Polycystic kidney disease Earlier diagnosis using ultrasound

POLYCYSTIC

KIDNEY

Earlier

Diagnosis

EDWARD

G. LUFKIN,

ALLEN

C. ALFREY,

Using Ultrasound M.D.t

M.D.

MARK E. TRUCKSESS, JOSEPH

DISEASE*

H. HOLMES,

M.D. M.D.

From the Department of Medicine, Colorado Medical Center, Denver,

University Colorado

of

ABSTRACT-A unique family study is presented, representing 124 member.9 11 J; ,I Sixty-four patients were studied clinically, and 31 were found to have sono;S~~~; 111 : polycystic kidney disease. Findings on intravenous urography were positive in !:‘t:/)! I Ultrasound is particularly useful in younger patients in whom urinary sympt,om (I: urographic abnormalities are infrequent. The merits of early diagnosis of this tli.;‘! : : risk are discussed. Ultrasound offers definite advantages over standard urogn. j I ! methods in the early diagnosis of polycystic kidney disease. ---.._ _

Recent progress in the management of chronic renal disease has made earlier diagnosis of polycystic kidney disease more urgent. In families at risk, early diagnosis permits selection of proper donors from the family for renal transplantation, guides career planning, influences medical care during pregnancy and surgical procedures, and facilitates marital and genetic counseling. Ultrasound offers unique advantages in the early diagnosis of polycystic kidney disease. Cystic lesions are especially well displayed by ultrasonic techniques, as shown by previous experience at this institution.1*2 No studies are available comparing the effectiveness of ultrasonic techniques with other diagnostic methods in polycystic kidney disease. The availability of a large kindred afflicted with polycystic kidney disease presented a unique opportunity to accomplish this goal. A total of 64 members of a family of 173 persons was evaluated clinically. Of this group, only 6 had had a previous diagnosis of polycystic kidney disease. *Study supported t Present 53901.

UROLOGY

address:

/

by U.S. Public Health Grant HE 02115. Mayo

JULY 1974

/

Clinic,

VOLUME

Rochester,

IV, NUMBER

Minnesota

1

I ,’ I I :I j ; !o i I , I iI

Method i II I I Members ofthe kindred were ~er.;:t~:~rir~t:~:l a two-month period. A con’,] I!I:~IX hi st~:~,r physical examination were p~~d‘ortnc:~cl. specimens were collected for Ireuatc~c~1~ ! II nalysis, and serum creatinine clf:tc.:.rn!i:rlatic:w II I each patient ultrasonic scanning IO/‘the, i;i :I I ‘8’ (and liver in some) and intrEn,czlllo1.1:,I~I:I;JI ;I 1 t were performed. Isotopic rer-.a.1 >cmnin: t I performed in 3 cases. The ultrasonic equipment used has ‘III ‘: I described in detail previously,:j as well ,I’. i :: application in the study of visceral lesion 11;..:I We employed compound scanning arld B III II I,: II:, ~‘t,li, display using a 2 megahertz trarisducer. compound scanning was accomplished t 1b ,;I. mechanical sector scan 30 degrees to eac11 :,i’c~I:’ of vertical, while the trallsduuer C’il:I‘Il*lL,I.‘ mounted on an overhead rack ‘was being rno~ecl simultaneously across the abdomen or h:td:.. The resulting pulse echo display on a I L oscilloscope screen was photographed for 1)ermanent record using self-developing film. 1it Iuid petrolatum applied generously to the sk-in afforded ultrasonic coupling between the transducer and the body surface. The kidneys were

•l

PATIENTS

cl

PROBABLE

n

DEFINITE

A t

STUDIE PKD PKD

CONSANGUINITY DEAD

FIGURE

1.

Genealogy

showing

scanned first in the prone position and then in right lateral positions. Cross sectional scans were made at 2-cm. intervals extending from the tenth intercostal space to the iliac crest. For liver scanning the patient was in the supine position, and scanning sections were made from 6 cm. above to 2 cm. below the right costal margin. Intravenous urography was performed following overnight water deprivation. Fifty ml. diatrizoate (Renovist) was injected and exposures made at three, five, ten, and twenty minutes. Urograms on 9 patients were obtained from other medical centers. The intravenous urograms were interpreted by 2 members of the radiology department without knowledge of physical findings or sonographic results. The ultrasonic photographs were coded and were interpreted by two of the authors without knowledge of the patient’,s identity. Prior experience in the interpretation of a sonogram had been achieved by ultrasonic studies of more than 20 patients with polycystic kidney disease whose diagnosis was proved by urographic, surgical, or necroscopic study. Positive sonograms were defined as those showing unequivocal,‘ .multiple, rounded echo patterns within the renal outline which surrounded circular or oval clear black areas of varying size. Furthermore, these clear, black

6

124 members

in four generations.

areas would not fill in with echoes when receiver sensitivity was increased, another characteristic of cyst fluid. These were easily distinguished from normal calyceal and renal pelvic echo patterns, which ordinarily do not intersect with cyst echoes. Additional diagnostic criteria included an increase in size of the kidney echo outline and distortion of the shape of the renal echo outline. Probably positive sonograms are defined as those showing suggestive or incomplete rounded patterns within the outline of at least one kidney. Four sonograms demonstrated different intrinsic echo displays from the usual calyceal pattern and were suspiciously positive but labeled negative because of absence of rounded outlines. Normal sonograms showed a renal echo pattern similar to the patterns from 22 normal medical students who served as controls. Results Based on the findings of this study and reported information from other family members, a family genealogic chart was prepared for 124 members from four generations (Fig. 1). This shows the incidence of polycystic kidney disease in the four generations selected. Inspection of the genealogic chart reveals an autosomal dom-

UROLOGY

/ JULY 1974 I

VOLUME

IV, NUMBER

1

TABLE

Case Number

Group I:

Age

Sex

Physical Findings

History

Patients with evidence

of polycystic

I.

Clinical

Blood I-Pressure (mm. Hg) pH

data*

Urinalysis---_1 Specific Gravity Sediment+

Serum Creatinine (mg./lOO ml.)

Intravenous Pyelogram

Ultrasound

Pos. Pos. L

Prob. B Prob. R Pas. B Prob. L

disease

Neg. Neg. RFM Hand deformity RFM Neg.

120180 128172 llO/SO 100/65

6 5 5 8

1.009 1.010 1.003 1.028

Neg. Neg. Neg. P+

120182 112174

6 7

1.016 1.015

.74 .53

Neg. Neg.

I’os. B Prob. R

Neg.

110/70

5

1.023

.89

Pos. B

Prob. B

M

ITTI, PKD Neg.

Neg.

M

Neg.

M

110/60 140/80 160/80 130/80 110/76 140/90

6 6 5 6 7 7

1.016 1.025 1.006 1.015 1.026

.81 .81 .85 .93 .57

Pos. B Neg. Neg. Neg. Neg. Pos. I>

Pos. B Pos. B Prob. B Pos. B Pas. B Prob. L

F F

BP Neg. P BP,UTI, Diabetes, PKD UT1 UT1

Neg. RFM Varicocele Neg. RFM

WBC+ RBC+ WBCt WBCtt RBCttt Neg. WBC+ Neg. Neg. P+ P-t

Neg. BFM

110/75 98170

6 6

1.024

.65 .72

Neg. Pos. B

Prob. L Pos. B

40

F

P,BP,H

152/98

5

1.019

.80

Pos. B

Pos. B

17 18

40 44

F M

108/72 150/88

5 6

Neg. Neg.

.80 1.09

Pos. B Pos. B

Prob. B Pos. B

19 20 21 22

45 46 46 46

F F M M

Neg. BFM BFM Neg.

130/80 145184 138185 110/70

6 5.5 6 6

1.010 1.003

WBC+ P+ WBC++ Neg.

.92 .91 .87 1.03

Neg. Pos. B Pos. B Neg.

Prob. B 1’0s. B Pos. B Pas. B

23

Fjg

M

UT1 P,S,BP, PKD,UTI Diabetes UT1 P Gout, BP,P P, PKD

Hepatomegaly, BFM Neg. BFM

Neg. RBC+ P+ Neg.

110/70

6

1.018

P+ RBC+

.90

Pos. B

Pas. B

24 25 26 27

SO 50 50 52

F F F M

Finger deformity, BFM Neg. Neg. Neg. LFM

120/90 125/75 llO/SO 2IO/130

6 . 5 5.5

1.012 1.015 1.005 1.020

WBC+

.76 .61 .93 1.61

Neg. Neg. Pos. B

Prob. B Prob. B Prob. B Pos. B

28 29

53 53

M M

BFM BFM

180/120 6 144194 7

1.015

Pos. B Pos. B

Pos. B Pos. B

30

54

M

BP, P

150/80

1.016

31

55

F

UT1

BFM, Short thumbs LFM

3 4

12 15 19 19

F F M M

Neg. UT1 H Neg.

5 6

19 21

M F

Neg. Neg.

7

23

F

8 9 10 11 12 13

23 24 26 27 29 35

14 15

35 37

16

1 2

Group II: 32 33 34 35

M M F

Neg. P,UTI Neg. P,BP, H,PKD BP BP

1.015

Neg..” 4-5 casts

170/94

5

1.005

RBC+ RBCttO-3 casts Pt+ RBCtt WBC+ Neg.

90/65 120172 118/76 120/80

6 5 6 6

1.006 1.000 1.020 1.005

Neg. Neg. Neg. Neg.

.61 .91 1.16 1.06

.87 .87

.49

Neg.

Pos. B

.61 .42 .68 .84

. .. Neg. Neg.

susp.

Prob. B

Patients with suspicious sonograms 9 12 20 39

M

Neg.

F

Neg.

F F

Neg. UT1

Neg. RFM ?LFM Goiter

SUSp.

susp. susp.

*KEY: Neg. = negative; Pos., positive; Prob., probably positive; Susp., suspicious; UTI, urinary tract infections; BP, hypertension; H, hematuria; P, flank pain; S, renal stones; R, right; L, left; B, bilateral; PKD, previous diagnosis ofpoIycystic kidney disease; RFM, right flank mass; LFM, left flank mass; BFM, bilateral flank mass. t + = 1 to 5 cells per high-power field, ++ = 6 to 25 cells, +++ = over 25 ceils, P = proteinutia, trace - one pius.

UROLOGY

I

JULY

1974

/

VOLUME

IV, NUMBER

I

TABLE II. Relative effectiveness sonographic

Age Range 11to20 21 to 30 31 to 40 41to50 51 to 60 TOTALS

Number of Cases

History of Polycystic Kidney Disease

5 7 5 9 5 31

0 1 2 3 2 s

evidence

of diagnostic measures in 31 patients of polycystic kidney disease

History of Urinary Symptoms 2 2 5 6 2 17

inant mode of inheritance, as expected.4 Consanguinity was present in one instance, a marriage between second cousins, involving Case 19. This woman and her two sons had polycystic kidney disease. Her husband was not studied, but at 62 years was well. None of his 8 siblings were known to have polycystic kidney disease. The patients were divided into 2 groups: Group I consisted of 31 patients with ultrasonic findings consistent with polycystic kidney disease; Group II consisted of 4 patients with sonograms which were neither normal nor characteristic of polycystic kidney disease. Clinical findings for both groups are presented in Table I. The remaining 29 individuals examined showed no positive diagnostic findings by ultrasound. Only 6 of the 64 patients examined had a previous diagnosis of polycystic kidney disease. Review of the medical histories of those with positive sonograms revealed that 9 of the 31 patients had had one or more urinary tract infections; 9 had complained of flank pain; 3 had noted hematuria in the past; and 9 had a history of hypertension. There was 1 patient in whom proteinuria had been discovered previously. One patient had had renal stones. Of the 29 members with negative sonograms, 5 had a history of repeated upper urinary tract infections and 2 a history of hematuria. In one of these, the hematuria was thought due to recurrent urinary tract infection and, in the other, to prostatitis. The physical finding most characteristic of polycystic kidney disease was a palpable flank mass (or masses) representing enlarged kidneys. In Group I there were 8 patients with bilateral flank masses and 6 with a unilateral flank mass. Hypertension (systolic over 140 mm. Hg, diastolic over 90 mm. Hg) was also a common finding. There were 9 patients in Group I with polycystic kidney disease who had a systolic pressure of over 140 mm. Hg, and 5 with a dias-

8

Hypertension 0 1 1 2 5 9

Flank Mass(es) 2 1 3 4 5 i-5

with

Abnormal Urinalysis 2 4 2 5 4 i7

Abnormal Intravenous Pyelogram 2 2 4 4 3 15

of3 of 7 of5 of8 of4 of 27

tolic pressure over 90 mm. Hg. In the 29 patients with negative sonographic findings, there were only 2 with an elevation in systolic pressure (148 and 150 mm. Hg). There was no elevation of the diastolic pressure in any patient in this group. Urinalysis revealed positive findings in 17 of the 31 patients in Group I (Table I). Hematuria and pyuria were graded as follows: 1 plus, 1 to 5 cells per high-power field; 2 plus, 6 to 25 cells; and 3 plus, over 25 cells. Six of the patients had 1 plus proteinuria, and 1 patient had 2 plus. Eight patients showed hematuria (5 had 1 plus, 2 had 2 plus, 1 had 3 plus). Eight patients had pyuria (6 had 1 plus, 2 had 2 plus). One patient had granular casts. Serum creatinine level was slightly elevated in 1 patient, and markedly elevated in another who was uremic. In 15 of the 31 patients in Group I, urographic findings were consistent with the diagnosis of polycystic kidney disease. These radiologic changes included renal enlargement, elongation of the calyces, rounded deformities of the collecting system, and localized areas of diminished dye concentration. Of the 29 patients who had no evidence of polycystic kidney disease, all had normal findings on intravenous pyelograms. In Group II, of the 4 patients who had suspicious sonograms, urographic findings were normal in all (Table I). Isotopic renal scanning with 85 mercury was performed in 3 patients (Cases 7, 11, 19) with polycystic kidney disease. Two scans showed multiple “cold” areas consistent with the diagnosis of polycystic kidney disease. Ultrasonic liver scans were performed in 5 cases. Three patients (Cases 8,9, 16) showed abnormalities which were consistent with polycystic liver disease; each had associated polycystickidneydiseasedemonstrablebyultrasound. The relative effectiveness of urography and sonography in detection of polycystic kidney disease is shown in Table II.

UROLOGY

/ JULY1974 I VOLUMEIV,NUMBERl

Case Abstracts Case 1 This twelve-year-old girl had been well, and results of physical examination, urinalysis, and intravenous pyelogram were normal. However, sonography revealed enlargement and cystic changes of the right kidney in comparison with the left which appeared to be normal (Fig. 2). Case

FIGURE 2. Case 1. Sonogram of kidneys; right kidney is enlarged and cystic; left kidney is normal.

11

A twenty-seven-year-old man had an unreand physical examination markable history (Table I). Sonograph ic results revealed evidence of bilateral polycystic kidney disease (Fig. 3A and B). There were also abnormalities in the

FIGURE 3. Case 11. (A) patterns indicating cysts. skin is subcutaneous fat. pyelogram demonstrating

Sonogram of right kidney; note marked renal enlargement and multiple rounded echo (B) Left kidney; note multiple echo patterns consistent with cysts; clear area beneath (C) 85Hg renal scan showing multiple cold areas consistent with cysts. (D) Intravenous normal findings.

UROLOGY

VOLUME

/ JULY 1974

I

IV, NUMBER

1

FIGURE 4. Case 19. (A) Sonogram of right kidney showing multiple echo patterns consistent with cysts; echoes from spine are seen in bottom center. (B) Left kidney showing increased echo activity suggestive of multiple cysts. (C) 85Hg renal scan showing multiple cold areas. (D) Intravenous pyelogram demonstrating normal findings; dilation of right pelvis due to abdominal compression during procedure.

isotopic renal scan, particularly on the left, which were nonspecific in appearance (Fig. 3C). Findings on intravenous pyelogram were normal (Fig. 3D).

Case 19 This forty-five-year-old white woman, the mother of patient in Case 11, had been well except for a urinary infection years previously. Blood pressure was 170/94 mm. Hg. A mass was palpable in the left flank which appeared to transmit the aortic pulse. Results of urinalysis were negative (Table I). Sonography revealed bilaterally enlarged and cystic kidneys (Fig. 4A and B). Abnormalities were noted on the isotopic renal scan (Fig. 4C); however, as was the case with her son, the intravenous pyelogram showed normal findings (Fig. 4D). Case

29

A fifty-three-year-old white man was well except for hypertension of four years’ duration. Examination showed blood pressure 144/94 mm. Hg and bilateral flank masses. Urinalysis revealed trace proteinuria and 7 to 10 red blood

10

cells per high-power field. Bilateral renal enlargement and multiple cysts were noted on sonography (Fig. 5A and B). There were urologic abnormalities consisting of renal enlargement, elongation of calyces, and curved indentations of the pelvis (Fig. 5C). Comments The results of this study clearly reveal the capability of improved and earlier diagnosis of polycystic kidney disease using ultrasound. As shown in Table I, 15 patients had both sonographic and urographic evidence of the disease, and 6 additional patients were shown to have the disease by sonography when urography gave negative results. Thus it appears that sonography is more sensitive than urography in the diagnosis of this disease; perhaps because sonography outlines a cyst wall directly and graphically, whereas urography demonstrates cysts indirectly through distortion of the renal collecting system. This distortion does not occur early in the course of the disease when cysts are small. Because of its insidious course and infrequency, polycystic kidney disease remains a

UROLOGY

I JULY1974 I VOLUMEIV,NUMBERl

FIGURE 5.

Case 29. (A) Sonogram

o.f

right kidney; note multiple cysts, renul enlargement, and marked irregularity of renal surface. (B) Left kidney also showing multiple cysts. (C) lntruvenous pyelogram showing bilateral renal enlargement and multiple distortions due to large cysts.

diagnostic challenge “so that it is not remarkable that the presence of polycystic kidneys is often demonstrated unexpectedly at operation or autopsy.“4 Improved diagnostic tools would be welcomed by anyone dealing with this disease. Earlier recognition of polycystic kidney disease by sonography is shown in Table II. In the age group under thirty, 12 patients showed sonographic evidence of the disease, of whom only 4 showed urographic evidence. Of those patients over thirty years of age, 19 had sonographic evidence of the disease, of whom 11 had urographic evidence. Symptoms and physical findings were uncommon in our younger patients with the disease. Of I2 patients under thirty years, urinary symptoms were present in only 4 (gross hematuria in 2, and recurrent urinary infections in 2). A palpable flank mass was present in 3, and 1 patient also had hypertension. These findings were elicited by physicians searching specifically for them. Without surgical confirmation, we cannot be certain of a diagnosis using sonography alone. Figure 3 demonstrates, how-

UHOLOCY

/

JULY 1974

/

VOLUME IV, NUMBER 1

ever, that dramatic renal sonographic abnormalities may be obtained in patients at risk of having polycystic kidney disease who have normal findings on history, physical, and urographic examination. Improvements in scanning technique and equipment can be expected. Present needs are especially for improved transducer focusing and sensitivity, and for stability of electronic circuitry. Follow-up evaluation of the patients in this series after a period of years will allow confirmation or denial of earlier findings in uncertain cases. Ultrasound techniques are rapidly becoming familiar to specialists who deal with renal mass lesions. Useful information can be obtained sonographically to distinguish renal cysts from tumors,s-X and isolated cases of polycystic kidney disease have been mentioned in the differential diagnosis of renal masses.5s7.x Aspiration and biopsy of cystic lesions is facilitated by sonographic monitoring.!’ Ultrasound presents distinct advantages over other diagnostic techniques. Examinations are

11

performed rapidly, with no discomfort to the patient and no special preparation by the patient. Results are immediately available for interpretation. There is no tissue toxicity at the lowpower levels used (less than 20 milliwatts per square centimeter skin surface). Use during pregnancy is safe since no ionizing radiation is involved. Uremia does not decrease the effectiveness of sonography.

Denver, Colorado 80220 (DR. HOLMES)

ACKNOWLEDGMENTS. We gratefully acknowledge the technical assistance of Mrs. Jacqueline Carlson and Mr. Clifford Williams, and the secretarial assistance of Mrs. Lorraine Carlson and Deborah Longhofer.

12

References 1. HOLMES, J. H., and HOWRY, D. H.: Ultrasonic diagnosis of abdominal disease, Am. J. Dig. Dis. 8: 12 (1963). 2. GOTTESFELD, K. R., TAYLOR, E. 8, THOMPSON, H. E., and HOLMES, J. H.: Diagnosis of hydatidiform mole by ultrasound, Obstet. Cynecol. 30: 163 (1967). 3. HOLMES, J. H., et al.: Ultrasonic contact scanner for diagnostic application, Am. J. Med. Obstet. 4: 147 (1965). 4. DALGAARD, 0. Z.: Bilateral polycystic disease of the kidneys, Acta Med. Sand. (Suppl. 328) 158: 1 (1957). 5. MOUNTFORD, R. A., et al.: The use of ultrasound in the diagnosis of renal disease, Br. J. Radiol. 44: 860 (1971). 6. GOLDBERG, B. B., OSTRUM, B. J.,and ISARD, H. J.: Nephrosonography: ultrasound differentiation of renal masses, Radiology 90: 1113 (1968). 7. BARNETT, E., and MORLEY, I’.: Ultrasound in the investigation of space-occupying lesions of the urinary tract, Br. J. Radiol. 44: 733 (1971). 8. STUBER, J. L., TEMPLETON, A. W., and BISHOP, K.: Ultrasonic evaluation of the kidneys, Radiology 104: 139 (1972). 9. GOLDBERG, B. B., and POLLACK, H. M.: Ultrasonic aspiration- biopsy transducer, ibid. 108: 667 (1973).

UROLOGY / JULY 1974 / VOLUME IV, NUMBER

1