Captopril-enhanced renal scintigraphy in the diagnosis of pediatric hypertension

Hypertension in childhood is no longer a rare condition mainly secondary to renal, or renovascular diseases, as a growing proportion of children are obese and hypertensive, with the phenotype of metabolic syndrome. Thus, we need to reconsider our practice in the examination of the hypertensive child and redefine the place of non-invasive methods for screening of renovascular hypertension, and specifically, to evaluate the value of captopril-enhanced renal scintigraphy at the two ends of the palette: the obese child with hypertension and the severely hypertensive prepubertal child. Renal artery stenosis in children is mainly due to fibromuscular dysplasia and stenoses associated with syndromes involving single or multiple smaller branch vessels. This explains the low specificity and sensitivity of the color-Doppler ultrasound method and captopril renal scintigraphy. Even the more sophisticated computed tomography (CT) and magnetic resonance imaging (MRI) angiographic techniques are, at present, not sensitive enough to exclude stenoses of the small branches definitely. Thus, children in whom there is a strong suggestion of renovascular hypertension should undergo angiography with a view to endovascular treatment, as non-invasive imaging has no significant benefit and might lead to a delay in treatment. In the cases when the probability of renovascular disease is moderate a basic assessment of renal function and structure is sufficient. In the neonate, catheter-associated thromboembolic disease is among the most common causes hypertension. It should be controlled medically until the patient is old enough to undergo angiography and angioplasty successfully. Thus, in this age group, there is a place for functional imaging with renal sonography and angiotensin-converting enzyme inhibitor (ACEI) renography to detect hemodynamically significant renovascular disease, with the limitations mentioned above. However, the rapid technical evolution of non-invasive methods requires periodic re-consideration of the actual standpoints.     

Hypertension and segmental renal infarction in children: apropos of two cases

Segmental renal infarction (SRI) is a rare condition that causes renovascular hypertension (RVH), which accounts for 8–10% of all causes of pediatric hypertension. We report the clinical course of two children with idiopathic SRI who suffered severe arterial hypertension associated with hyponatremia. Hypertension was diagnosed during the study of hematuria in the first case and due to a hypertensive emergency in the second case. The etiology was found to be renovascular in both patients, involving the occlusion of small renal arteries and causing SRI. Our first patient was treated with partial nephrectomy, and the second patient was treated with antihypertensive medication given the impossibility of removing the infarcted renal area. The occlusion of small renal arteries is a rare disease of unknown origin in which the gold standard for diagnosis is selective renal arteriography. The definitive treatment is surgical segmentectomy. If segmentectomy is not feasible because of the localization of the infarcted area, as in our second patient, medical treatment is required. In view of the importance of RVH in children and the rareness of the particular etiology here reported (SRI), a review of the literature was done.     

Angiotensin-converting enzyme inhibition ameliorates the defect in glomerular size selectivity in hyponatremic hypertensive syndrome

The glomerular size-selective properties in a patient with "hyponatremic hypertensive syndrome" were investigated before and after administration of the angiotensin-converting enzyme inhibitor enalapril. Hyponatremic hypertensive syndrome is a rare condition of renovascular hypertension characterized by electrolyte abnormalities (hyponatremia, hypokalemia), polyuria, and high renin activity. In this patient a marked increase in urinary protein excretion was observed. Treatment with enalapril normalized BP, corrected electrolyte abnormalities, and reduced proteinuria. Glomerular filtration rate (GFR), renal plasma flow (RPF), and the clearance of neutral dextrans of graded sizes were measured before and after 6 months of enalapril (20 mg/d) administration. Theoretical analysis of dextran and inulin clearance data with a model of glomerular size selectivity were adopted to separate effects of hemodynamic changes on macromolecule filtration from changes of intrinsic membrane selective properties. After enalapril urinary protein excretion decreased, GFR was unchanged and RPF almost doubled. Fractional clearance values of dextran molecules were markedly elevated in comparison with the corresponding values measured in a group of normal controls and were normalized by enalapril. Theoretical calculation of membrane pore characteristics showed that enalapril treatment reduced the radius of all membrane pores by approximately 1 nm. Altogether these results indicate that enalapril normalized glomerular filtration of neutral macromolecules and circulating proteins in a human condition of angiotensin II-induced proteinuria. Enalapril effectively restored glomerular size-selective function, reducing dimensions of membrane pores, independently of its effect on renal hemodynamics.     

HIV/AIDS-related hyponatremia: an old but still serious problem

Hyponatremia is the most common electrolyte disorder in hospitals. Many medical illnesses, including congestive heart failure, liver failure, renal failure and pneumonia, may be associated with hyponatremia. In addition, hyponatremia in patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) was first reported in 1993. The evidence suggests that severe hyponatremia is associated with increased morbidity and mortality in human immunodeficiency virus (HIV)/AIDS patients; however, the incidence of hyponatremic syndrome in HIV/AIDS patients remains very high in clinical practice, as almost 40% of HIV/AIDS inpatients in Xinjiang, a developing region of China, are hyponatremic. A method for identifying the pathogenesis and therapeutic treatments for hyponatremia in HIV/AIDS patients is needed. This review focuses on the clinical and pathophysiological aspects of hyponatremia and highlights the causes, presentation and treatment recommendations for hyponatremic patients with HIV/AIDS.     

Unilateral renal ischemia causing the hyponatremic hypertensive syndrome in children—more common than we think?

A case report in the journal Pediatric Nephrology describes a 15-month-old girl with the syndrome of hypertension and hyponatremia (HH syndrome) due to underlying unilateral renal artery stenosis. This syndrome is typically associated with hypokalemia and severe volume depletion and sometimes proteinuria, all of which, along with hypertension and hyponatremia, are usually corrected by resolution of the underlying renal ischemia. Gross and probably sudden activation of the renin-angiotensin system in response to renal ischemia is central to the pathophysiology although the cardiac atrial and B-type natriuretic peptides probably contribute also. Initial control of the severe hypertension may, in some cases, require careful volume repletion prior to introduction of blockade of the renin–angiotensin system in order to avoid first-dose hypotension, after which correction of the underlying renal ischemia is required. Whereas the syndrome has rarely been reported in children, it is possible that, as in adults, this reflects its lack of recognition by clinicians. The HH syndrome due to unilateral renal ischemia in children may be much more common than we think.     

The current status of surgical therapy for renal artery disease

The first reports of surgically curable hypertension in the late 1930s led to enthusiasm among clinicians for removing kidneys with arterial stenosis in hypertensive patients. The development of vascular surgical techniques in the 1950s made it possible to achieve successful renal revascularization in many of these cases. However, the cause and effect relationship between a stenotic renal artery lesion and hypertension was poorly understood and many patients treated surgically had no improvement of blood pressure postoperatively. Continued experience in this field during the past two decades has significantly improved our understanding of the natural history and functional significance of renovascular disorders. Patients with renovascular hypertension can now be identified with a high degree of accuracy and successful renal revascularization is possible in most cases. Nevertheless, multiple factors must be weighed in determining whether medical or surgical therapy is more appropriate for a given patient. These include the causal relationship of renovascular disease to hypertension, the adequacy of blood pressure control with medical therapy, the natural history of untreated renovascular disease with particular regard for the risk of sustaining impaired renal function, the medical condition of the patient, the morbidity and results of surgical therapy, and the availability of other therapeutic options such as percutaneous transluminal dilatation.     

A case of transient blindness in a postoperative hyponatremic child

Hyponatremia represents a common electrolyte disorder in postoperative patients. Headache, nausea, emesis, weakness and lethargy are all consistent symptoms of hyponatremia in children. Among the neurologic symptoms that are infrequently seen in severe hyponatremic pediatric patients seizure is included while visual disorders are not. We report a case of an 8-year-old boy who underwent abdominal surgery and developed severe hyponatremia. Five days after surgery the child suffered a seizure and successively experienced bilateral visual loss. However, after prompt correction of serum sodium concentration, a complete resolution of the blindness was obtained. Thus, we discuss the present case speculating on the pathogenesis of hyponatremic blindness and on its possible therapeutic approach. In conclusion, we suggest that blindness is to be considered a rare symptom that can occur in the clinical scenario of hyponatremia and we report its complete reversibility after timely treatment of hyponatremia.     

Imaging techniques in the evaluation of pediatric hypertension

Moderate or severe hypertension occurs in a small percentage of hypertensive children, but it is within this group that the surgically correctable causes of hypertension are found. Since cure rates up to 90% have been reported, it is important to diagnose a secondary cause of hypertension. Excretory urography is recommended to screen for renovascular hypertension and renal parenchymal disease. Renal scintigraphy can be substituted for the urogram, but the anatomical resolution is poorer. If renovascular hypertension is suggested by abnormal results of screening examination, arteriography should be part of the evaluation. Ultrasonography is reserved primarily for evaluating neonatal hypertension which most frequently is related to thrombosis. If this diagnosis is documented, renal function should be assessed with radionuclide techniques. If a hormonally active tumor is suspected, evaluation of the adrenals and retroperitoneum is accomplished best by CT.     

New aspects in the pathogenesis, prevention, and treatment of hyponatremic encephalopathy in children

Hyponatremia is the most common electrolyte abnormality encountered in children. In the past decade, new advances have been made in understanding the pathogenesis of hyponatremic encephalopathy and in its prevention and treatment. Recent data have determined that hyponatremia is a more serious condition than previously believed. It is a major comorbidity factor for a variety of illnesses, and subtle neurological findings are common. It has now become apparent that the majority of hospital-acquired hyponatremia in children is iatrogenic and due in large part to the administration of hypotonic fluids to patients with elevated arginine vasopressin levels. Recent prospective studies have demonstrated that administration of 0.9% sodium chloride in maintenance fluids can prevent the development of hyponatremia. Risk factors, such as hypoxia and central nervous system (CNS) involvement, have been identified for the development of hyponatremic encephalopathy, which can lead to neurologic injury at mildly hyponatremic values. It has also become apparent that both children and adult patients are dying from symptomatic hyponatremia due to inadequate therapy. We have proposed the use of intermittent intravenous bolus therapy with 3% sodium chloride, 2 cc/kg with a maximum of 100 cc, to rapidly reverse CNS symptoms and at the same time avoid the possibility of overcorrection of hyponatremia. In this review, we discuss how to recognize patients at risk for inadvertent overcorrection of hyponatremia and what measures should taken to prevent this, including the judicious use of 1-desamino-8d-arginine vasopressin (dDAVP).     

Renovascular hypertension in children.

OBJECTIVE: To study the etiology, clinical spectrum. image findings, management and outcome of children with renovascular hypertension (RVH). MATERIAL AND METHODS: Twenty children (aged 5 days to 15 years) were studied and treated for RVH during 1977-1998. In 14 cases hypertension was found during a routine examination. Six cases had heart failure and/or hypertensive encephalopathy. Diagnosis was made with aortography. Post-captopril renography and Doppler ultrasonography were obtained in 8 patients and spiral computed tomography angiography in 2. Treatment consisted of surgery (8 patients), percutaneous transluminal angioplasty (PTA) (5) or antihypertensive drugs only (8). RESULTS: Initial blood pressure was 62 +/- 31 mmHg > 95th percentile for systolic and 44 +/- 22 mmHg for diastolic blood pressure. Twelve children had unilateral and 8 had bilateral arterial stenosis. In 3 cases lesions were intrarenal. RVH was due to fibromuscular dysplasia (7 patients) and associated to middle aortic syndrome (5). neurofibromatosis (3), William's syndrome (2). Takayasu's arteritis (1) and pheochromocytoma (1). Treatment of choice was decided depending on the size of the child and location and severity of the stenosis. At the end of the follow-up (78 +/- 49 months), 9 patients are normotensive without medication and 7 are normotensive with drugs. Three patients have died, 2 for unrelated causes and I for cardiac failure; 1 child was lost to the follow-up. CONCLUSIONS: Although symptoms are relatively uncommon. renovascular disease is a frequent cause of severe hypertension in childhood. Non-invasive diagnostic techniques appear useful as screening methods. Treatment by surgery or PTA is successful if patients are carefully selected.     

Washout urography in the diagnosis of renal hypertension

Washout urography was used as a screening test for 100 hypertensive patients. Eleven patients had renal hypertension. These were 4 cases of unilateral renal artery stenosis, 6 cases of unilateral pyelonephritis and one case of bilateral pyelonephritis with atherosclerosis of the right renal artery. The increase in size of the affected kidneys after Lasix injection was much restricted relative to the normal contralateral kidneys. The test proved valuable for screening cases of renovascular hypertension and unilateral pyelonephritis.     

Severe hypertensive retinopathy. Increased incidence in renoparenchymal hypertension

In 205 patients with histologically evaluated glomerulonephritis, 69 patients with essential hypertension and 12 patients with renovascular hypertension, the retina was examined and evaluated by fundus photography. Changes of the retina were classified according to the recommendations of WHO: mild to severe changes of retinal arteries were termed as mild hypertensive retinopathy, and exaggerated changes, including exudates, hemorrhages and optic disc changes, as severe hypertensive retinopathy. In spite of the short duration of renal disease and the young age of the patients in many cases, retinal changes in patients with renal hypertension were significantly more severe: especially in focal segmental sclerosis and membranoproliferative glomerulonephritis was severe hypertensive retinopathy observed. Mild hypertensive retinopathy was more prevalent in essential hypertension. When renal disease progresses the retinal findings tended to deteriorate as well. Since the 24-hour blood pressure profile was comparable in most of the groups studied, it was supposed that the vulnerability of the retina and probably other vascular beds (e.g. kidneys) was increased. We conclude that the retina of these patients should be examined even in the case of relatively mild hypertension (greater than 180/100 mm Hg) and early antihypertensive treatment is an important requirement.     

Therapeutic experience in renal hypertension: response treatment in 47 cases.

We report our experience in the treatment of 47 cases of renal hypertension patients with renovascular hypertension or hypertensive reno-parenchymal disease surgical therapy is essential and non-surgical therapy has its limitations. The necessity for an operation can be based on the determination of bilateral renal vein plasma renin values. Blood should be drawn from both renal veins in patients in an upright position. Surgical treatment usually produces excellent results in patients in whom renin activity on the side of the lesion is more than normal and more than 2 times that on the uninvolved side. It is advisable to perform an operation within 4 years of the onset of renal hypertension. Complete surgical cure of renal hypertension is accomplished more frequently in patients with fibromuscular dysplasia than in those atherosclerosis. The therapeutic effect of an operation in correcting hypertension is virtually the same, regardless of whether the arterial stenotic lesions are in the main renal artery or in the intrarenal arterial branches. We have found nephrectomy or dacron bypass graft to be the surgical procedure of choice in renovascular hypertension cases.     

ACE inhibition scintigraphy in the management of hypertension in children

Angiotensin converting enzyme (ACE) inhibition scintirenography was performed to help establish the diagnosis and plan treatment of renovascular hypertension (RVH) in 57 hypertensive pediatric patients, 33 infants and 24 children older than 1 year. In 16 of 33 hypertensive infants, ACE inhibition scintirenography established the diagnosis of RVH from renal ischemia (due to aortic or renal arterial thrombi). Two scintigraphic criteria were used for the diagnosis of RVH: criterion I, ischemic and damaged kidney (a non-functioning kidney on or off ACE inhibition) and criterion II, ischemic but not damaged kidney (ACE inhibition induced deterioration of function of the kidney). When criterion I was present and the contralateral kidney was normal, ACE inhibitors could be used for treatment of hypertension without deterioration of renal function; kidneys satisfying criterion I eventually involuted or manifested growth arrest and frequently caused persistent RVH, even after resolution of the thrombus, requiring nephrectomy. When criterion II was present bilaterally, or it was associated with criterion I contralaterally, the use of antihypertensive drugs other than ACE inhibitors was necessary in order to prevent renal insufficiency or failure from ACE inhibitors. However, kidneys with criterion II showed normal growth and, following retraction or dissolution of the aortic thrombus, hypertension resolved. In 2 of 24 hypertensive children older than 1 year, the test was diagnostic of branch renal artery stenosis; RVH was cured by selective angioplasty. ACE inhibition scintirenography is useful in the evaluation and planning of treatment in children with hypertension and may predict the outcome of therapy and ultimate renal function. Received: 7 May 1997 / Revised: 3 September 1998 / Accepted: 3 September 1998     

Captopril scintigraphy in the study of arterial hypertension in pediatrics

Renovascular hypertension (RVH) is responsible for 10% of arterial hypertension in children. The early diagnosis of RVH permits specific treatment leading to the cure of hypertension and avoidance of parenchymal damage. Captopril renal scintigraphy (CRS) provides information on the renovascular cause of the arterial hypertension. To validate the usefulness of CRS in hypertensive children, clinical, scintigraphic, and radiological data from 20 patients (mean age 6.1±5.5 years) were reviewed. Two patients were newborns. All had renal ultrasound scans and 9 had aortograms. In 7 children, RVH was confirmed by angiography, and CRS was positive for RVH in 6 of these. CRS was negative for RVH in 12 of 13 children without RVH. CRS was non-diagnostic in 3 children with abnormal baseline renal scintigraphy and severely decreased relative renal function (<35%), 1 of whom had RVH. No side effects of captopril renography were observed. Captopril renography provides a logical, non-invasive, safe, and cost-effective approach in the evaluation of children suspected of having RVH.     

Cerebral salt-wasting syndrome: does it exist?

Cerebral salt-wasting syndrome (CSWS) has been regarded as a misnomer of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). We take the position that CSWS does exist and might be more common than SIADH. Differentiation between groups has been difficult because of overlapping signs, symptoms, and associated diseases. Euvolemia in SIADH and hypovolemia in CSWS may be the only contrasting variables. However, clinical assessment of extracellular volume is accurate in about 50% of these patients. Determination of serum urate and fractional excretion rates of urate can differentiate one group from the other. In both groups, hyponatremia coexists with hypouricemia and increased fractional excretion of urate. When the hyponatremia is corrected by water restriction, hypouricemia and elevated FEurate correct in SIADH but persist in CSWS. Persistent hypouricemia and elevated FEurate were commonly noted with pulmonary and/or intracranial diseases. The absence of intracranial diseases in some patients suggests that renal salt wasting might be a more appropriate term than CSWS. A review of renal/CSWS reveals three studies involving hyponatremic neurosurgical patients who had decreased blood volume, decreased central venous pressure, and inappropriately high urinary sodium concentrations in the majority of them, suggesting that CSWS was more common than SIADH in neurosurgical patients. Evidence for the presence of a plasma natriuretic factor in CSWS is presented.     

Renovascular injury: an argument for renal preservation

BACKGROUND: Renovascular injury is uncommon among children. This study hypothesized that preservation of the severely injured kidney can be achieved safely without renal insufficiency, postinjury hypertension, or the need for hemodialysis. METHODS: Retrospective chart review of renal injuries seen between 1997 and 2001 at a level 1 pediatric trauma center was conducted. Severity of injury was graded by the American Association for the Surgery of Trauma Organ Injury Severity Scale. The outcome variables included the need for hemodialysis, impaired renal function (creatinine), and postinjury hypertension. RESULTS: In this study, 34 children presented with grade 1, 2, or 3 injury (74%), whereas 13 children presented with grade 4 or 5 renovascular injury (28%). The children with unilateral renovascular injury who underwent either nephrectomy or renal preservation had comparable outcomes with no hypertension, hemodialysis, or renal insufficiency in either group. CONCLUSIONS: The treatment outcomes were not different between the patients who underwent renal preservation and those who had immediate nephrectomy. The authors conclude that renal preservation should be attempted for all children with grade 4 or 5 renovascular injury.     

Reno-vascular hypertension in childhood: a nationwide survey

Renovascular disease accounts for 8–10% of all cases of paediatric hypertension, whereas, in adults, its incidence is approximately 1%. The Turkish Paediatric Hypertension Group aimed to create the first registry database for childhood renovascular hypertension in Turkey. Twenty of the 28 paediatric nephrology centres in Turkey responded to the survey and reported 45 patients (27 girls, 18 boys) with renovascular hypertension between 1990 and 2005. The age at presentation ranged from 20 days to 17 years. The mean blood pressure at the diagnosis was 169/110 mmHg. Chief complaints of symptomatic patients were headache (38%), seizure (18%), epistaxis (4%), growth retardation (4%), cognitive dysfunction (4%), polyuria (2%), palpitation (2%), and hemiplegia (2%). Renovascular hypertension was found incidentally in 11 children. The diagnosis of renovascular hypertension was established with conventional angiography in 39 patients, MR angiography in three, CT angiography in two, and captopril diethylene triamine penta-acetic acid (DTPA) scintigraphy in one patient. Twenty-one children had bilateral renal artery stenosis and 24 had unilateral renal artery stenosis. Of these, 14 (31%) had fibromuscular dysplasia; 12 (27%) Takayasu’s arteritis; six (13%) neurofibromatosis; two (5%) Williams syndrome; one (2%) Kawasaki disease; one (2%) mid-aortic syndrome; one (2%) extrinsic compression to the renal artery, and eight (18%) unspecified bilateral renal artery stenosis. Hypertension was controlled with antihypertensive drugs in 17 patients. Percutaneous transluminal angioplasty (PTRA) or surgery had to be performed in 28 patients: PTRA in 16 patients, PTRA + surgery in one patient and surgery in 11 patients (four nephrectomies). The importance of vasculitic disease, especially Takayasu’s arteritis, should not be underestimated in children with renovascular hypertension.     

The sympathetic nervous system in clinical and experimental hypertension

In summary, many lines of evidence indicate that the sympathetic nervous system, via the renal nerves, plays an important role in the pathogenesis of renovascular hypertension in humans and laboratory animals. Patients with established renovascular hypertension have increased sympathetic nervous system activity, as evidenced by increased plasma and urinary norepinephrine levels, elevated excretion of catecholamine metabolites, and an exaggerated depressor response to centrally acting sympatholytic agents. The observation that converting enzyme inhibitors can cause both blood pressure and urinary norepinephrine excretion to return to normal in patients with renovascular hypertension is consistent with the interpretation that activation of the sympathetic nervous system in these subjects is, at least in part, angiotensin-induced. The sympathetic nervous system, via the efferent renal nerves, plays a role in the pathogenesis of hypertension in a number of experimental models. In the spontaneously hypertensive rat of the Okamoto strain (SHR) and in the DOCA/NaCl hypertensive model, increased renal efferent nerve activity contributes to the development of hypertension by causing increased renal sodium retention. In both of these experimental models, renal denervation delays the development and blunts the severity of hypertension. This delay is associated with increased urinary sodium excretion, suggesting a renal efferent mechanism. In contrast to the predominantly efferent renal nerve mechanisms observed in the DOCA-NaCl and SHR models, studies of the effects of renal denervation in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats suggest that renal afferent nerves are important in these models of hypertension. Total renal denervation in rats with established 1K, 1C and 2K, 1C hypertension attenuates the severity of the hypertension without altering sodium intake or excretion, renin activity, water intake, or renal function. Thus, efferent renal nerve activity does not appear to be involved in the development of maintenance of 1K, 1C or 2K, 1C hypertension. In contrast with the findings in SHR and DOCA-NaCl rats, these studies provide indirect evidence that the renal afferent nerves play a role in the pathogenesis of this form of experimental hypertension. The major effect of renal denervation in these models appears to be an interruption of renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure.(ABSTRACT TRUNCATED AT 400 WORDS)     

A successful case of ascending aorta--abdominal aorta bypass for middle aortic syndrome

The middle aortic syndrome (MAS) is a rare disease affecting children and young adults, and it occurs in about 0.5% to 2.0% of all aortic coarctation cases. Congenital, acquired, inflammatory, and infectious etiologies have been described. In the majority of cases, there is a short, isolated or diffuse tubular narrowing of the descending thoracic and abdominal aorta, often accompanied by ostial stenosis or occlusion of the renal and visceral branches, which leads to renovascular hypertension and visceral ischemia. Surgical treatment should be considered in cases of uncontrollable hypertension, evidence of end-organ damage such as cardiac failure, progressive renal insufficiency, or severe intermittent claudication. Several surgical treatments for this condition have been reported, including bypass grafting, graft replacement, or patch angioplasty. We report a successful case of ascending aorta-abdominal aorta bypass for MAS in a 11-year-old boy.