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J Clin Ultrasound 14595-600.

October 1986

Increased Renal Cortical Echogenicity


in Pediatric Renal Disease:
Histopathologic Correlations
A. Norman Brenbridge, MD,* Robert L. Chevalier, MD,t and
Donald L. Kaiser, PhD$

Abstract: Retrospective comparisonsbetween sonographicrenal cortical echogenicity


and the results of renal biopsies were made for 65 pediatric patients ranging in age
from neonate to 18 years. There was a positive correlation between an increase in renal
cortical echoes and interstitial infiltration as well as with glomerular obsolescence,
tubular atrophy, and vascular changes. Since the sonographic changes were hetero-
geneous in origin, they are not specific. The sonographic findings also correlated pos-
itively with the clinical severity of disease. However, the heterogeneous origins of the
sonographic finding and the absence of strong correlations indicate that gray-scale
sonography cannot act as a prognostic index of the type or severity of disease in pediatric
patients. Indexing Words: Pediatric renal disease * Cortical echogenicity * Prognostic
indices

Ultrasonography is now well established as a use- evaluations followed within 24 h by sonographi-


ful tool in the delineation of abdominal anatomy. cally guided biopsies a t the University of Virginia.
It is especially valued as a method for imaging The data from 65 patients who had both techni-
the kidneys in pediatric patients since it utilizes cally adequate sonograms and adequate biopsy
no ionizing radiation, is noninvasive, and is tol- specimens were analyzed retrospectively. The
erant of some patient motion. Considerable effort sonographic and pathologic findings were evalu-
has been expended in characterizing the normal ated independently.
echographic patterns of children’s kidneys and in The patients ranged in age from 1 week to 18
determining what constitutes a deviation from the years at the time of biopsy (mean age 9.86 [ & 5.98
normal. However, the question still remains what SDI years); there were 32 females and 33 males.
significance to place in any deviations from the All had clinical renal disease based on clinical and
norm. We addressed the question of the relation- laboratory findings. None had clinical or labora-
ship between sonographic findings and the clinical tory evidence of hepatic, splenic, or hematologic
and pathologic parameters of pediatric renal dis- disease.
ease by correlating the sonographic findings with The clinical-pathologic diagnoses are listed in
the pathologic results of pediatric renal biopsies Table 1. The patients were individually scored 0
performed during a 5-year period. to 4 for increasing clinical severity of disease based
on decreasing creatinine clearance (Table 2).
MATERIALS AND METHODS All sonograms were obtained with commercial
units utilizing 3.5-MHz, S-MHz, and 6-MHz trans-
Between March 1979 and March 1984, 77 pedi- ducers. The TGC curves had been adjusted for each
atric patients with renal disease had sonographic transducer and patient; gains had been altered to
optimal levels according to the individual’s size
From the *Department of Radiology, tDepartment of Pediat- and body habitus. All patients had dynamic (real-
rics, and $Department of Internal Medicine, Division of Bio- time) scans, and most also had static (contact)scans.
statistics, University of Virginia Medical Center, Charlottes-
ville, Virginia. For reprints contact A. Norman Brenbridge, The left and right kidneys were evaluated inde-
MD, Department of Radiology, Box 170, University of Virginia pendently for the intensity of cortical echoes. In
Medical Center, Charlottesville, Virginia 22908. two patients the left kidney was sufficiently well
0 1986 by John Wiley & Sons, Inc. 595
0091-2751/86/080595-06 $04.00
596 BRENBRIDGE ET AL.

TABLE 1 TABLE 3
Distribution of Diagnoses Renal Cortical Echogenicity
Clinical-Pathologic Diagnosis Frequency Percentage Frequency Percentage
Negative 5 7.7 Grade 1: echogenicity less than 6 4.7
Lipoid nephrosislminimalchange 15 23.1 liver/spleen
Lupus nephritis 5 7.7 Grade 2: echogenicity equal to 73 57.0
Glomerulonephritis, idiopathic 15 23.1 liverkpleen
Glomerulonephritis, familial and 3 4.6 Grade 3: more echogenic than 37 28.9
hereditary liverlspleen
End-stage renal disease 1 1.5 Grade 4: echogenicity equal to central 12 9.4
Interstitial nephritis 1 1.5 renal sinus or portal vein
Henoch-Schonlein disease 4 6.2 Total 128 100
Berger's disease 1 1.5
Senior's syndrome 1 1.5
Wegener's syndrome 3 4.6
Sickle cell glomerulopathy 1 1.5
Diabetic glomerulosclerosis 4 6.2 be slightly more echogenic than the liver. None
Congenital nephrotic syndrome 2 3.1 of our four infants fell into these two categories.
Nephrocalcinosis 2 3.1
Thrombosis, arterial 1 1.5
A score of 3 was assigned to echogenicity signif-
Thrombosis, venous 1 1.5 icantly greater than that of the liver (three term
Total 65 100.0 neonates 1, 2, and 3 wk of age, respectively). A
score of 4 was granted to intense cortical echo-
genicity approximately equal to that surrounding
seen to permit successful biopsy but was techni- the portal vein (one term infant of 2 months) (Ta-
cally inadequate for echographic analysis. These ble 3).
two kidneys were eliminated from the study, but In all cases, sonographically guided renal biop
the right kidneys were retained. sies were obtained from the lower pole of the left
Using the well-known relationships between kidney using either a Vim-Silverman needle with
renal cortical echogenicity and that of adjacent Franklin modification or disposable Tru-Cut
structures (the liver, spleen, and renal sinus), the (Travenol Laboratories) biopsy needle. Written
echogenicity of the renal cortex was scored on a
1to 4 basis.14 For the 62 children over 6 months
of age, a score of 1 was given to normal cortical
echogenicity less than that of the adjacent liver
or spleen. A score of 2 was given to those with
modestly increased echogenicity equal to that of
the liver or spleen. A score of 3 was utilized for
those cortices more echogenic than liver or spleen,
and 4 was given those with most marked echo-
genicity, equaling that of the central renal sinus
(Table 3) (Figs. 1-4).
For our four infants below 6 months of age, in
whom it is recognized that renal cortical echoes
may normally be as echogenic as the adjacent liver
or spleen and in whom renal sinus echoes are often
poorly defined, the scoring of the echogenicity was
a l t e ~ - e d . ~A- ~score of 1 was proposed for echoes
less than or equal to that of the liver or spleen,
and a score of 2 for those subjectively judged to

TABLE 2
Clinical Severity of Diseases Based on Cteatinine Clearance
__ -. -- FIGURE 1. Parasagittal sonogram through the right kidney of a 13-
0 = Normal or in remission (creatinine clearance > 90') year-old male with a negative renal biopsy. The renal cortical echoes
1= Mild (creatinine clearance > 75) (largearrow) are less intense than those of the liver (LI. This is normal,
2 = Moderate (creatinine clearance = 50-75) grade 1. Within the kidney, the intensely reflective central complex is
3 = Severe (creatinine clearance = 10-50) the renal sinus (S). The poorly echoic spaces are the renal pyramids
4 = End-stage renal disease (creatinine clearance < 10)
(small arrow). At the bases of the pyramids are linear echoes, which
'Creatinine clearance given in mllmin per 1.73 m*. are the arcuate vessels demarcating the corticomedullary junction.

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RENAL CORTICAL ECHOGENICITY 597

ffiURE 2. Parasagittal sonogram through the right kidney (crosses)


of an 11-year-old male with lipoid nephrosis. The renal cortex is is-
oechoic with the adjacent liver. This is grade 2.

informed consent was obtained from each child's FIGURE 3. Parasagittal sonogram through the right kidney of a 10-
parent(s). The renal biopsies were evaluated by year-old female with systemic lupus erythematosus. The renal cortical
echoes are more intense than those of the adjacent liver but less than
pathologists using routine histopathologic cri- those of the central renal sinus. This is grade 3.
teria.
A single examiner (ANB)classified the sono-
graphic findings with the knowledge that all pa-
tients had clinical renal disease necessitating bi- normally distributed populations. The Pearson
opsy but without prior knowledge of the clinical technique is very robust; the probabilities derived
information or biopsy results. Two examiners (ANB from its application retain substantial accuracy
and RC)reviewed the pathologic reports and clas- even when some of the assumptions of their de-
sified the results without reference to the sono- rivation have been violated. It is also one of the
graphic findings. Four histologic characteristics most available programs for computer analysis.
were evaluated: glomerular alterations, intersti- Therefore, this correlation coefficient is widely ap-
tial disease, tubular atrophy, and vascular cel- plied in studies such as that reported here, al-
lular infiltration and sclerosis. These were then though it was not originally designed for discon-
evaluated 0 (normal) to 4 dependent on the in- tinuous data.
creasing severity of disease (Table 4). Glomerular Differences between the sexes for individual in-
changes were further divided into four subgroups dices were examined using a t statistic. Because
based on the type of glomerular involvement, many relationships among indices were exam-
whether focal proliferative, diffuse proliferative, ined, a more conservative a level (P< 0.01)was
focal nonproliferative, or diffuse nonproliferative used to consider the significance of individual re-
(Table 5). sults.
Renal cortical echogenicity was correlated with
the estimated severity of disease, the type of dis-
RESULTS
ease, and individual pathologic criteria, including
the type of glomerular disease and the extent of We found no significant age relationships, and this
glomerular, interstitial, tubular, and vascular in- factor was eliminated from further considera-
volvement. Age and sex relationships were also tions. There were slight differences between the
evaluated. Pearson correlation coefficients were sexes for various criteria. The differences were not
used to examine relationships among interval in- statistically significant and were likely a result
dices. This method was derived using continuous of the smaller sample sizes when the data were
interval data, which are assumed to be drawn from analyzed by sex. However, there may be some pro-
VOL. 14, NO. 8, OCTOBER 1986
598 BRENBRIDGE ET AL.

flGURE 4. Parasagittal sonogram through the right kidney of a 16-year-old male with Wegener's disease.
The renal cortical echoes are not onlv more intense than those of the liver but eaual to those of the central
renal sinus. This is grade 4.

pensity for certain diseases to occur in one sex or correlation ( r = 0.45802, P = 0.001) with clinical
the other. Sex was eliminated from further anal- severity.
ysis.
Renal cortical echogenicity (N = 128) corre-
DISCUSSION
lated most strongly with the degree of interstitial
infiltration (r = 0.43883, P = 0.0003). There was Renal sonography is usually performed in chil-
a weaker positive correlation between echogen- dren who have palpable abdominal masses, oli-
icity and the severity of glomerular disease (r = guria, or clinical or laboratory evidence of renal
0.32615, P = 0.0080). No specific differences were abnormalities. Sonographically, kidneys are ex-
found among the four subgroups of glomerular amined for size, position, and contour, and note is
disease. made of the relative echogenicity and pattern of
The correlation (r = 0.33062,P = 0.0071)of the cortex and medulla. Urosurgical conditions
vascular infiltration and sclerosis with echogen- are usually distinguished from medical conditions
icity was similar to that for glomerular disease. with ultrasonography, and the patient's evalua-
Tubular atrophy had the weakest correlation with tion is directed appropriately.
echogenicity (r = 0.31583, P = 0.0104) of those Medical renal disease may affect any or all of
four parameters. the four constituents of the kidney, the glo-
Increasing cortical echogenicity had a positive merulus, the tubules, the interstitium, and the

TABLE 4
Pathologic Severity of Disease
Grade Glomerular Interstitial Tubular Vascular
0 No change No change No change No change
1 Minimal change Minimal cellular Minimal Slight intra- or perivascular
infiltration or fibrosis cellular infiltrate
2 < 50% glomerular Moderate cellular Focal atrophy Prominent intra- or
obsolescence infiltration or fibrosis perivascular cellular
infiltrate
3 50-90% glomerular Marked cellular Marked atrophy Marked intra- or perivascular
obsolescence infiltration or fibrosis cellular infiltrate
4 > 90% glomerular Severe cellular infiltration Severe atrophy Vascular sclerosis
obsolescence and fibrosis

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RENAL CORTICAL ECHOGENICITY 599

TABLE 5 ity does not seem to differentiate acute, subacute,


Distribution of Glomerular Pathologies or chronic phases of any disease.’
- ~ ~

Glomerular Pathology Frequency Percentage The mechanism of increased echogenicity is un-


-~ certain, although a variety of possibilities have
Normal 15 23.1
Focal proliferative 9 13.8
been postulated, including altered perfusion, cell
Diffuse proliferative 25 38.5 infiltration, and deposition of connective tissue,
Focal nonproliferative 10 15.4 calcium, and fat. In a 1982 study of 109 biopsies
Diffuse nonproliferative 6 9.2
Total 65 100
on patients betwen ages 8 years and 78 years,
- _ _ -~ -~ - Hricak et al.3 found a positive correlation between
increased cortical echogenicity and glomerular
changes. In 1981, Rosenfield and Siege12 had al-
vessels. The nature and extent of the involvement ready noted a positive correlation between cortical
vary with the type and severity of disease, and echogenicity and interstitial changes in 25 pa-
the primary effect on any constituent(s) of the kid- tients but did not find a relationship to the glo-
ney may affect the other(s). Diseases are catego- merular lesions.
rized according to the nature and distribution of We sought to find what relationships, if any,
renal involvement. Carried to their ultimate con- held true for pediatric patients. It is well accepted
clusion, in end-stage renal disease, all constitu- that the disease of children may differ from those
ents are so severely altered that the original dis- of adults, as may the manifestations of disease.
ease may be unrecognizable pathologically. Their sonographic patterns may differ in various
Prognosis and therapeutic plans are based on age groups, and, as a consequence of these sup-
the diagnosis and severity of disease. Although positions, so may their sonograpbic responses to
clinical and laboratory data may be suggestive of
the identity of the disease process and its severity, Although renal cortical echogenicity correlated
renal biopsy is, at present, the only accurate method most closely with interstitial infiltration, corre-
of diagnosis. This is also true for the monitoring lations with glomerular, vascular, and tubular af-
of the progression or regression of the disease. flictions were similar. (The respective p2 values
Although percutaneous biopsy is not without in- for interstitial, glomerular, vascular, and tubular
herent short- and long-term risks, these are gen- changes are 19.2%,10.6%,10.9%,and 10.0%.)This
erally acceptable. Still, one might hope for a non- leads one to conclude that hyperechogenicity of
invasive method of diagnosis. There are many the renal cortex is a multifactorial response re-
ongoing efforts nationwide to characterize tissues lated to multiple alterations in the structural in-
sonographically, but no reports to date of un- tegrity of the tissue.
qualified success. Five of the biopsies were interpreted as without
Although tissue typing is not yet possible, gray- histologic change by light microscopy. Three of
scale ultrasonography is still a useful modality. these children bore the clinical diagnosis of sys-
This is especially true in the pediatric population temic lupus erythematosus and two of interstitial
in whom there is a great desire to avoid invasive nephritis. Of these five, three showed no signifi-
or ionizing procedures. Real-time sonography is cant electron microscopic abnormalities. Two
also tolerant of the almost inevitable movement showed slight basement membrane abnormalities
encountered in young children. on electron microscopic examination (both were
Among various sonographic factors, particular lupus patients). All five patients had laboratory
attention has been paid to renal cortical echogen- evidence of prior renal dysfunction, but four were
icity. In normal kidneys, the renal cortex is less in clinical remission with grade 0 clinical severity
echogenic than is the adjacent liver or spleen and (normal creatinine clearance), and one (with in-
considerably less echogenic than the renal si- terstitial nephritis) had only mild dysfunction
nus.1:2 The exception is in the neonatal and early (grade 1 severity, creatinine clearance over 75%).
infantile period; under 6 months of age, renal cor- The cortical echoes of all 10 kidneys were grade
tical echogenicity may be equal to that of the liver? 2, slightly increased. If these kidneys were ac-
(All four of our neonates had hyperechogenic cor- tually affected in some way, either our biopsy
tices, and all four had profoundly diseased kidneys specimens missed the abnormalities or changes
pathologically.) Certain patterns have been sug- are not detectable by routine histologic procedures
gested, especially for those with polycystic kidney (light, electron, and immunofluorescence micros-
disease (both adult and infantile forms) a s well as copy).
end-stage renal disease (ESRD) of any etiology. It has also been tempting to speculate that the
However, except for ESRD, increased echogenic- degree of change of renal cortical echogenicity may
600 BRENBRIDGE ET AL.

act a s a prognostic indicator of the severity of pe- index of the severity of disease, nor is it indicative
diatric disease. By grading the severity of echo- of the type of pathologic involvement.
genicity, one might then have an index of the de-
gree of pathologic involvement and, possibly, its
REFERENCES
etiology. Unfortunately, this does not appear to
be the case. There are many variables changing 1. Rosenfield AT, Taylor KJW, Crade M, et al: Anat-
to different degrees in various disease states. No omy and pathology of the kidney by gray scale ul-
one index has an overwhelmingly positive rela- trasound. Radiology 128:737-744, 1978.
tionship. Comparison of increasing cortical echo- 2. Rosenfield AT, Siege1 NJ: Renal parenchymal dis-
genicity with overall clinical severity does have ease: Histopathologic-sonographic correlation. A m
J Roentgen01 137:793-798,1981.
a positive correlation coefficient ( r = 0.45802, 3. Hricak H, Cruz C, Romanski R Renal parenchymal
P = 0.0001). However, an ? of 20.9%,although disease: Sonographic-histologic correlation. Radiol-
a positive correlation, is far from a strong one. ogy 144:141-147, 1982.
Therefore, neither this category nor any of the 4. Haller JO, Berdon WE, Friedman A P Increased renal
other lesser positive correlations obtained be- cortical echogenicity: A normal finding in neonates
tween cortical echogenicity and types of cortical and infants. Radiology 142:173-174, 1982.
alteration may be considered definitive. 5. Hricak H, Slovis TL, Callen CW, et al: Neonatal
kidneys: Sonographic anatomic correlation. Radiol-
ogy 1471699-702, 1983.
CONCLUSION 6. Hayden CK, Santa-Cruz FR, Amparo EG, et al: Ul-
Certain patterns of sonographic renal cortical trasonographic evaluation of the renal parenchyma
in infancy and childhood. Radiology 152:413-417,
changes have been reported in specific congenital 1984.
diseases and end-stage renal disease. In medical 7. Krensky AM, Reddish JM,Teele R L Causes of in-
renal diseases occurring in pediatric patients, there creased renal echogenicity in pediatrics patients. Pe-
is a positive correlation between the severity of diatrics 722340-846, 1983.
disease and increased cortical echogenicity. How- 8. Babcock DS, Slovis TL, Han BK, et al: Renal trans-
ever, the correlation appears to be nonspecific and plants in children: Long-term follow-up using so-
is not strong enough to be considered a prognostic nography. Radiology 156:165-167, 1985.

JOURNAL OF CLINICAL ULTRASOUND

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