Edema is the abnormal accumulation of fluid in the interstitial compartment of tissues within the body. In nephrotic syndrome, edema is often seen in dependent areas such as the legs, but it can ...progress to cause significant accumulation in other areas leading to pulmonary edema, ascites, and/or anasarca. In this review, we focus on mechanisms and management of edema in children with nephrotic syndrome. We review the common mechanisms of edema, its burden in pediatric patients, and then present our approach and algorithm for management of edema in pediatric patients. The extensive body of experience accumulated over the last 5 decades means that there are many options, and clinicians may choose among these options based on their experience and careful monitoring of responses in individual patients.
Background
Ambulatory blood pressure monitoring (ABPM) measures mean arterial pressure (MAP) then extrapolates systolic and diastolic blood pressure (BP) values. Pediatric guidelines recommend using ...calculated systolic and diastolic BP rather than measured MAP for diagnosis of ambulatory hypertension (HTN). The 95th percentile BP that defines ambulatory HTN is higher in some children than thresholds used to define ambulatory HTN in adults.
Methods
This is a retrospective study of patients who underwent 24-h ABPM. The level of agreement in ambulatory HTN diagnosis using MAP vs. systolic/diastolic BP was evaluated using Cohen’s kappa coefficient. Similar analysis was done to assess agreement in HTN diagnosis using adult vs. pediatric criteria for males taller than 165 cm.
Results
A total of 263 ABPM studies were included. There was good agreement for diagnosis of HTN using MAP or systolic/diastolic BP (
k
= 0.75; 95% CI: 0.67–0.83). However, there was disagreement between the methods in 12% (
n
= 31) of subjects. Similarly, there was good agreement (
k
= 0.70; 95% CI: 0.56–0.85) between pediatric and adult criteria for HTN diagnosis. Nineteen patients were found to be hypertensive (9 using MAP criteria, 10 using adult criteria) who would not have met ambulatory HTN criteria using current pediatric guidelines.
Conclusions
Inclusion of MAP along with systolic and diastolic BP in ABPM analysis alongside using adult criteria for diagnosing HTN in male children ≥ 165 cm may improve accuracy of pediatric HTN diagnosis and reduce false negative rate. Larger studies are needed to assess the clinical validity of these results.
Graphical abstract
The prevalence of hypertension is increasing in pediatric populations. While clinical data and practice guidelines identify the impact of hypertension on organ dysfunction and emphasize the ...importance for end-organ damage screening, the bidirectional effects of pediatric hypertension on neurocognitive and psychological outcomes are understudied. The objective of this review is to highlight the association between hypertension and cognition, attention, learning, and mental health in children and adolescents. In doing so, this review provides a framework and toolkit to integrate neuropsychology and psychology into the screening and management stages of pediatric hypertension. By recognizing the effects of hypertension on cognition, behavior, and mental health, screenings and interventions can be implemented to proactively and comprehensively improve the health outcomes for children with blood pressure concerns.
Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that can affect multiple organ systems and is heterogenous in its presentation and response to therapy. When diagnosed in ...childhood, SLE is associated with increased morbidity and mortality compared to adult SLE, often requiring substantial immunosuppression with the risk of significant side effects. There remains a significant unmet need for new therapies that can improve disease control and reduce glucocorticoid and other toxic medication exposure for patients with severe or refractory disease. The pathogenesis of SLE involves B cell dysregulation and autoantibody production, which are a hallmark of the disease. Currently approved B cell directed therapies often result in incomplete B cell depletion and may not target long-lived plasma cells responsible for SLE autoantibodies. It is hypothesized that by persistently eliminating both B cells and plasmablasts, CAR T therapy can halt autoimmunity and prevent organ damage in patient's refractory to current B cell-depleting treatments. Herein we summarize the current preclinical and clinical data utilizing CAR T cells for SLE and discuss the future of this treatment modality for lupus. Keywords: SLE, CAR T, B cells
Diabetic nephropathy (DN) is one of the most common microvascular complications in type 1 diabetes Mellitus (T1D). Urinary markers of renal damage or oxidative stress may signal early stages of DN. ...The association of these markers with blood pressure (BP) patterns and glycemic variability (GV) in children is yet to be explored.
Subjects between the ages of 10 and 21 years with T1D were enrolled. Continuous glucose monitoring (CGM) and ambulatory blood pressure monitoring (ABPM) were performed on each subject. Urine samples were collected and analyzed for albumin, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) and pentosidine.
The study included 21 subjects (62% female) with median age of 16.8 (IQR: 14.5, 18.9). Median HbA1C was 8.4 (IQR: 7.5, 9.3). While microalbuminuria was negative in all but one case (4.8%), urinary NGAL/Cr and pentosidine/Cr ratios were significantly elevated (P<0.001) in diabetic patients despite having normal microalbuminuria, and they correlated significantly with level of microalbumin/Cr (r=0.56 CI: 0.17, 0.8 and r=0.79 CI: 0.54, 0.91, respectively). Using ABPM, none had hypertension, however, poor nocturnal systolic BP dipping was found in 48% of cases (95% CI: 28-68%). Urinary NGAL/Cr negatively correlated with nocturnal SBP dipping (r=-0.47, CI: -0.76, -0.03). Urine NGAL/Cr also showed a significant negative correlation with HbA1c measurements, mean blood glucose, and high blood glucose index (r=-0.51 CI: -0.78, -0.09, r=-0.45 CI: -0.74, -0.03, and r=-0.51 CI: -0.77, -0.1, respectively). Median urinary NGAL/Cr and pentosidine/Cr ratios were higher in the high GV group but were not significantly different.
This pilot study explores the role of ABPM and urinary markers of tubular health and oxidative stress in early detection of diabetic nephropathy. GV may play a role in the process of this diabetic complication.
Childhood nephrotic syndrome is a challenging and often persistent renal disorder, and its incidence varies between different ethnicities and regions. Corticosteroids have been the main treatment for ...decades and are effective in most children with idiopathic NS, although 10-15% of these children become steroid resistant. Furthermore, some initially steroid sensitive children follow a steroid dependent or frequently relapsing course and are therefore at increased risk for developing steroid toxicity. In such children, alternative immunosuppressive medications are used to induce and/or maintain remission of NS. One such drug, rituximab, is a monoclonal antibody directed against the B lymphocyte CD20 marker which induces depletion of B cells, and has shown promising results in the management of NS in children. In this review, we summarize recent studies on the efficacy and safety of rituximab in the different types of childhood nephrotic syndrome, the known and potential mechanisms of action of rituximab, its possible complications and side effects, and the available and potential biomarkers of rituximab activity.
Background
Eculizumab is approved for the treatment of atypical hemolytic uremic syndrome (aHUS). Its use off-label is frequently reported. The aim of this study was to describe the broader use and ...outcomes of a cohort of pediatric patients exposed to eculizumab.
Methods
A retrospective, cohort analysis was performed on the clinical and biomarker characteristics of eculizumab-exposed patients
<
25 years of age seen across 21 centers of the Pediatric Nephrology Research Consortium. Patients were included if they received at least one dose of eculizumab between 2008 and 2015. Traditional summary statistics were applied to demographic and clinical data.
Results
A total of 152 patients were identified, mean age 9.1 (+/−6.8) years. Eculizumab was used “off-label” in 44% of cases. The most common diagnoses were aHUS (47.4%), Shiga toxin-producing
Escherichia coli
HUS (12%), unspecified thrombotic microangiopathies (9%), and glomerulonephritis (9%). Genetic testing was available for 60% of patients; 20% had gene variants. Dosing regimens were variable. Kidney outcomes tended to vary according to diagnosis. Infectious adverse events were the most common adverse event (33.5%). No cases of meningitis were reported. Nine patients died of noninfectious causes while on therapy.
Conclusions
This multi-center retrospective cohort analysis indicates that a significant number of children and young adults are being exposed to C5 blockade for off-label indications. Dosing schedules were highly variable, limiting outcome conclusions. Attributable adverse events appeared to be low. Cohort mortality (6.6%) was not insignificant. Prospective studies in homogenous disease cohorts are needed to support the role of C5 blockade in kidney outcomes.
BackgroundAcute tubulointerstitial nephritis (TIN) is a significant cause of acute renal failure in paediatric and adult patients. There are no large paediatric series focusing on the aetiology, ...treatment and courses of acute TIN.Patients, design and settingWe collected retrospective clinical data from paediatric patients with acute biopsy-proven TIN by means of an online survey. Members of four professional societies were invited to participate.ResultsThirty-nine physicians from 18 countries responded. 171 patients with acute TIN were included (54% female, median age 12 years). The most frequent causes were tubulointerstitial nephritis and uveitis syndrome in 31% and drug-induced TIN in 30% (the majority of these caused by non-steroidal anti-inflammatory drugs). In 28% of patients, no initiating noxae were identified (idiopathic TIN). Median estimated glomerular filtration rate (eGFR) rose significantly from 31 at time of renal biopsy to 86 mL/min/1.73 m2 3–6 months later (p<0.001). After 3–6 months, eGFR normalised in 41% of patients (eGFR ≥90 mL/min/1.73 m2), with only 3% having severe or end-stage impairment of renal function (<30 mL/min/1.73 m2). 80% of patients received corticosteroid therapy. Median eGFR after 3–6 months did not differ between steroid-treated and steroid-untreated patients. Other immunosuppressants were used in 18% (n=31) of patients, 21 of whom received mycophenolate mofetil.ConclusionsDespite different aetiologies, acute paediatric TIN had a favourable outcome overall with 88% of patients showing no or mild impairment of eGFR after 3–6 months. Prospective randomised controlled trials are needed to evaluate the efficacy of glucocorticoid treatment in paediatric patients with acute TIN.
Background
Focal segmental glomerulosclerosis (FSGS) is the most common glomerular condition leading to end-stage renal disease (ESRD) and the third most common cause of ESRD in pediatric patients.
...Methods
This is a retrospective study consisting of 22 pediatric patients with FSGS and heavy proteinuria. After demonstrating steroids resistance, the patients were treated with tacrolimus, targeting a trough level 5–8 ng/mL. The primary outcome is the induction of remission with tacrolimus.
Results
Thirteen patients (59%) achieved remission (complete in 31.8% and partial in 27.2%) and 12 patients showed stable or improved renal function over an average follow-up of 2.9 years (range: 0.5–7 years). There was no significant difference in response rate between African American and Caucasian patients. None of the patients had significant side-effect to tacrolimus and none of the repeat biopsies showed an increase in interstitial fibrosis compared to baseline. The best renal outcome was for patients who achieved complete remission. Partially responsive patients had improved renal function compared with resistant patients.
Conclusion
Tacrolimus is a viable option in the treatment of children with idiopathic steroid resistant FSGS.
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