Nephrogenic Rests - What are they?
A couple of parents have written to me privately and wondered about a term they had heard called
'nephrogenic rests'. This is some of the info on nephrogenic rests that I've pieced together:
Clusters of abnormally retained embryonic
kidney precursor cells are called 'nephrogenic rests'. Wilms may develop from these clusters [but NOT always].
In a 1994 article by Max Coppes in the New england journal of
medicine sept 1, pg 586 volume 331, #9
"The kidneys of virtually all children with inherited susceptibility to
Wilms tumour contain nephrogenic rests, which are evidence of a
constitutional defect in kidney development. However, 25-40% of children
with sporadic Wilms tumour also have nephrogenic rests within otherwise
normal kidney tissue."........"thus nephrogenic restes may represent clonal
precusor lesion, derived from the same transformed renal stem cells that
give rise to Wilms tumour. The natural history of these rests is
variable:some regress spontaneously, whereas others degenerate into Wilms
tumour..."
A parent should speak to their physician about what this means for
their child, if indeed we are speaking about 'rests'. To discuss the genetic
aspects, further they may want some input from a geneticist.
Links on Nephrogenic Rests:
Nephrogenic rests and the pathogenesis of Wilms tumor: developmental and clinical considerations
Nephroblastomatosis
Taken from The Wilms Tumour PDQ statement on Wilms:
"Approximately one third of Wilms' tumors have loss of genetic material in
the tumor cells from the short arm of chromosome 11, encompassing one or
both of the Wilms' tumor gene regions on this chromosome. Genes on other
chromosomes may also have an etiologic role in Wilms' tumor, and loss of
genetic material from chromosome 16 and/or chromosome 1p occurs in some
tumors.12,13 Many Wilms' tumors appear to arise from abnormally retained
embryonic kidney precursor cells arranged in clusters termed nephrogenic
rests. The different genetic lesions are associated with different subtypes
of nephrogenic rests.
Despite the number of genes that appear to be involved in the development of
Wilms' tumor, hereditary Wilms' tumor (either bilateral tumors or a family
history of the neoplasm) is uncommon, with 4% to 5% of patients having
bilateral tumors and 1% to 2% of patients having a positive family history
for Wilms' tumor. The risk of Wilms' tumor among offspring of persons who
have had unilateral (i.e., sporadic) tumors is quite low (<2%).17 Siblings
of children with Wilms' tumor have a low likelihood of developing Wilms'
tumor. A second Wilms' tumor may develop in the remaining kidney of 1% to 3%
of children treated successfully for Wilms' tumor. The incidence of such
metachronous bilateral Wilms' tumors is much higher in children whose
original Wilms' tumor was diagnosed at less than 12 months of age and/or
whose resected kidney contains nephrogenic rests. Periodic abdominal
ultrasound is recommended for early detection of metachronous bilateral
Wilms' tumor as follows: children with nephrogenic rests in the resected
kidney (if < 48 months of age at initial diagnosis) - every 3 months for 6
years; children with nephrogenic rests in the resected kidney (if > 48
months of age at initial diagnosis) - every 3 months for 4 years; other
patients - every 6 months for 2 years, then yearly for an additional 1 to 3
years."
Taken from Urologyweb:
"MULTICYSTIC DYSPLASTIC KIDNEYS
Wilms tumor usually arises from abnormal remnants of developmentally
immature nephrogenic cells in the postnatal kidney which are termed
"nephrogenic rests" or "nodular renal blastema."
Because these abnormal cell remnants are present in 20-40% of kidneys
resected for Wilms tumor and because these same remnants have been found in
kidneys with multicystic dysplasia (MCD) and in the kidneys of infants and
children with congenital obstructive uropathy, it was suggested that
multicystic dysplastic kidneys should be resected to prevent the possibility
of Wilms tumor formation.
However, 0.01% of live-born infants are destined to develop a Wilms tumor.
On the other hand, these primitive nephrogenic rests that may predispose to
tumor formation are much more numerous in younger infants than in older
ones, suggesting that many of these rests disappear spontaneously.
Therefore, the majority of these primitive nephrogenic rests do not give
rise to Wilms tumor, and most of them involute spontaneously without forming
tumors. In part, this may be because nephrogenic rests appear to be of two
types: (a) perilobar, commonly found in routine autopsies with little
likelihood of giving rise to Wilms tumor, or (b) intralobar, which carry a
high risk.
Studies reviewing the incidence of Wilms tumor in severely dysplastic and
congenitally obstructed kidneys show that the risk for developing Wilms
tumors is close to that of the general population, and therefore the risk
seems too low to justify routine nephrectomy in children with multicystic
dysplasia or congenitally obstructed kidneys unless other urological/
medical conditions apply."
Does nephroblastomatosis influence the natural history and relapse rate in Wilms' tumour? A single centre experience over 11 years.
2001 Feb
Bergeron C, Iliescu C, Thiesse P, Bouvier R, Dijoud F, Ranchere-Vince D, Basset T, Chappuis JP, Buclon M, Frappaz D, Brunat-Mentigny M, Philip T.
Centre Leon Berard, Departement de pediatrie, 28 rue Laennec 69373, Lyon, cedex 08, France. bergeron@lyon.fnclcc.fr
The presence of multifocal or diffuse nephrogenic rests (NRs) in one or both kidneys is termed nephroblastomatosis (Nbm). Nbm may be a predisposing factor for Wilms' tumour (WT). The aim of this retrospective study was to evaluate the impact of Nbm on the outcome of WT in children. We assessed the outcome of 81 children with Wilms tumours and practical implications of Nbm in the treatment and follow-up. All the pathology slides have been reviewed in 1997. 63 had WT without Nbm (group A) and 18 had WT associated with Nbm (group B). There was no statistical difference between the two groups according to the age at diagnosis and histology. Clinical abnormalities were more frequent in group B (33 versus 8%). There was no statistical difference between the percentage of stage IV in both groups, but bilaterality (stage V) was present only in the group B. Relapse was observed in 20/81 patients (25%): 11 (17%) in group A and 9 (50%) in group B. Mean delay of relapse was longer (25 months) in group B than in group A (10 months). For the whole population, with a median follow-up of 9 years, the event-free survival (EFS) and the overall survival (OS) probabilities were respectively 74%+/-10 and 83%+/-9 at 120 months. The difference in EFS between groups A (82+/-9%) and B (38%+/-29) was significant (P=0.004). The discovery of Nbm in the non-tumoral part of the kidney with WT can be an adverse factor and in particular favours the subsequent development of a new Wilms tumour. It justifies separate follow-up guidelines.
PMID: 11239761 [PubMed - indexed for MEDLINE]
Expression of MIB and BCL-2 in patients with nephrogenic rests with and without associated Wilms' tumors.
2001 Apr
Wunsch L, Flemming P, Gluer S.
Department of Pediatric Surgery, Hannover Medical School, Germany. wuensch.lutz@medinf.mu-luebeck.de
Nephrogenic rests (NR) are foci of persistent embryonal renal tissue. Because it has been suggested that NRs are precursor lesions to Wilms' tumor (WT), they are of considerable clinical interest. NRs vary from microscopic foci to macroscopic renal tumors, but only a few progress to WT. In this study, patients with NRs detected during the treatment of bilateral WT were compared to a group of patients with NRs incidentally discovered in various clinical settings. Because mechanisms leading to NR growth and WT formation are poorly understood, bcl-2 and MIB expression were studied by immunohistochemistry in both groups. Bcl-2 is an oncoprotein with inhibitory effects on apoptosis and MIB is a well-established marker of cell proliferation. Both mechanisms may be of interest for the growth, regression and transformation of NRs. Intense positive staining for bcl-2 was found in microscopic NRs. Blastemal cells and cells with epithelial differentiation were bcl-2-positive. The same pattern of bcl-2 expression was found in NRs with and without associated WT. High proliferative activity with intense MIB expression was found in blastemal areas of WT. Bcl-2 expression in NR is reported for the first time. Inhibition of apoptosis as a mechanism of NR formation is suggested. This is of special interest, because bcl-2 is under transcriptional control of the WT-1 gene.
PMID: 11371029 [PubMed - in process]
I hope this info helps and is a start for you finding more info.
I agree with our geneticist, you should talk to your doctor/oncologist about
what [if any] genetic link they may think nephrogenic rests mean. In
some of the literature, it seems that nephrogenic rests don't necessarily
mean anything, however, they could indicate a genetic disorder, most common
one named is Beckwith-Wiedemann (see other genetic disorders).
Ask the doctor/oncologist if they suspect
another genetic disorder and also ask if you should be seeing a geneticist
who can answer any questions you may have about what the 'genetic
ramifications' of what this may mean to your child [can they pass it on to
their children?].
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