follow-up of patients with pSLE.

Medication adherence in pediatric renal transplant patients: The role of family functioning and parent health locus of control.

Children and adolescents with renal disease experience daily social, emotional, and medical challenges. Renal transplantation can help to improve quality of life but requires a lifelong regimen of immunosuppressant medication to maintain health. Adherence to a daily complex regimen can be difficult, particularly for adolescents who are beginning to develop autonomy from caregivers and are faced with a unique set of socio-emotional challenges. This study examines two factors that have shown to influence adherence in other pediatric populations, namely family functioning and parent health locus of control, from mothers' perspectives, in predicting medication non-adherence for adolescents (ages 12-19 years) 1 year post-transplant. Non-adherence was defined as the percentage of missed doses and late doses of the weekly immunosuppressant doses prescribed. Regression results demonstrated that mothers' perceptions of poorer overall family functioning predicted missed medication doses (ΔR2  = 0.383, F(7, 21) = 2.570, P = 0.044) with significant contributions in the domains of problem-solving (ß = -0.795, t(21) = -2.927, P = 0.008) and affective involvement (ß = 0.872, t(21) = 3.370, P = 0.003). Moreover, mothers who perceived that their adolescent had control over his/her health also predicted more missed medication doses (ΔR2  = 0.133, F(1, 27) = 5.155, P = 0.031). Important implications for these findings include implementation of family-based interventions that promote developmentally appropriate skills for adolescents and cultivate emotional involvement within the family.

Cardiovascular disease risk among children with focal segmental glomerulosclerosis: a report from the chronic kidney disease in children study.

BACKGROUND: The aims were to compare the cardiovascular disease (CVD) risk among children with chronic kidney disease (CKD) secondary to focal segmental glomerulosclerosis (FSGS) with the CVD risk of children with CKD due to other diagnoses. METHODS: Casual blood pressure (BP), ambulatory blood pressure monitoring (APBM), echocardiogram, lipids, carotid intima medial thickness (cIMT), and uric acid obtained from participants in the Chronic Kidney Disease in Children (CKiD) cohort were analyzed longitudinally. Seventy-nine children with FSGS (FSGS-CKD) were compared to 196 children with non-FSGS glomerular disease (GDO-CKD) and 616 children with non-glomerular disease (NG-CKD). RESULTS: At baseline, FSGS-CKD (median 14 years) had ambulatory hypertension (24.6%), masked hypertension (46.2%), left ventricular hypertrophy (LVH) (26.3%), and dyslipidemia (60.0%). In adjusted models, FSGS-CKD had higher systolic BP z-score (0.52 vs 0.11 and 0.23, p = 0.002 and 0.02), triglycerides (133 vs 109 and 102 mg/dl, p = 0.007 and < 0.001), and non-high density lipoprotein (144 vs 132 and 119 mg/dl, p = 0.07 and < 0.001) at baseline when compared to GDO-CKD and NG-CKD, respectively. Left ventricular mass index (LVMI) (36.0 vs 31.7 g/m2.7, p < 0.001) and the odds of LVH (OR 3.38, 95% CI 1.42, 8.08) at baseline were greater in FSGS-CKD compared to NG-CKD. Adjusted longitudinal analysis showed that FSGS-CKD had a faster decline in LVMI than NG-CKD, and FSGS-CKD had a faster increase in uric acid compared to both groups. CONCLUSIONS: Children with CKD due to FSGS had a relatively high prevalence of CVD risk factors. FSGS was associated with greater CVD risk when compared to other CKD diagnoses.

Imaging studies in pediatric fibromuscular dysplasia (FMD): a single-center experience.

BACKGROUND: Fibromuscular dysplasia (FMD) is a non-inflammatory vascular disease that in children unlike in adults shows no sex predilection. FMD is often underdiagnosed, and its pathophysiology is unclear. Delayed diagnosis may lead to refractory hypertension and decreases the chance of successful treatment. Doppler ultrasound (US), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and catheter-based angiography (angiography) are currently used to help make a clinicoradiological diagnosis of FMD. The main aim of the study was to compare the efficacy of imaging modalities which can allow for earlier and improved detection. Furthermore, an anatomical mapping of the location of lesions can help determine the best treatment modalities. METHODS: All patients with non-syndromic non-inflammatory renovascular hypertension were recruited from the Nephrology Department at the Children's Hospital of Philadelphia (CHOP) and enrolled in the U.S. FMD Registry maintained at the University of Michigan. Clinical presentation and imaging findings on US, CT, and MRI of children diagnosed with FMD were evaluated. RESULTS: Mean age at diagnosis was 7 ± 4.9 years (4 months-17 years). Family history of hypertension (HTN) (52%), FMD (8.7%), Caucasian (60%), headache (48%), and HTN (80%) were the most prevalent symptom and sign at presentation. Bruits were 100% specific for renal artery stenosis (RAS) diagnosis but were heard in the minority of patients (3 patients, 12%). FMD was mainly unifocal within a single site (68%) or multiple sites (28%) and involved the main or first order renal branch in about 68% of children. Isolated distal lesions beyond the second order branches were found in about 25% of children. US imaging was significantly less sensitive than angiography (28%, p = 0.003). MRA had a better sensitivity (62.5%, p = 0.3) than US. Overall, CTA had the best sensitivity (84.2%, p = 0.4) compared to angiography; however, only angiography showed distal vessel disease. CONCLUSIONS: Limitations of the study include the sample size and biases-only patients diagnosed with FMD were included in this study and most patients were referred to a pediatric nephrologist for unexplained hypertension. Angiography should be performed as part of the initial work-up of any child suspected of having renovascular FMD, regardless of the findings seen on US, MRA, or CTA.

The Phenotypic Spectrum of Nephropathies Associated with Mutations in Diacylglycerol Kinase ε.

The recent discovery of mutations in the gene encoding diacylglycerol kinase ε (DGKE) identified a novel pathophysiologic mechanism leading to HUS and/or MPGN. We report ten new patients from eight unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity. Most patients presented with HUS accompanied by proteinuria, whereas a subset of patients exhibited clinical and histologic patterns of MPGN without TMA. We also report the first two patients with clinical and histologic HUS/MPGN overlap. DGKE-HUS typically manifested in the first year of life but was not exclusively limited to infancy, and viral triggers frequently preceded HUS episodes. We observed signs of complement activation in some patients with DGKE-HUS, but the role of complement activation remains unclear. Most patients developed a slowly progressive proteinuric nephropathy: 80% of patients did not have ESRD within 10 years of diagnosis. Many patients experienced HUS remission without specific treatment, and a few patients experienced HUS recurrence despite complete suppression of the complement pathway. Five patients received renal allografts, with no post-transplant recurrence reported. In conclusion, we did not observe a clear genotype-phenotype correlation in patients with DGKE nephropathy, suggesting additional factors mediating phenotypic heterogeneity. Furthermore, the benefits of anti-complement therapy are questionable but renal transplant may be a feasible option in the treatment of patients with this condition.

Variation in Preventive Care in Children Receiving Chronic Glucocorticoid Therapy.

OBJECTIVE: To assess preventive care measure prescribing in children exposed to glucocorticoids and identify prescribing variation according to subspecialty and patient characteristics. STUDY DESIGN: Retrospective cohort study of children initiating chronic glucocorticoids in the gastroenterology, nephrology, and rheumatology divisions at a pediatric tertiary care center. Outcomes included 25-hydroxyvitamin D (25OHD) and lipid testing, pneumococcal polysaccharide (PPV) and influenza vaccination, and stress dose hydrocortisone prescriptions. RESULTS: A total of 701 children were followed for a median of 589 days. 25OHD testing was performed in 73%, lipid screening in 29%, and PPV and influenza vaccination in 16% and 78%, respectively. Hydrocortisone was prescribed in 2%. Across specialties, 25OHD, lipid screening, and PPV prescribing varied significantly (all P < .001). Using logistic regression adjusting for specialty, 25OHD testing was associated with older age, female sex, non-Hispanic ethnicity, and lower baseline height and body mass index z-scores (all P < .03). Lipid screening was associated with older age, higher baseline body mass index z-score, and lower baseline height z-score (all P < .01). Vaccinations were associated with lower age (P < .02), and PPV completion was associated with non-White race (P = .04). CONCLUSIONS: Among children chronically exposed to glucocorticoids, 25OHD testing and influenza vaccination were common, but lipid screening, pneumococcal vaccination, and stress dose hydrocortisone prescribing were infrequent. Except for influenza vaccination, preventive care measure use varied significantly across specialties. Quality improvement efforts are needed to optimize preventive care in this high-risk population.

Acquired Multiple Cysts of the Kidney in Neuroblastoma Survivors.

Cystic kidney disease includes a wide range of hereditary, developmental, and acquired conditions of the kidneys. Some of the inherited causes of cystic kidney disease include autosomal dominant polycystic kidney diseases (caused by mutations in PKD1 or PKD2), autosomal recessive polycystic kidney disease, tuberous sclerosis complex, von Hippel-Lindau disease, oral-facial-digital syndrome type I, and Hadju-Cheney syndrome. Acquired cystic kidney disease has been reported in patients receiving long-term hemodialysis or peritoneal dialysis and in children after liver transplantation. Acute kidney injury can occur in patients with neuroblastoma, usually as a result of thrombotic microangiopathy associated with bone marrow transplantation. End-stage renal disease is described in long-term survivors. However, in this case report, we provide what is to our knowledge the first description of multiple kidney cysts in long-term survivors of stage IV neuroblastoma. None of the 7 patients we describe with neuroblastoma and multiple kidney cysts had a family history of autosomal dominant polycystic kidney disease. Also, all lacked stigmata of tuberous sclerosis complex, von Hippel-Lindau disease, or Hadju-Cheney syndrome. Two patients progressed to end-stage renal disease; in addition, one of them developed an oncocytoid renal cell carcinoma.

Differences between the pediatric and adult presentation of fibromuscular dysplasia: results from the US Registry.

BACKGROUND: Fibromuscular dysplasia (FMD) is a non-inflammatory arteriopathy that causes significant morbidity in children. METHODS: The clinical features, presenting symptoms, and vascular beds involved are reviewed in the first 33 patients aged <18 years who are enrolled in the United States Registry for FMD from five registry sites and compared with 999 adult patients from 12 registry sites. RESULTS: Mean age at diagnosis was 8.4 ± 4.8 years (16 days to 17 years). Compared with adults, pediatric FMD occurs in more males (42.4 vs 6 %, p < 0.001). Children with FMD have a stronger previous history of hypertension (93.9 vs 69.9 %, p = 0.002). Hypertension (100 %), headache (55 %), and abdominal bruits (10.7 %) were the most common presenting signs and symptoms. FMD affects renal vasculature in almost all children (97 vs 69.7 %, p = 0.003). The extra-cranial carotid vessels are less commonly involved in children (23.1 vs 73.3 %, p < 0.001). The mesenteric arteries (38.9 vs 16.2 %, p = 0.02) and aorta (26.3 vs 2.4 %, p < 0.001) are more commonly involved in children. CONCLUSIONS: In the United States Registry for FMD, pediatric FMD affects children from infancy throughout childhood. All children presented with hypertension and many presented with headache and abdominal bruits. In children, FMD most commonly affects the renal vasculature, but also frequently involves the mesenteric arteries and abdominal aorta; the carotid vessels are less frequently involved.

The US pediatric nephrology workforce: a report commissioned by the American Academy of Pediatrics.

The US pediatric nephrology workforce is poorly characterized. This report describes clinical and nonclinical activities, motivations and disincentives to a career in pediatric nephrology, future workforce needs, trainee recruitment, and possible explanations for personnel shortages. An e-mail survey was sent in 2013 to all identified US-trained or -practicing pediatric nephrologists. Of 504 respondents, 51% are men, 66% are US graduates, and 73% work in an academic setting. About 20% of trained pediatric nephrologists no longer practice pediatric nephrology. Among the 384 respondents practicing pediatric nephrology full or part-time in the United States, the mean work week was 56.1±14.3 hours, with time divided between patient care (59%), administration (13%), teaching (10%), clinical research (9%), basic research (6%), and other medical activities (3%). Most (>85%) care for dialysis and transplantation patients. The median number of weeks annually on call is 16, and 29% work with one or no partner. One-third of US pediatric nephrologists (n=126) plan to reduce or stop clinical nephrology practice in the next 5 years, and 53% plan to fully or partially retire. Almost half the division chiefs (47%) report inadequate physician staffing. Ongoing efforts to monitor and address pediatric nephrology workforce issues are needed.

Fertility preservation in patients receiving cyclophosphamide therapy for renal disease.

Cyclophosphamide continues to have an important role in the treatment of renal disease, including nephrotic syndrome and lupus nephritis, despite known complications of gonadotoxicity and potential infertility in both male and female patients. It is important that the physician recommending this therapy mitigates the effect of the drug on fertility by adhering to recommendations on dosing limits and offering fertility-preserving strategies. In addition to well-established methods, such as sperm banking and embryo cryopreservation, advances in reproductive technology have yielded strategies such as oocyte cryopreservation, resulting in more fertility-preserving options for the pediatric patient. Despite these advances, there continues to be a significant barrier to referral and access to sperm banks and fertility specialists. These issues are further complicated by ethical issues associated with the treatment of pediatric patients. In this review we explore the development of recommended dosing limits and include a discussion of the available fertility-preserving methods, strategies for increasing access to fertility specialists, and the ethical considerations facing the pediatric healthcare provider.

Neonatal atypical hemolytic uremic syndrome from a factor H mutation treated with eculizumab.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) results from an inherited dysregulation of the alternative complement pathway leading to thrombotic microangiopathy consisting of hemolytic anemia, thrombocytopenia, and renal injury. The complement inhibitor eculizumab is an approved treatment, but its reported use in neonates - who have an inherently high risk of infection - is limited. CASE DIAGNOSIS/TREATMENT: A 28-day-old female presented with gross hematuria and hypertension. aHUS was suspected based on anemia with schistocytes, thrombocytopenia, low C3, and acute kidney injury requiring peritoneal dialysis. A septic work-up initiated on day 2 for hypothermia and respiratory failure was negative. There was no improvement after 6 days of plasma therapy. Despite being < 6 weeks old she was vaccinated with pneumococcal-13 conjugate, meningococcal (groups C and Y) polysaccharide, and Haemophilus b tetanus toxoid conjugate vaccines and started on penicillin prophylaxis. After 1 dose of eculizumab 300 mg, dialysis was discontinued and her hematological parameters improved. Genetic testing revealed a complement factor H mutation. After 11 months of follow-up, she remains on eculizumab and penicillin without recurrence of aHUS or any infectious complications. CONCLUSIONS: Eculizumab is a safe and effective treatment option for aHUS even in neonates at high risk for infection.