Sustained hypertension is important condition hospital practice. In majority of children with severe hypertension, the raised blood pressure constitutes an association or complication of an underlying disorder that is easily detectable. However hypertension may manifest for the first time without obvious features of a renal or cardiovascular disorder. Reports from Europe(1,2) and the United States(3) suggest that the common causes of sustained hypertension include chronic glomerulonephritis (GN), reflux nephropathy and obstructive uropathy. Recent studies suggest that essential (primary) hypertension may be anmore prevalent than previously unrecognized (1).Essential hypertension is being increasingly recognized among school going children in India(4,5). Hypertension in these cases is usually mild and most children are asympto-matic. There is however, a paucity of data on the causes of hypertension in children, in India. We therefore examined the etiology of sustained hypertension in 246 patients at a referral hospital in north India.

Patients and Methods

The records of all patients below the age of 16 years with sustained hypertension admitted

hari et al. sustained hypertension 

to a tertiary-care hospital between January 1983 and December 1996 were reviewed. Sustained hypertension was defined as systolic or diastolic blood pressure above the 95th percentile for height by age and sex that persisted for at least 4 weeks(6). Patients with transient hypertension due to acute glomerulonephritis (GN), Guillain-Barre syndrome, raised intracranial tension, corticosteroid toxicity and other acute disorders were excluded.

All patients initially underwent urinalysis and culture, complete blood counts and blood levels of sodium, potassium, urea, creatinine, calcium and phosphorus. A chest roent-genogram, electrocardiogram and abdominal ultrasound were obtained in all cases. Echo-cardiogram, urinary catecholamine levels, nuclear or radiocontrast voiding cystourethro-gram (VCUG), intravenous pyelogram (IVP), 99mTc-diethylenetriamine pentaacetic acid (DTPA) or glucoheptonate (GHA) renal scans, percutaneous renal biopsy, digital subtraction angiography and aortography were performed whenever indicated. Essential hypertension was diagnosed only if detailed evaluation did not show an identifiable etiology.

Results

Of 21,980 pediatric admissions during the study period, 246 (1.1%) had sustained hypertension. Of these, 180 were boys. The age at presentation ranged from 2 months to 16 years; 15 were below the age of 1 year and 59 between 2-6 years (Table I). Hypertension was associated with a known underlying disease in 198 (80.5%) children, whereas the rest presented with either nonspecific symptoms or those due to the complications of hypertension.

Thirty-five patients presented with com-plications of hypertension, including congestive cardiac failure in 21 patients, encephalopathy in 23 and visual loss in 1. These symptoms were present for a mean duration of 3.0 months 

(range 7 days to 4 years) before hypertension was detected. Thirteen patients were found to have hypertension while being investigated for unexplained fever, mononeuritis multiplex, vertigo, bronchial asthma, failure to thrive, abdominal mass, stridor, headache, obesity, claudication pain and cryptorchidism. In these children, hypertension was due to renal artery stenosis, pelvi-ureteric junction obstruction and reflux nephropathy in 2 patients each, polyarteritis nodosa, coarctation of aorta and aortoarteritis in one patient each and essential hypertension in four.

The etiology was determined in 98.4% patients while 4 children were diagnosed as essential hypertension. As shown in Table I coarctation of aorta was the commonest etiological disease for hypertension in infancy. Beyond one year of age chronic glomerulo-nephritis was the commonest cause of sustained hypertension. Obstructive uropathy, reflux nephropathy and renovascular hypertension were other significant causes of hypertension beyond infancy.

Glomerulonephritis: Chronic GN was present in 121 (49.2%) children; 66 were boys. The mean age at onset of symptoms was 7.1±3.5 years. The chief features included edema in 116 (95.9%), nephrotic syndrome in 68 (56.2%), microscopic hematuria in 58 (47.9%) and azotemia in 51 (42.1%) cases. Renal biopsy in 114 patients showed membranoproliferative GN in 31.6%, focal segmental glomerulosclerosis in 25.4%, and crescentic GN in 13.2%. Most patients with crescentic GN had features of rapidly progressive GN. However a few had insidious development of heavy proteinuria, hypertension and azotemia; some of these cases were reported previously(7). Other glomerular diseases included mesangial proliferative GN (7.9%), and GN related to systemic lupus erythematosus (7.0%) and Henoch Schonlein nephritis (3.5%), IgA nephropathy (2.6%), Alport's syndrome (0.9%) and microscopic polyarteritis nodosa (1.7%).

Obstructive Uropathy: Posterior urethral valves with bilateral hydronephrosis was seen in 22 patients and pelvi-ureteric junction obstruction in 6. Other causes of urinary tract obstruction included renal calculi, neurogenic bladder and vesicoureteric junction obstruction in 3 patients each, while one each had rectourethral fistula and urethral stricutre. Chronic renal insuffi-ciency was present in 29 patients with obstruc-tive uropathy.

Reflux Nephropathy: Reflux nephropathy was diagnosed in 30 patients; 24 were boys. The mean age at diagnosis was 9.4±3.5 years. Hypertension was the initial manifestation of reflux nephropathy in 5 cases. Oliguria and anasarca were seen in 22 patients and 11 had a history of recurrent urinary tract infections. Twenty-five patients had vesicoureteric reflux on VCUG (bilateral in 21) with severe renal cortical scarring. Vesicoureteric reflux was not detected in 5 cases. The diagnosis of reflux nephropathy in them was made in view of history of recurrent urinary tract infection and 

bilateral renal scars. Chronic renal failure was present in 11 cases.

Renal Thrombotic Microangiopathy: Fifteen patients (6.1%) presented with gradual onset of oligoanuria, anemia, variable degrees of thrombocytopenia, severe azotemia and hypertension. The blood pressure ranged between 150/100 and 210/170 mm Hg. None had a preceding diarrheal or respiratory illness. Renal biopsy showed thrombotic microangio-pathy involving arteries and arterioles with variable degrees of glomerular involvement and renal cortical necrosis. Eight patients died of uremia or progressed to end stage renal failure over a mean period of 4.7 months; some of these patients have been previously reported(8).

Coarctation of Aorta: Of 9 patients with coarctation of aorta, 8 had congestive cardiac failure and one had stridor. Other anomalies in these patients included bicuspid aortic valves in 4 patients and ventriculoseptal defect, double outlet right ventricle, patent ductus arteriosus and aberrant subclavian artery in one each.

Takayasu's Arteritis (Aortoarteritis): Eleven patients had Takayasu's disease. The presenting features included palpitations and dyspnea on exertion in 8 patients, hypertensive encephalo-pathy in 3 and claudication pain in the limbs in one. Seven patients had asymmetric pulses and an abdominal bruit was audible in 2. Angio-graphy revealed long tubular stenosis of the abdominal aorta in 9 cases. There was associated stenosis of the ostial and the proximal portion of the renal artery in 7 patients. Four patients had involvement of the aortic arch with stenosis of subclavian or carotid arteries. Mantoux test showed induration of 10 mm or more in 4 patients.

Isolated renal artery stenosis was diagnosed in 3 cases and was bilateral in one. Two of them were incidentally found to be hypertensive while being investigated for low-grade fever, and one presented with altered sensorium and seizures.

Five children with aortoarteritis and renal artery stenosis were subjected to percutaneous transluminal renal angioplasty. One child each underwent unilateral nephrectomy and renal autotransplantation. Seven patients were managed with one or more antihypertensive agents. Clinical benefit occurred in all patients with technically successful angioplasty either with normalization of blood pressure or reduced requirement of antihypertensive drugs.

Essential Hypertension: Four patients were considered to have primary hypertension. The mean age at diagnosis of hypertension was 9.9 years (range 8-14 years). The blood pressure ranged between 120/86 and 140/110 mm Hg. In two children, one parent each had essential hypertension. The presenting complaints in these patients included persistent headache in 2, and obesity (160% of the expected weight for height) and vertigo in one each.

Endocrine: These included pheochromocy-toma, paraganglioma and adrenal carcinoma in one case each. Surgical removal of tumors in these patients resulted in normalization of blood pressure.

Discussion

Sustained severe hypertension in children, can almost always be related to a definite cause. However, in population-based epidemiological studies, primary hypertension is predominant among apparently healthy children. In a study of healthy school going children from northern India between 5 and 14 years of age, prevalence of hypertension was found to be 11.7%(5). A secondary cause was found in 4.1% of hypertensive children and the rest were considered to have primary hypertension. As the blood pressure measurements in this study were performed at one time, this considerably high prevalence rate of hypertension would also include transient hypertension. Therefore, this figure does not represent the prevalence of sustained hypertension in healthy children.

We examined the etiology of sustained hypertension in 246 children who were referred for evaluation to this hospital. An underlying cause was found in most of our patients with sustained hypertension. Renal parencymal disease was most common among all age groups except infancy, when coarctation of aorta was seen in 53.3% of patients. The chief renal disorders were GN, obstructive uropathy and reflux nephropathy. Our observations are comparable to those from other groups(2,3,9,10). However, this study was in children that were referred to a tertiary center. Our findings may thus, not represent the etiology of sustained hypertension in the population. A study in 23 children from northern India revealed that renal parenchymal disease was the commonest cause of chronic persistent hypertension and essential hyper-tension was uncommon(11).

Chronic GN is reported to be the commonest cause of sustained hypertension in studies from various part of the world (Table II). Reflux nephropathy has also emerged as a frequent cause of pediatric hypertension in children accounting for 16%-33% cases in different studies(1-3,9,10).

Most patients with mild to moderate hypertension are asymptomatic. Symptoms of hypertension could be specific to the underlying disease, which most frequently lead to detection of the raised blood pressure. The manifestations of hypertension could be related to complica-tions of severe hypertension such as congestive heart failure and hypertensive encephalopathy or may be nonspecific in a small proportion of children. In this study, few patients were detected to be hypertensive while being investigated for unexplained fever, weight loss, obesity and headache.

Renal artery stenosis and thrombosis are important conditions resulting in renovascular hypertension(1,3). In the present study, however the commonest cause of renovascular disease was Takayasu's disease. This condition is a common cause of hypertension in children in India(12). The arteritis is of undetermined etiology involving the aorta and proximal portion of its major branches, the thoraco-

abdominal aorta being the commonest site. One or both renal arteries may be affected in more than two-thirds of patients(12). Patients with Takayasu's disease usually present with complications of severe hypertension or non-specific symptoms. Absent or feeble peripheral pulses are typically present and the diagnosis is confirmed on arteriography. An association with tuberculosis has been reported in 50% of cases with aortoarteritis examined at this center(12). Significant improvement may be observed following percutaneous transluminal angioplasty(13) as was also observed in this study.

Hemolytic uremic syndrome with no ante-cedent history of a diarrheal illness is charac-terized by occlusive thrombotic microangio-pathy of interlobular arteries and arterioles on renal biopsy. The disorder has insidious onset and is characterized by azotemia, severe hypertension, heavy proteinuria and edema; progression to end stage renal failure occurs in most patients(8). Clinical features of this condition may resemble rapidly progressive GN and a renal biopsy is necessary to establish the proper diagnosis.

The incidence of essential hypertension in children is reported to vary from 1%-45% in 

various hospital-based studies from developed countries(1-3,10). Arar et al.(3) found primary hypertension in 30(22.7%) such cases of sustained hypertension. They concluded that primary hypertension may be more prevalent in children than previously recognized. Elevation of blood pressure in these patients is usually mild. An infrequent diagnosis of essential hypertension in the present study could be due to referral of symptomatic and severe hypertension to the hospital. Screening studies for essential hypertension in school going children in India show a prevalence of 0.46%-11.7%(4,5,14).

In summary, most children with sustained hypertension were found to have an underlying etiology. All children with sustained hyper-tension should initially undergo screening studies. Definitive investigations to establish the underlying etiology are guided by the results of the screening investigations, and vary at different ages. In most patients hypertension was recognized as an association of a known underlying disorder. Occasionally, it was detected incidentally with no clinically obvious renal or cardiovascular cause. Conditions such as stenosis of main renal artery or its branches and pheochromocytoma may present with raised blood pressure alone. The diagnosis in these instances may be difficult and requires detailed evaluation. Surgical treatment is possible in a small number of patients whereas others require prolonged antihypertensive treatment.

Contributors: PH and AB were involved in data collection, analyses and drafting of the manuscript. AB will act as guarantor for the paper. RNS coordinated the study.

Funding: None.
Competing Interests: None stated.

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