Background
The temporality between the mandated reduction of salt in processed food and the decrease of death from stroke and ischemic heart disease, the association of hypertension, and ...cardiovascular disease led many public health organizations to recommend reducing dietary sodium to a maximum of 2300 mg per day. It turns out that some nuances can be brought about to this universally shared belief.
Methods & Results
Indeed, consideration of health outcomes instead of only blood pressure as a surrogate marker of cardiovascular disease and prognosis gave contradictory results whereas low sodium intake is associated to an excess of death and cardiovascular events.
Conclusions
Accordingly, sodium intake should be adapted to individual risk factors, and evidence is still clearly lacking to support indiscriminate recommendations in healthy people. By contrast, a restricted sodium diet is certainly useful in patients with chronic kidney disease exposed to salt retention, and by reciprocity, low sodium diet must be absolutely avoided in all patients presenting renal or extra renal sodium wasting where sodium depletion is a life-threatening condition.
Primary hyperoxaluria type 1 is caused by hepatic overproduction of oxalate, leading to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. This trial tested whether an ...oligonucleotide drug can reduce the production of hepatic oxalate.
BSA ingested in food can escape the intestinal barrier and induce antibovine serum albumin antibodies. The authors of this study identified circulating BSA in patients with membranous nephropathy and ...in immune deposits in four children.
Membranous nephropathy is the most common cause of the nephrotic syndrome in adults but is rare in children.
1
,
2
The central pathogenesis involves the formation of subepithelial immune deposits that are responsible for functional impairment of the glomerular capillary wall.
1
,
3
Two major antigens have been identified. The first is neutral endopeptidase, the alloantigen involved in neonatal cases of membranous nephropathy,
4
and the second is the M-type phospholipase A
2
receptor (PLA
2
R), which has been identified in idiopathic membranous nephropathy.
5
Idiopathic membranous nephropathy is considered an autoimmune disease, whereas secondary forms involve exogenous antigens such as viral, bacterial, . . .
Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease that was first recognized in children but also affects adults. This study assessed the disease presentation and ...outcome in a nationwide cohort of patients with aHUS according to the age at onset and the underlying complement abnormalities.
A total of 214 patients with aHUS were enrolled between 2000 and 2008 and screened for mutations in the six susceptibility factors for aHUS and for anti-factor H antibodies.
Onset of aHUS occurred as frequently during adulthood (58.4%) as during childhood (41.6%). The percentages of patients who developed the disease were 23%, 40%, 70%, and 98% by age 2, 18, 40, and 60 years, respectively. Mortality was higher in children than in adults (6.7% versus 0.8% at 1 year) (P=0.02), but progression to ESRD after the first aHUS episode was more frequent in adults (46% versus 16%; P<0.001). Sixty-one percent of patients had mutations in their complement genes. The renal outcome was not significantly different in adults regardless of genetic background. Only membrane cofactor protein (MCP) and undetermined aHUS were less severe in children than adults. The frequency of relapse after 1 year was 92% in children with MCP-associated HUS and approximately 30% in all other subgroups.
Mortality rate was higher in children than adults with aHUS, but renal prognosis was worse in adults than children. In children, the prognosis strongly depends on the genetic background.
Background
Steroid-sensitive nephrotic syndrome (SSNS) is, in most patients, a chronic disease with 80% experiencing at least one relapse after first flare. B cell depletion using rituximab is ...effective in preventing relapse in steroid-dependent (SDNS) patients but fails to maintain long-term remission following B cell recovery, possibly due to development of autoreactive long-lived plasma cells. We investigated sequential combination of antiCD20 antibody targeting all B cell subsets, and antiCD38 antibody with high plasma cell cytotoxicity in patients with uncontrolled SDNS after failure of one or several attempts at B cell depletion.
Methods
Fourteen patients with median disease duration 7.8 years received 1000 mg/1.73 m
2
obinutuzumab followed by 1000 mg/1.73 m
2
daratumumab 2 weeks later. Oral immunosuppression was discontinued within 6 weeks, and biological monitoring performed monthly until B cell recovery.
Results
Median age at treatment was 11.0 IQR 10.4–14.4 years. B cell depletion was achieved in all patients, and B cell reconstitution occurred in all at median 9.5 months after obinutuzumab injection. After median follow-up 20.3 months (IQR 11.5–22.6), 5/14 patients relapsed including 4 within 100 days following B cell repletion. Relapse-free survival was 60% at 24 months from obinutuzumab infusion. Mild infusion reactions were reported in 3/14 patients during obinutuzumab and 4/14 during daratumumab infusions. Mild transient neutropenia (500–1000/mm
3
) occurred in 2/14 patients. Intravenous immunoglobulins were given to 12/14 patients due to hypogammaglobulinemia. Low IgA and IgM levels were noted in 8 and 14 patients, respectively. No severe infection was reported.
Conclusion
Global antiB cell strategy combining obinutuzumab and daratumumab induces prolonged peripheral B cell depletion and remission in children with difficult-to-treat SDNS.
Steroid sensitive nephrotic syndrome is marked by a massive proteinuria and loss of podocytes foot processes. The mechanism of the disease remains debated but recent publications suggest a primary ...role of Epstein-Barr Virus (EBV). EBV replication in the peripheral blood is found in 50% of patients during the first flare of the disease. The genetic locus of steroid sensitive nephrotic syndrome was also identified as influencing antibodies directed against EBNA1. EBV is able to establish, latent benign infection in memory B cells that display phenotypes similar to antigen-selected memory B cells. Consistently, memory B cells reconstitution after rituximab infusion is a predictor of the relapse of proteinuria. We suggest that a specific anti-EBNA1 antibody internalized in the podocytes via the neonatal Fc receptor might cross-react with a major protein present in the same cell trafficking compartment. The diversion of this major podocyte protein in the urinary space and the subsequent depletion is supposed to result in podocyte damages with loss of foot processes and massive proteinuria. Immunosuppression of B cells and subsequent clearance of anti-EBNA1 antibodies would lead to a restoration of the normal level of the protein allowing recovery of proteinuria and of normal podocyte morphology.
Background
Rituximab is a chimeric anti-CD20 monoclonal antibody that induces sustained remission in children with steroid-dependent nephrotic syndrome. However, there is no consensus on the optimal ...regimen and monitoring of rituximab. In other autoimmune diseases, anti-rituximab antibodies (ARA) have been reported in 10–40% of patients, but their clinical relevance remains unclear. In nephrotic syndrome, data are scarce.
Methods
We report a single-center retrospective study with immuno- and pharmacological monitoring of rituximab treatment in children with frequent relapsing (FR) or steroid-dependent nephrotic syndrome (SDNS). We analyzed the monthly monitoring of 24 children, receiving a dose of rituximab (375 mg/m
2
) between December 2017 and April 2018 at the Pediatric Nephrology Department of Robert-Debré hospital, Paris.
Results
ARA were detected in 7/24 patients (29%), sometimes after the first infusion of rituximab. ARA were present at baseline in two patients previously treated with rituximab. Both displayed no B-cell depletion. ARA were also reported in 5/22 patients during follow-up, with antibodies always detected in the first month following B-cell recovery. An incomplete CD19+CD20− B-cell depletion at M1 (5–25/mm
3
) and low serum rituximab levels was predictive of developing ARA. The development of de novo ARA during follow-up was not associated with shorter B-cell depletion.
Conclusions
This study shows that ARA are frequent in children with FR/SDNS and that close immuno- and pharmacological monitoring may help personalizing rituximab treatment in patients needing repeated injections.
Fabry disease (FD), a rare X‐linked disease, can be treated with bi‐monthly infusion of enzyme replacement therapy (ERT) to replace deficient α‐galactosidase A (AGAL‐A). ERT reduces symptoms, ...improves quality of life (QoL), and improves clinical signs and biochemical markers. ERT initiation in childhood could slow or stop progressive organ damage. Preventative treatment of FD from childhood is thought to avoid organ damage in later life, prompting a French expert working group to collaborate and produce recommendations for treating and monitoring children with FD. Organ involvement should be assessed by age 5 for asymptomatic boys (age 12‐15 for asymptomatic girls), and immediately for children diagnosed via symptoms. The renal, cardiac, nervous and gastrointestinal systems should be assessed, as well as bone, skin, eyes, hearing, and QoL. The plasma biomarker globotriaosylsphingosine is also useful. ERT should be considered for symptomatic boys and girls with neuropathic pain, pathological albuminuria (≥3 mg/mmol creatinine), severe GI involvement and abdominal pain or cardiac involvement. ERT should be considered for asymptomatic boys from the age of 7. Organ involvement should be treated as needed. Early diagnosis and management of FD represents a promising strategy to reduce organ damage, morbidity and premature mortality in adulthood.
Henoch-Schönlein purpura is a systemic vasculitis characterized by IgA deposits, which target the skin, joints, and kidneys, among other organs. In children, prognosis is often good but little is ...known about biomarkers of pediatric nephritis. We hypothesized that biological markers, including cytokines, immunoglobulins, IgA-immune complexes, IgA glycosylation and neutrophil gelatinase-associated lipocalin (NGAL), may discriminate IgA vasculitis (IgAV) pediatric patients with renal involvement from those without renal involvement. Fifty children at the time of IgAV rash between 2010 and 2015 were prospectively enrolled and compared to 21 controls. All patients were assessed for clinical and biological parameters at the time of diagnosis, including the levels of cytokines, immunoglobulins, immune complexes, IgA glycosylation and NGAL in serum and urine. Among IgAV patients, 33 patients exhibited nephritis (IgAV-N) and 17 children were without nephritis (IgAV-woN). The serum level of galactose-deficient (Gd)-IgA1 (p<0.01) and the urinary concentrations of IgA, IgG, IgM, IL-6, IL-8, IL-10, IgA-IgG complexes and IgA-sCD89 complexes (p<0.001 for all) were higher in the IgAV-N patients than in the IgAV-woN patients. Among those markers, urinary IgA and IgM had the highest AUC (0.86 and 0.87 respectively, p<0.0001). This prospective cohort study furthers our understanding of the pathophysiology of IgAV. We identified biomarkers that are able to distinguish patients initially with or without nephritis. To conclude, serum Gd-IgA1 and urinary IgA, IgG, IgM, IL-6, IL-8, IL-10, and IgA-IgG and IgA-sCD89 complexes could identify IgAV pediatric patients with renal involvement at the time of diagnosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Exposure to Maternal Diabetes Induces Salt-Sensitive Hypertension and Impairs Renal Function in Adult Rat Offspring
Touria Nehiri 1 ,
Jean-Paul Duong Van Huyen 1 2 ,
Mélanie Viltard 1 ,
Céline Fassot ...1 ,
Didier Heudes 1 2 ,
Nicole Freund 1 ,
Georges Deschênes 3 ,
Pascal Houillier 1 4 ,
Patrick Bruneval 1 2 and
Martine Lelièvre-Pégorier 1
1 Institut National de la Santé et de la Recherche Médicale, Unite Mixte de Recherche S872, Centre de Recherche des Cordeliers,
Paris, France; Université Paris Descartes, Unite Mixte de Recherche S872, Paris, France; Université Pierre et Marie Curie-Paris
6, Unite Mixte de Recherche S872, Paris, France
2 Laboratoire d'Anatomie Pathologique, Hôpital Européen Georges Pompidou, Paris, France
3 Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, France
4 Service de d'Explorations Fonctionelles, Hôpital Européen Georges Pompidou, Paris, France
Corresponding author: Martine Lelièvre-Pégorier, martine.lelievre-pegorier{at}crc.jussieu.fr
Abstract
OBJECTIVE— Epidemiological and experimental studies have led to the hypothesis of fetal origin of adult diseases, suggesting that some
adult diseases might be determined before birth by altered fetal development. We have previously demonstrated in the rat that
in utero exposure to maternal diabetes impairs renal development leading to a reduction in nephron number. Little is known
on the long-term consequences of in utero exposure to maternal diabetes. The aim of the study was to assess, in the rat, long-term
effects of in utero exposure to maternal diabetes on blood pressure and renal function in adulthood.
RESEARCH DESIGN AND METHODS— Diabetes was induced in Sprague-Dawley pregnant rats by streptozotocin on day 0 of gestation. Systolic blood pressure, plasma
renin activity, and renal function were measured in the offspring from 1 to 18 months of age. High-salt diet experiments were
performed at the prehypertensive stage, and the abundance of tubular sodium transporters was evaluated by Western blot analysis.
Kidney tissues were processed for histopathology and glomerular computer-assisted histomorphometry.
RESULTS AND CONCLUSIONS— We demonstrated that in utero exposure to maternal diabetes induces a salt-sensitive hypertension in the offspring associated
with a decrease in renal function in adulthood. High-salt diet experiments show an alteration of renal sodium handling that
may be explained by a fetal reprogramming of tubular functions in association or as a result of the inborn nephron deficit
induced by in utero exposure to maternal diabetes.
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 28 April 2008.
T.N. and J.-P.D.V.H. contributed equally to this work.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted April 20, 2008.
Received June 8, 2007.
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