Pediatr Radiol (1995) 25:472-475

Pediatric Radiology 9 Springer-Verlag 1995

Renal dysplasia in infants: appearance on 99mTc DMSA scintigraphy P. J. R o a c h 1, H. J. Paitiel 1, A . P e r e z - A t a y d e 2, R. J. Tello% R. T. D a v i s 1, S. T. Treves 1 I Department of Radiology, Division of Nuclear Medicine, The Children's Hospital and Harvard Medical School, Boston, MA, USA 2 Department of Pathology, The Children's Hospital and Harvard Medical School, Boston, MA, USA Received: 3 October 1994/Accepted: 22 November 1994

Abstract. Infantile renal dysplasias, including multicystic

dysplastic kidneys (MCDK), are reported rarely to accumulate radiopharmaceuticals on renal scintigraphy. 99mTc DMSA is a highly sensitive tracer for detecting functioning renal cortical tissue and may be more suited to studying renal dysplasia than 99mTc DTPA. We reviewed the ultrasound studies and 99mTc DMSA scintigrams of 42 infants (age range 1-12 months) with known or suspected MCDK. Overall, uptake on 99mTc DMSA scintigraphy was evident in 6/41 (15 %) dysplastic kidneys. Of the 18 patients who underwent nephrectomy, histopathological examination revealed that uptake correlated closely with the presence of mature renal cortical tissue in the affected kidney. Our study shows that a small, but significant number of MCDK will show low-grade uptake on DMSA scintigraphy. This finding may be relevant given the reliance placed on renal scintigraphy in planning treatment for infants with suspected MCDK, particularly with the increasing trend for the non-operative management of this condition. Multicystic dysplastic kidney (MCDK) is a common cause of abdominal masses in the neonate [1, 2]. This condition is readily identified by either in utero or postnatal ultrasound (US) in most cases [1, 3, 4]. When the US appearance is not typical, renal scintigraphy is frequently performed [1, 4]. The absence of uptake generally allows differentiation of MCDK from the more common and potentially reversible hydronephrosis secondary to congenital ureteropelvic junction (UPJ) obstruction, which reportedly always shows activity on renal scintigraphy [1, 5]. While there are several case reports and small series describing uptake of radiopharmaceuticals, such as 99mTc diethylene-triamine-pentaacetic acid (DTPA) and 99mTc mercapto-acetyl-triglycine (MAG-3) in MCDK [6-11], the percentage of dysplastic kidneys which concentrate these agents is not clearly established. There are only isolated reports [12] Correspondence to: S. T. Treves

of the use of 99mTc dimercaptosuccinic acid (DMSA), a radiopharmaceutical with potentially better uptake characteristics in MCDK than 99mTc DTPA. The aim of this study was to evaluate the findings of 99mTc DMSA scintigraphy in infants with renal dysplasias, including MCDK.

Materials and m e t h o d s 99mTc DMSA scintigrams and US studies of all patients referred with suspected or known MCDK were reviewed. In each case, the US was performed within 3 months of the scintigraphic study (mean 2 weeks). Over a 3-year period (1990-1993) studies were performed in 42 infants. All US studies were reviewed by one experienced pediatric radiologist (H. E), blinded to clinical history and results of other investigations. A n assessment was made of renal size, the presence and number of cysts and the size and location of the largest cyst. The contralateral kidney was also assessed for size and the presence of any abnormality. Kidneys were classified as being consistent with MCDK if there were multiple randomly-arranged noncommunicating cysts with little or no renal parenchyma identified. Patients with hydronephrosis were excluded and the group with one cyst or with non-cystic dysplastic changes were analyzed separately. In each case, scintigraphy was performed 4 h after injection of 50 gCi/kg [1.8 MBq/kg] 99mTc DMSA. Planar images (500,000 counts) were obtained using a Siemens Orbiter gamma camera interfaced to an Icon computer and equipped with an ultrahigh-resolution parallel-hole collimator. Images were reported independently by two nuclear medicine physicians (R R., S.T.T.), blinded to the results of clinical history and US findings. Uptake in the region of each kidney was assessed using a four-point scale (see Fig. 1): 9 9 9 9

Grade Grade Grade Grade

0: no uptake 1: uptake seen only with background enhancement 2: minimal visualization without computer enhancement 3: easily visualized/normal

In the event of disagreement in grading between the readers, the studies were reviewed and a consensus reading obtained. Regions of interest were drawn around each kidney in the posterior projection and differential renal cortical function was calculated. In the group of patients who underwent nephrectomy, the histopathological specimens and reports were reviewed. Haematoxy-

473

Fig.1. 99mTcDMSA classification of infantile renal dysplasia: grade 0, no uptake; grade 1, uptake seen only with background enhancement; grade 2, minimal visualization without computer enhancement; grade 3, easily visualized/normal

lin and eosin-stained slides were examined in all patients by an experienced pathologist (A.R), blinded to clinical, radiological and scintigraphic findings. The gross appearance of the kidney was ascertained from the initial report of the specimen. Careful assessment was made for the presence of normal appearing renal tissue, as we postulated that its appearance may correlate with uptake on scintigraphic studies. Specimens were classified in four groups: 9 Group 1: no evidence of mature renal tissue 9 Group 2: rare loci of non-dysplastic mature renal cortical tissue (glomeruli and convoluted tubules without the presence of renal medullary tissue, e.g. collecting ducts) 9 Group 3: occasional foci of non-dysplastic mature renal cortical tissue in continuity with dysplastic medullary tissue 9 Group 4: occasional foci of non-dysplastic mature renal cortical tissue in continuity with non-dysplastic medullary tissue

Results

Of the 42 infants in this study, 25 (60 %) were boys and 17 (40 %) were girls. The left kidney was affected in 27 cases (64 %) and the right in 15 (36 %). Results of 99mTc D M S A scintigraphy are shown in Table 1. Uptake was demonstrated in 5/34 (15 %) MCDK. Uptake was either grade 1 (four cases) or grade 2 (one case). Differential cortical function ranged from 1-6 % (mean 3 %). None of the patients with one cyst and only one (20%) of the non-cystic dysplastic kidneys demonstrated uptake on renal scintigraphy. Overall, 99mTc D M S A scintigraphy showed activity in 6/42 dysplastic kidneys (14%). One infant with a duplex kidney showed normal renal appearance in the lower pole and multicystic changes in the upper pole on US. As 99mTc D M S A scintigraphy revealed uptake only in the normal appearing lower pole, the infant was included in the absent uptake group (group 0). In all cases where scintigraphy was positive, the degree of uptake was only low grade and the area of uptake was less than 25 % the size of the contralateral kidney. Abnormalities were identified by US in the contralateral kidney in seven patients. These abnormalities included increased parenchymal echogenicity (n = 3), pelvicalyceal dilatation (n = 1), mild ureteral dilatation (n = 1) and minimal pelvic ectasia (n = 1). None of these patients demonstrated uptake in the affected kidney on scintigraphy. In the remaining patient with grade 2 uptake in the affected kidney, US revealed mild hydronephrosis and increased parenchymal echogenicity in the contralateral kidney (see Fig. 1).

A total of 18 patients underwent nephrectomy and specimens comprising two to eight slides (median four) were available for analysis. In each case, the distorted kidney was replaced by cysts of varying size and number with intervening connective tissue. The light microscopic findings confirmed the diagnosis of cystic dysplasia in all the nephrectomy specimens. Dysplastic changes included primitive ducts surrounded by fibrous or smooth muscle tissue, islands and hyaline cartilage and primitive mesenchymal tissue consistent with abnormal metanephric differentiation. Areas of chronic inflammation, fibrosis and residual nephron units were observed in most cases. Using the four categories described above, the number of patients in each group are shown in Table 2. Of the six patients who showed uptake of tracer on 99mTc D M S A scintigraphy, nephrectomy was performed in four. Uptake on scintigraphy was rarely seen in the least differentiated forms of M C D K (see Table 2). Of the 12 kidneys with complete absence or only rare loci of mature renal cortical tissue (groups 1 and 2), uptake was demonstrated in only one case (8 %). In contrast, patients with the more differentiated form of M C D K (grades 3 and 4), demonstrated uptake in three of six cases (50 %).

Discussion

M C D K accounts for more than 20 % of abdominal masses in the neonate [2]. Bilateral involvement, a condition incompatible with life, occurs in 5-20 % cases [1, 13, 14]. The exact aetiology of M C D K is unknown. While the more common pelvoinfundibular atresia is thought to be due to derangements in the pattern of ampullary branching at 8-10 weeks of gestation [2, 15-17], it is thought that some cases may be caused by ureteral obstruction during the metanephric stage of intrauterine development [18]. Other authors have postulated that the condition may reflect a continuum between these two events [1]. The microscopic features of M C D K include the relative absence of glomerular and tubular structures and the presence of cysts of variable size and shape [19]. While intravenous urography generally shows no concentration of contrast medium, occasionally calyceal crescents may be seen [1]. Mature tubules and normal glomeruli may occasionally be found in cases of MCDK, thus explaining why residual renal function is sometimes observed [20, 21].

474 Table 1. Number of patients and grade of uptake on 99mTcDMSA scintigraphy according to appearance on US Multicystic dysplasia Grade Number 99mTcDMSA 1 2 3 of cysts uptake >5 3/20 (15 %) 2 1 0 2-5 2/14 (14 %) 2 0 0 Total

1

0/3 (0%)

0

0

0

0

1/5 (20 %) 6/42 (14 %)

0 4

1 2

0 0

Table 2. Number of patients with uptake on 99~TcDMSA scintigraphy compared with histopathological grading of nephrectomy specimens Grade No. of patients 99mTCDMSA uptake 1 3 0 (0 %) 2 9 1 (11%) 3 5 2 (40 %) 4 1 1 (100%)

Infants usually present with a unilateral abdominal mass which is typically mobile and lobulated [1,191. Presenting symptoms which have been reported to occur later in life include pain, infection and hypertension [22, 23]. While compensatory hypertrophy is noted in most contralateral kidneys, other urological anomalies, such as UPJ obstruction (12 %), vesicoureteric reflux (18 %) and obstructed megaureters, may also occur [10, 13, 14, 24, 25]. In our series, contralateral abnormalities were demonstrated on US in seven cases (17 %). With the increasing use of prenatal US, the diagnosis is commonly made in utero [1, 5, 10, 26]. Although cysts begin to develop in the first trimester of pregnancy, it is not until the second or, more commonly, third trimester that the condition can be readily identified sonographically [10]. One recent study based on US assessment of the natural history of MCDK found that approximately two-thirds of affected kidneys will progressively decrease in size either in utero or postnatally, and in some cases disappear [10]. Of the remainder, 10 % increased in size and the rest remained unchanged. In another series, 73 % showed no change and 14 % decreased in size over the mean follow-up period of 33 months [25]. The tendency of MCDKs to involute presumably accounts for their observed change from cystic dysplasia to predominantly dysplasia, leading in some cases to "aplasia" [10, 25, 27]. The appearance of MCDK is usually diagnostic on US [9, 10]. The classic US criteria for the diagnosis of MCDK include: multiple oval or round non-communicating cysts, presence of interfaces between cysts, a non-medial location of the largest cyst, absence of an identifiable renal sinus, absence of a parenchymal ring and presence of tiny cysts in an eccentric location [1, 3, 4, 10, 21]. The critical feature is the presence of cysts with smooth thin walls without solid components [1]. While a massively dilated collecting system caused by ureteral or pelvic obstruction may be confused with

MCDK, direct communication can usually be shown between the calyces and the pelvis in these cases [1]. Misdiagnosis may occur with US if cysts are arranged around a larger central cyst, particularly when a renal pelvis is present [4, 5, 7, 8, 21]. If this larger cyst is located medially, differentiation from hydronephrosis may be particularly difficult [9]. When the US appearance is not characteristic of MCDK, renal scintigraphy is often performed [1, 4]. The typical finding is a complete absence of tracer uptake. This contrasts with hydronephrosis where some accumulation will always be detected [1, 5, 6, 9]. Some authors have noted that any uptake should raise the question of reversible obstruction causing hydronephrosis [1]. While there are several case reports and small series describing occasional uptake of 99mTc DTPA, 99mTcDMSA, 99mrc glucoheptonate and 99mTc MAG-3 [6-11], the frequency with which this occurs is not clearly established. In Strife's review (to our knowledge the only other large series in which scintigraphy was routinely performed), 44 of 46 (96 %) cases of MCDK showed no uptake when studied with 99mTc DTPA [10]. Others have reported that abnormalities may only be seen on 99mTc DTPA and 99mTc glucoheptonate scintigraphy when delayed imaging of up to 24 h is performed [6]. A similar observation has been made with delayed intravenous pyelography imaging, where puddling of contrast medium may be noted [4, 7, 8, 10, 281. 99mTcDMSA is a radiopharmaceutical which binds to functioning proximal tubular cells regardless of urine flow [29]. This agent may be better suited for the detection of renal function in MCDK than 99mTc DTPA, which is cleared almost exclusively by glomerular filtration. MCDK is characterized by dysplastic renal ductal and tubular tissue so that radiopharmaceuticals which bind to cortical tubules may be preferable in the evaluation of this condition [11]. Since focal areas of renal parenchyma may be present, an agent which binds to the proximal tubules enabling delayed static imaging to be performed should be more sensitive in detecting functioning tissue than a more rapidly cleared radiopharmaceutical. The isolated reports on the use of 99mTCDMSA suggest that, like 99mTc DTPA, tracer uptake in the affected kidney is almost never seen [11]. Our study shows that while most cases of MCDK reveal no scintigraphic activity, approximately 14% will show low grade uptake in the affected kidney when studied with 99mTc DMSA. This is more than was noted in Strife's series, which showed uptake in only 4 % of MCDK with 99mTc DTPA [10]. Uptake on scintigraphy appears to be related to the presence of a small amount of functioning cortical tubular tissue in the dysplastic kidney [29]. Review of nephrectomy specimens in our series confirmed that uptake on scintigraphy was most likely to be seen in the better differentiated forms of infantile renal dysplasia. Uptake in each case was low grade and background enhancement was necessary to detect functioning tissue in four of the six kidneys. The contribution of the affected kidney to overall renal cortical func-

475 tion was no higher than 6 % and in most cases was app r o x i m a t e l y 2 %. With advances in g a m m a c a m e r a and c o m p u t e r technology (including SPECT), the ability to detect areas of very low grade u p t a k e of radiopharmaceuticals, such as 99rnTc D M S A , is now increased. Although S P E C T was not p e r f o r m e d in this series, it is likely that this technique might also increase the detection of renal cortical tissue. As n o t e d by others, we found scintigraphy with 99mTc D M S A to be a safe, non-invasive investigation which was p e r f o r m e d easily and without complication in the infants in our series [11]. It has b e e n claimed that when the typical US and scintigraphic a p p e a r a n c e s are present, the diagnosis can be m a d e with virtually complete certainty [1, 3, 4, 21]. The distinction b e t w e e n M C D K and hydronephrosis, the two c o m m o n e s t causes of abdominal masses in the neonate, is i m p o r t a n t because of the different t r e a t m e n t for each condition. While severe neonatal hydronephrosis requires p r o m p t pyeloplasty to preserve renal function and allow reconstitution of functioning renal parenc h y m a [7], there is an increasing trend for a non-operative a p p r o a c h in the m a n a g e m e n t of M C D K [4, 5, 10, 20, 25, 27, 30-32]. This is occurring because m a n y of these kidneys are thought to undergo involution, while complications such as infection, hypertension and malignancy are thought to be exceptionally rare [10, 25, 30]. The finding of 99mTc D M S A u p t a k e in renal dysplasias, including M C D K , m a y have implications for mana g e m e n t of these infants. We have shown that the presence of low grade renal u p t a k e does not totally exclude the diagnosis of M C D K or other renal dysplasia. While the presence of renal activity will indicate h y d r o n e p h r o sis in most cases, renal dysplasia m a y also account for this a p p e a r a n c e in some cases. This would a p p e a r to be largely related to the presence of functioning m a t u r e renal cortical tissue. While the combination of both US and scintigraphy should be diagnostic in nearly all cases, surgical exploration and either pyeloplasty or nep h r e c t o m y m a y be required if uncertainty remains. In summary, we have shown that a small, but significant n u m b e r of infants with M C D K and renal dysplasia will show low grade activity in the affected kidney when studied with 99mTc D M S A . Clearly, the presence of scintigraphic uptake m a y not definitively exclude M C D K as the cause of renal cystic disease shown by US in the infant.

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