A Cross-sectional Study on Fibroblast Growth Factor 23 and Other Markers of Mineral Metabolism in Healthy Children in India.

Fibroblast growth factor 23 (FGF23) plays a significant role in phosphate homeostasis but data on children are limited. We aimed to detect FGF23 levels in 107 healthy children aged 6-16 years and evaluate its correlation with markers of phosphate and calcium metabolism, and the dietary intake of calcium, phosphate, and proteins. Height, weight, and Tanner stages were measured, and dietary intake was calculated. Biochemical analyses of hemoglobin, serum calcium, phosphate, creatinine, Vitamin D, and plasma parathyroid hormone (PTH) and FGF23 levels were performed, alongside their associations with FGF23. Of the children, 65.4% were males. Their mean body mass index was 15.79 ± 2.96 for males and 16.5 ± SD 2.72 for females. The mean Vitamin D and PTH levels were 29.7 ± 1.1 ng/mL and 29.2 ± 1.2 pg/mL, respectively. The mean FGF23 levels were 159 ± 15.2 reference units (RU)/mL. The mean FGF23 levels were significantly higher in females (209.3 ± 31 RU/mL) than in males (132.3 ± 15.1 RU/mL). All biochemical parameters were within the normal range. FGF23 correlated with age, weight, and height, but not Vitamin D, PTH, or dietary calcium and phosphate. FGF23 showed a negative correlation with hemoglobin levels (r = -0.23). Since most children had a nonvegetarian diet, the FGF23 levels were not assessed in vegetarians. These observations were attributed to the rural lifestyle favoring adequate exposure to sunlight and physical activity. The increased FGF23 levels in females, the trends in urban settings, and the levels in strictly vegetarian diets need further study.

Embracing the (r)evolution of social media and digital scholarship in pediatric nephrology education.

Free Open-Access Medical Education (FOAMed) has transformed medical education in the past decade by complementing and substituting for traditional medical education when needed. The attractiveness of FOAMed resources is due to their inexpensive nature, wide availability, and user ability to access on demand across a variety of devices, making it easy to create, share, and participate. The subject of nephrology is complex, fascinating, and challenging. Traditional didactic lectures can be passive and ineffective in uncovering these difficult concepts and may need frequent revisions. Active teaching methods like flipped classrooms have shown some benefits, and these benefits can only be multifold with current social media tools. Social media will inspire the involvement of students and allow them to create and share educational content in a "trendy way," encouraging the participation of their peers and thus building an educational environment more conducive to them while promoting revision and retainment. FOAMed also promotes asynchronous learning, spaced learning, microlearning, and multimodal presentation with a meaningful variation. This article discusses the evolution of digital education, social media platforms, tools for creating and developing FOAMed resources, and digital scholarship.

Clinical characteristics of hospitalised children with acute post-streptococcal glomerulonephritis in the Top End of Australia.

AIMS: Despite the declining incidence of acute post-streptococcal glomerulonephritis (APSGN) in Australia, there is still a significant burden of disease amongst Aboriginal and Torres Strait Islander people in the Northern Territory. Childhood APSGN has been highlighted as a predictor of chronic kidney disease in this population. We aimed to describe clinical characteristics and outcomes of hospitalised children with APSGN in the Northern Territory. METHODS: Single-centre, retrospective cohort study of children (<18 years) with APSGN admitted to a tertiary hospital in the Top End of the Northern Territory between January 2012 and December 2017. Cases were confirmed using the Centre for Disease Control case definition guidelines. Data were extracted from the case notes and electronic medical records. RESULTS: There were 96 cases of APSGN with median age of 7.1 years (interquartile range (IQR) 6.7-11.4). Majority were Aboriginal and Torres Strait Islander (90.6%) and from rural and remote areas (82.3%). Preceding skin infections were identified in 65.5% and sore throat in 27.1%. Severe complications included hypertensive emergencies (37.4%), acute kidney injury (43.8%) and nephrotic-range proteinuria (57.7%). All children improved from their acute illness with supportive medical therapy; however, only 55 out of 96 (57.3%) children were followed up within 12 months of their acute illness. CONCLUSIONS: APSGN disproportionately affects Aboriginal and Torres Strait Islander children and highlights the need for continued and improved public health response. There is room for significant improvement in the medium- and long-term follow-up of affected children.

Rising Incidence of End-Stage Kidney Disease and Poorer Access to Kidney Transplant Among Australian Aboriginal and Torres Strait Islander Children and Young Adults.

INTRODUCTION: Details of the pediatric population with end-stage kidney disease (ESKD) in Australia and New Zealand have been published previously. There is, however, a paucity of studies exploring the trends in incidence, etiology, renal replacement therapy (RRT) modality, and transplant access among the Aboriginal and Torres Strait Islander children and young adults (ATCYAs) residing in Australia. METHODS: An observational study was undertaken and data on Australian patients who commenced RRT at ≤24 years of age between 1963 and 2017 were extracted from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). The incidence and prevalence rates were restricted from 1997 to 2017 because of the unavailability of Aboriginal- and Torres Strait Islander status-specific census data before 1997. RESULTS: A total of 3629 children and young adults received RRT during the observation period, including 178 (4.9%) who identified as ATCYAs and 3451 (95.1%) other children and young adults (OCYAs). Compared with OCYAs, incident rates have risen among ATCYAs since 2000, with the biggest rise for young adults 20 to 24 years of age. Fewer ATCYAs received a kidney transplant compared with OCYAs (56.2% vs. 89.3%, P < 0.001). Pre-emptive kidney transplants were less common in ATCYAs compared with OCYAs (3.4% vs. 16.8%, P < 0.001). Living related donor transplants were less common among ATCYAs than OCYAs (10.7% vs. 35.9%, P < 0.001). CONCLUSIONS: Our study shows rising incident rates and poorer access to kidney transplantation among ATCYAs in Australia. The reasons for this health care disparity and barriers to transplantation need to be explored further and must be addressed.

Incidence and predictors of vascular events following end-stage kidney disease in childhood.

AIM: Cardiovascular death is a leading cause of mortality in paediatric end-stage kidney disease (ESKD). There is however little known about the clinically relevant vascular disease in this population. We aimed to describe the incidence of new onset vascular disease and vascular death in Australian children receiving renal replacement therapy (RRT). We also aimed to identify demographic or childhood risk factors for these endpoints, and whether vascular disease predicts mortality. METHODS: Data on Australian patients who commenced RRT at <18 years of age from 1991 to 2017 were extracted from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). Multivariable competing risks regression was used to identify factors associated with vascular events. RESULTS: A cohort of 1268 patients were followed up for a median of 10.31 years. Vascular disease was reported in 5.4%, and vascular death in 4.1%. The cumulative incidence of any vascular event, that is, disease or death, at 10 and 20 years was 5.5% and 12.8%, respectively. Childhood vascular events were associated with non-Caucasian, non-Indigenous ethnicity, and for the 804 patients followed up after 18 years of age, vascular events were associated with lack of childhood transplantation, longer childhood dialysis duration and Indigenous ethnicity. Vascular disease was only reported for 25.49% of patients who had a vascular death, and although a significant risk factor for mortality, it had limited ability to predict mortality. CONCLUSION: Cumulative incidence of vascular events is significant after commencing RRT during childhood and is associated with ethnicity, longer childhood dialysis duration and lack of childhood transplantation.

Urinary Neutrophil Gelatinase Associated Lipocalin - A Sensitive Marker for Urinary Tract Infection in Children.

Early antibiotic treatment for urinary tract infection (UTI) in young children can prevent renal scarring. Sensitivity of pyuria and positive urine nitrite test as indicators of UTI are low, whereas results of urine culture, the gold standard for diagnosing UTI, may not be available for 48--72 h. Novel markers for rapid and accurate diagnosis of UTI would help in the early initiation of treatment in children with suspected UTI. We studied the utility of urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of UTI. This study included 100 children between 3 months and 5 years with suspected UTI. After parental consent, a midstream clean catch or suprapubic aspirate urine specimen was sent for culture and NGAL analysis. Sensitivity and specificity of urine NGAL as a marker of UTI were estimated. Of the 100 children evaluated, urine culture was positive in 34%. Median urine NGAL values were higher in culture-positive children than in culture-negative children (223.20 vs 13.65, P = 0.0001). Receiver operating curve analysis showed an optimal cutoff level of 27 ng/ml for urine NGAL (odds ratio, 8.2, 95% confidence interval, 3.1--22.1) correlating best with culture positivity. Sensitivity and specificity of urine NGAL estimation were significantly better (79.4% and 68.2%) when compared with urine white blood cell estimation (70.6% and 53%). Urine NGAL is a sensitive and specific marker to predict UTI in children with a cutoff level of 27 ng/ml. It may serve as a screening test for detecting simple, uncomplicated UTI in young children.

Acute Post-Streptococcal Glomerulonephritis in the Northern Territory of Australia: A Review of Data from 2009 to 2016 and Comparison with the Literature.

Acute post-streptococcal glomerulonephritis (APSGN) is an inflammatory kidney disease following infection with nephritogenic strains of Group A Streptococcus. In 1991, APSGN became notifiable in the Northern Territory (NT) of Australia with cases recorded on the NT Notifiable Disease Database (NTNDS). The case definition of a confirmed case requires laboratory definitive evidence or laboratory suggestive evidence in conjunction with a clinically compatible illness. Probable cases require clinical evidence only. Acute post-streptococcal glomerulonephritis notifications from 2009 to 2016 were extracted from the NTNDS. Of the 322 cases, 261 were confirmed and 61 probable. The majority, 304 (94%), were Aboriginal and the median age was 8 years (range: 0-62 years). Incidence for confirmed cases was 13.8/100,000 person-years, with inclusion of probable cases increasing incidence to 17.0/100,000 person-years. Highest incidence of confirmed cases was in Aboriginal children less than 15 years of age at 124.0 cases/100,000 person-years. The rate ratio of confirmed cases in Aboriginal to non-Aboriginal Australians was 18.9 (95% confidence interval: 11.4-33.6). Recent trends show a consistently high number of notifications annually with less frequent outbreaks. The Aboriginal population of the NT continues to have high rates of APSGN with recent trends showing higher rates than previously reported. Sustained preventative efforts and continued surveillance strategies are needed.

Pediatric acute kidney injury and the subsequent risk for chronic kidney disease: is there cause for alarm?

Acute kidney injury (AKI) is characterized clinically as an abrupt decline in renal function marked by reduced excretion of waste products, disordered electrolytes, and disrupted fluid homeostasis. The recent development of a standardized AKI definition has transformed our understanding of AKI epidemiology and outcomes. We now know that in the short term, children with AKI experience greater morbidity and mortality; additionally, observational studies have established that chronic renal sequelae are far more common after AKI events than previously realized. Many of these studies suggest that patients who develop AKI are at greater risk for the subsequent development of chronic kidney disease (CKD). The goal of this review is to critically evaluate the data regarding the association between AKI and CKD in children. Additionally, we describe best practice approaches for future studies, including the use of consensus AKI criteria, the application of rigorous definitions for CKD and renal sequelae, and the inclusion of non-AKI comparator groups. Finally, based upon existing data, we suggest an archetypal approach to follow-up care for the AKI survivors who may be at greater CKD risk, including children with more severe AKI, those who endure repeated AKI episodes, patients who do not experience full recovery, and those with pre-existing CKD.

The path to chronic kidney disease following acute kidney injury: a neonatal perspective.

The risk of acute kidney injury (AKI) in hospitalized critically ill neonatal populations without primary renal disease continues to be high, in both term and premature infants. Observational studies have revealed high rates of chronic kidney disease (CKD) in survivors of neonatal AKI. Proposed mechanisms underlying the progression of CKD following AKI include nephron loss and hyperfiltration, vascular insufficiency and maladaptive repair mechanisms. Other factors, including prematurity and low birth weight, have an independent relationship with the development of CKD, but they may also be positive effect modifiers in the relationship of AKI and CKD. The large degree of heterogeneity in the literature on AKI in the neonatal population, including the use of various AKI definitions and CKD outcomes, has hampered the medical community's ability to properly assess the relationship of AKI and CKD in this vulnerable population. Larger prospective cohort studies with control groups which utilize recently proposed neonatal AKI definitions and standardized CKD definitions are much needed to properly quantify the risk of CKD following an episode of AKI. Until there is further evidence to guide us, we recommend that all neonates with an identified episode of AKI should have an appropriate longitudinal follow-up in order to identify CKD at its earliest stages.

Plasma exchange for paediatric kidney disease-indications and outcomes: a single-centre experience.

BACKGROUND: Outcome data in paediatrics regarding the use of plasmapheresis for immunological kidney disease are scarce. OBJECTIVES: We aimed to evaluate the role of plasmapheresis in children presenting with severe renal impairment secondary to immunological kidney diseases. METHODS: A retrospective chart review of children admitted between January 2009 and August 2013 to the Paediatric Nephrology Unit, Christian Medical College, Vellore, India, and requiring plasma exchange was undertaken. Demographic and clinical data were studied and descriptive statistics applied for analysis. RESULTS: Sixteen children underwent plasmapheresis with a male:female ratio of 10:6 and a mean age of 10.2 years (range 5-15 years). Twelve children had atypical haemolytic uraemic syndrome, two had anti-glomerular basement disease and one each had lupus nephritis with neurological manifestation and anti-nuclear cytoplasmic antibody-associated vasculitis. The mean serum creatinine at presentation was 6.52 [interquartile range (IQR) 4.96-7.85] mg/dL with a mean eGFR of 43 (IQR 27.54-56.7) mL/min/1.73 m(2). Other presenting features included nephrotic range proteinuria (69%), gross haematuria (27%), hypertension (94%) and seizures (37.5%). All children received 1.5 times plasma volume plasmapheresis (mean 11 sessions, range 5-26), dialysis and immunosuppressive therapy. The mean duration of follow-up was 4 months (range 2-24 months) with a majority of the children (15/16, 93.75%) surviving acute illness. One child died of overwhelming sepsis and another was lost to follow-up. Of the survivors, eight had eGFR >60 mL/min/1.73 m(2), while eGFR was 15-60 mL/min/1.73 m(2) in the remaining six children. Eight children were still requiring antihypertensive medications and two were continuing peritoneal dialysis at the last follow-up. Thus early introduction of plasmapheresis along with other supportive therapy in immunological kidney disease may improve outcome.

Clinical efficacy and pharmacokinetics of tacrolimus in children with steroid-resistant nephrotic syndrome.

BACKGROUND: Tacrolimus has gained acceptance in the management of steroid-resistant nephrotic syndrome (SRNS) in children. Due to limited data, therapeutic range is extrapolated from pediatric renal transplant recipients. This study was designed to assess therapeutic efficacy of tacrolimus in children with SRNS and its correlation with inter-dose area under concentration curve (AUC0-12 h) and trough concentration (C0). METHODS: Pre dose, 0.5, 1.0, 1.5, 2.0, 2.5, 3, 4, 8, and 12 h after drug administration blood samples were collected in 25 children who were on tacrolimus for a minimum of 3 months and AUC0-12 h was calculated. RESULTS: There was an 80% (20/25) response rate with 64% (16/25) children achieving complete remission. Median C0 in remission was higher than in relapse group (2.95 ng/ml, versus 1.20 ng/ml, p = 0.005). Median AUC0-12 h in remission was higher compared to those in relapse group (79.75 versus 35.15 µg × h/l; p = 0.025). Maximum concentration after drug administration (Cmax) among the groups was not significantly different. There was a significant correlation between C0 and AUC0-12 h (r = 0.79); and Cmax and AUC0-12 h (r = 0.84). Five patients had a rise in serum creatinine, of which four were still proteinuric and had lower C0 and AUC0-12 h. No other adverse effect was noted. CONCLUSIONS: Tacrolimus had beneficial clinical response in SRNS. Target C0 and AUC0-12 h level for treatment remission was higher than those in relapse in children with SRNS but was lower than required in transplant recipient.

Slit2-Robo signaling in inflammation and kidney injury.

Acute kidney injury is an increasingly common global health problem and is associated with severe morbidity and mortality. In addition to facing high mortality rates, the survivors of acute kidney injury are at increased risk of developing chronic kidney disease and end-stage renal disease. Renal ischemia-reperfusion injury (IRI) is the most common cause of acute kidney injury, and results from impaired delivery of oxygen and nutrients to the kidney. Massive leukocyte influx into the post-ischemic kidney is one of the hallmarks of IRI. The recruited leukocytes exacerbate tissue damage and, if uncontrolled, initiate the progressive changes that lead to renal fibrosis and chronic kidney disease. Early on, recruitment and activation of platelets promotes microthrombosis in the injured kidney, further exacerbating kidney damage. The diversity, complexity, and multiplicity of pathways involved in leukocyte recruitment and platelet activation make it extremely challenging to control these processes, and past efforts have met with limited success in human trials. A generalized strategy to inhibit infiltration of inflammatory leukocytes and platelets, thereby reducing inflammation and injury, may prove to be more beneficial. In this review, we summarize recent findings demonstrating that the neuronal guidance cues, Slit and Roundabout (Robo), prevent the migration of multiple leukocyte subsets towards diverse inflammatory chemoattractants, and have potent anti-platelet functions in vitro and in vivo. These properties uniquely position Slit2 as a novel therapeutic that could be used to prevent acute kidney injury associated with IRI.

Pharmacological interventions for hypertension in children.

BACKGROUND: Hypertension is a major risk factor for stroke, coronary artery disease and kidney damage in adults. There is a paucity of data on the long-term sequelae of persistent hypertension in children, but it is known that children with hypertension have evidence of end organ damage and are at risk of hypertension into adulthood. The prevalence of hypertension in children is rising, most likely due to a concurrent rise in obesity rates. In children with hypertension, non-pharmacological measures are often recommended as first-line therapy, but a significant proportion of children will eventually require pharmacological treatment to reduce blood pressure, especially those with evidence of end organ damage at presentation or during follow-up. A systematic review of the effects of antihypertensive agents in children has not previously been conducted. OBJECTIVES: To determine the dose-related effects of different classes of antihypertensive medications, as monotherapy compared to placebo; as combination therapy compared to placebo or a single medication; or in comparisons of various doses within the same class, on systolic or diastolic blood pressure (or both) in children with hypertension. SEARCH METHODS: We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), Ovid MEDLINE (1946 to October 2013), Ovid EMBASE (1974 to October 2013) and bibliographic citations. SELECTION CRITERIA: The selection criteria were deliberately broad due to there being few clinical trials in children. We included randomised controlled trials (RCTs) of at least two weeks duration comparing antihypertensive agents either as monotherapy or combination therapy with either placebo or another medication, or comparing different doses of the same medication, in children with hypertension. Hypertension was defined as an average (over a minimum of three readings) systolic or diastolic blood pressure (or both) on the 95(th) percentile or above for age, height and gender. DATA COLLECTION AND ANALYSIS: Two authors independently selected relevant studies, extracted data and assessed risk of bias. We summarised data, where possible, using a random-effects model. Formal assessment of heterogeneity was not possible because of insufficient data. MAIN RESULTS: A total of 21 trials evaluated antihypertensive medications of various drug classes in 3454 hypertensive children with periods of follow-up ranging from three to 24 weeks. There were five RCTs comparing an antihypertensive drug directly with placebo, 12 dose-finding trials, two trials comparing calcium channel blockers with angiotensin receptor blockers, one trial comparing a centrally acting alpha blocker with a diuretic and one trial comparing an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker. No randomised trial was identified that evaluated the effectiveness of antihypertensive medications on target end organ damage. The trials were of variable quality and most were funded by pharmaceutical companies. Among the angiotensin receptor blockers, candesartan (one trial, n = 240), when compared to placebo, reduced systolic blood pressure by 6.50 mmHg (95% confidence interval (CI) -9.44 to -3.56) and diastolic blood pressure by 5.50 mmHg (95% CI -9.62 to -1.38) (low-quality evidence). High dose telmisartan (one trial, n = 76), when compared to placebo, reduced systolic blood pressure by -8.50 (95% CI -13.79 to -3.21) but not diastolic blood pressure (-4.80, 95% CI -9.50 to 0.10) (low-quality evidence). Beta blocker (metoprolol, one trial, n = 140), when compared with placebo , significantly reduced systolic blood pressure by 4.20 mmHg (95% CI -8.12 to -0.28) but not diastolic blood pressure (-3.20 mmHg 95% CI -7.12 to 0.72) (low-quality evidence). Beta blocker/diuretic combination (Bisoprolol/hydrochlorothiazide, one trial, n = 94)when compared with placebo , did not result in a significant reduction in systolic blood pressure (-4.0 mmHg, 95% CI -8.99 to -0.19) but did have an effect on diastolic blood pressure (-4.50 mmHg, 95% CI -8.26 to -0.74) (low-quality evidence). Calcium channel blocker (extended-release felodipine,one trial, n = 133) was not effective in reducing systolic blood pressure (-0.62 mmHg, 95% CI -2.97 to 1.73) or diastolic blood pressure (-1.86 mmHg, 95% CI -5.23 to 1.51) when compared with placebo. Further, there was no consistent dose response observed among any of the drug classes. The adverse events associated with the antihypertensive agents were mostly minor and included headaches, dizziness and upper respiratory infections. AUTHORS' CONCLUSIONS: Overall, there are sparse data informing the use of antihypertensive agents in children, with outcomes reported limited to blood pressure and not end organ damage. The most data are available for candesartan, for which there is low-quality evidence of a modest lowering effect on blood pressure. We did not find evidence of a consistent dose response relationship for escalating doses of angiotensin receptor blockers, calcium channel blockers or angiotensin-converting enzyme inhibitors. All agents appear safe, at least in the short term.