Archives ofDisease in Childhood 1990; 65: 881-884

Fetal and infantile hypertension caused by unilateralrenal arterial disease

D I Wilson, R E Appleton, M G Coulthard, R E J Lee, C Wren, H H Bain

AbstractThree children who presented with heartfailure in infancy caused by severe hyper-tension as a result of unilateral renal arterialdisease are described. One presented at 3days of age with persistent fetal circulationand heart failure. He had abnormal greatvessels that indicated that the hypertensionwas of long standing and therefore fetal; thishas not been described previously. The othertwo children failed to thrive because of un-recognised hypertension and subsequentlypresented with heart failure. All three under-went unilateral nephrectomy which curedtheir hypertension, and all were thriving at thetime of writing. The benefits of nephrectomyoutweighed the operative risks and loss ofrenal function. Blood pressure should bemeasured in children who are failing to thriveas part of routine clinical practice.

Hypertension in the neonatal period and earlyinfancy is underdiagnosed. We describe herethree children with hypertension associatedwith unilateral renal arterial disease all of whompresented with life threatening cardiac failure.All three were successfully treated by unilateralnephrectomy. In one patient the hypertensionhad developed in utero, a finding that has not toour knowledge been previously reported.

Department of ChildHealth, SirJames SpenceBuilding, Royal VictoriaInfirmary,Newcastle upon TyneNEI 4LPD I WilsonR E AppletonM G CoulthardR E J LeeDepartment of PaediatricCardiology, FreemanHospital,Newcastle upon TyneC WrenH H BarnCorrespondence to:Dr Coulthard.Accepted 28 March 1990

Case reportsCASE 1

This boy was born at 38 weeks' gestationweighing 3980 g to a 26 year old mother who hadinsulin dependent diabetes mellitus. There wasno relevant family history, and the pregnancyhad been normal. Delivery was by NevilleBarnes forceps and was complicated by a leftErb's palsy and fractures of the left clavicle andleft sixth rib. No resuscitation was required.Blood glucose concentrations and physicalexaminations at 4 and 20 hours of age showedno abnormalities. He was well until day 3, whenhe developed respiratory distress and a sinustachycardia. Peripheral perfusion was poor andthe systolic blood pressure was 80 mm Hg,measured using a Doppler vascular flow detec-tor and 2 5 cm cuff. The rest of the physicalexamination showed no abnormality. Chestradiography showed cardiomegaly, and crosssectional echocardiography showed biventricularand septal hypertrophy with poor ventricularcontractility. Cultures of blood, urine, andcerebrospinal fluid were sterile. He was nursedin oxygen and the oxygen saturation increased

from 75 to 95% when he was given an infusionof tolazoline. On day 5 he developed increasingrespiratory distress and required ventilation.Twenty four hours later his systolic bloodpressure increased from 90 mm Hg to 145mm Hg, confirmed by Doppler measurement,auscultation, and palpation. Intravenoushydralazine given by infusion controlled hisblood pressure, but 12 hours later an intra-venous infusion of labetalol was also required.Both infusions were discontinued after fivedays. Thirty six hours later the systolic bloodpressure increased to 100 mm Hg, whichresponded to propranolol and hydralazine givenorally.

Results of the following investigations werenormal: full blood count; plasma concentrationsof urea, creatinine, electrolytes, calcium, andphosphate; alkaline phosphatase and cardiacenzyme activities; concentrations of thyroxine,cortisol, and 17 a hydroxyprogesterone; andurinary 4-hydroxy-3-methoxy mandelic acid(HMMA):creatinine and homovanillic acid(HVA):creatinine ratios. Antibodies (acute andconvalescent) to Coxsackie, herpes, rubella,cytomegalovirus, mumps, and adenovirus werenot detected in serum.

Renal ultrasonography showed no abnor-mality. A dimercaptosuccinic acid nucleide(DMSA) scan showed that the left kidneycontributed less than a quarter of the total renalfunction. An abdominal aortogram showed anormal right kidney with a normal vasculartree. The left main renal artery was normal, butthe intrarenal arteries were abnormal withleashes of smaller vessels. A left selective renalarteriogram showed a patchy nephrogram withsome areas of dense uptake and others withalmost none (fig 1). It was not possible to carryout a right selective renal arteriogram. A thoracicaortogram showed pronounced dilatation of theaortic -arch (fig 2). The carotid arteries weredilated and tortuous, as were the subclavianvessels, although these tapered into brachialarteries of normal diameter. Plasma reninactivities in the left renal vein, inferior venacava, and right atrium were raised at 7-5-8-6ng/l/sec (27 000-31 000 ng/l/hour) (upper limitof reference range for age is 2-5 (9100)). Theright renal vein could not be sampled.

Plasma renin activity must be interpretedwith caution in patients receiving hypotensivedrugs or under general anaesthesia and theprincipal value of sampling the renal vein is forcomparison of the two sides.' With such highactivities, together with the radiological asym-metry, however, it was concluded that theinfant had renin driven hypertension, probably

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Wilson, Appleton, Coulthard, Lee, Wren, Bain

Figure I Left renal arteriogram in the venous phaseshowing a patchy nephrogram with some areas ofdenseuptake and others with almost no uptake.

Figure 2 Thoracic arteriogram showing a grossly widened aorta and tortuous and dilatedcarotid and subclavian arteries.

caused by the abnormal left kidney. He wastreated with hydralazine and propranolol. A leftnephrectomy was carried out without compli-cations when he was 3 months old, and thereafterthe systolic blood pressure remained between 70and 80 mm Hg without treatment. At 17months of age physical examination showed noabnormality, and echocardiography and peri-pheral plasma renin activity were normal.

Histological examination of the left kidneyshowed patchy areas of abnormal cortex withextensive fibrosis and a chronic inflammatorycell infiltrate with deposits of haemosiderin,indicating previous haemorrhage. Loss oftubules (mainly proximal) was evident, andmany of the surviving tubules seemed immatureand contained hyaline casts. Arteries within thedamaged cortical areas were thick walled butnot characteristic of fibromuscular dysplasia,and the vessels at the hilum were normal. Therewas no evidence of renal dysplasia.

CASE 2This boy was born at full term weighing 3300 gafter a normal pregnancy and delivery. Therewas no relevant family history. The perinatalperiod was normal and he was well until 12months of age when he presented with failure tothrive. No cause was identified, but his bloodpressure was not measured. Weight gainremainded poor and he became progressivelymore lethargic. On admission to hospital at theage of 2-3 years he had both left and right heartfailure. The blood pressure in both arms was144/95 mm Hg by Doppler measurement andauscultation. His weight was below the thirdcentile. Chest radiography showed cardiomegalyand pulmonary oedema. Electrocardiographyshowed sinus tachycardia, and right atrial andleft ventricular hypertrophy. Cross sectionalechocardiography showed that the left ventriclewas dilated and hypertrophied, and contractingpoorly together with regurgitation through themitral and tricuspid valves and hypertrophy ofthe papillary muscles.

Results of the following investigations werenormal: full blood count; plasma concentrationsof creatinine and electrolytes, calcium, phos-phate and immunoglobulins; tests of thyroidfunction; cardiac enzyme activities, 24 hoururinary HVA and HMMA excretion, and urineculture. Intravenous urography showed a smallleft kidney with a normal caliceal appearanceand normal excretion. The right kidney washypertrophied. A DMSA isotope scan showedthat the left kidney contributed less than 15% oftotal renal function. Renal arteriography showedcomplete occlusion of the left main renal artery.The left kidney was small and supplied by atortuous vessel from the aorta. The right kidneywas enlarged and had a normal vascular tree.Plasma renin activities from both renal veinswere increased to greater than 26-7 ng/l/sec(96 000 ng/l/hour) (upper limit of referencerange for age is 0-7 (2610)). The samples wereinsufficient to repeat the assay at dilutions, sothat any discrepancy between the two sidescould not be measured.He was treated with digoxin, spironolactone,

chlorothiazide, and hydralazine and his cardiacfailure improved. His blood pressure remainedraised at 150/95 mm Hg. After the addition ofpropranolol and captopril to his regimen, theblood pressure fell to 100/45 mm Hg.The above investigations indicated that the

patient's heart failure was secondary to reno-vascular induced hypertension as a result ofstenosis of the main left renal artery. A left

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Fetal and infantik hypertension caused by unilateral renal arterial disease

nephrectomy was performed when he was 2-5years old. Histological examination ofthe kidneyshowed no evidence of renal artery dysplasia.His postoperative recovery was uncomplicatedand antihypertensive drugs were withdrawnover the following three months. At 4 years ofage he was well with a normal blood pressure(105/50 mm Hg), and physical examinationshowed no abnormality. His height and weightwere on the 25th centile. Echocardiography andthe peripheral plasma renin activity werenormal.

CASE 3This girl was born at full term weighing 3200 gafter a normal pregnancy. She was well until 10months of age when she developed gastro-enteritis. On admission to a local hospital shewas seriously ill: her weight was below the thirdcentile, she had poor peripheral perfusion, anda systemic blood pressure of 70/40 mm Hg. Sherequired resuscitation with an intravenousinfusion of plasma but immediately developedsevere right and left heart failure. She wastransferred to this hospital for ventilatory sup-port. After resuscitation with dobutamine andsodium bicarbonate her blood pressure rose to160/100 mm Hg, and remained at that level.Ventilatory support was withdrawn after fivedays. Blood pressure control was difficult andshe required nitroprusside and labetalol intra-venously, and subsequently propranolol andhydralazine orally.

Respiratory syncytial virus was isolated fromtracheal secretions. Cultures of blood, urine,and cerebrospinal fluid were sterile and pairedserum viral antibody titres excluded any recentinfection. Chest radiography showed pulmonaryoedema and left atrial enlargement. Crosssectional echocardiography showed a dilated leftventricle with poor contractility and mitral andtricuspid regurgitation. A renal ultrasound scanshowed a small right, and an enlarged left,kidney. A DMSA isotope scan showed that theright kidney contributed 23% of total renalfunction. Renal arteriography showed severestenosis of the main right renal artery anda normal left side. Peripheral plasma reninactivity (with the patient conscious but receivinghypotensive drugs), was raised at 4-9 ng/l/sec(17 600 ng/l/hour) (upper limit of referencerange for age is 0-9 (3130)).The heart failure improved after the hyper-

tension had been controlled. Surgical repair orballoon dilatation of the stenosed right renalartery were considered but were not thought tobe technically feasible. Medical management,with a view to future surgical repair, was alsoconsidered but the blood pressure remainedlabile. Despite the risk of reducing glomerularfiltration in the right kidney further, captoprilwas introduced to her regimen and this success-fully controlled the blood pressure. After this, adiethylene triamine penta-acetic acid (DTPA)scan showed no function of the right, butnormal function of the left, kidney. A rightnephrectomy was carried out. There was noevidence of renal artery dysplasia on histologicalexamination of the kidney. Her postoperative

recovery was uneventful and four days later allantihypertensive drugs were withdrawn. Tenmonths after nephrectomy her weight had risento the 25th centile and she remained well with ablood pressure of 80/60 mm Hg. The peripheralplasma renin activity and echocardiographicfindings had returned to normal.

DiscussionAll three patients presented with severe heartfailure, a complication of sytemic hypertensionin neonates and young children which is under-diagnosed. Angiography showed that stenosis ofthe renal arteries (main artery in cases 2 and 3,intrarenal arteries in case 1), was the cause ofthe hypertension.

Case 1 developed symptoms on the third dayof life. The finding of cardiac ventricularhypertrophy indicated a chronic change,presumably as a result of fetal hypertension. Itis likely that the tortuous dilation of theproximal arteries of the aortic arch were alsocaused by fetal hypertension rather than beingthe result of a generalised vascular disorder.There was no other evidence to suggest avasculopathy in this patient. As far as we areaware, fetal hypertension presenting in a neonatehas not been previously described. A reno-vascular cause for hypertension secondary to anabnormality of the left kidney was suggested bythe findings on renal arteriography and by thegrossly increased plasma renin activities,although the latter must be interpreted withcaution in patients receiving hypotensive drugsand during general anaesthesia. ' Althoughhistology of the left kidney confirmed theangiographic findings of intrarenal segmentalarterial stenosis, it was not possible to define theaetiology of the vascular abnormality.The most frequently reported causes of neo-

natal hypertension are stenosis of the proximalrenal artery and renal artery thrombosis orembolisation after umbilical arterial catheteris-ation.2 Renal vein thrombosis has also beenimplicated as a cause of neonatal hypertension,3and has been described as a complication ofmaternal diabetes mellitus.4 None ofour patientshad undergone catheterisation of the umbilicalarteries and in case 1 (whose mother haddiabetes mellitus) renal ultrasonography andarteriography excluded thrombosis of the renalvessels. Evans et al described a neonate withhypertension detected within 24 hours of birth,with associated renal vein thrombosis.3 Evidencewas presented that suggested that the thrombosishad occurred antenatally, but not the hyper-tension. In a necropsy series of neonates withrenal vein thrombosis, one infant who died at 48hours of age had biventricular hypertrophy.3No blood pressure recordings were given, butthe cardiac hypertrophy may have beensecondary to systemic hypertension.Our second and third patients had failed to

thrive because of hypertension. Case 2 had beeninvestigated for over 12 months, but his bloodpressure had not been recorded. Case 3 presentedduring an intercurrent -infection when shebecame dehydrated and seriously ill, possibly asa result of further renal ischaemia secondary to

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884 Wilson, Appleton, Coulthard, Lee, Wren, Bain

impaired circulating blood volume or renalinfarction. Both patients thrived once theirhypertension was controlled. Failure to thriveand acute or chronic heart failure are commonlyencountered in neonates and older children.Although hypertension is known to cause heartfailure and failure to thrive, blood pressure isfrequently not measured routinely in thesechildren. A working party of the British Hyper-tension Society has recommended that sickchildren should have their blood pressuremeasured whenever a general medical examin-ation is undertaken.5 It is clear that this shouldinclude children who are failing to thrive, andthat earlier measurement of blood pressure in atleast one of our patients (case 2) would haveresulted in reduced morbidity. All three caseemphasise the importance of the early detectionand appropriate treatment of hypertension.Each of our patients had unilateral renal

arterial disease and was 'cured' by unilateralnephrectomy. Nephrectomy may be associatedwith operative or anaesthetic complications andresults in some reduction in overall kidneyfunction. It does not guarantee a cure of thehypertension, as subtle abnormalities may existin the apparently normal kidney that couldcontinue to drive the hypertension. Sometimes,however, the potential benefits outweigh therisks. A successful nephrectomy provides adefinitive cure, and removes the need for lifelong drug treatment and the risk of furtherpotentially serious episodes of hypertension thatmay be caused either by non-compliance withmedication or by labile blood pressure.

Patients with bilateral intrarenal vasculardisease have no alternative to life long drugtreatment. In patients with unilateral intrarenaldisease, however, the choice is between drugtreatment and unilateral nephrectomy, thedecision being based on a balance between thedegree of functioning renal tissue that is lost,

the amount of hypotensive medication that isrequired, and the difficulties with compliancewith medication and monitoring of follow up.In case 1 unilateral nephrectomy resulted in theloss of less than a quarter of total kidneyfunction and avoided the need for life long drugtreatment.

Reconstructive vascular surgery or balloondilatation may be feasible in patients withextrarenal arterial stenosis, but do not guaranteesuccess.6 In case 2 the stenosis was extrarenalbut was tight; this would have necessitatedmajor reconstructive surgery to save the func-tion of a small kidney, or long term medicationwith several drugs, or both. In case 3 thestenosis was also extrarenal, but the bloodpressure was dangerously high until captoprilwas introduced into the regimen. This causedloss of function of the affected kidney, pre-sumably as a result of a reduced glomerularfiltration pressure,7 and consequently this kidneycontributed nothing to total renal function. Inthis patient, therefore, nephrectomy did notresult in any further loss of renal function.

The authors are grateful to Miss Sharon White for her help inpreparing the manuscript.

I Dillon MJ. Clinical aspects of hypertension. In: HollidayMA, Barratt TM, Verner RL, eds. Pediatric nephrology.2nd Ed. Baltimore: Williams and Wilkins, 1987:743-57.

2 Adelman RD. The hypertensive neonate. Clin l'enrnatol1988;15:567-85.

3 Evans DJ, Silverman M, Bowley NB. Congenital hyperten-sion due to unilateral renal vein thrombosis. Arch Dis Child1981 ;56:306-8.

4 Takeuchi A, Benirschke K. Renal venous thrombosis of thenewborn and its relation to maternal diabetes. Biol Neonate1%91;3:237-56.

5 de Swiet M, Dillon M J, Littler W, O'Brien E, Padfield P L,Petrie J C. Measurement of blood pressure in children:recommendations of a working party of the BritishHypertension Society. Br MedJt 1989;299:497.

6 Anonymous. Operating on renovascular hypertension[Editorial]. Lancet 1983;ii: 1007-8.

7 Wenting G J, Ton-Tjiong HL, Derx FHM, de Bruyn JHB,Man in 't Veld AJ, Schalekamp MADH. Split renalfunction after captopril in unilateral renal artery stenosis.Br Med J 1984;288:886-90.

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