To date there are thirteen species validly assigned to the genus Anaerococcus. Most of the species in this genus are anaerobic and of human origin. Anaerococcus urinimassiliensis sp. nov., strain ...Marseille-P2143
is member of family Peptoniphilaceae, which was isolated from the urine of a 17-year-old boy affected by autoimmune hepatitis and membranoproliferative glomerulonephritis using the culturomic approach. In the current study, a taxono-genomics method was employed to describe this new species. The strain Marseille-P2143
was gram positive cocci with translucent colonies on blood agar. Its genome was 2,189,509 bp long with a 33.5 mol% G + C content and exhibited 98.48% 16S rRNA similarity with Anaerococcus provencensis strain 9,402,080. When Anaerococcus urinomassiliensis strain Marseill-P2143
is compared with closely related species, the values ranged from 71.23% with A. hydrogenalis strain DSM 7454
(NZ_ABXA01000052.1) to 90.64% with A. provencensis strain 9402080
(NZ_HG003688.1). This strain has implemented the repertoire of known bacteria of the human urinary tract.
Galloway-Mowat syndrome is a rare autosomal-recessive condition characterized by nephrotic syndrome associated with microcephaly and neurological impairment. Through a combination of autozygosity ...mapping and whole-exome sequencing, we identified WDR73 as a gene in which mutations cause Galloway-Mowat syndrome in two unrelated families. WDR73 encodes a WD40-repeat-containing protein of unknown function. Here, we show that WDR73 was present in the brain and kidney and was located diffusely in the cytoplasm during interphase but relocalized to spindle poles and astral microtubules during mitosis. Fibroblasts from one affected child and WDR73-depleted podocytes displayed abnormal nuclear morphology, low cell viability, and alterations of the microtubule network. These data suggest that WDR73 plays a crucial role in the maintenance of cell architecture and cell survival. Altogether, WDR73 mutations cause Galloway-Mowat syndrome in a particular subset of individuals presenting with late-onset nephrotic syndrome, postnatal microcephaly, severe intellectual disability, and homogenous brain MRI features. WDR73 is another example of a gene involved in a disease affecting both the kidney glomerulus and the CNS.
Human urine was considered sterile for a long time. However, 416 species have been previously cultured, including only 40 anaerobic species. Here, we used culturomics, particularly those targeting ...anaerobes, to better understand the urinary microbiota. By testing 435 urine samples, we isolated 450 different bacterial species, including 256 never described in urine of which 18 were new species. Among the bacterial species identified, 161 were anaerobes (35%). This study increased the known urine repertoire by 39%. Among the 672 bacterial species isolated now at least once from urine microbiota, 431 (64.1%) were previously isolated from gut microbiota, while only 213 (31.7%) were previously isolated from vagina. These results suggest that many members of the microbiota in the urinary tract are in fact derived from the gut, and a paradigm shift is thus needed in our understanding.
Background
For 10 consecutive years, the ESPN/ERA-EDTA Registry has included data on children with stage 5 chronic kidney disease (CKD 5) receiving kidney replacement therapy (KRT) in Europe. We ...examined trends in incidence and prevalence of KRT and patient survival.
Methods
We included all children aged <15 years starting KRT 2007–2016 in 22 European countries participating in the ESPN/ERA-EDTA Registry since 2007. General population statistics were derived from Eurostat. Incidence and prevalence were expressed per million age-related population (pmarp) and time trends studied with JoinPoint regression. We analyzed survival trends using Cox regression.
Results
Incidence of children commencing KRT <15 years remained stable over the study period, varying between 5.5 and 6.6 pmarp. Incidence by treatment modality was unchanged over time: 2.0 for hemodialysis (HD) and peritoneal dialysis (PD) and 1.0 for transplantation. Prevalence increased in all age categories and overall rose 2% annually from 26.4 pmarp in 2007 to 32.1 pmarp in 2016. Kidney transplantation prevalence increased 5.1% annually 2007–2009, followed by 1.5% increase/year until 2016. Prevalence of PD steadily increased 1.4% per year over the entire period, and HD prevalence started increasing 6.1% per year from 2011 onwards. Five-year unadjusted patient survival on KRT was around 94% and similar for those initiating KRT 2007–2009 or 2010–2012 (adjusted HR: 0.98, 95% CI:0.71–1.35).
Conclusions
We found a stable incidence and increasing prevalence of European children on KRT 2007–2016. Five-year patient survival was good and was unchanged over time. These data can inform patients and healthcare providers and aid health policy makers on future resource planning of pediatric KRT in Europe.
Mutations in factor H (CFH), factor I (IF), and membrane cofactor protein (MCP) genes have been described as risk factors for atypical hemolytic uremic syndrome (aHUS). This study analyzed the impact ...of complement mutations on the outcome of 46 children with aHUS. A total of 52% of patients had mutations in one or two of known susceptibility factors (22, 13, and 15% of patients with CFH, IF, or MCP mutations, respectively; 2% with CFH+IF mutations). Age <3 mo at onset seems to be characteristic of CFH and IF mutation-associated aHUS. The most severe prognosis was in the CFH mutation group, 60% of whom reached ESRD or died within <1 yr. Only 30% of CFH mutations were localized in SCR20. MCP mutation-associated HUS has a relapsing course, but none of the children reached ESRD at 1 yr. Half of patients with IF mutation had a rapid evolution to ESRD, and half recovered. Plasmatherapy seemed to have a beneficial effect in one third of patients from all groups except for the MCP mutation group. Only eight (33%) of 24 kidney transplantations that were performed in 15 patients were successful. Graft failures were due to early graft thrombosis (50%) or HUS recurrence. In conclusion, outcome of HUS in patients with CFH mutation is catastrophic, and posttransplantation outcome is poor in all groups except for the MCP mutation group. New therapies are urgently needed, and further research should elucidate the unexplained HUS group.
Background
The peculiarity of the cardiovascular risk profile with increased arterial vulnerability is well known in adults with chronic kidney disease (CKD). It is explained by an increased ...incidence of traditional cardiovascular risk factors together with other comorbidities related to the uremic condition and cardiorenal syndrome (CRS). The present study aimed to determine the cardiovascular impact of the uremic condition in a pediatric population with advanced CKD.
Methods
From 2016 to 2018, 39 consecutive patients with advanced CKD who underwent echocardiographic evaluation were included. All echocardiographic examinations were performed by the same operator (FE). Demographic, clinical, biological, and echocardiographic data were collected.
Results
The mean age at echocardiographic exam was 9.7 ± 4.6 years. Twenty-four (61.5%) patients were on hemodialysis; 17 (43.6%) patients were in a peritoneal dialysis program of whom 11 switched at a later stage to hemodialysis. Eight (20.5%) patients had an arteriovenous fistula (AVF). Hypertension was present in 30 (76.9%) patients while left ventricular hypertrophy (LVH) was described in 13 (33.3%) patients. Dilatation of the ascending aorta (Z-score > 2) was found in 15 (38.4%) patients and was statistically (in univariate analysis) related to gender, hypertension, the presence of an AVF, and the use of hemodialysis after peritoneal dialysis (
p
= 0.024,
p
= 0.016,
p
= 0.006,
p
= 0.009, respectively).
Conclusion
In addition to classical and predictable abnormalities related to CKD, we found a high prevalence of dilatation of the ascending aorta in children with advanced CKD. Hypertension, AVF, and hemodialysis were associated factors.
Graphical abstract
Transplantation is a saving therapeutic that has heavy consequences. The quality of life (QoL) of transplanted children and their parents has been little studied and should help physicians better ...manage these patients. The objectives of the study were to assess: (1) the QoL of transplanted children and parents and compare it with that of children with other chronic conditions associated with long-term consequences, and (2) potential variables modulating the QoL. This cross-sectional study was performed in a multidisciplinary paediatric unit (Timone Hospital, Marseille, France). Children were less than 18 years old; had a liver, kidney or heart transplant; and had a time since transplantation of 1-10 years. Socio-demographics and clinical data were recorded from medical forms. The QoL was assessed using the VSP-A (Vécu et Santé Perçue de l'Adolescent et de l'Enfant) and the WhoQoL self-reported questionnaires. Forty-five families were included (response rate: 76%). The transplanted organs were the liver for 20 children, the kidney for 15 children, and the heart for 10 children. The QoL of transplanted children reported by their parents was better than that of children with inborn errors of metabolism and similar to that of childhood leukaemia survivors. The QoL of parents of transplanted children was better than that of parents of children with inborn errors of metabolism and did not differ from French norms. The QoL did not differ according to the nature of the transplanted organ, sex or the main sociodemographic data. The main modulators decreasing QoL were residual treatment level, medications switch and the presence of another regular treatment. Transplanted children and their families reported a fairly preserved QoL compared to children with other chronic health conditions. Special attention should be given to QoL modulators related to therapeutic management (medication switches, regular treatments) that might be amenable to improve the QoL.
Assessing the initial severity of immunoglobulin A vasculitis nephritis (IgAV-N) is important due to its determining effect on kidney management and outcomes. This paper describes a multicentre ...paediatric cohort of IgAV-N patients and discusses relationships among clinical presentation, histological features, and kidney outcome. We retrospectively studied a cohort of 170 children with biopsy-proven IgAV-N, diagnosed between 2007 and 2017. One-quarter of the cohort (27%) presented with initial nephrotic syndrome (NS). Kidney biopsy revealed International Study of Kidney Disease (ISKDC) grade II or grade III in 83% of cases. Endocapillary proliferation was observed in 73% of patients, and chronic lesions were observed in 25%. Data analysis showed a significant association between NS at onset and endocapillary proliferation and cellular crescents. After a median follow-up of 21 months (IQR 12–39), 30% of patients had persistent proteinuria or decreased eGFR. At the end of follow-up, kidney impairment was more often observed in patients with NS at onset and those with cellular crescents and chronic lesions on initial kidney biopsy.
Conclusion
: This study highlights the relationship between the clinical and histological presentation of IgAV-N and the factors that affect kidney outcome. The ISKDC classification may be improved by including lesions that are more discriminating for disease severity and prognosis.
What is Known:
• Nephrotic syndrome (NS) or kidney failure at diagnosis and cellular crescents in more than 50% of the glomeruli are recognized as risk factors for poor kidney outcome in immunoglobulin A vasculitis nephritis (IgAV-N).
• The reference histological classification of the International Study of Kidney Disease in Children (ISKDC) is primarily based on the presence and number of affected glomeruli (mesangial proliferation, cellular crescents). The updated Oxford classification, which emphasizes tubular atrophy and interstitial fibrosis, is also used to group pathological features of IgAV-N. Both classifications have limitations.
What is New:
• Medical treatment should not be postponed in patients with IgAV-N and NS until after biopsy, as NS at diagnosis is associated with initial histological severity and poorer kidney outcome. This proposal needs to be verified in further studies.
• Endocapillary proliferation is associated with the initial severity of IgAV-N at diagnosis, while chronic glomerular changes and interstitial fibrosis are associated with poorer short- and medium-term kidney outcomes.
Non-steroidal anti-inflammatory drugs (NSAIDs) are often used as analgesic and antipyretic drugs. Nephrotoxicity is a common side effect and leads in 1-5% of pediatric cases to acute kidney injury ...(AKI). The nephrotoxic effects of NSAIDs arise mainly from two pathological mechanisms: (1) acute tubulo-interstitial nephritis (ATIN) following immune reaction and (2) prerenal failure because of reduced renal plasma flow. Histological examinations are required to confirm the pathomechanism of AKI after NSAID exposure. The aim of this study was to illustrate the risk of ATIN in children with AKI after NSAID exposure.
The medical records of all 100 pediatric patients with biopsy-proven AKI treated between January 2006 and 2016 at La Timone Hospital, Marseille, France, were analyzed retrospectively. Twenty-five of these patients had ATIN, four of which were healthy children who had been treated with NSAIDs. In other words, NSAID side effects accounted for 4% of all cases of biopsy-proven AKI and 16% of all cases of ATIN. None of the patients had hypovolemia when they received NSAIDs. Clinical symptoms were non-specific. All patients had abdominal pain and vomiting but normal urine volume output. Maximum serum creatinine levels ranged from 300 to 512 μmol/l, with estimated minimum creatinine clearances of 12-26 ml/min/1.73 m
. None of the patients had significant proteinuria. One child had hyperechogenic enlarged kidneys. Three patients were treated with steroids, one of whom also received intravenous methylprednisolone. Renal function improved gradually in all patients, but the patient who received methylprednisolone developed moderate chronic kidney disease (CKD).
Biopsy proven-AKI secondary to NSAID use can be severe and be associated with ATIN. Since NSAID-induced ATIN can lead to CKD, clinicians using NSAIDs should focus on preventing AKI.
Intrauterine growth restriction (IUGR) is a risk factor for hypertension (HT) and chronic renal disease (CRD). A reduction in the nephron number is proposed to be the underlying mechanism; however, ...the mechanism is debated. The aim of this study was to demonstrate that IUGR-induced HT and CRD are linked to the magnitude of nephron number reduction, independently on its cause.
Systolic blood pressure (SBP), glomerular filtration rate (GFR), proteinuria, nephron number, and glomerular sclerosis were compared between IUGR offspring prenatally exposed to a maternal low-protein diet (9% casein; LPD offspring) or maternal administration of betamethasone (from E17 to E19; BET offspring) and offspring with a normal birth weight (NBW offspring).
Both prenatal interventions led to IUGR and a similar reduction in birth weight. In comparison to NBW offspring, BET offspring had a severe nephron deficit (-50% in males and -40% in females, p < 0.01), an impaired GFR (-33%, p < 0.05), and HT (SBP+ 17 mmHg, p < 0.05). Glomerular sclerosis was more than twofold higher in BET offspring than in NBW offspring (p < 0.05). Long-term SBP, GFR, and glomerular sclerosis were unchanged in LPD offspring while the nephron number was moderately reduced only in males (-28% vs. NBW offspring, p < 0.05).
In this study, the magnitude of nephron number reduction influences long term renal disease in IUGR offspring: a moderate nephron number is an insufficient factor. Extremely long-term follow-up of adults prenatally exposed to glucocorticoids are required.
PDF
