Intrarenal Reflux and Renal Damage

THE

Vol. 115, March Printed in U.S.A.

JOURNAL OF UROLOGY

Copyright© 1976 by The Williams & Wilkins Co.

INTRARENAL REFLUX AND RENAL DAMAGE HAL H. BOURNE, VIRGIL R. CONDON, TERRY S. HOYT

AND

G. WILLIAM NIXON

From the Divisions of Urology and Radiology, Primary Children's Medical Center, Salt Lake City, Utah

ABSTRACT

The retrograde flow of dye from the calices into the collecting tubules (intrarenal reflux) seen during cystography in children and its effect on the kidneys were evaluated. A retrospective analysis was made of 175 patients with excretory urograms revealing cortical atrophy. Of these patients 68 per cent had cystograms revealing vesicoureteral reflux. Intrarenal reflux was seen in 8 patients less than 6 years old, an incidence of 13.5 per cent in that age group. There was a high correlation, 7 of 8 or 87.5 per cent, between the areas of intrarenal reflux, and associated renal cortical atrophy and calicectasis. Intrarenal reflux provides a pathway by which bacteria and hydrostatic pressure may produce injury to the renal parenchyma. The presence of intrarenal reflux is an absolute indication for ureteroneocystostomy. The discovery of vesicoureteral reflux has done much to clarify the pathway by which bacteria reach the pelviocaliceal system of the kidney. The phenomenon seen radiographically during voiding cystography when contrast material passes from the pelviocaliceal system into the collecting tubules defines a route by which bacteria may enter and inoculate the parenchyma of the kidney (fig. 1). This process has been called pyelotubular backflow, renal tubular reflux, calicotubular backflow, renal reflux and intrarenal reflux. We prefer the latter term because of its association with vesicoureteral reflux. Herein we describe this phenomenon in 8 children and its apparent effect on the kidneys.

obtained if reflux is noted. If there is moderate or severe reflux the renal pelvis and ureter are evaluated for peristaltic activity and rate of emptying. The patient is asked to void again and a subsequent scout film is obtained 15 to 30 minutes before IVP. Most of these patients had been evaluated radiographically because of urinary tract infections. Severity of vesicoureteral reflux was classified by the method of Rolleston and associates as slight, moderate or severe. 1 Slight reflux resulted in incomplete filling of the upper urinary tract without dilation, moderate when the entire upper urinary tract filled without dilatation and severe when complete filling occurred with ballooning or dilation of the calices and ureter.

METHOD AND MATERIALS

From 1962 to 1972, 175 excretory urograms (IVPs) were coded as showing cortical thinning with associated calicectasis. voiding cystourethrography was performed on all patients and reviewed retrospectively. Of these patients 119 (68 per cent) had vesicoureteral reflux and 8 had intrarenal reflux. Patient age ranged from 4 months to 19 years. TECHNIQUE OF VOIDING CYSTOURETHROGRAPHY

A conventional preliminary anteroposterior abdomen film is obtained following catheterization of the bladder. The bladder is filled using a gravity drip method through an intravenous tubing from contrast medium placed 30 cm. above the bladder level. The contrast agent is a sterilized solution of oral hypaque in approximately a 10 per cent concentration. The bladder is filled by gravity drip until the contrast material does not run or until the patient complains of discomfort, at which time the catheter is clamped and the filling tube is disconnected. Anteroposterior and oblique abdomen films are then obtained. Subsequently, the patient is moved to a radiographic fluoroscopic room and, if old enough to stand, is placed in a plastic bag and allowed to void under fluoroscopic observation. The female patients are positioned in an anteroposterior position while the male patients are in a 45-degree oblique position. The voiding study is observed fluoroscopically and recorded on video tape and 70 mm. spot films. After completion of voiding a brief scan of the renal areas is performed to further look for intrarenal reflux. Additional spot films of these areas are then Accepted for publication July 18, 1975. Read at annual meeting of Western Section, American Urological Association, Portland, Oregon, April 13-17, 1975. 304

FIG. 1

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INTRARENAL REFLUX AND RENAL DAMAGE

Patients with cortical thinning Age (yrs.) Cystograms Vesicoureteral reflux Intrarenal reflux

RESULTS

1 2 3 4 5 6 7 8 9 10 11 12 13 >14 14 175 4 8 15 16 23 14 15 17 16 13 9 7 4 10 119 (68%) 3 3 12 16 13 11 9 12 12 8 5 4 I -

1 -

4

2

1- -

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-

-

-

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8

Of the 175 patients with IVPs revealing cortical thinning and anatomically associated calicectasis 119 (68 per cent) had vesicoureteral reflux. The age range was 4 months to 19 years (see table). There were 55 male and 120 female patients. All 8 cases of intrarenal reflux occurred in patients less than 6 years old. In this same age group there were 59 cystourethrograms performed, producing an incidence of intrarenal reflux of 13.5 per cent. All 8 patients with intrarenal reflux were investigated because of recurring urinary tract infections documented with positive cultures and colony counts of more than 100,000 organisms. Vesicoureteral reflux was classified as severe in all of these patients. Renal damage was focal or generalized and defined as 1) cortical thinning, 2) calicectasis and 3) decrease these 8 patients 7 (87.5 per cent) had renal in renal size. damage which corresponded to the exact area or areas of intrarenal reflux. Figure 2 illustrates generalized intrarenal .reflux with associated calicectasis, cortical thinning and decrease in renal size. Figure 3 is an illustration of focal superior caliceal and cortical

Or

DISCUSSION

"Chronic pyelonephritis is the end result of a bacterial infection of the kidney in which pathological changes are found in both the parenchyma and the pelvicalyceal system. " 8 Pathologic and radiographic changes of caliceal dilation and distortion with loss of cupping can be seen in the pelviocaliceal structures. The parenchymal changes are thinning of the cortex overlying the caliceal changes with focal or generalized

FIG. 2

HISTORY OF INTRARENAL REFLUX

Pyelotubular backflow that occurs during retrograde pyelography is well known. In 1912 Blum injected cadaver kidneys with collargol and demonstrated radial streaks from the apices of the calices to the outermost portion of the cortex.2 In 1965 Brodeur and associates demonstrated vesicoureteral reflux in 18 children using micropaque barium. 3 Of these children 5 had intrarenal reflux. Followup films taken 24 hours later revealed that the barium was no longer evident in the renal parenchyma in the first 4 patients and the barium remained within the renal parenchyma on periodic films during a 6-month period in 1. Renal tubular casts containing barium particles were found during a 2-month period thereafter. In 1970 Amar reported 8 cases of what he termed calicotubular backflow during voiding cystography. 4 He proposed this route as the way bacteria invade the renal parenchyma and initiate, complicate and perpetuate pyelonephritis. Hodson and associates have produced intrarenal reflux in piglets. 5 - 7 Intrarenal reflux also has been reported by Rolleston and associates. '· •

FIG. 3

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BOURNE AND ASSOCIATES

reduction in renal size. "This is a combination of findings unique for chronic pyelonephritis and not mimicked by other conditions with the possible exception of papillary necrosis." 8 Triangular cortical scars are often noted. Histologically, there is a loss or atrophy of the tubules with conversion of some of the tubules into thyroid-like areas. Periglomerular interstitial fibrosis with infiltration by chronic inflammatory cells completes the picture. Historically, we have talked about 3 possible routes by which bacteria reach the kidney: 1) by an ascending pathway from the bladder up the ureter to the pelviocaliceal system (vesicoureteral reflux), 2) by the blood stream and 3) by the lymphatics. Only vesicoureteral reflux seems to have any real significance as an entry route with the rare exception of blood borne coagulase positive organisms. How do bacteria find their way from the pelviocaliceal system to the renal substance?_ The 4 possible routes are by: 1) an ascending pathway from calix through the papilla and collecting ducts to tubules (intrarenal reflux), 2) the blood stream, 3) the lymphatics and 4) direct extension. Intrarenal reflux may well provide the primary entry site for bacterial invasion of the renal parenchyma. The high degree of correlation between the areas of intrarenal reflux and renal damage in these 8 patients (88 per cent) suggests that this is a route by which bacteria gain entry to the renal parenchyma. Hodson has observed the development of pyelonephritic scars in piglet kidneys with intrarenal reflux under sterile conditions. 7 The scars developed only in those areas with intrarenal reflux, suggesting that sterile hydrodynamic renal damage can occur without superimposed infection. Ransley and Risdon also have studied the renal papillae in piglets with intrarenal reflux. 9 They found that intrarenal reflux is most common in the papillae of the upper and lower poles and that the duct orifice on the larger compound papillae of the upper and lower poles cannot be occluded by a rise in pressure within the calix. This is in contrast to the mid-zonal papillae where the orifices close readily with caliceal pressure. In the mid-zonal papillae the papillary ducts have slit-like orifices that open obliquely on the convex surface of the papillae. In the polar areas the ducts are larger, wide open and open directly into concave papillae (fig. 4). Their studies suggest that there are competent and incompetent collecting ducts. The failure to find intrarenal reflux in patients more than 6 years old suggests that a maturation process at the papillary level may occur. The exact incidence of intrarenal reflux is unknown. However, Rolleston and associates have reported an incidence of 6. 7 per cent of intrarenal reflux in children less than 5 years old. 6 Brodeur and associates, using barium as the contrast material, found intrarenal reflux in 27 per cent of children with vesicoureteral reflux. Better bowel preparation, increased awareness of intrarenal reflux, improved contrast media and better radiographic technique may reveal intrarenal reflux to be more prevalent than we had supposed.

FIG. 4. Reprinted with permission' REFERENCES

1. Rolleston, G. L., Shannon, F. T. and Utley, W. L.: Relationship of infantile vesicoureteric reflux to renal damage. Brit. Med. J., l:

460, 1970. 2 · Kohler, R.: Investigations on backflow in retrograde pyelography; roentgenological and clinical study. Acta Radio!., suppl. 99, pp. 1-92, 1953. 3.

4.

5. 6.

~: 9.

Brodeur, A. E., Goyer, R. A. and Melick, W.: A potential hazard of barium cystography. Radiology, 85: 1080, 1965. Amar, A. D.: Calicotubular backflow with vesicoureteral reflux: relation to pyelonephritis. J.A.M.A., 213: 293, 1970. Hodson, C. J.: Fifth International Congress of Nephrology, Mexico. Abstract 598, 1972. Rolleston, G. L., Maling, T. M. and Hodson, C. J.: Intrarenal reflux and the scarred kidney. Arch. Dis. Child., 49: 531, 1974. Hodson, C. J.: Personal communication. Heptinstall, R.H.: The enigma of chronic pyelonephritis. J. Infect. Dis., 120: 104, 1969. Ransley, R. G. and Risdon, R. A.: Renal papillae and intrarenal reflux in the pig. Lancet, 2: 114, 1974.