PEDIATRICS Vol. 107 No. 1 January 2001, pp. 185-186

EXPERIENCE AND REASON:
Perinatal Renal Ischemia Resulting in Hypertensive Cardiomyopathy

	ABSTRACT

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Three neonates presented with malignant hypertension during the first week of life; 2 of them had congestive heart failure. Although none had indwelling umbilical artery catheters, unilateral renovascular lesions were diagnosed by nuclear perfusion scans. Angiotensin-converting enzyme inhibitor therapy produced rapid recovery. Hypertension must be included in the differential diagnosis of infants presenting with congestive heart failure and acidosis. Ultrasonography is not sensitive enough to exclude renovascular lesions. We emphasize the importance of early diagnosis and treatment.

Renal hypoperfusion causes hypertension through activation of the renin angiotensin system.¹ Chronic and acute causes of renovascular hypertension in children are well-described, as is cardiomyopathy related to severe or long-standing hypertension.² The most common cause of neonatal renovascular hypertension is related to umbilical artery catheter placement.³ Modern imaging techniques can establish the presence of renovascular lesions, particularly those resulting in high-grade occlusion. We report 3 full-term neonates, 2 with congestive heart failure (CHF), never treated with indwelling umbilical artery catheters, who developed life-threatening renovascular hypertension in the first week of life.

	CASE REPORTS

Case 1

A 5-day-old white boy was admitted to the intensive care unit because of severe CHF and metabolic acidosis after 2 days of initially mild but progressive diaphoresis and difficulty in feeding. After an uneventful term pregnancy, this 4.74-kg infant had undergone spontaneous vaginal delivery and had required only usual care.

Dobutamine was administered. An echocardiogram showed very poor systolic function (shortening fraction: 8%; normal, >35%) and no structural abnormalities. Although perfusion and overall status improved, the blood pressure rose to 130/72 mm Hg. Hypertension persisted despite maximal doses of nitroglycerin. Renal ultrasonography showed kidneys of normal size (Fig 1). However, a technetium 99 (^99mTc)-mercaptotriglycylglycine (MAG₃) renal scan showed a paucity of flow to the right kidney and normal flow to the left kidney (Fig 2).

View larger version (43K): [in this window] [in a new window]   Fig. 1.   Ultrasonography of right and left kidneys (arrows) showing sizes 5.0 cm and 5.7 cm, respectively.

View larger version (158K): [in this window] [in a new window]   Fig. 2.   Representative image of 99mTc-labeled MAG3 renal scan with furosemide wash out. The left kidney (arrow) and ureter (open arrow) were well-visualized but no functional renal mass was present on the right.

Captopril therapy was initiated and the infant's blood pressure rapidly normalized (70-80/40-50 mm Hg). Mechanical ventilation and inotropic agents were discontinued and the infant was discharged on the 10th day of life. Follow-up has shown progressive atrophy of the right kidney with nearly complete loss of function as assessed by renal scans, and compensatory left kidney hypertrophy. By 6 months of age, myocardial function had returned to normal and captopril was discontinued without recurrent hypertension. Development at 3 years of age was normal.

Case 2

A 5-day-old Asian girl presented with respiratory distress, hypotension, and acidosis. The 3.4-kg product of an uneventful term pregnancy, the infant had been delivered vaginally without assisted extraction. A large cephalohematoma was noted, but the infant was otherwise well until presentation.

The infant was placed on a mechanical ventilator and inotropic agents were administered. The infant's overall status improved but the blood pressure increased (114-123/69-87 mm Hg) despite weaning of inotropic agents. Echocardiography showed a dilated and poorly contracting left ventricle (shortening fraction: 15%) but no important structural abnormalities. Renal ultrasonography showed a left kidney of 4.9 cm greatest dimension and a right kidney of 3.9 cm with increased echogenicity of the pyramids; biphasic blood flow was found bilaterally. A ^99mTc-diethylenetriamine pentaacetic acid (DTPA) scan showed no blood flow to the right kidney. Peripheral renin activity at that time was 54 001 ng/dL/hour (normal range: 235-3700).

Digoxin and captopril therapy was initiated on day of life 6 with immediate resolution of hypertension. The infant rapidly was weaned from mechanical ventilation. Heart size as assessed by chest radiograph normalized and the patient was discharged on the ninth day of life. By 3 months of age cardiac function was normal (shortening fraction 34%) and digoxin was discontinued. Hypertension remained controlled with captopril and the infant was developing normally.

Case 3

An 8-day-old white girl was referred for evaluation of severe hypertension 2 days after discharge from the nursery. The product of an uncomplicated pregnancy and delivery, the infant underwent no special procedures. Hypertension was noted at 13 hours of life. At that time, hydralazine therapy was initiated and blood pressures reportedly normalized. Abdominal ultrasound, echocardiogram, head computed tomography, and sepsis evaluation showed no abnormalities. Hydralazine was discontinued on the fourth day of life, and after 2 subsequent days of stable blood pressure measurements, the infant was discharged from the nursery.

The infant was admitted to Children's Medical Center at 8 days of age with a blood pressure of 159/123 mm Hg. The infant weighed 2.23 kg, was in no distress, and showed no evidence of CHF. Renin activity was 6150 ng/dL/hour (normal range: 235-3700) and aldosterone was 551 ng/dL (normal range: 5-175). Sonography showed normal kidneys measuring 4.2 cm on the right and 4.3 cm on the left. A ^99mTc glucoheptonate scan revealed marked asymmetry with the right accounting for 18% and the left for 82% of function. The infant was subsequently treated with captopril and hydralazine and hypertension resolved.

Follow-up sonography showed the severe atrophy of the right kidney without uptake on renal scans. There was compensatory left renal hypertrophy. Antihypertensive therapy was eventually discontinued, but mild hypertension recurred. At age 4 years the development and overall health of the child was excellent although she continued to be treated with captopril. An elective right nephrectomy was performed and the hypertension resolved completely, without additional treatment.

	DISCUSSION

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We describe 3 neonates who never had indwelling umbilical artery catheters but yet had renovascular lesions and presented with malignant hypertension. In 2, near-fatal CHF developed and the third received early antihypertensive therapy, which may have prevented that outcome. Each of the infants rapidly responded to angiotension-converting enzyme (ACE) inhibitor therapy and have since shown normal development. Similar treatment of an infant with catheter-related renal artery thrombosis and malignant hypertension also reversed severe myocardial dysfunction.⁴

Cases 1 and 2 demonstrate that severe hypertension in the first week of life can present with cardiomyopathy. The blood pressures in each case were significantly higher than the 90% for a term neonate (76/68 in boys and 87/68 in girls).⁵ The acuity of the cardiogenic shock in cases 1 and 2 and the severity of hypertension in case 3 following relatively asymptomatic periods leads us to the conclusion that these infants suffered perinatal ischemic renal insults or infarctions. Presumably, early fetal ischemic events would have significantly impaired renal growth. Indeed, long-term follow-up of cases 1 and 3 has demonstrated severe atrophy of the affected kidneys. It is important to note that functional renal scans like the ones used in these cases clearly demonstrated persistent unilateral hypoperfusion that cannot be demonstrated by ultrasonography. Correspondingly, the plasma renin activity was high in the 2 infants in whom it was measured, markedly so in case 2.

Review of the literature produced case reports of 7 neonates who developed heart failure in the first week of life secondary to renovascular hypertension not related to umbilical artery catheter placement.^6-11 Death occurred in 2, hypertension was cured by unilateral nephrectomy in 4 cases^6,7,9,10 and by captopril therapy in 1 case.¹¹ Although exceedingly rare in general, congenital renal artery stenosis was the most common cause found during pathologic examination. It is notable that despite stenosis, the kidney was of normal weight in 1,⁶ decreased weight in another,⁸ and was sonographically normal in the third.⁹

Several other mechanisms, also very rare, may cause perinatal, isolated, and unilateral renovascular lesions. Renovascular embolism from a thrombosing ductus arteriosum or ductus diverticulum has been postulated but this etiology more characteristically results in multiorgan ischemic lesions from widespread emboli.^11-14 Thrombosis in situ was demonstrated in 2 infants described by Woodard et al.¹⁰

It is worthwhile to consider how neonates with hypertension secondary to congenital renal artery stenosis can demonstrate normal kidney growth and development. Fetal renal blood flow equals 2 to 4% of the cardiac output and may be mostly trophic since glomerular filtration is low and the placenta plays the major role in metabolic clearance.¹⁵ Following birth, renal blood flow increases as renal vascular resistance decreases and systemic blood pressure rises.¹⁵ Hypothetically, if renal vascular resistance fails to decrease appropriately to meet increased perfusion requirements, renin-mediated hypertension followed by ischemia could occur.

This report presents 3 cases of life-threatening neonatal hypertension secondary to isolated unilateral perinatal ischemic renal insults despite the absence of umbilical artery catheters. In each case, medical treatment allowed rapid recovery. Malignant hypertension should be considered a cause of CHF in neonates. Renal arteriography, a procedure with potential morbidity in neonates, was not necessary to make the diagnosis in these cases. Functional renal scans with ultrasonography can be diagnostic of renovascular lesions. In such cases, ACE inhibition is an effective treatment for CHF and hypertension.

Jeffrey M Saland, MD^*
Lynn Mahony, MD^*
Michel Baum, MD^*,
Departments of ^* Pediatrics and  Internal Medicine
University of Texas Southwestern Medical Center
Dallas, TX 75390-9063

	FOOTNOTES

Received for publication Apr 26, 2000; accepted Jul 12, 2000.

Reprint requests to (M.B.) Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75235-9063. E-mail: mbaum{at}mednet.swmed.edu

	ABBREVIATIONS

CHF, congestive heart failure; ^99mTc, technetium 99; MAG₃, mercaptotriglycylglycine; DTPA, diethylenetriamine pentaacetic acid; ACE, angiotensin-converting enzyme.

	REFERENCES

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