Biopsy-proven Henoch-Schönlein purpura nephritis: a single center experience

Background: Knowledge on normal progress and treatment of Henoch-Schönlein purpura nephritis (HSPN) is limited. This study reviews outcome, clinical, pathological, and therapeutic factors affecting the prognosis of HSPN patients. Methods: Forty-nine children with biopsy-confirmed HSPN diagnosed between September 2008 and 2018 were included. Demographics, clinical and laboratory data, treatment, and outcome were recorded at the time of biopsy, 3, 6, 12, and 24 months and at last visit. Clinical outcome was graded according to Meadow’s criteria. Results: The median age at time of biopsy was 10.1 years (IQR:5.7) and female/male ratio 24/25. At presentation, 40.8% of patients had nonnephrotic proteinuria, 18.4% nephrotic syndrome (NS), 4.1% nephritic syndrome (NephrS), and 36.7% NephrS+NS. There were 11 patients with an estimated glomerular filtration rate below 90 ml/min/1.73 m2. Biopsy specimens were classified according to International Study of Kidney Diseases in Children (ISKDC) and Oxford Classification MEST-C scoring systems. Forty-one patients received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 37 patients steroids, and 35 patients other immunosuppressive medications. At last visit, 24 patients had stage 1 chronic kidney disease (CKD), three stage 2 CKD, and two had stage 5 CKD. Neither clinical parameters nor ISKDC biopsy grade or treatment modalities effected the final outcome. The Oxford classification showed significantly increased segmental glomerulosclerosis in patients with unfavorable outcome. Favorable outcome was associated with shorter time from kidney involvement to biopsy and start of treatment. Conclusion: A large proportion of patients continued to show signs of CKD at last follow-up while only a small proportion developed stage 5 CKD

Urinary tract infections in children and the risk of ESRF.

Paediatric guidance on diagnosis and treatment of urinary tract infections (UTIs) has in the past largely focused on identifying children with vesicoureteral reflux, thought to be at greatest risk of renal scarring. This practice has been questioned, specifically the accepted association between UTI and end-stage renal failure (ESRF) through renal scarring. The aim of this article is to ascertain whether we can predict with confidence the true level of risk that a child with a first-time UTI will subsequently develop ESRF attributable to UTI

Cyclophosphamide and rituximab in frequently relapsing/steroid-dependent nephrotic syndrome

BACKGROUND: Steroid-sensitive nephrotic syndrome is the most common form of nephrotic syndrome in childhood, defined by the response to treatment with glucocorticoids with consequent remission. While most children eventually experience spontaneous resolution of the disease, some have a difficult course with frequent relapses or steroid dependence nephrotic syndrome (FRSDNS). The consequent steroid toxicity often prompts administration of other immunosuppressive drugs, traditionally cyclophosphamide. Recently, rituximab has been reported as effective in this disorder, but long-term experience is lacking. METHODS: Retrospective note review of all children with FRSDNS treated with a first course of cyclophosphamide and/or rituximab in our center between December 2006 and April 2015. We reviewed time to first relapse after treatment, co-medications, and side effects. RESULTS: A total of 102 children were treated with cyclophosphamide (79) and/or rituximab (42). Of these, 34 received cyclophosphamide prior to rituximab. Median time to first relapse was 7 months after cyclophosphamide and 14 months after rituximab. Documented side effects of cyclophosphamide included neutropenia, hair loss, and hemorrhagic cystitis (1). Rituximab was associated with an allergic reaction at infusion in two patients. CONCLUSIONS: Rituximab was used in children with the most difficult to treat FRSDNS, yet was associated with longer remission time and less side effects than cyclophosphamide. A randomized controlled trial is needed to directly compare these drugs

The cardiovascular phenotype of childhood hypertension: a cardiac magnetic resonance study

BACKGROUND: The cardiovascular phenotype is poorly characterized in treated pediatric hypertension. Cardiovascular magnetic resonance imaging (MRI) can be used to better characterize both cardiac and vascular phenotype in children with hypertension. OBJECTIVE: To use MRI to determine the cardiac and vascular phenotypes of different forms of treated hypertension and compare the results with those of healthy children. MATERIALS AND METHODS: Sixty children (15 with chronic renal disease with hypertension, 15 with renovascular hypertension, 15 with essential hypertension and 15 healthy subjects) underwent MRI with noninvasive blood pressure measurements. Cardiovascular parameters measured include systemic vascular resistance, total arterial compliance, left ventricular mass and volumetric data, ejection fraction and myocardial velocity. Between-group comparisons were used to investigate differences in the hypertension types. RESULTS: Renal hypertension was associated with elevated vascular resistance (P≤0.007) and normal arterial compliance. Conversely, children with essential hypertension had normal resistance but increased compliance (P=0.001). Renovascular hypertension was associated with both increased resistance and compliance (P≤0.03). There was no difference in ventricular volumes, mass or cardiac output between groups. Children with renal hypertension also had lower systolic and diastolic myocardial velocities. CONCLUSION: Cardiovascular MRI may identify distinct vascular and cardiac phenotypes in different forms of treated childhood hypertension. Future studies are needed to investigate how this may inform further optimisation of blood pressure treatment in different types of hypertension

International validation of a urinary biomarker panel for identification of active lupus nephritis in children.

Conventional markers of juvenile-onset systemic lupus erythematosus (JSLE) disease activity fail to adequately identify lupus nephritis (LN). While individual novel urine biomarkers are good at detecting LN flares, biomarker panels may improve diagnostic accuracy. The aim of this study was to assess the performance of a biomarker panel to identify active LN in two international JSLE cohorts.Novel urinary biomarkers, namely vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), lipocalin-like prostaglandin D synthase (LPGDS), transferrin (TF), ceruloplasmin, alpha-1-acid glycoprotein (AGP) and neutrophil gelatinase-associated lipocalin (NGAL), were quantified in a cross-sectional study that included participants of the UK JSLE Cohort Study (Cohort 1) and validated within the Einstein Lupus Cohort (Cohort 2). Binary logistic regression modelling and receiver operating characteristic curve analysis [area under the curve (AUC)] were used to identify and assess combinations of biomarkers for diagnostic accuracy.A total of 91 JSLE patients were recruited across both cohorts, of whom 31 (34 %) had active LN and 60 (66 %) had no LN. Urinary AGP, ceruloplasmin, VCAM-1, MCP-1 and LPGDS levels were significantly higher in those patients with active LN than in non-LN patients [all corrected p values (p c) < 0.05] across both cohorts. Urinary TF also differed between patient groups in Cohort 2 (p c = 0.001). Within Cohort 1, the optimal biomarker panel included AGP, ceruloplasmin, LPGDS and TF (AUC 0.920 for active LN identification). These results were validated in Cohort 2, with the same markers resulting in the optimal urine biomarker panel (AUC 0.991).In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an 'excellent' ability for accurately identifying active LN in children

Elevated atmospheric CO2 and humidity delay leaf fall in Betula pendula, but not in Alnus glutinosa or Populus tremula × tremuloides

Context: Anthropogenic activity has increased the level of atmospheric CO2, which is driving an increase of global temperatures and associated changes in precipitation patterns. At Northern latitudes, one of the likely consequences of global warming is increased precipitation and air humidity. Aims: In this work, the effects of both elevated atmospheric CO2 and increased air humidity on trees commonly growing in northern European forests were assessed. Methods: The work was carried out under field conditions by using Free Air Carbon dioxide Enrichment (FACE) and Free Air Humidity Manipulation (FAHM) systems. Leaf litter fall was measured over 4 years (FACE) or 5 years (FAHM) to determine the effects of FACE and FAHM on leaf phenology. Results: Increasing air humidity delayed leaf litter fall in Betula pendula, but not in Populus tremula × tremuloides. Similarly, under elevated atmospheric CO2, leaf litter fall was delayed in Betula pendula, but not in Alnus glutinosa. Increased CO2 appeared to interact with periods of low precipitation in summer and high ozone levels during these periods to effect leaf fall. Conclusions: This work shows that increased CO2 and humidity delay leaf fall, but this effect is species specific

Defining remission in childhood-onset lupus:PReS-endorsed consensus definitions by an international task force

Objective: To derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. Methods: The cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria.Results: The Task Force proposed two definitions of remission: ‘cSLE clinical remission on steroids (cCR)’ and ‘cSLE clinical remission off steroids (cCR-0)’. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score &lt; 0.5 (0–3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. Conclusions: cSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.</p

Interleukin-4 and 13 concentrations in infants at risk to develop Bronchopulmonary Dysplasia

BACKGROUND: An exaggerated inflammatory response occurs in the first few days of life in infants who subsequently develop bronchopulmonary dysplasia (BPD). The increase of inflammatory cytokines in many disease processes is generally balanced by a rise in anti-inflammatory cytokines. Interleukin-4 (IL-4) and interleukin-13 (IL-13) have been shown to inhibit production of several inflammatory cytokines important in the development of BPD. METHODS: We sought to determine if a correlation exists between the presence or absence of IL-4 and IL-13 in tracheal aspirates (TA) during the first 3 weeks of life and the development of BPD in premature infants. Serial TAs were prospectively obtained from 36 very low birth weight infants and IL-4 and IL-13 concentrations were determined by ELISA. RESULTS: Infants who developed BPD (n = 19) were less mature (25.3 ± 0.02 wks vs. 27.8 ± 0.05 wks; p < 0.001), and had lower birth weights (739 ± 27 g vs.1052 ± 41 g; p < 0.001). IL-4 and IL-13 were detectable in only 27 of 132 and 9 of 132 samples assayed respectively. Furthermore, the levels detected for IL-4 and IL-13 were very low and did not correlate with the development of BPD. CONCLUSIONS: TA concentrations of IL-4 and IL-13 do not increase significantly during acute lung injury in premature infants