Henoch Schönlein Nephritis Clinical Trial
Official title:
Interest to Perform a Renal Biopsy Early in the Course of the Henoch-Schoenlein Nephritis
Henoch-Schönlein (HS) purpura is a common cause of renal glomerular injury in children. This
condition is responsible for 10-15% of glomerulonephritis in children. The outcome is
generally favorable, but up to 5% of patients develop kidney failure. The outcome of
patients with kidney biopsy is less favorable with 7-50% of them progressing to chronic
renal failure.
Prevalence of HS is difficult to determine from literature. Annual incidence is estimated at
6.1 / 100,000 children in the Netherlands and up to 20.4 / 100 000 children in the United
Kingdom. The proportion of children with HS who develop renal disease is difficult to
determine because the numbers reported in the literature are variable and depend greatly on
the type of the reporting center, whether or not specialized in pediatric nephrology. Thus
the proportion of renal disease varies from 20% to 100% of children with a HS.
The treatment of HS nephropathy (HSN) usually depends on the severity of histological
lesions but histological classification is discussed and there is currently no consensus.
Randomized studies are scarce and often do not allow to draw clear conclusions. A
meta-analysis suggested a positive effect of corticosteroids on renal prognosis of severe
forms but in this study the definition of renal disease was very heterogeneous. The only
classification of the HSN recognized is from the International Study Group of Kidney Disease
in Childhood (ISKDC) which is the following: grade I: minimal glomerula abnormalities, grade
II: pure proliferation, grade III: crescents/ segmental lesions <50%,grade IV: crescents/
segmental lesions 50 to 75%, grade V: crescents/ segmental lesions > 75%, grade VI:
pseudomesangiocapillary. However, this classification is questioned because it ignores other
significant histological lesions such as interstitial fibrosis, tubular lesions, glomerular
and interstitial inflammation, the appearance of crescents (segmental or totally
encompassing the glomerulus, fibrous or cellular), segmental sclerosis, fibrosis and
arteriolar appearance in immunofluorescence.
There is currently no consensus on the criteria indicating the initiation of corticosteroid
therapy whether oral or intra venous bolus. Some patients with severe clinical and / or
histological initial presentation can evolve to remission spontaneously while others who
have more moderate initial symptoms will evolve later to kidney failure. The management is
therefore heterogeneous. In France, some centers perform a kidney biopsy almost always
before starting treatment (or in the days following the start of treatment), while in other
centers's treatment decision is based on the biology resulting from the glomerular disease,
kidney biopsy being performed possibly in a second time in case of failure of the initial
treatment.
Principal objective of the study: assessment of the interest for the long term outcome of
performing early a kidney biopsy (before the establishment of treatment or within 15 days
after the start of treatment) in children with HSN compare to kidney biopsy performed later
(depending on the response to initial therapy) or not performed.
Secondary objective: assessment of the impact of early kidney biopsy (before the
establishment of treatment or within of 15 days after the start of treatment) on the initial
treatment HSN : does it modify or not the treatment started right before it (decided on
clinical and biological criteria).
If in the past the HSN could be considered a rather benign disease not requiring specific
active treatment, the studies evaluating the long-term outcome have shown the risk of
progression to Chronic Kidney Disease (CKD) and have lead to recommend the use of
corticosteroids and immunosuppressors even in not rapidly progressive glomerulonephritis
forms (24,25). Unfortunately clinical studies are scarce, often with few patients and
uncontrolled (17,26,27). However, the efficacy of methylprednisolone pulses followed by oral
steroids has been suggested in several studies, as in the study conducted at the Hospital
Necker, where prospective patients receiving pulses of methylprednisolone were compared to
an historical cohort from the same center (28) in a control arm of a randomized controlled
trial (29), and in studies where patients received combinations of several immunosuppressive
drugs (30-32).
Thus, the current French way to manage severe HSN is to give methylprednisolone pulses
followed by oral steroids. Anti-proteinuric medications are for initially mild forms or
sequelae. Immunosuppressor is added to steroid in the forms not responding well to initial
corticosteroid therapy.
If these therapies are used by most of pediatric teams, practice in kidney biopsy (KB)
varies from one center to another. Some teams routinely perform KB before the start of
steroid therapy (and adapt the treatment to the results), while others first establish the
treatment and perform the KB only if the evolution is not as expected. This second approach
reduces the number of KB since patients with favorable outcome will never be biopsied.
The question is which of these two attitudes is the best. Do the biopsied patients have a
better prognosis at 5 years (because the lesions were better evaluated in comparison to
clinical evaluation, because the diagnosis was confirmed, despite the risk taken to perform
KB, because there is no excess of treatment) than those who were not biopsied at the initial
period (with possible errors in assessing the severity of injury ), or is there is no
difference (because the treatment is the same whether KB was performed or not, because
clinical criteria prevail in the therapeutic decision on histological criteria, because KB
may falsely reassure and may lead to stop treatment too early (sample problem)).
The aim of the study is to answer these questions, to improve patients care by identifying
the most effective strategy to improve long term prognosis, and to standardize practices to
make randomized control trials easier to drive in the future.
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Observational Model: Cohort, Time Perspective: Retrospective