Vol. 118, Octob~r Printed in U .SA.

THE JOURNAL OF UROLOGY

Copyright© 1977 by The Williams & Wilkins Co.

PEDIATRIC HYPERTENSION AS A DELAYED SEQUELA OF REFLUXINDUCED CHRONIC PYELONEPHRITIS JOHN F. STECKER, JR.,* BISHOPP. READ

AND

EUGENE F. POUTASSE

ABSTRACT

Chronic pyelonephritis secondary to vesicoureteral reflux has been shown to cause occasionally systemic hypertension. The hypertension rnay occur in the presence or absence of bacterial urinary infection, is renin-rnediated and rnay develop years after ureteral reimplantation. Surgical excision of a scarred atrophic renin-producing segment may result in amelioration of the hypertension or at least provide better medical control with less toxic antihypertensive agents. Surgical removal of renal tissue is not recommended in patients with depressed renal function unless the hypertension is malignant and uncontrolled. Hypertension in childhood is not common but, when discovered, is most often owing to an underlying remedial cause.'· 2 Recent reports have suggested that vesicoureteral reflux with or without associated urinary tract infection may result in chronic pyelonephritis with possible development of systemic hypertension. 3--5 Whether ureter al reimplantation will protect against the development of this renal-mediated hypertension is not well established. Herein we review our experience with patients who underwent vesicoureteral reimplantation for reflux to determine the incidence of hypertension postoperatively. MATERIALS AND METHODS

Seventy patients, between 2 and 23 years old, who had undergone unilateral or bilateral vesicoureteral reimplantation were evaluated 1 to 19 years postoperatively. Blood pressures were determined in both arms with the patients in the supine as well as sitting positions and repeated in 30 minutes if abnormal. Normal age-related blood pressures as determined by the Pediatric Council on Hypertension were used (table l)." Of the 70 patients 3 were hypertensive. CASE REPORTS

Case 1. A 14-year-old white boy was hospitalized with headaches and a resting blood pressure of 180/130. History included transurethral resection of posterior urethral valves followed by bilateral vesicoureteral reimplantation for continued reflux when he was 7 years old. The boy continued to have recurrent urinary tract infections until he was 9 years old, when a left vesicoureteral reimplantation was done for continued reflux. An excretory urogram (IVP) revealed a scarred atrophic left kidney, measuring 10 cm. in length with moderate calicectasis but no ureteral dilatation. The right kidney measured 14 cm. in length with a normal collecting system. A cystogram failed to demonstrate reflux. Renin determinations were peripheral 872, left renal vein 1,294 and right renal vein 587. A renal angiogram failed to reveal any main renal artery or branch arterial lesions. Creatinine clearance was 71 cc per minute per square meter. A left nephrectomy was performed and the pathology revealed chronic atrophic pyelonephritis with medial hyperplasia of the arterioles. Blood pressure stabilized at 110/70 and has remained normal without antihypertensive agents. Case 2. A 6-year-old white girl was hospitalized with a sudden onset of headaches and blood pressure of 210/160. Accepted for publication December 10, 1976. *Requests for reprints: 100 Hague Medical Center, 400 W. Brambleton Ave., Norfolk, Virginia 23510. 644

History included recurrent urinary tract infections and bilateral vesicoureteral reflux, resulting in bilateral ureteral reimplantations when she was 2 years old (fig. 1, A). She had no documented urinary tract infections after reimplantation and no voiding difficulties. The hypertensive IVP revealed mild calicectasis and renal scarring bilaterally with moderate atrophy of the left lower pole (fig. 1, B). Creatinine clearance was 77 cc per minute. Angiography revealed normal renal arteries without evidence of narrowing (fig. 2). Because of the severity of the hypertension nitroprusside, methyldopa and reserpine were administered with reasonable control. Peripheral renin was 1,900. Selective renal vein renins were obtained but unfortunately they were lost. A left lower pole nephrectomy was done 3 days after hospitalization. Pathology of the removed renal segment revealed chronic inflammatory scarring with medial thickening of the segmental arteries (fig. 3). Blood pressure decreased to 150/90 but postoperative peripheral renins remained elevated. The patient was started on propranolol hydrochloride with a further decline of the blood pressure to 130/90 and a repeat renin determination before she was discharged from the hospital was 480. Propranolol hydrochloride was tapered gradually and, presently, she is taking methyldopa and hydrochlorothiazide with a blood pressure of 110/70 and a peripheral renin of 430. Case 3. An 11-year-old black boy was hospitalized with a blood pressure of 125/90 and recurring episodes of acute pyelonephritis. History included transurethral resection of posterior urethral valves and bilateral vesicoureteral reimplantation for reflux associated with mild ureterovesical junction obstruction when he was 18 months old. Because of continued pyelonephritis, upper tract deterioration and urinary inconti-

TABLE

1. Percentile values for blood pressure by age* Systolic Pressure

Diastolic Pressure

Age 0 to 6 mos. 3 yrs. 5 yrs. 10 yrs. 15 yrs.

50%

95%

50%

95%

80 95 97 110 116

110 112 115 130 138

45 64 65 70 70

60 80

* Adapted from the Pediatric Council on Hypertension. TABLE

84

92 95 6

2. Causes of childhood and adolescent hypertension

Renal artery stenosis Chronic pyelonephritis Hydronephrosis Renal hypoplasia/dysplasia Renal tumors (Wilms, reninoma) Adrenal tumors (pheochromocytoma, neuroblastoma)

PEJJIA TRIC HYPERTENSION

Fm. Case 2. A, when patient was 2 years old reveals bilateral vesicoureteraJ reflux with caliceal blunting. B, nephrogram afte:r renal angiogram de1rnons1t:rates cortical atrophy and scarring bilaterally

Fm. 2. Case 2-renai angiogram demonstrates normal main and segmental renal arteries

revealed a with calicectasis. s cm. and the left 10.5 cm. Creatinine clearance in the left cc per minute and 10 cc per minute in the Renal angiography revealed no main renal artery or branch stenosis. Peripheral renin determinations were with mandelic acid and catecholamines within was administered and blood pressure is ll0/70. 0 ~'"'''""'""

DISCUSSION

The incidence

nence bilateral cutaneous ureterostomy was done when he was old. The had occasional of acute that re:,vcmctect to antibiotics. he was 10 blood pressure was 140/90. An !VP at that time

-v·,-----

in childhood

646

STECKER, READ AND POUTASSE

associated with childhood hypertension. 1- 5 , 7 • 8 The association of systemic hypertension and chronic pyelonephritis was established as early as 1939 by Weiss and Parker, who demonstrated that 15 to 20 per cent of patients with malignant hypertension exhibited pathologic changes consistent with chronic pyelonephritis. 9 Whether the pyelonephritis initiated, aggravated or merely was a result of the hypertension remains to be established. 9 It later became evident that patients with bilateral pyelonephritis or reduced renal function leading to azotemia/uremia had a much higher incidence of hypertension. 10--12 In addition, surgical removal of unilateral pyelonephritic kidneys was shown to cure occasionally systemic hypertension. 8• 13 The relationship of vesicoureteral reflux and pyelonephritis has been well established by many investigators. 1a- 15 Even in the absence of urinary tract infection sterile reflux may result in interstitial nephritis, a clinical entity essentially indistinguishable from chronic pyelonephritis, except for the absence of bacterial urinary tract infection. 3 Recently, a definite cause and effect reiationship between reflux-induced pyelonephritis and systemic hypertension has been demonstrated. 3 • 5 • 7 As in our 3 patients peripheral renins were elevated but the renal angiogram failed to reveal any renovascular disease. However, all patients demonstrated radiographic changes of chronic pyelonephritis, including calicectasis, segmental renal atrophy and renal scarring. Since hypertension may occur years after vesicoureteral reimplantation (4 to 10 years in our patients) obviously elimination of reflux does not protect against its development. This may reflect a relative segmental renal ischemia or further loss of renal medullary tissue. Despite renal growth the location and appearance of renal scarring change little. Possibly, as the child matures and renal growth occurs the increased renal mass outstrips its blood supply, particularly in areas compromised by pyelonephrotic scarring and arteriolar narrowing, resulting in a relative segmental renal ischemia. In addition, the renal medulla has been shown to produce a vasodepressor substance, prostaglandin E2, which will attenuate the vasoconstrictor activity of angiotensin II. u;-is Possibly, loss of renal medullary tissue in the chronic pyelonephrotic kidney results in decreased secretion of prostaglandin E2, thus upsetting the balance between vasopressor/vasodepressor activity. However, hypertension appears to be renin-mediated. With lateralization ofrenal vein renins and further localization of increased renin secretion to a particular scarred atrophic segment, surgical removal of that renal segment may be beneficial in ameliorating or allowing better medical management of the hypertension. 7 The prospective management of patients with renin-mediated hypertension secondary to chronic pyelonephritis depends on whether the renal involvement is unilateral or bilateral, the level of renal function and the degree of hypertension. Surgical removal of a poorly functioning atrophic renin-producing pyelonephrotic kidney certainly would be indicated provided the contralateral kidney is normal, as in case 1. If the disease is bilateral and elevated renin secretion can be localized to a particular atrophic renal segment we recommend excision of that segment provided that renal function is normal or only mildly depressed as in case 2. If azotemia is present or removal of a renin-producing renal segment will compromise renal function, as in case 3, medical management with antihypertensives is indicated.

Despite the association of reflux and dysgenetic renal segments, and renal dysgenesis with hypertension (Ask-Upmark kidney) no dysgenetic segments were noted in our cases. 19• 20 Rather, medial hyperplasia of the arterioles and arteriolar nephrosclerosis were the prominent pathologic findings.

100 Hague Medical Center, 400 W. Brambleton Ave., Norfolk, Virginia (J. F. S.)

REFERENCES

1. Korobkin, M., Pick, R., Merten, D., Perloff, D. andPalubinskas, A.: Etiologic radiographic findings in children and adolescents with nonuremic hypertension. Radiology, 110: 615, 1974. 2. Loggie, J. and Rauh, L.: Persistent systemic hypertension in the adolescent. Med. Clin. N. Amer., 59: 1371, 1975. 3. Stickler, G. B., Kelalis, P. P., Burke, E. C. and Segar, W. E.: Primary interstitial nephritis with reflux. A cause of hypertension. Amer. J. Dis. Child., 122: 144, 1971. 4. Bailey, R. R.: The relationship of vesico-ureteric reflux to urinary tract infection and chronic pyelonephritis-reflux nephropathy. Clin. Nephrol., 1: 132, 1973. 5. Siegler, R. L.: Renin-dependent hypertension in children with reflux nephropathy. Urology, 7: 474, 1976. 6. Mitchell, S. C., Blount, S. G., Jr., Blumenthol, S., Hoffman, J., Jesse, M., Lauer, R. and Weidman, W.: The pediatrician and hypertension. Pediatrics, 56: 3, 1975. 7. Javadpour, N., Doppman, J. L., Scardino, P. T. and Bartter, F. C.: Segmental renal vein renin assay and segmental nephrectomy for correction of renal hypertension. J. Urol., 115: 580, 1976. 8. Haycock, G. B.: Hypertension associated with unilateral renal disease in childhood. Acta Pediatr. Scand., 64: 299, 1975. 9. Weiss, S. and Parker, F., Jr.: Relation of pyelonephritis and other urinary tract infections to arterial hypertension. New Engl. J. Med., 223: 959, 1940. 10. Brod, J.: Chronic pyelonephritis. Lancet, 1: 973, 1956. 11. Heale, W. F.: Chronic pyelonephritis in the adult. Aust. New Zeal. J. Med., 1: 283, 1971. 12. Dillon, M. J.: Renin and hypertension in childhood. Arch. Dis. Child., 49: 831, 1974. 13. Smith, H. W.: Unilateral nephrectomy in hypertensive disease. J. Urol., 76: 685, 1956. 14. Zimmerman, S., Uehling, D. and Burkhalter, P.: Vesicoureteral reflux nephropathy. Urology, 2: 534, 1973. 15. Salvatierra, 0., Kountz, S. and Belzer, F.: Primary vesicoureteral reflux and end stage renal disease. J.A.M.A., 226: 1454, 1973. 16. Daniels, E., Hinman, J., Leach, D. and Muirhead, E.: Identification of prostaglandin E2 as a principle vasodepressor lipid of rabbit renal medulla. Nature, 215: 1298, 1967. 17. McGiff, J. C., Crowshaw, K., Terragno, N. A., Lonigro, A. J., Strand, J.C., Williamson, M.A., Lee, J.B. and Ng, K. K. F.: Prostaglandin-like substances appearing in canine renal venous blood during renal ischemia. Their partial characterization by pharmacologic and chromatographic procedures. Circ. Res., 27: 765, 1970. 18. Aiken, J. W. and Vane, J. R.: Intrarenal prostaglandin release attenuates the renal vasoconstrictor activity of angiotensin. J. Pharmacol. Exp. Ther., 184: 678, 1973. 19. Stecker, J. F., Jr., Rose, J. G. and Gillenwater, J. Y.: Dysplastic kidneys associated with vesicoureteral reflux. J. Urol., 110: 341, 1973. 20. Fay, R., Winer, R., Cohen, A., Brosman, S. A. and Bennett, C.: Segmental renal hypoplasia and hypertension. J. Urol., 113: 561, 1975.

Pediatric hypertension as a delayed sequela of reflux-induced chronic pyelonephritis.

Vol. 118, Octob~r Printed in U .SA. THE JOURNAL OF UROLOGY Copyright© 1977 by The Williams & Wilkins Co. PEDIATRIC HYPERTENSION AS A DELAYED SEQUEL...
190KB Sizes 0 Downloads 0 Views