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Ultrasound findings in renal parenchymal disease: Comparison with histological appearances
ClinicalRadiology(1994)49, 867-870
Ultrasound Findings in Renal Parenchymal Disease: Comparison With Histological Appearances J. E. PAGE, S. H. MORGAN*, J. B. EASTWOOD*, S. A. SMITH*, D. J. WEBB*, S. A. DILLYt, J. CHOWt, A. POTTIER~ and A. E. A. JOSEPH
Departments of Diagnostic Radiology, *Biochemical Medicine, t Histopathology and ~Public Health Sciences, St George's Hospital Medical School, London Ultrasound examination was carried out in 55 patients undergoing renal biopsy for suspected renal parenchymal disease. Analysis of sonographic and histological findings showed statistically significant positive correlations between renal size and the extent of glomerular byper-eellularity and crescent formation and between cortical eehogenieity and severity of glomerular sclerosis, crescent formation, interstitial inflammatory cell infiltration, tubular atrophy and interstitial fibrosis. Positive correlation was also observed between prominence of the medullary pyramids and glomerular sclerosis. The most marked sonographic abnormalities were seen in proliferative (including crescentic) glomernionephritis, diabetic glomerulosclerosis and tubulo-interstitial nephritis. IgA, membranous and minimal change nephropathy were less likely to be associated with sonographie abnormalities. We conclude that certain sonographie appearances in renal parenehymal disease reflect the presence and severity of fight microscopical abnormalities but, although ultrasound assessment provides a high positive predictive value for renal parenchymal disease, specific conditions cannot be distinguished. Page, J.E., Morgan, S.H., Eastwood, J.B., Smith, S.A., Webb, D.J., Dilly, S.A., Chow, J., Pottier, A. & Joseph, A.E.A. (1994). Clinical Radiology 49, 867-870. Ultrasound Findings in Renal Parenchymal Disease: Comparison With Histological Appearances
Accepted for Publication 27 July 1994
The value of ultrasound as an indicator of renal parenchymal disease is unclear. Studies in adults and children and in both native and transplant kidneys have given conflicting results [1-3]. Sonographic criteria used for assessing renal parenchymal disease have included renal size, clarity of outline, preservation of cortico-medullary differentiation, cortical thickness, renal sinus echoes and prominence of the medullary pyramids [2,3,6]. In the native kidney, diffuse increase in cortical echoes is the hallmark of renal parenchymal disease but, though a sensitive indicator, echogenicity is relatively non-specific [7]. Correlations have been found between increased cortical echogenicity and severity of histological changes, but not between specific sonographic appearance and type of renal disease [2,5,8]. Increased echogenicity is most noticeable in patients in whom biopsy shows active interstitial disease [2,9,10] and a strong correlation has been shown between cortical echogenicity and the nature and severity of interstitial but not glomerular disease [3,10]. We report a prospective study of all patients in one hospital undergoing diagnostic renal biopsy over a 2 year period; we investigated the relationship between sonographic and histological findings in the kidney, especially looking for sonographic pointers to specific renal diagnoses.
Correspondenceto: Dr A. E. A. Joseph,Departmentof Radiology, St George'sHospital,BlackshawRoad,LondonSW180QT.
PATIENTS AND METHODS Twenty-four male and 31 female patients aged between 19 and 83 years who had renal biopsy over a 2 year period were studied. Indications for biopsy were acute renal failure or impaired renal function (29 patients), nephrotic syndrome (8), asymptomatic proteinuria (3) and haematuria (15). Ultrasound examination of the kidneys was performed before the biopsy in all cases. Usually, the ultrasound examination was performed on the morning of the biopsy, the biopsy site being marked on the skin at the same time. All US examinations were performed by the same operator (AEAJ) and the renal biopsies by three operators (SHM, SAS, JBE). Clinical details were withheld from the radiologist. All scans were carried out using either an ATL Ultramark 9 or Aloka SSD-650 with a 3.5MHz sector annular array probe or curvilinear probe. The right kidney was examined in the supine and fight anterior oblique positions and the left in the right lateral position. The left kidney was chosen for biopsy in all patients and the site marked with the patient in the prone position. Biopsy was performed freehand following localization of the kidney on ultrasound, using either a Trucut (Travenol) or a Vim-Silverman needle. Three cores were taken where possible. The kidneys were assessed for three features: cortical echogenicity (normal, slight increase or moderate to marked increase), appearance of the medullary pyramids (prominent or not prominent) and renal size (normal, small or large). Renal size was assessed using
868
CLINICAL RADIOLOGY
Table 1 - Grading o f the five selected light microscopical features
Table 2 - Renal histological diagnoses in the 55 patients
Area assessed
Feature
Grading
Diagnosis
No. of patients
Glomeruli
Sclerosis
(< 10%) (< 10%) (absent)
Crescentic glomerulonephritis Proliferative glomerulonephrifis IgA nephropathy Membranous nephropathy Diabetic glomerulosclerosis Tubulo-interstitial nephritis Minimal change nephropathy/thin membrane disease Miscellaneous, e.g. haemolytic-uraemic syndrome, amyloid Normal
9 6 6 5 3 7 2
Hypercellularity Crescents
Tubulointerstitium
Inflammatory cell infiltrate Tubular atrophy/ interstitial fibrosis
+ (10-50%) + (10-50%) + (present)
++ (> 50%)* ++ (> 50%)*
+ (< 10%) (10-30%) + (< 10%) (10-30%)
++ (> 30%)t ++ (> 30%)t
* Figures indicate percentage of glomeruli affected. t Figures indicate percentage of area affected.
8 9
RESULTS
the length, mainly by visual assessment, although occasional measurements were made in borderline cases as an aid to the subjective assessment. Nine cm was taken as the lower limit of normal. Volume measurements were not done. For diagnostic purposes, renal tissue was divided to provide material for frozen, paraffin and, in selected cases, plastic and electron-microscopical processing. The tissue was fixed in buffered formol-saline before being processed for embedding in paraffin wax or JH4 resin. Paraffin sections were cut at 2#m for staining with haematoxylin and eosin and at 5 #m for staining with Jones' methenamine silver, congo red, elastic haematoxylin and eosin and Martius scarlet blue. Plastic sections were cut at 1.5 #m and stained with haematoxylin and eosin, toluidine blue and Jones' methenamine silver. Two assessments of the biopsy specimen were made. A few days after the biopsy, a histological report was issued with access to full clinical details. Later, the paraffin and plastic-embedded sections were assessed 'blind' by two independent observers (SAD, JC) who 'scored' the specimens on the basis of a wide range of light microscopical criteria graded for severity. The relationships between the sonographic and light microscopical criteria were tested using the X2 test for trend. Certain features were found to be non-discriminatory and were excluded; namely, oedema, calcification and vascular appearances (hyalinization and hypertrophy). Five criteria remained (Table 1).
Ultrasound and Cfinieopathologieai Diagnosis The histological diagnoses in the 55 patients, based on the results of light microscopy, immunofluorescence and, when necessary, electron microscopy are given in Table 2. The relationships between sonographic appearances and clinicopathological diagnosis are given in Table 3. Twenty-eight patients had increased renal cortical echogenicity and in a further 10 there was mildly increased echogenicity. There was markedly increased echogenicity in patients with crescentic and proliferative glomerulonephritis, diabetic glomerulosclerosis and tubulo-interstitial nephritis. Appearances were much more variable in patients with membranous or IgA nephropathy. Three of the eleven patients whose biopsies showed normal light microscopical appearances (including two patients with minimal change nephropathy) were reported to have mildly altered echo texture. The medullary pyramids were found to be abnormally prominent in 22 patients, all of whom also had increased cortical echogenicity. The appearance of the medullary pyramids was non-discriminatory, although none of the patients with normal histology had prominent pyramids. Abnormalities in renal size were recorded on US in only nine patients, all of whom also had abnormal echo texture. The kidneys were found to be large in four patients and small in five patients. Renal size was unhelpful in discriminating between different conditions.
Table 3 - Ultrasound appearances and histological diagnosis
Histological diagnosis
n
Renal size N
Crescentic glomerulonephritis Proliferative glomerulonephritis IgA nephropathy Membranous nephropathy Tubulo-interstitial nephropathy Diabetic glomerulosclerosis Minimal change nephropathy Miscellaneous Normal Total
9 6 6 5 7 3 2 8 9
Medullary pyramids
Cortical echoes S
L
N
5 5 6 5 6 2 2 7 8
1 1 1 1 1
3 1 -
3 2 1 2 3 6
46
5
4
17
+
++
NP
1 1 3 1 1 3
8 5 2 6 2 5
3 2 5 3 3 2 2 4
6 4 1 2 4 1 4
--
9
-
10
28
33
22
N, Normal; S, small; L, large; NP, not prominent; P, prominent; +, slight increase; + + medium-severe increase.
P
US AND MICROSCOPICAL APPEARANCES IN RENAL PARENCHYMAL DISEASE Table 4 - Relationship between the severity or extent of the five light microscopical features and the grading of the three ultrasound parameters
P value
Glomerular sclerosis Glomerular hypercellularity Crescents Tubular atrophy/ interstitial fibrosis Interstitial inflammatory cell infiltrate
Cortical echoes
Prominent pyramids
Renal size
0.004*
0.018"
0.213
0.858 0.016"
0.273 0.063
0.012" 0.008"
0.002*
0.254
0.714
0.0003*
0.118
0.063
* P < 0.05.
Three pa'dents reported as showing mildly increased cortical echogenicity on US had normal renal biopsies. Ultrasound and Selected Light Microscopical Criteria X 2 test for trend showed that there was a statistically significant positive relationship between cortical echogenicity and the histological features of severity of glomerular sclerosis, crescent formation, tubular atrophy/interstitial fibrosis, and inflammatory interstitial infiltrate. There was a statistically significant positive relationship between prominence of medullary pyramids and glomerular sclerosis. Positive correlation was also noted between renal size and degree of glomerular hypercellularity and crescent formation (Table 4). Ultrasound was reported as normal in 10 patients with abnormal kidneys on biopsy. These comprised two patients With membranous glomerulonephritis, including one with proliferative glomerulonephritis, three with IgA nephritis, one with acute interstitial nephritis, one patient with haemolytic uraemic syndrome and two patients with non-specific glomerular sclerosis. However, in three of these patients there was no abnormality using the five selected light microscopic criteria, and in another five the changes were predominantly glomerular, e.g. thickening of basement membrane and increase in mesangial matrix, and the interstitium was not hypercellular. Clinical Usefulness of Ultrasound Screening The overall sensitivity of US in detecting renal parenchymal disease with light microscopic abnormalities was 77% with a specificity of 73% and positive predictive value of 92%. Ultrasound was regarded as abnormal if any one of the three criteria (size, cortical echogenicity or prominence of pyramids) was abnormal. In practice, the echogenicity was invariably abnormal if the other features were affected. DISCUSSION This study has demonstrated that renal ultrasonography can achieve a sensitivity of 77% and specificity of 73% for detecting microscopically confirmed parenchymal changes. For some of the histological features there was a positive correlation between the degree of sonographic abnormality and the severity of the
869
microscopical changes. However, the ultrasonographic appearances did not predict the type of microscopical abnormality nor the ultimate histological diagnosis derived from the combination of clinical, light microscopical and immunofluorescence data. Therefore, it appears that the US appearance may be a useful clinical adjunct for deciding whether a renal biopsy is likely to reveal significant parenchymal disease but will not be helpful in indicating the specific histological diagnosis. Ultrasound is most accurate in conditions associated with increased cellularity, such as crescentic and proliferative glomerulonephritis and tubulo-interstitial nephropathy. In many renal conditions, it is not just one compartment of the kidney that is affected but several. For example, proliferative glomerulonephritis does not only have hypercellular glomeruli but also tubular damage and an interstitial reaction. Therefore, it was important not only to correlate the sonographic findings with the pathological diagnosis to determine the clinical value of US but also to undertake a more detailed examination of specific microscopical features to try to establish which tissue abnormalities were best detected ultrasonically. In the normal kidney the renal cortex produces backscattered echoes of lower intensity than normal liver, spleen or the renal sinus. By comparison, renal medulla is relatively hypoechoic. The difference is believed to be due to the large number of acoustic interfaces in the cortex [11,12]. It has been suggested that it may be influenced by collagen content, calcium deposition and some acute processes [3,6]. Since glomeruli in the adult kidney occupy only 8% of the renal cortex, it is possible that early changes confined to the glomerulus will not be detected on US [13] and that increased cortical echoes will be due (o either purely interstitial changes or a combination of glomerular and interstitial changes [2,3,9]. Rosenfield and Siegel [10] state that, when abnormalities are confined to glomeruli, US is not helpful in determining either the nature or the severity of the disease. In our study sonographic abnormalties, in particular increased echogenicity, were more common in patients with crescentic glomerulonephritis, proliferative glomerulonephritis, diabetic glomerulosclerosis and tubulo-interstitial nephropathy. Such patients had high scores for tubulo-interstitial damage, supporting the contention that active interstitial disease produces the most noticeable increase in echogenicity on US [2,9,10]. Half the US false negatives in our study were patients with membranous or IgA nephritis in whom the light microscopical changes were restricted predominantly to the glomerulus (e.g. increase in mesangial matrix, thickening of the basement membrane) and there was no glomerular hypercellularity. Prominence of the medullary pyramids is a non-specific finding [4] and thought by one group of authors to be due to medullary congestion [13]. Most of our biopsies were from the cortex and microscopically evident oedema did not correlate with any of the ultrasonographical features so we are unable to substantiate this point. The finding of prominent medullary pyramids in conjunction with increased cortical echogenicity was always indicative of renal disease in our study and was seen in two-thirds of our patients. Although these changes are non-specific, our results are at variance with those of others who state that prominent pyramids are rare [7]. Our results suggest that
870
CLINICAL RADIOLOGY
there is a specific relationship between prominence of the medullary pyramids and the presence of glomerular sclerosis. The significance of this association is unclear and difficult to explain but may be an indirect reflection of accentuation of cortico-medullary differentiation due to increased cortical echogenicity rather than a direct manifestation of reduced medullary echogenicity. Hricak et al. [11] have demonstrated an inverse correlation between renal length and the presence of sclerosis, atrophy and casts but our results do not demonstrate any correlation (positive or negative) between size and these features. However, we did find a direct relationship between increasing renal size and glomerular hypercellularity including crescent formation. In generation, we found renal size unhelpful as an indicator of renal parenchymal disease, largely because it was normal in the vast majority of our patients. It has been suggested that kidneys tend to be large in patients with acute renal failure and small in chronic renal failure [7,13]. In our study, it was nondiscriminatory in determining specific disease processes.
REFERENCES
1 Platt JF, Rubin JM, Bowerman RA et al. The inability to detect kidney disease on the basis of echogenicity. American Journal of Roent g enology 1988;151:317-319.
2 Hricak H, Cruz C, Romanski R et al. Renal parenchymal disease: sonographic-histologic correlation. Radiology 1982;144:141-147. 3 Rosenfield AT, Taylor KJW, Jaffe CC. Clinical applications of ultrasound tissue characterisation. Radiologic Clinics of North America 1980;18(1):31-58. 4 Lovett I, Doust B, Orr N. The role of ultrasound in the diagnosis of parenchymal disease in transplanted kidneys. Australasian Radiology 1988;32:104-106. 5 Hayden CK, Santa-Cruz FR, Amparo EG et at. Ultrasonographic evaluation of the renal parenchyma in infancy and childhood. Radiology 1984;152:413-417. 6 Rosenfield AT, Taylor KJW, Crade M et al. Anatomy and pathology of the kidney by grey scale ultrasound. Radiology 1978; 128:737-744. 7 Moccia WA, Kaude JV, Wright PG et al. Evaluation of chronic renal failure by digital grey-scale ultrasound. Urologic Radiology 1980;2:1-7. 8 Erwin B, Carroll B, Muller H. A sonographic assessment of neonatal renal parameters. Journal o f Ultrasound in Medicine 1985;4:217-220. 9 Amis E, Hartman D. Renal ultrasonography: a practical overview. Radiologic Clinics of North America 1984;22:315-332. 10 Rosenfield AT, Siegel NJ. Renal parenchymal disease: histopathologic-sonographic correlation. American Journal of Roentgenology 1981;137:793-798. 11 Hricak H, Slovis TL, Callen CW et al. Neonatal kidneys: sonographic anatomic correlation. Radiology 1983;147:699-702. 12 Haller JO, Berdon WE, Friedman AP. Increased renal cortical echogenicity: a normal finding in neonates and infants. Radiology 1982;142:173-174. 13 Huntington DK, Hill SC, Hill MC. Sonographic manifestations of medical renal disease. Seminars in Ultrasound, CT and M R 1991; 12(4):290-307.
Ultrasound Findings in Renal Parenchymal Disease: Comparison With Histological Appearances J. E. PAGE, S. H. MORGAN*, J. B. EASTWOOD*, S. A. SMITH*, D. J. WEBB*, S. A. DILLYt, J. CHOWt, A. POTTIER~ and A. E. A. JOSEPH
Departments of Diagnostic Radiology, *Biochemical Medicine, t Histopathology and ~Public Health Sciences, St George's Hospital Medical School, London Ultrasound examination was carried out in 55 patients undergoing renal biopsy for suspected renal parenchymal disease. Analysis of sonographic and histological findings showed statistically significant positive correlations between renal size and the extent of glomerular byper-eellularity and crescent formation and between cortical eehogenieity and severity of glomerular sclerosis, crescent formation, interstitial inflammatory cell infiltration, tubular atrophy and interstitial fibrosis. Positive correlation was also observed between prominence of the medullary pyramids and glomerular sclerosis. The most marked sonographic abnormalities were seen in proliferative (including crescentic) glomernionephritis, diabetic glomerulosclerosis and tubulo-interstitial nephritis. IgA, membranous and minimal change nephropathy were less likely to be associated with sonographie abnormalities. We conclude that certain sonographie appearances in renal parenehymal disease reflect the presence and severity of fight microscopical abnormalities but, although ultrasound assessment provides a high positive predictive value for renal parenchymal disease, specific conditions cannot be distinguished. Page, J.E., Morgan, S.H., Eastwood, J.B., Smith, S.A., Webb, D.J., Dilly, S.A., Chow, J., Pottier, A. & Joseph, A.E.A. (1994). Clinical Radiology 49, 867-870. Ultrasound Findings in Renal Parenchymal Disease: Comparison With Histological Appearances
Accepted for Publication 27 July 1994
The value of ultrasound as an indicator of renal parenchymal disease is unclear. Studies in adults and children and in both native and transplant kidneys have given conflicting results [1-3]. Sonographic criteria used for assessing renal parenchymal disease have included renal size, clarity of outline, preservation of cortico-medullary differentiation, cortical thickness, renal sinus echoes and prominence of the medullary pyramids [2,3,6]. In the native kidney, diffuse increase in cortical echoes is the hallmark of renal parenchymal disease but, though a sensitive indicator, echogenicity is relatively non-specific [7]. Correlations have been found between increased cortical echogenicity and severity of histological changes, but not between specific sonographic appearance and type of renal disease [2,5,8]. Increased echogenicity is most noticeable in patients in whom biopsy shows active interstitial disease [2,9,10] and a strong correlation has been shown between cortical echogenicity and the nature and severity of interstitial but not glomerular disease [3,10]. We report a prospective study of all patients in one hospital undergoing diagnostic renal biopsy over a 2 year period; we investigated the relationship between sonographic and histological findings in the kidney, especially looking for sonographic pointers to specific renal diagnoses.
Correspondenceto: Dr A. E. A. Joseph,Departmentof Radiology, St George'sHospital,BlackshawRoad,LondonSW180QT.
PATIENTS AND METHODS Twenty-four male and 31 female patients aged between 19 and 83 years who had renal biopsy over a 2 year period were studied. Indications for biopsy were acute renal failure or impaired renal function (29 patients), nephrotic syndrome (8), asymptomatic proteinuria (3) and haematuria (15). Ultrasound examination of the kidneys was performed before the biopsy in all cases. Usually, the ultrasound examination was performed on the morning of the biopsy, the biopsy site being marked on the skin at the same time. All US examinations were performed by the same operator (AEAJ) and the renal biopsies by three operators (SHM, SAS, JBE). Clinical details were withheld from the radiologist. All scans were carried out using either an ATL Ultramark 9 or Aloka SSD-650 with a 3.5MHz sector annular array probe or curvilinear probe. The right kidney was examined in the supine and fight anterior oblique positions and the left in the right lateral position. The left kidney was chosen for biopsy in all patients and the site marked with the patient in the prone position. Biopsy was performed freehand following localization of the kidney on ultrasound, using either a Trucut (Travenol) or a Vim-Silverman needle. Three cores were taken where possible. The kidneys were assessed for three features: cortical echogenicity (normal, slight increase or moderate to marked increase), appearance of the medullary pyramids (prominent or not prominent) and renal size (normal, small or large). Renal size was assessed using
868
CLINICAL RADIOLOGY
Table 1 - Grading o f the five selected light microscopical features
Table 2 - Renal histological diagnoses in the 55 patients
Area assessed
Feature
Grading
Diagnosis
No. of patients
Glomeruli
Sclerosis
(< 10%) (< 10%) (absent)
Crescentic glomerulonephritis Proliferative glomerulonephrifis IgA nephropathy Membranous nephropathy Diabetic glomerulosclerosis Tubulo-interstitial nephritis Minimal change nephropathy/thin membrane disease Miscellaneous, e.g. haemolytic-uraemic syndrome, amyloid Normal
9 6 6 5 3 7 2
Hypercellularity Crescents
Tubulointerstitium
Inflammatory cell infiltrate Tubular atrophy/ interstitial fibrosis
+ (10-50%) + (10-50%) + (present)
++ (> 50%)* ++ (> 50%)*
+ (< 10%) (10-30%) + (< 10%) (10-30%)
++ (> 30%)t ++ (> 30%)t
* Figures indicate percentage of glomeruli affected. t Figures indicate percentage of area affected.
8 9
RESULTS
the length, mainly by visual assessment, although occasional measurements were made in borderline cases as an aid to the subjective assessment. Nine cm was taken as the lower limit of normal. Volume measurements were not done. For diagnostic purposes, renal tissue was divided to provide material for frozen, paraffin and, in selected cases, plastic and electron-microscopical processing. The tissue was fixed in buffered formol-saline before being processed for embedding in paraffin wax or JH4 resin. Paraffin sections were cut at 2#m for staining with haematoxylin and eosin and at 5 #m for staining with Jones' methenamine silver, congo red, elastic haematoxylin and eosin and Martius scarlet blue. Plastic sections were cut at 1.5 #m and stained with haematoxylin and eosin, toluidine blue and Jones' methenamine silver. Two assessments of the biopsy specimen were made. A few days after the biopsy, a histological report was issued with access to full clinical details. Later, the paraffin and plastic-embedded sections were assessed 'blind' by two independent observers (SAD, JC) who 'scored' the specimens on the basis of a wide range of light microscopical criteria graded for severity. The relationships between the sonographic and light microscopical criteria were tested using the X2 test for trend. Certain features were found to be non-discriminatory and were excluded; namely, oedema, calcification and vascular appearances (hyalinization and hypertrophy). Five criteria remained (Table 1).
Ultrasound and Cfinieopathologieai Diagnosis The histological diagnoses in the 55 patients, based on the results of light microscopy, immunofluorescence and, when necessary, electron microscopy are given in Table 2. The relationships between sonographic appearances and clinicopathological diagnosis are given in Table 3. Twenty-eight patients had increased renal cortical echogenicity and in a further 10 there was mildly increased echogenicity. There was markedly increased echogenicity in patients with crescentic and proliferative glomerulonephritis, diabetic glomerulosclerosis and tubulo-interstitial nephritis. Appearances were much more variable in patients with membranous or IgA nephropathy. Three of the eleven patients whose biopsies showed normal light microscopical appearances (including two patients with minimal change nephropathy) were reported to have mildly altered echo texture. The medullary pyramids were found to be abnormally prominent in 22 patients, all of whom also had increased cortical echogenicity. The appearance of the medullary pyramids was non-discriminatory, although none of the patients with normal histology had prominent pyramids. Abnormalities in renal size were recorded on US in only nine patients, all of whom also had abnormal echo texture. The kidneys were found to be large in four patients and small in five patients. Renal size was unhelpful in discriminating between different conditions.
Table 3 - Ultrasound appearances and histological diagnosis
Histological diagnosis
n
Renal size N
Crescentic glomerulonephritis Proliferative glomerulonephritis IgA nephropathy Membranous nephropathy Tubulo-interstitial nephropathy Diabetic glomerulosclerosis Minimal change nephropathy Miscellaneous Normal Total
9 6 6 5 7 3 2 8 9
Medullary pyramids
Cortical echoes S
L
N
5 5 6 5 6 2 2 7 8
1 1 1 1 1
3 1 -
3 2 1 2 3 6
46
5
4
17
+
++
NP
1 1 3 1 1 3
8 5 2 6 2 5
3 2 5 3 3 2 2 4
6 4 1 2 4 1 4
--
9
-
10
28
33
22
N, Normal; S, small; L, large; NP, not prominent; P, prominent; +, slight increase; + + medium-severe increase.
P
US AND MICROSCOPICAL APPEARANCES IN RENAL PARENCHYMAL DISEASE Table 4 - Relationship between the severity or extent of the five light microscopical features and the grading of the three ultrasound parameters
P value
Glomerular sclerosis Glomerular hypercellularity Crescents Tubular atrophy/ interstitial fibrosis Interstitial inflammatory cell infiltrate
Cortical echoes
Prominent pyramids
Renal size
0.004*
0.018"
0.213
0.858 0.016"
0.273 0.063
0.012" 0.008"
0.002*
0.254
0.714
0.0003*
0.118
0.063
* P < 0.05.
Three pa'dents reported as showing mildly increased cortical echogenicity on US had normal renal biopsies. Ultrasound and Selected Light Microscopical Criteria X 2 test for trend showed that there was a statistically significant positive relationship between cortical echogenicity and the histological features of severity of glomerular sclerosis, crescent formation, tubular atrophy/interstitial fibrosis, and inflammatory interstitial infiltrate. There was a statistically significant positive relationship between prominence of medullary pyramids and glomerular sclerosis. Positive correlation was also noted between renal size and degree of glomerular hypercellularity and crescent formation (Table 4). Ultrasound was reported as normal in 10 patients with abnormal kidneys on biopsy. These comprised two patients With membranous glomerulonephritis, including one with proliferative glomerulonephritis, three with IgA nephritis, one with acute interstitial nephritis, one patient with haemolytic uraemic syndrome and two patients with non-specific glomerular sclerosis. However, in three of these patients there was no abnormality using the five selected light microscopic criteria, and in another five the changes were predominantly glomerular, e.g. thickening of basement membrane and increase in mesangial matrix, and the interstitium was not hypercellular. Clinical Usefulness of Ultrasound Screening The overall sensitivity of US in detecting renal parenchymal disease with light microscopic abnormalities was 77% with a specificity of 73% and positive predictive value of 92%. Ultrasound was regarded as abnormal if any one of the three criteria (size, cortical echogenicity or prominence of pyramids) was abnormal. In practice, the echogenicity was invariably abnormal if the other features were affected. DISCUSSION This study has demonstrated that renal ultrasonography can achieve a sensitivity of 77% and specificity of 73% for detecting microscopically confirmed parenchymal changes. For some of the histological features there was a positive correlation between the degree of sonographic abnormality and the severity of the
869
microscopical changes. However, the ultrasonographic appearances did not predict the type of microscopical abnormality nor the ultimate histological diagnosis derived from the combination of clinical, light microscopical and immunofluorescence data. Therefore, it appears that the US appearance may be a useful clinical adjunct for deciding whether a renal biopsy is likely to reveal significant parenchymal disease but will not be helpful in indicating the specific histological diagnosis. Ultrasound is most accurate in conditions associated with increased cellularity, such as crescentic and proliferative glomerulonephritis and tubulo-interstitial nephropathy. In many renal conditions, it is not just one compartment of the kidney that is affected but several. For example, proliferative glomerulonephritis does not only have hypercellular glomeruli but also tubular damage and an interstitial reaction. Therefore, it was important not only to correlate the sonographic findings with the pathological diagnosis to determine the clinical value of US but also to undertake a more detailed examination of specific microscopical features to try to establish which tissue abnormalities were best detected ultrasonically. In the normal kidney the renal cortex produces backscattered echoes of lower intensity than normal liver, spleen or the renal sinus. By comparison, renal medulla is relatively hypoechoic. The difference is believed to be due to the large number of acoustic interfaces in the cortex [11,12]. It has been suggested that it may be influenced by collagen content, calcium deposition and some acute processes [3,6]. Since glomeruli in the adult kidney occupy only 8% of the renal cortex, it is possible that early changes confined to the glomerulus will not be detected on US [13] and that increased cortical echoes will be due (o either purely interstitial changes or a combination of glomerular and interstitial changes [2,3,9]. Rosenfield and Siegel [10] state that, when abnormalities are confined to glomeruli, US is not helpful in determining either the nature or the severity of the disease. In our study sonographic abnormalties, in particular increased echogenicity, were more common in patients with crescentic glomerulonephritis, proliferative glomerulonephritis, diabetic glomerulosclerosis and tubulo-interstitial nephropathy. Such patients had high scores for tubulo-interstitial damage, supporting the contention that active interstitial disease produces the most noticeable increase in echogenicity on US [2,9,10]. Half the US false negatives in our study were patients with membranous or IgA nephritis in whom the light microscopical changes were restricted predominantly to the glomerulus (e.g. increase in mesangial matrix, thickening of the basement membrane) and there was no glomerular hypercellularity. Prominence of the medullary pyramids is a non-specific finding [4] and thought by one group of authors to be due to medullary congestion [13]. Most of our biopsies were from the cortex and microscopically evident oedema did not correlate with any of the ultrasonographical features so we are unable to substantiate this point. The finding of prominent medullary pyramids in conjunction with increased cortical echogenicity was always indicative of renal disease in our study and was seen in two-thirds of our patients. Although these changes are non-specific, our results are at variance with those of others who state that prominent pyramids are rare [7]. Our results suggest that
870
CLINICAL RADIOLOGY
there is a specific relationship between prominence of the medullary pyramids and the presence of glomerular sclerosis. The significance of this association is unclear and difficult to explain but may be an indirect reflection of accentuation of cortico-medullary differentiation due to increased cortical echogenicity rather than a direct manifestation of reduced medullary echogenicity. Hricak et al. [11] have demonstrated an inverse correlation between renal length and the presence of sclerosis, atrophy and casts but our results do not demonstrate any correlation (positive or negative) between size and these features. However, we did find a direct relationship between increasing renal size and glomerular hypercellularity including crescent formation. In generation, we found renal size unhelpful as an indicator of renal parenchymal disease, largely because it was normal in the vast majority of our patients. It has been suggested that kidneys tend to be large in patients with acute renal failure and small in chronic renal failure [7,13]. In our study, it was nondiscriminatory in determining specific disease processes.
REFERENCES
1 Platt JF, Rubin JM, Bowerman RA et al. The inability to detect kidney disease on the basis of echogenicity. American Journal of Roent g enology 1988;151:317-319.
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