The diagnosis of congenital renal anomalies with ultrasound

FETUS, PLACENTA, AND NEWBORN

The diagnosis of congenital renal anomalies with ultrasound II. Infantile polycystic kidney disease Roberto Romero, M.D., Mark Cullen, M.D., Philippe Jeanty, M.D., Peter Grannum, M.D., E. Albert Reece, M.D., Ingeborg Venus, M.S., and John C. Hobbins, M.D. New Haven, Connecticut Infantile polycystic kidney disease is an autosomal recessive disorder which in its severe form is characterized by bilateral renal enlargement and renal failure. The present study was undertaken to assess the diagnostic accuracy of antenatal sonography in a population at risk. Nineteen patients with fetuses at risk for infantile polycystic kidney disease were referred for ultrasound examination to the Perinatal Unit at Yale-New Haven Hospital. Ten infants had infantile polycystic kidney disease (53%). A positive antenatal sonographic diagnosis was made by the presence of oligohydramnios, an absent urinary bladder, bilateral renal enlargement as measured by the kidney circumference-to-abdominal circumference ratio, and the typical hyperechogenic appearance of the kidneys in the disease. A correct antenatal diagnosis was made in nine of the 10 affected infants. There were no false positive diagnoses. A false negative diagnosis occurred in an infant with a less severe form of the disease. Ultrasound is a valuable tool in the antenatal diagnosis of infantile polycystic kidney disease. (AM J OesTET GYNECOL 1984;150:259-62.)

Infantile polycystic kidney disease is an autosomal recessive disorder with an incidence of two per 100,000 births. 1 It can occur alone or be part of other genetic disorders (for instance, Meckel syndrome). The disease has a wide spectrum of renal and hepatic involvement and carries a poor prognosis with death occurring frequently in the postnatal period. Improved resolution of gray-scale ultrasonography has allowed the diagnosis of congenital anomalies when deviations in size, texture, and function of fetal organs are observed. 2 Incidental case reports have documented that sonography may be helpful in establishing the antenatal diagnosis of infantile polycystic kidney disease. 2 - 5 The purpose of this communication is to report the diagnostic value and limitations of sonography in the antenatal diagnosis of infantile polycystic kidney disease in a population at risk.

From the Department of Obstetrics and Gynecology, Yale University School of Medicine. This work was supported by a grant from the Philip and Anne Schaif Foundation for Medical Research. Received for publication April28, 1983; revised March 6, 1984; accepted May 4, 1984. Reprint requests: Roberto Romero, M.D., Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06510.

Material and methods Nineteen patients with fetuses at risk for infantile polycystic kidney disease were referred to the Perinatal Unit at Yale University School of Medicine for sonographic examinations between 1977 and 1981. All patients had a previous child with pathologically confirmed infantile polycystic kidney disease. This report limits itself to pure infantile polycystic kidney disease and does not address the diagnosis of polycystic kidney disease in the context of other genetic syndromes. Ultrasound examinations were performed with a static B scanner with a 3.5 MHz transducer (Picker, Northford, Connecticut) and/or real-time equipment with a 3.5 MHz transducer (ADR Ultrasound, Tempe, Arizona, or General Electric Dataline, Rancho Cordova, California). Particular attention was paid to the presence or absence of oligohydramnios and to the fetal urinary bladder, kidney size, as measured by the kidney circumference-to-abdominal circumference ratio, and renal texture. The kidney circumference-to-abdominal circumference ratio was calculated by the technique previously described by Grannum et al. 6 Oligohydramnios was defined as the absence of 1 em of amniotic fluid in any dimension. A positive antenatal diagnosis was made by the combination of oligohydramnios, absence of a fetal bladder, enlarged fetal kidneys (a kidney

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Table I. Ultrasound findings and pregnancy outcome of the affected infants Case No.

2 3

4

5 6

Clinical data

Gravida 3, para 2, age 30 Gravida 2, para I. age 24 Gravida 2, para I, age 23 Gravida 2, para I, age 29 Gravida 3, para 0, age 29 Gravida 3, para I, age 31

Gestational age at time of scan

Oligohydramnios

Bladder

18 wk 24 wk 18 wk 23 wk 25 wk 24.7 wk 33 wk

Not present Present Not present Not present Present Present

30 wk

Present

Not present

22 wk

Present

Not present

18 20 23 26

Not present Present Present Present

Equivocal Not present Not present Not present

wk wk wk wk

Not Not Not Not Not Not

present present present present present present

7

Gravida 2, para I, age 20

8

Gravida 5, para 3, age(?)

19 wk

Present

Not present

9

Gravida 2, para 0, age 28

22.3 wk

Present

Not present

10*

Gravida 2, para I, age 26

18 wk 23 wk 30 wk

Not present Not present Not present

Equivocal Present

Kidney circumferenceto-abdominal circumference ratio

0.28 0.38 <0.30 <0.30 0.40 0.42

0.40 0.45 <0.30 0.26-0.27 0.56 <0.33 0.37 0.46 <0.30 <0.30 0.33

*False negative.

circumference-to-abdominal circumference ratio >2 SD above the mean), and the typical hyperechogenic texture of the kidneys. 2 • 4 • 5 Follow-up was available in all cases. In nine of the 10 cases, diagnosis was made by histopathologic examination at autopsy. In one instance (Case No. 8) autopsy was refused but the diagnosis was accepted because of the association of a family history, bilateral flank masses, distended abdomen, anuria, and early neonatal death. In all negative cases physical examination, urinalysis, and creatinine levels were normal in the neonatal period. Seven of the nine infants with negative results also had normal renal sonography in the neonatal period. Results

Of the 19 fetuses at risk for infantile polycystic kidney disease, there were 10 infants with a positive postnatal diagnosis, for a prevalence of 53%. Table I shows the gestational age at the time of examination, ultrasound findings, outcome, and autopsy results in infants with a positive final diagnosis. All unaffected neonates at the time of ultrasound examination were found to have normal bladders, normal amniotic fluid volume, and normal kidney texture.

The kidney circumference-to-abdominal circumference ratio was normal in eight of the nine unaffected infants. The one normal infant displayed nephromegaly in serial so no graphic examinations. Postnatal sonography demonstrated a mildly enlarged but otherwise normal kidney anatomy and normal function. Of 19 patients examined, the antenatal diagnosis was made in nine cases. There were no false positive results and one false negative result (Case No. 10). The false negative result occurred in a case in which a fetal bladder was present and the amount of amniotic fluid was not decreased. The kidney circumference-to-abdominal circumference ratio at 30 weeks was normal and kidney texture was also thought to be normal. This infant had some residual kidney function at birth but died at 4 weeks of age after rapidly progressive renal failure and hypertension. In the 10 cases with affected fetuses, five women had elective midtrimester termination of pregnancy, two women had normal spontaneous deliveries, and three infants were born by cesarean section. The cesarean section performed in our institution was an elective repeat operative procedure. Of the two cesarean sections performed in other hospitals, one was done because of

Diagnosis of renal anomalies with ultrasound. II

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Renal texture

Pregnancy outcome

Normal H yperechogenic Normal Questionable H yperechogenic H yperechogenic

Prostaglandin abortion at 24 wk; bilateral infantile polycystic kidney disease Prostaglandin abortion at 25 wk; bilateral infantile polycystic kidney disease

H yperechogenic H yperechogenic Normal Texture questionable Hyperechogenic H yperechogenic H yperechogenic

H yperechogenic

Inadequate scan Normal Normal

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Normal spontaneous vaginal delivery at 34 wk; bilateral infantile polycystic kidney disease Cesarean section (repeat), breech; bilateral infantile polycystic kidney disease Saline abonion at 23 wk; bilateral infantile polycystic kidney disease Prostaglandin abortion at 23 wk; bilateral infantile polycystic kidney disease

Cesarean section at 37 wk (elective); bilateral infantile polycystic kidney disease Prostaglandin abortion at 20 wk; no autopsy; clinically Potter's Class I (bilateral flank masses, distended abdomen) Normal spontaneous vaginal delivery at 39 wk; bilateral infantile polycystic kidney disease Cesearean section at 40 wk (failure oflabor to progress) ; bilateral infantile polycystic kidney disease ; progressive renal failure, hypertension; died within 4 wk

failure of progress in labor, and one was elective for unclear indications.

Comrrient Infantile polycystic kidney disease is an autosomal recessive disorder with an incidence of two per 100,000 and a recurrence rate of 25%. The disease is associated with a poor prognosis and in its severe forms is uniformly fatal. Severe infantile polycystic kidney disease is clinically suspected in the neonatal period by bilateral flank masses, abdominal distention, and progressive renal failure. Pathologically, the kidneys are uniformly enlarged, proportional to the degree of renal involvement. Cylindrical cysts extending from the papillae to the cortex are present and represent proliferation and dilatation of the proximal collecting tubules. At this time the basic embryologic insult resulting in infantile polycystic kidney disease remains to be established. Subdivisions of infantile polycystic kidney disease have been proposed by Blyth and Ockenden 7 on the basis of the clinical presentation (age of onset) and the degree of renal involvement (histopathology). These subdivisions are: (l) perinatal with onset of renal failure in utero or at birth (the kidneys are massively dilated

Fig. 1. A transverse scan of normal fetal kidneys demonstrating the renal capsule (RC) and renal pelvis(P). The spine(S) is casting acoustic shadowing (AS) .

with 90% involvement, and there is rapid neonatal death); (2) neonatal (this group has smaller kidney size with 60% involvement, and there is mild hepatic fibrosis; death occurs within 1 year); (3) infantile (the disease presents by 3 to 6 months with 20% renal involvement, moderate hepatic fibrosis, and hepatosplenomegaly; it progresses to chronic renal failure, hypertension, and portal hypertension); (4) juvenile (the disease presents at 6 months to 1 year; there is less renal involvement; the course of the disease is similar to that in the infantile subgroup; and recurrences tend to be group-specific [this observation has been challenged8 ]). The use of ultrasound for examination of the fetal urinary tract is well documented in the literature.2 - 6 • 9 - 12 Both kidneys and bladder can be consistently imaged from 18 to 20 weeks on. Prior to 25 weeks the kidneys appear as hypoechogenic paraspinal structures. As gestation progresses the capsule and the pyelocaliceal system become apparent (Fig. 1) . A computer-assisted search (Medline) indicated that there have been seven documented cases of infantile polycystic kidney disease diagnosed antenatally. 2 - 5 The present communication constitutes the largest reported series and the only one in which the entire population referred for examination is documented. The diagnosis of infantile polycystic kidney disease in utero depends upon both abnormal renal anatomy (kidney size and texture) and the consequences of renal failure (oligohydramnios and the absence of a fetal bladder). Although it is generally recognized that se-

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broad spectrum of renal compromise, the in utero diagnosis may be limited to the severe forms. This is illustrated by our Case No. 10 which demonstrated virtually normal findings in utero and some residual renal function in the neonatal period. In conclusion, ultrasound is a helpful tool in the antenatal diagnosis of infantile polycystic kidney disease. The association of a positive family history, bilaterally enlarged kidneys, oligohydramnios, absence of a bladder, and the typical kidney texture is diagnostic. Diagnosis of a severe form can be made before 24 weeks when the option of elective termination of pregnancy is available. Serial sonographic examinations are recommended as the disease may become manifest after an original negative scan.

REFERENCES l. Potter EL. Normal and abnormal development of the

Fig. 2. Typical hyperechogenic sonographic image of a fetus affected with infantile polycystic kidney disease. PK, Polycystic kidneys. S, Spine. The kidney circumference-to-abdominal circumference ratio measured 0.38. vere forms of infantile polycystic kidney disease are associated with large kidneys, our data in the three patients with serial kidney measurements suggest that progressive enlargement occurs in utero and that kidney size may be normal in the early stages of the disease. The typical hyperechogenic renal texture seen in infantile polycystic kidney disease is thought to be due to sound enhancement by the microscopic cystic structures present in the renal parenchyma (Fig. 2). It seems that this typical texture evolves as the kidneys enlarge. Whether this occurs partially because of limitations of spatial resolution with present equipment or with the progression of the disease remains to be established. It must be stressed that enlargement of the kidney is not specific for infantile polycystic kidney disease. Benign nephromegaly in an otherwise normal child has been reported in the literature 13 and in this communication. As infantile polycystic kidney disease presents with a

kidney. Chicago-Year Book, 1972. 2. Hobbins JC, Grannum PAT, Berkowitz RL, et a!. Ultrasound in the diagnosis of congenital anomalies. AM J 0BSTET GYNECOL 1979;134:331. 3. Reilly KB, Rubin SP, Blanke BG, eta!. Infantile polycystic kidney disease: a difficult antenatal diagnosis. AM J 0BSTET GYNECOL 1979;133:580. 4. Hung JH, Luthy DA, Hirsch JH, eta!. Serial ultrasound of a pregnancy at risk for infantile polycystic kidney disease (PKD). Birth Defects 1982;18:173. 5. Habif DV, Berdon WE, Yeh MN. Infantile polycystic kidney disease: in utero sonographic diagnosis. Radiology 1982;142:475. 6. Grannum P, Bracken M, Silverman R, et a!. Assessment

7. 8. 9. 10. 11. 12. 13.

of fetal kidney size in normal gestation by comparison of ratio of kidney circumference to abdominal circumference. AMJ 0BSTET GYNECOL 1980;136:249. Blyth H, Ockenden BG. Polycystic disease of kidneys and liver presenting in childhood. J Med Genet 1971;8:257. Resnick J, Vernier RL. Cystic disease of the kidney in the newborn infant. Clin Perinatal 1981;8:375. Hadlock FP, Deter RL, Carpenter R, eta!. Sonography of fetal urinary tract anomalies. AJR 1981;137:261. Kaffe S, Rose JS, Godmilow L, eta!. Prenatal diagnosis of renal anomalies. Am] Med Genet 1977;1:241. Harrison MR, Filly RA, Parer JT, et a!. Management of the fetus with a urinary tract malformation. JAMA 1981;246:635. KnochelJQ, Lee TG, Melendes MG, eta!. Fetal anomalies involving the thorax and abdomen. Radio! Clin North Am 1982;20:297. Stapleton FB, Hilton S, Wilcox J. Transient nephromegaly simulating infantile polycystic disease of the kidneys. Pediatrics 1981;67:554.