Case report: Withdrawal of angiotensin-converting enzyme inhibitors in children with advanced chronic kidney disease and rapidly declining kidney function

BackgroundIt is not known whether withdrawal of angiotensin-converting enzyme inhibitors (ACEIs) in children with advanced chronic kidney disease (CKD) is beneficial similar to adults. We report a case series of children with advanced CKD whose ACEIs were stopped.MethodsIn the last 5 years, we stopped ACEIs in seven consecutive children on ACEI therapy with rapidly declining CKD stage 4–5. The median age was 12.5 years (range 6.8–17.6); the median estimated glomerular filtration rate (eGFR) at stopping ACEIs was 12.5 ml/min/1.73 m2 (range 8.8–19.9).ResultsSix to twelve months after stopping ACEIs, the eGFR increased in five children (71%). The median absolute increase of eGFR was 5.0 ml/min/1.73 m2 (range −2.3 to +20.0) and relative increase of eGFR was 30% (range −34 to +99). The median follow-up after stopping ACEIs was 2.7 (range 0.5–5.0) years, either until the start of dialysis (n = 5) or until the last follow-up without dialysis (n = 2).ConclusionsThis case series showed that withdrawal of ACEIs in children with CKD stage 4–5 and rapidly declining kidney function may lead to an increase in eGFR

Corticosteroids and regional variations in thickness of the human cerebral cortex across the lifespan

International audienceExposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4–97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis

Background: A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers. ----- Methods: A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated. ----- Results: High levels of sC5b-9 (soluble membrane attack complex), low serum C3 levels and young age at onset (13 years) were characteristic for Cluster 1 with a high prevalence of likely pathogenic variations (LPVs) and C3 nephritic factor, whereas for Cluster 2-which is not reliable because of the small number of cases-strong immunoglobulin G staining, low C3 levels and high prevalence of nephritic syndrome at disease onset were observed. Low plasma sC5b-9 levels, decreased C3 levels and high prevalence of LPV and sclerotic glomeruli were present in Cluster 3, and patients with late onset of the disease (median: 39.5 years) and near-normal C3 levels in Cluster 4. A significant difference was observed in the incidence of end-stage renal disease during follow-up between the different clusters. Patients in Clusters 3-4 had worse renal survival than patients in Clusters 1-2. ----- Conclusions: Our results confirm the main findings of the original cluster analysis and indicate that the observed, distinct pathogenic patterns are replicated in our cohort. Further investigations are necessary to analyse the distinct biological and pathogenic processes in these patient groups

C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy

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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