Vol. 52, No. 2
Printed in U.S.A.
T H E AMERICAN JOURNAL OF CLINICAL PATHOLOGY
Copyright © 1969 by The Williams & Wilkins Co.
CONGENITAL BILATERAL OLIGONEPHRONIC RENAL HYPOPLASIA WITH
HYPERTROPHY OF NEPHRONS
(OLIGOMEGANEPHRONIE)
S T U D I E S BY
MICRODISSECTION
GEORGE H. FETTERMAN, M.D., AND RENEE HABIB, M.D.
WITH THE TECHNICAL ASSISTANCE OF NANCY S. FABRIZIO, B.S.,
AND FRANCIS M. STUDNICKI,
B.S.
Departments of Pathology of Children's Hospital of Pittsburgh and the School of Medicine of the University
of Pittsburgh, Pennsylvania 15218, and I'Unile de Recherches sur les Maladies du MMabolisme
chez I'Enfant (I.N.S.E.R.M. [Inslitut National de la Sante et de la Recherche
Midicale]), Paris, France
ABSTRACT
Fetterman, George H., and Habib, Ren6e: Congenital bilateral oligonephronic
renal hypoplasia with hypertrophy of nephrons (oligomSganephronie). Studies
by microdissection. Am. J. Clin. Path., 52: 199-207, 1969. The accidental
death of a 13-year-old child with the syndrome of congenital bilateral oligonephronic renal hypoplasia with hypertrophy of nephrons (oligome'ganephronie)
provided an opportunity for morphologic study of the nephrons in the intermediate stage of this disease. Microdissection by the method of Oliver confirmed the
existence of greatly hypertrophied glomeruli and proximal tubules, and permitted study of the abnormal configuration of the nephrons. Anatomic correlates
of glomerulotubular balance in the reduced population of nephrons showed a
markedly disproportionate enlargement of proximal tubules, relative to glomerular size. A brief description of the clinical and pathologic features of oligomegan&phronie is included in the report.
Although several reports are available in
the French literature 6 •14 •16 concerning the
syndrome of congenital bilateral renal
hypoplasia with hypertrophy of nephrons,
the condition has received but little attention1 in the American literature.
The purposes of this report are to call
attention to the syndrome and to present
findings concerning the configuration and
degree of hypertrophy of the glomeruli and
proximal tubules as observed by microdissection of renal tissue from a typical example.
R E V I E W O F L I T E R A T U R E AND D E S C R I P T I O N
O F T H E SYNDROME
In 1962, Habib and associates 6,15 described a syndrome which they termed
"I'hypoplasie renale bilaUrale congSnitale
avec reduction du nombre et hypertrophie
des nephrons chez I'enfant." Since then, they
have also referred to the syndrome as
Received November 4, 1969.
This study was aided by Grant HD 00659 of
the National Institute of Child Health and Development.
"hypoplasie oligonephronique" (HON) or
"oligomiganephronie." Of these abbreviated
expressions, the term oligome'gane'phronie is
most accurately descriptive and will be used
in this report, since it cannot easily be
transformed into an English word.
The syndrome is congenital but apparently
not genetically determined. The clinical
picture is that of progressive chronic renal
insufficiency, the first symptoms usually
presenting in early infancy.
Certain of the clinical manifestations are
distinctive. Vomiting, bouts of unexplained
fever, and bouts of dehydration may occur
in the first weeks or months of fife. Then,
renal insufficiency continues for many years
at a stable level as evidenced by clearance
studies, renal plasma flow, and T m determinations, not adjusted for body surface.
Finally, usually after 14 to 15 years or so,
one observes a rapid progression of the
disease, ending with terminal uremia.
The abnormalities in concentrating ability,
in acid base balance, and in calcium metabolism displayed by these patients are those
199
200
FETTERMAN AND
HABIB
Vol. 52
common to the chronic renal diseases of had been feeding difficulty during his 1st
childhood. These disturbances, as well as year of life. During the 2nd year, he disdeficiencies in body growth, are often played polyuria and polydipsia, rickets,
particularly evident in oligomeganephronie. slight proteinuria, and moderate azotemia.
Proteinuria is always moderate and Addis
There was no medical follow-up between
counts are usually normal.
his 2nd and 13th years. At the age of 13,
Proof of the identity of this lesion rests when studied for the last time, his weight
upon anatomic and structural characteris- and height were noted to be below normal,
tics. Material from 16 biopsies and eight his blood pressure normal. An intravenous
necropsies from examples of the disease have pyelogram showed a normal urinary tract
been studied by Royer and associates,14 and but bilaterally small kidneys.
the following salient points are based on
Laboratory findings. Urinalysis: no pyuria,
their observations.
no leukocyturia, no hematuria. Proteinuria:
The kidneys as encountered at autopsy 200 mg. per 24 hr.; total urine volume, 2000
are very small, weighing as little as 20 Gm. to 2200 ml. per 24 hr. Urinary calcium: 0.7
each. The cortical surfaces are granular. On mg. per kg. per 24 hr. RBC: 3,760,000 per
cut surfaces, the cortex and medulla are cu. mm. Blood chemistries: BUN, 77 to 102
difficult to distinguish from each other. mg. per 100 ml.; calcium, 99 mg. per 1.;
Each kidney contains a diminished number phosphorus, 55 mg. per 1. Alkaline phosof reniculi (no more than five or six). The phatase: 3.4 Bodanski units. The child
renal arteries tend to be narrowed. Urinary suffered accidental death during his 13th
year.
passages are normal.
The histologic appearance of the kidneys
This case was chosen for microdissection
varies according to the stage of the disease. because the untoward accidental death
The picture is characteristic in the first 2 or provided renal tissue without the severe
3 years. At this stage one finds a reduced scarring and regressive changes present in
number of nephrons with striking increase the kidneys of those patients with oligomegain the size of individual nephrons, including nephronie whose disease has progressed to
glomeruli, juxtaglomerular bodies, and proxi- the stage of total renal insufficiency.
mal tubules. As the disease progresses,
Necropsy findings. Gross examination reinterstitial fibrosis and tubular atrophy vealed nothing of significance except that
take place. Glomerular alterations, such as the kidneys were small, measuring 6 and 7
sclerosis, occur very late in the disease. In cm. in diameter and weighing 30 and 35 Gm.,
end stages the histologic appearance of the respectively, a total renal weight approxikidney may be difficult to distinguish from mately one-third that of a normal child of
the end stage appearance of glomerulone- his age. No urinary tract anomalies were
phritis or pyelonephritis. The extreme en- present.
largement of glomeruli in oligomeganephronie
Histologic examination of kidneys revealed
may persist and suggest the correct diagnosis. the glomeruli to be markedly hypertrophied
The anatomic and histologic charac- (Fig. 1), often with correspondingly large
teristics of oligomeganephronie are thus juxtaglomerular bodies. One or two presented
quite different from those of other varieties pericapsular thickening. Several glomeruli
of congenital renal hypoplasia and also the were sclerotic, occasional ones showing
progressive renal atrophies such as familial fibrous obliteration. The residual glomerular
scars were unusually large. Nearly all corjuvenile nephronophthisis.
tical (proximal) tubules were of increased
R E P O R T OF CASE
diameter.
Interstitial fibrosis was moderate and
The case under consideration is that
listed as No. S in the comprehensive report patchy. In a few areas, a light sprinkling of
by Royer and associates.14 H. A., a Cauca- lymphocytes and plasma cells was noted.
sian boy, had presented evidence of chronic Remnants of small atrophic tubules were
renal insufficiency since his 2nd year. There usually present in the interstitial scars.
F i o . 1. A (upper), photomicrograph of section of kidney in case of oligomegani'phronie; note large
glomeruli and tubules in comparison with B. X 46. B (lower), photomicrograph of section of kidney of
age control. Note that this is under the same magnification as A . X 46.
201
202
PETTERMAN AND HABIB
Occasional hyaline casts were present in
tubules assumed to be of the distal convoluted or collecting variety.
Vessels were not conspicuous.
Glomerulometric studies. Zolnai and Palkovits found by morphometric methods16
that there was only one-fifth the normal
number of glomeruli in the kidneys of this
patient. 11
Microdissection Studies
Method. Blocks of formalin-fixed kidney
were studied by the Oliver technic2 • 10 for
microdissection of the nephron.
A total of 24 proximal tubules with attached glomeruli were isolated, mounted,
and measured. Eight nephrons were taken
from the outer third of the cortex and eight
each from middle and inner thirds of the
cortex. The nephrons dissected were otherwise taken at random, there being no discrimination because of size.
Results. All of the nephrons dissected from
the renal tissue were hypertrophied. In
Figure 2 mosaic photomicrographs of two of
the largest proximal tubules of the population of nephrons studied are shown, with a
camera lucida silhouette of an average
proximal tubule from kidney of an age
control included for comparison. Careful
examination of the isolated proximal tubules
revealed in most (18 of 24) the presence of
small diverticula (Fig. 3). A smaller proportion of distal convoluted tubules examined
(six of 30) presented similar small diverticula.
The values for the measurements of the
population of nephrons studied in this case
are given in Table 1, along with comparable
figures for nephrons of an age control from
a series of normals previously reported by
one of us. 3
The great hypertrophy of the nephrons
from the case of oligomAganiphronie can be
appreciated in the figures given in Table 1
by reference to the normal values provided.
The mean glomerular diameter in the oligome'ganephronie series is more than twice
that of normal, the mean glomerular surface
area is 5 times that of normal, and the mean
glomerular volume is 12 times normal.
Mean proximal tubular length in the popula-
Vol. 52
tion of nephrons from the oligome'ganiphronie
kidney is four times that of normal and the
mean proximal volume is 17 times normal.
The best anatomic correlates of glomerulotubular balance in normal human kidneys
appear to be glomerular surface area and
proximal volume. 3,9
In Figure 4 a graph is constructed to show
the presence or absence of correlation of
values of glomerular surface area and proximal volume for individual nephrons in the
oligomegane'phronie kidney. The correlation
is seen to be fair. The coefficient of correlation for these values is 0.34.
Oliver and MacDowell9 have suggested
using the ratio of glomerular surface area to
proximal volume as the anatomic expression
of glomerulo-tubular balance. For a single
nephron the ratio of the glomerular surface
area to the volume of its attached proximal
convolution (GS/PV) would be designated
as r, and the mean value of r for all nephrons
studied in a kidney would be termed R. In
the kidney under study, the range of r values
for the 24 nephrons measured is from 0.75
to 3.34. The R value for the entire 24
nephrons is 1.78. This may be compared
with the R value of 5.44 of our normal age
control kidney and also with the R value of
3.17 for the "composite adult kidney" of
Oliver and MacDowell. The low R value
in the case of oligomigane'phronie indicates
that, in the massive hypertrophy of nephrons
which has taken place, the proximal tubular volume is disproportionately increased.
Thus, the theoretical glomerular activity
for this population of nephrons is low.
The value of r/R may be calculated for
each nephron in order to express its theoretical glomerular activity as compared with the
kidney as a whole. To get some idea of the
uniformity or the heterogeneity of a population of nephrons based upon r/R values,
these may be arranged in a histogram. This
has been done for the r/R values of the 24
nephrons studied in the present case (Fig. 5).
The histogram reveals considerable uniformity and a pronounced skew to the right.
Both of these features may also be noted in
the superimposed r/R histogram shown for
a normal age control in the same figure.
Furthermore, histograms of r/R values for
0
^
1
\
"Hrtf^
**H«k
J"
^
I
>
5
/V
F i o . 2. Mosaic photomicrograph of two typical proximal tubules dissected from kidney of patient
with oligomeganephronie. The silhouette in top center is a diagrammatic representation, to scale, of an
average proximal tubule from kidney of an age control, lieduced to X 6 from X 27.
203
204
FETTERMAN AND
Vol. 62
HABIB
TABLE 1
COMPARATIVE D I M E N S I O N S OF GLOMERULI AND P R O X I M A L T U B U L E S FROM C A S E OF
SOJflE
AND FROM KlDNEY OF AGE
MD 203 (Oligombgantphronie)
OLIGOM'EOAXEPH-
CONTROL*
Age Control (13 Years)
Mean GD
Range of GD
0.546 mm.
0.463-0.664 mm.
0.239 mm.
0.179-0.288 mm.
Mean GSA
Range of GSA
0.947 sq. mm.
0.675-1.384 sq. mm.
0.181 sq. mm.
0.101-0.261 sq. mm.
Mean GV
Range of GV
0.088 cu. mm.
0.052-0.153 cu. mm.
0.007 cu. mm.
0.003-0.013 cu. mm.
Mean PTL
Range of PTL
52.54 mm.
24.23-83.48 mm.
12.88 mm.
6.33-18.78 mm.
Mean PTD
Range of PTD
0.120 mm.
0.106-0.143 mm.
0.059 mm.
0.047-0.070 mm.
Mean PTV
Range of PTV
0.600 eu. mm.
0.257-1.341 eu. mm.
0.035 cu. mm.
0.015-0.062 cu. mm.
* G D , glomerular diameter; GSA, glomerular surf ace area; GV, glomerular volume; P T L , proximal
t u b u l a r length; P T D , proximal t u b u l a r diameter; P T V , proximal t u b u l a r volume.
the nephrons of the "composite adult
kidney" of Oliver and MacDowell (Reference 3, p. 612 and Reference 9, p. 1107) also
present comparable uniformity and a skew
to the right.
DISCUSSION
The microdissection studies in this case
have confirmed the presence of marked nephronic hypertrophy in oligomeganiphronie
and have indicated the configuration of the
affected nephrons and the degree of magnitude of their hypertrophy.
The glomeruli and proximal tubules are
much larger than those of the normal adult.
The proximal tubules are greatly elongated
and quite voluminous. The presence of diverticula in many of the proximal tubules
is probably a manifestation of the general
hypertrophy and hyperplasia thereof.4 • 8
The diverticula of proximal tubules cannot
be considered normal, although there is some
evidence that the occurrence of diverticula
in small numbers in distal convoluted
tubules may be a normal finding.
These studies have shown that, despite
the maintenance and progression of hyper-
trophy in these nephrons for many years,
they still present a degree of the structural
uniformity found among nephrons of normal
kidneys.
The r values of the individual nephrons
and the R value of the population of nephrons studied indicate that the proximal
tubules have become disproportionately
enlarged in relation to the glomeruli. The
findings of Kolberg,6 who reported a shift
toward tubular functional predominance in
the hyperplastic kidney remnants of dogs
following three-quarter nephrectomy, and
also in patients with kidney remnants, is of
interest in this regard. Kolberg pointed out
that the situation in subjects with hyperplastic kidney remnants is different from
that in subjects with chronic Bright's disease, wherein the influence of other pathologic processes might alter the picture.
To judge from the population of nephrons
studied from the case of oligomeganiphronie,
the heterogeneity of the nephrons in regard
to glomerulo-tubular relationship is no
greater than that in a normal kidney. There
is, however, slightly increased heterogeneity
as regards proximal tubular length.
Aug.
1969
MICRODISSECTION OF OLIGOMEGANEPHORNIE
205
F I G . 3. Mosaic photomicrograph of portion of proximal tubule in box in Figure 2.
At this magnification a number of diverticula may be seen. Three of these are marked
with arrows. X 29.
These nephrons, then, have grown tremendously since birth and, despite their
great increase in length and bulk, have
preserved or attained a considerable degree
of homogeneity. There may be a greater
capacity for compensator}' hypertrophy of
nephrons in infancy and childhood than in
later years. MacKay and associates7 found
206
FETTERMAN AND HABIB
GLOMERULAR SURFACE AREA / PROXIMAL VOLUME
T
IS
Vol. 52
Robert Piatt's Lumleian Lecture, delivered
in 1952.12 Further considerations of functional glomerulotubular balance in oligomeganephronie are discussed by Royer and
associates.15
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.40
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FIG. 4. Each nephron sampled from kidney of
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FIG. 5. Histogram of r/R values is shown for
nephron population studied from case of oligomb7. MacKay, E. M., MacKay, L. L., and Addis,
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that the degree of compensatory hyperChronic Brights' disease. New York: Paul
B. Hoeber, 1939, pp. 1-257.
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9. Oliver, J., and MacDowell, M.: The structural
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pathogenesis of acute renal failure associfibrosis do not intervene until the approach
ated with traumatic and toxic injury. Renal
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mental models for an analogous syndrome
Etudes glomerulometriques dans un cas
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tre), in preparation.
Kolberg 6 are particularly apropos. A most 12. Piatt, R.: Structural and functional adaptation in renal failure. Brit. M. J., / : 1372interesting discussion, relevant to problems
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in oligom6gan6phro7iie, is contained in Sir 13. Piatt, R., Roscoe, M. H., and Smith, F. W.:
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Experimental renal failure. Clin. Sc., 11:
217-231, 1952.
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Basel: Karger, 1967, pp. 251-275.
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OLIGOMEGANEPHRONIE
207
tecuisse, V.: L'hypoplasie renale bilate>ale
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Ann. Pediat. (Paris), 38: 753-766, 1962.
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of the glomeruli in man. Acta Biol. Acad.
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