Gary M. Lum

Solitary renal myofibromatosis: an unusual cause of infantile hypertension.

Introduction. Renovascular disease accounts for the vast majority of cases of infantile hypertension with complications resulting from umbilical arterial catheterization predominating in the neonatal period and fibrodysplastic lesions of the renal artery predominating outside the neonatal period. We report a previously undescribed cause of renovascular hypertension: solitary renal myofibromatosis. Case Report. A 9-month-old male infant was transported to the intensive care unit at Childrens Hospital in Denver, Colorado, for evaluation and treatment of a dilated cardiomyopathy and severe systemic hypertension. The child was full-term with no perinatal problems. Specifically, the child never required umbilical arterial catheterization. He was well until 6 months of age when his parents noted poor weight gain. At 9 months of age, he was evaluated at the referral hospital for failure to thrive. On examination he was noted to have a blood pressure of 170/110 mm Hg, but no other abnormalities. A chest radiograph showed cardiomegaly. Laboratory studies demonstrated normal electrolytes, blood urea nitrogen, and creatinine. However, urinalysis demonstrated 4+ protein without red blood cells. An echocardiogram showed severe left ventricular dilatation with an ejection fraction of 16%. On admission the child was noted to be cachectic. His vital signs, including blood pressure, were normal for age. The physical examination was unremarkable. Serum electrolytes, blood urea nitrogen, and creatinine were normal. Echocardiographic studies suggested a dilated hypertrophic cardiomyopathy. He was started on digoxin and captopril. Subsequently, he demonstrated episodic hypertension ranging from 170/90 to 220/130 mm Hg. A repeat echocardiogram 24 hours after admission demonstrated a purely hypertrophic cardiomyopathy. Verapamil and nifedipine were added to the treatment regimen in an effort to better control the blood pressure without success. Urine and blood for catecholamines and plasma renin activity, respectively, were sent and treatment with phentolamine instituted because of a possible pheochromocytoma. A spiral abdominal computerized tomographic scan revealed a markedly abnormal right kidney with linear streaky areas of calcification around the hilum and also an area of nonenhancement in the posterior upper pole. The adrenals and the left kidney were normal. Doppler ultrasound revealed a decrease in right renal arterial flow. The urinary catecholamines were normal and surgery was scheduled after the blood pressure was brought under control by medical treatment. At surgery, tumorous tissue and thrombosis of the renal artery were found in the right upper pole. A right nephrectomy was performed. Pathologic examination of the kidney showed the presence of a diffuse spindle cell proliferation in the interstitium of the kidney. The angiogenic/angiocentric character of the proliferation was demonstrated in several large renal vessels. The lumen of most vessels was narrowed and some vessels were totally occluded with recanalization and dystrophic calcifications observed. Immunostaining of the tumor demonstrated strong desmin and vimentin positivity and minimal actin positivity in the spindle cells. Mitotic activity was not noted in the spindle cell process. These pathologic changes were consistent with a diagnosis of infantile myofibromatosis (IM). The childs preoperative plasma renin activity was 50 712 ng/dL/h (reference range, 235–3700 ng/dL/h). Discussion. The causes of systemic hypertension in infancy are many although renal causes are by far the most common. Renal arterial stenosis or thrombosis accounts for 10% to 24% of cases of infantile hypertension. Renal artery thrombosis is usually a consequence of umbilical arterial catheterization, which can also lead to embolization of the renal artery. Renal artery stenosis may result from fibrodysplastic lesions (74%), abdominal aortitis (9%), a complication of renal transplantation (5%), and renal hypoplasia (3%). IM of the solitary type has never been reported as a cause of systemic hypertension. In our patient the IM caused both fibrodysplastic lesions and thrombosis of the renal artery, which led to severe systemic hypertension. IM is one of the myofibroblastic diseases of infancy and has three clinicopathologic expressions—solitary, multifocal, and generalized. The solitary and multifocal forms are usually limited to the skin, soft tissues, and bone. There is little morbidity and virtually no mortality in these forms of the disease. The generalized form, in addition to skin and bone involvement, may involve multiple visceral organs including the lungs, kidney, heart, liver, adrenals, thyroid, and the gastrointestinal tract. This form of the disease is the least common, usually presents in the first 6 months of life, and is associated with a high morbidity and mortality with death occurring as a result of lung involvement and respiratory failure. To our knowledge, solitary involvement of a viscera without involvement of skin, soft tissues, bone, or other visceral organs has never been reported. All three forms of IM share a distinctive microscopic appearance of interlacing fascicles of spindle cells. These interlacing fascicles sometimes blend into compact bundles with a fibrohyalin stroma in the same tumor. Origination around the blood vessels, or angiocentricity, is usually present in all types of lesions. The blood vessels involved in these lesions show intimal hyperplasia leading to obliteration of the blood vessels. From these findings it has been postulated that IM is the result of a multifocal proliferation of mesenchymal or myofibroblast-like cells in the walls of blood vessels. These cells share morphologic and immunohistochemical characteristics of both fibroblasts and undifferentiated smooth muscle cells. There is usually no evidence of malignant characteristics in these cells. The solitary and multiple forms of these tumors usually undergo spontaneous regression. In this child we were unable to demonstrate evidence of multifocal myofibroblastic lesions. He seemed to have had a solitary myofibroblastic lesion in the right kidney which led to renal artery stenosis and thrombosis. This produced the renin-related hypertension, which responded only to tumor removal by nephrectomy. He is now growing and developing normally and his cardiomyopathy has resolved. He is presently normotensive and taking no medications. To date he has had no new or recurrent myofibroblastic lesions. Conclusion. This case demonstrates that IM can present with solitary visceral organ involvement. The absence of involvement of soft tissues, skin, or bone makes clinical diagnosis of IM nearly impossible when a single viscera is involved in isolation. A biopsy will be needed to make a diagnosis, and surgery may be needed depending on the organ of involvement and the clinical consequences.

Successful Utilization of High-Flux Hemodialysis for Treatment of Vancomycin Toxicity in a Child

Vancomycin is routinely used for empiric antibiotic therapy in children. Higher-serum-concentration targets for serious infections are now being recommended. This recommendation may result in aggressive dosing with increased potential for toxicity. We report a case of a pediatric patient who developed vancomycin toxicity and associated oliguric renal failure who was treated effectively with high-flux hemodialysis for vancomycin toxicity, clearing serum concentrations of vancomycin by over 75% in only 6 hours (213.2 mcg/mL to 51.8 mcg/mL) with subsequent return to baseline renal function and without adverse sequelae. While not historically considered a viable option for drug removal in cases of toxicity, new high-flux hemodialysis techniques can remove significant percentages of vancomycin in short periods of time.

Unexpected seizures during hemodialysis: effect of dialysate prescription

To assess the effects of the dialysate prescription on the intradialytic neurological stability of children requiring chronic hemodialysis (HD), continuous EEG monitoring (CEM) was performed on five children before, during and after HD against: (1) low sodium acetate (LAc: Na 132 mEq/l, acetate 38 mEq/l); (2) high sodium acetate (HAc: Na 144 mEq/l, acetate 41 mEq/l), and (3) low sodium bicarbonate (LBi: Na 133 mEq/l, bicarbonate 35 mEq/l) dialysate. Three children, two with clinically well-controlled seizure disorders and one with no seizure history, exhibited subclinical seizures on LAc and HAc but improved neurological stability on LBi. Two children had essentially unchanged CEM studies on any HD regimen. Symptoms of disequilibrium were noted in four of the five children on LAc, two of the five on HAc and only one of the five on LBi. The data suggest that bicarbonate HD may enhance intradialytic neurological stability, particularly in children with known seizure disorders. Furthermore, CEM was found to be a useful tool for evaluating the neurological stability of children during HD.

Descriptions of the participating centers and patient population in the Growth Failure in Children with Renal Diseases Study.

The Growth Failure in Children With Renal Diseases Study, a double-blind, multicenter clinical trial with 108 children entered into the control period over 4.3 years of patient enrollment (December 1984 to April 1989), is being extended for 3 years (December 1988 to December 1991) to provide the time needed to accrue additional patients, aged between 1 1/2 and 10 years, with glomerular filtration rates of 20 to 75 ml/min/1.73 m2. The study design of randomization to two treatment arms (1,25-dihydroxyvitamin D vs dihydrotachysterol) requires a total of 108 patients with a minimum of 6 months of treatment to test the long-term effectiveness and safety of 1,25-dihydroxyvitamin D, an essential part of the therapeutic regimen for children with chronic renal insufficiency. The frequent longitudinal assessments of nutrition and growth in children with chronic renal insufficiency can better define the natural history of renal disease and its influence on growth. Similar data in the treatment period will define the impact of treatment with 1,25-dihydroxyvitamin D3 versus dihydrotachysterol on this natural history. Linear growth must be observed long enough (6 to 12 months minimum) to permit valid quantitation and comparison of the two vitamin D treatment arms, the multiple confounding variables that affect growth (e.g., steroid therapy, diabetes mellitus, prior vitamin D treatment) must be rigorously excluded or controlled, and the assignment of patients to the two groups must be random. These controls--sufficient study duration, sufficient patient numbers, and randomization--should eliminate extraneous sources of variation, including seasonal periodicity. This carefully developed, double-blind clinical trial with multiple participating centers and an effective organizational structure is coming close to achieving the goals of the study. An explosion of data regarding the natural history of chronic renal insufficiency and its treatment with vitamin D metabolites will be forthcoming at the conclusion of the study.

Childhood membranoproliferative glomerulonephritis type I: limited steroid therapy

Nineteen patients with biopsy proven membranoproliferative glomerulonephritis type I (MPGN I) and a minimum of three years of follow-up (mean 6.5 +/- 0.7 years) have been treated with an uncontrolled regimen of limited corticosteroids. Initial therapy ranged from 20 mg per os (po) every other day to 30 mg/kg/day i.v. for three consecutive days, depending on clinical disease severity. Therapy was then decreased based on each patients improving clinical status. At diagnosis creatinine clearance (CCr) was less than 80 ml/min/1.73 m2 in 12 patients and less than 50 in 2. All patients had hematuria and proteinuria, with 15 in the nephrotic range. Hypertension, present at diagnosis in 13, developed in five others following institution of prednisone, and was controlled medically. Renal biopsy was repeated after two years of therapy prior to cessation of treatment (mean total treatment duration 38 +/- 3 months). Follow-up biopsy revealed decreased glomerular inflammatory activity in 88% of patients. All patients have now been off prednisone for 40 +/- 9 months. The mean CCr is 126 +/- 5 ml/min/1.73 m2. Eight patients have normal urinalyses. These data suggest that early therapy with a limited course of corticosteroids, and control of associated hypertension, may forestall progressive renal insufficiency in children with MPGN type I.