Renovascular disease and hypertension in children with neurofibromatosis

Neurofibromatosis type 1 (NF1) is associated with vascular lesions, such as renal artery stenosis, and secondary hypertension. The real prevalence is largely unknown, particularly in children. We observed 27 patients with NF1, mean age 12.8 years (range 4.2–24 years), for 2–10 years to assess the association of NF1 with vascular abnormalities and secondary hypertension. Patients were studied with angiography, 24-h blood pressure monitoring, a captopril test, and Doppler ultrasonography of aorta and renal arteries. The prevalence of hypertension was 18.5%; 61.5% of patients studied with angiography had vascular lesions, half of whom were apparently normotensive. However, they had abnormal 24-h blood pressure monitoring, which was a first sign of poor blood pressure control. Those patients with severe hypertension (11.1%) were successfully treated with percutaneous transluminal angioplasty (PTA); stenosis recurred in 2 of 3 patients after a 2-year follow-up period, and was responsive to drugs. We conclude that hypertension is a frequent complication of NF1 in pediatric patients, it is usually secondary to typical vascular lesions, and requires careful follow-up. Ambulatory blood pressure monitoring (24-h) is a sensitive method for detecting initial alterations of the blood pressure pattern. PTA may be an effective treatment in this condition. Received: 2 June 1999 / Revised: 1 November 1999 / Accepted: 1 November 1999     

Thyroid disease in children and adolescents

Thyroid diseases in children and adolescents are not common. The present paper describes 73 patients, aged 5 to 18 years, who had thyroid disease which was treated by surgery. Of these, 18 had diffuse simple goiter, 11 had diffuse toxic goiter and 44 had nodular goiter. Of those patients with nodular goiter, 34 had adenomatous goiter, one had lymphocytic thyroiditis, one had lymphosarcoma and eight had cancer. In the patients with nodular goiter under the age of ten years, 40% had cancer, and of those aged 11 to 18 years, 14.7% had cancer. Thyroid nodules were more frequent in girls than in boys, but the incidence of cancer in nodular goiter was higher in boys than in girls.     

Cushing's disease in children and adolescents

Fifty-seven unselected children and adolescents with Cushing's disease underwent transsphenoidal exploration and microadenomectomy before their 16th birthday. Hypercortisolism was corrected in 42 of the 57 patients (74%). The recurrence rate was 17% and the long-term remission rate was 57%. Diagnostic peculiarities specific surgical problems and outcome were reviewed. Direct transnasal submucosal surgery for Cushing's disease is successful, and pituitary function can be preserved in most of these young patients.     

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.     

Nodular thyroid disease in children and adolescents

Thyroid nodules in children are extremely uncommon. Most thyroid nodules, both benign and malignant, present as asymptomatic neck masses. A thyroid nodule in a child is significant because of the risk of malignancy. A review of medical records at our institution demonstrated 71 patients 20 years of age and younger with surgically managed thyroid nodules, of which 45 were benign and 26 were malignant. Our diagnostic workup, including serum thyroid studies, radiologic evaluation, and fine-needle aspiration, is discussed. Because of the possibility of malignancy, we recommend that all solitary thyroid nodules be excised in children unless fine-needle aspiration definitively determines a benign histology. The extent and type of surgical management is controversial and is still subject to much debate. Partial thyroidectomy appears adequate for benign disease, but even though there is no statistical difference in survival, we recommend total thyroidectomy for the management of malignant disease. (Otolaryngol Head Neck Surg 1996;116:604-9.)     

Renovascular hypertension and Takayasu's disease

A total of 18 patients underwent surgical correction of renal hypertension secondary to Takayasu's disease after unsuccessful maximum medical therapy. Although the patients required an extensive surgical procedure, the morbidity and mortality rates were low (1 perioperative death in 18 patients). Followup showed that 67 per cent of the patients were cured of the hypertension and 28 per cent were improved. The results appear as good as those seen in the treatment of renovascular hypertension owing to fibromuscular disease or atherosclerosis.     

Implications for kidney disease in obese children and adolescents

Increasing attention has been focused on the implications of obesity in adults on the development of kidney disease, but data on the obese pediatric population are lacking. The aim of this study was to investigate whether changes in various renal function indexes/markers, as expressed by the glomerular filtration rate [GFR, as estimated by the Schwartz formula (eGFR)], serum cystatin C (CysC) level, albumin excretion rate (AER), and modifications in nitric oxide (NO; an important modulator of renal function and morphology), urinary isoprostanes (markers of oxidative stress), and blood pressure (BP), can be detected in obese children and adolescents when compared to normal weight controls. Blood and urinary samples were collected to evaluate markers of renal function, serum and urinary NO, and urinary isoprostanes in 107 obese Caucasian subjects and 50 controls. Ambulatory BP monitoring (ABPM) was performed in all cases. Obesity was expressed by the body mass index standard deviation score (SDS-BMI), and insulin resistance by the homeostasis model assessment of insulin resistance (HOMA-IR). CysC and eGFR did not significantly differ between the two groups; AER was increased in obese children. CysC and GFR were related to HOMA-IR, and AER was related to HOMA-IR and SDS-BMI. Obese subjects had reduced NO levels and increased urinary isoprostanes and BP measurements; all three parameters were related to SDS-BMI and insulin resistance. ABPM showed an increased incidence of hypertension and non-dipping in the obese group. Based on our comparison of obese and nonobese children, we conclude that renal involvement is not an early clinically evident manifestation of adiposity in childhood, since no overt changes in eGFR and only a mild albuminuria were detected. A longer exposure to obesity is probably needed before renal function impairment appears.     

Renovascular disease and renal insufficiency--diagnosis and treatment

Renovascular disease as cause of end-stage renal disease has become more frequent during the last decade. In order to minimize the need for dialysis treatment non-invasive screening for the disease is needed. However, both ultrasonic duplex scanning and renal scintigraphy are not sufficient for detection of all stenosis. Furthermore, there is little data on non-invasive tests in patients with renal insufficiency. Renal arteriography is the gold standard for detection of renovascular disease. One disadvantage is the risk of contrast-agent induced acute renal insufficiency. This problem can be avoided using carbon dioxide angiography. In the near future spiral computed tomography and magnetic resonance angiography may be alternatives for identifying patients with renovascular disease. Ischaemic nephropathy is potentially curable. Percutaneous transluminal renal angioplasty is first line treatment in most cases. Intervention often results in improvement or preservation of renal function which is very important in order to avoid chronic dialysis.     

Kidney disease in children and adolescents with perinatal HIV-1 infection

Introduction

Involvement of the kidney in children and adolescents with perinatal (HIV-1) infection can occur at any stage during the child''s life with diverse diagnoses, ranging from acute kidney injury, childhood urinary tract infections (UTIs), electrolyte imbalances and drug-induced nephrotoxicity, to diseases of the glomerulus. The latter include various immune-mediated chronic kidney diseases (CKD) and HIV-associated nephropathy (HIVAN).

Discussion

The introduction of highly active anti-retroviral therapy (HAART) has dramatically reduced the incidence of HIVAN, once the commonest form of CKD in children of African descent living with HIV, and also altered its prognosis from eventual progression to end-stage kidney disease to one that is compatible with long-term survival. The impact of HAART on the outcome of other forms of kidney diseases seen in this population has not been as impressive. Increasingly important is nephrotoxicity secondary to the prolonged use of anti-retroviral agents, and the occurrence of co-morbid kidney disease unrelated to HIV infection or its treatment. Improved understanding of the molecular pathogenesis and genetics of kidney diseases associated with HIV will result in better screening, prevention and treatment efforts, as HIV specialists and nephrologists coordinate clinical care of these patients. Both haemodialysis (HD) and peritoneal dialysis (PD) are effective as renal replacement therapy in HIV-infected patients with end-stage kidney disease, with PD being preferred in resource-limited settings. Kidney transplantation, once contraindicated in this population, has now become the most effective renal replacement therapy, provided rigorous criteria are met. Given the attendant morbidity and mortality in HIV-infected children and adolescents with kidney disease, routine screening for kidney disease is recommended where resources permit.

Conclusions

This review focuses on the pathogenesis and genetics, clinical presentation and management of kidney disease in children and adolescents with perinatal HIV-1 infection.     

Visit-to-visit blood pressure variability in children and adolescents with renal disease

Background

Increase in blood pressure (BP) variability (BPV) is associated with cardiovascular events, target organ damage, and arterial stiffness in adults. We previously reported that 24-h BPV may be associated with arterial stiffness and underlie white-coat hypertension (WCH). In this study, we examined whether visit-to-visit variability (VVV) could predict WCH and whether VVV correlated with eGFR, eGFR slope, and albuminuria/proteinuria in children and adolescents with renal diseases.

Methods

VVV was determined as average real variability of office BP measurements between visits, and 24-h BPV as the standard deviation of 24-h ambulatory BP. In 35 renal patients (25 boys and 10 girls, 7–18 years of age), divided into normotension (NT), WCH, and hypertension (HTN), the relationships between VVV and 24-h BPV and VVV in each BP category were studied. In separate 48 renal patients (24 boys and 24 girls, 2–18 years of age), the correlation between VVV and eGFR, eGFR slope, urine albumin or protein excretion was examined.

Results

Systolic VVV was significantly correlated with systolic office BP index. There was no correlation between VVV and 24-h BPV or 24-h pulse pressure. In addition, VVV was not different among NT, WCH, and HTN. Systolic VVV was significantly negatively correlated with eGFR but not with eGFR slope, albuminuria, or proteinuria. A cut-off value of systolic VVV for detecting eGFR?<?60 ml/min per 1.73 m² was 8.5.

Conclusion

VVV could not predict WCH. Systolic VVV correlated with eGFR but not with eGFR slope, albuminuria/proteinuria. Increased VVV could be a marker of decreased eGFR.

     

Methylated arginine derivatives in children and adolescents with chronic kidney disease

Asymmetric dimethylarginine (ADMA), a methylated L: -arginine (Arg) derivative is associated with endothelial dysfunction, vasoconstriction, and hypertension in animals and humans. We examined the relationship between these derivatives, estimated glomerular filtration rate (eGFR), and awake (AW) and asleep (AS) blood pressure (BP) load in children and adolescents (n = 28) with stage 2-3 chronic kidney disease (CKD) and in matched intra-familial controls (n = 10). Plasma L: -Arg, ADMA, and symmetric dimethylarginine (SDMA) levels were measured by high-performance liquid chromatography-tandem mass spectrometry. Subjects wore a 24-hr ambulatory BP monitor with BP load >95th percentile. ADMA, SDMA/ADMA ratio and SDMA were 38-200% higher in CKD patients while L: -Arg/ADMA and L: -Arg/SDMA ratios and the L: -Arg level were 11-64% lower. The eGFR explained 42-60% of L: -Arg/SDMA, SDMA/ADMA, and SDMA variability (n = 38). Using linear regression, SDMA and SDMA/ADMA separately explained 15-38% of AW and AS systolic (S) BP and diastolic (D) BP load variability (p < 0.001-0.022). Using multivariate stepwise regression with eGFR held constant, SDMA/ADMA was a significant independent variable for AW DBP load (p = 0.03). In conclusion, BP load and a disproportionate elevation of SDMA are seen in children and adolescents with stage 2-3 (mild-moderate) CKD. SDMA is a strong marker for reduced eGFR and serves as a moderate but significant indicator of 24-hr BP load variability.     

Hepatitis C infection in children and adolescents with end-stage renal disease

The prevalence of hepatitis C virus (HCV) infection and the risk factors associated with its transmission are described in a contemporary cohort of 55 children and adolescents with end-stage renal disease (ESRD). Thirty-seven patients were on dialysis or had been transplanted (ESRD) and 18 had chronic renal failure (CRF) but had not yet received dialysis. Seven (19%) tested positive for HCV by enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR), or both. None of the children with CRF were infected. HCV infection was associated with length of time on dialysis, but not with age, gender, race, or units of blood transfused. These data corroborate earlier reports and confirm that children with ESRD continue to have a high prevalence of HCV. It is also shown for the first time that elevated transaminases should not be employed to predict HCV infection in this cohort, as all affected children had normal serum levels. Because of unique characteristics in this cohort, both ELISA and PCR are required to maximize HCV diagnostic sensitivity. Although HCV remains an important consideration in pediatric ESRD, the present study shows that recent advances in clinical practice have eliminated one of the major ways in which it was previously being transmitted. Received: 30 July 2001 / Revised: 2 January 2002 / Accepted: 4 January 2002     

Renovascular hypertension in children: current concepts in evaluation and treatment

Since 1981, we have evaluated and treated 22 children with renovascular hypertension (RVH). Seventeen patients had stenosis of their native renal arteries, and five had stenosis of the artery in a transplanted kidney. RVH was caused by fibromuscular dysplasia in 13 patients, by trauma in 2 patients, and by arteritis in 2 patients. Among the patients who had transplanted kidneys, three had technical causes for stenosis and two had stenosis due to rejection. The disease was unilateral in 10 patients, bilateral in 5, and present in a solitary kidney in 7, including the five renal transplants. Diagnostic studies that strongly suggested the presence of renovascular disease were an initial diastolic blood pressure greater than 100 mm Hg, an elevated peripheral vein renin activity level, and an abnormal renal scan if the patient's hypertension was being controlled with an angiotensin-converting enzyme inhibitor (ACEI). Only the renal arteriogram was 100% accurate in confirming the presence of RVH. Percutaneous angiographic correction was attempted in 13 patients and resulted in lasting improvement of the hypertension in five (38%). Surgical revascularization was attempted in 17 children, including the 8 with failed angioplasty, with improvement or cure of the hypertension in 15 patients (88%). Combining percutaneous transluminal angioplasty (PTA) and surgical results gave 20 of 22 patients (91%) with cure or improvement of their hypertension. Four of 27 affected kidneys (15%) could not be revascularized and were removed. We conclude from this series of patients that despite improvements in noninvasive studies, renal arteriogram remains the only study that is 100% accurate in evaluating children for RVH.(ABSTRACT TRUNCATED AT 250 WORDS)