Familial extra-adrenal pheochromocytoma. A new syndrome.

Pheochromocytomas in the same anatomic site, the right renal hilum, occurred in a family over three successive generations. For two patients in the latter two generations, scintigraphy with iodine 131-tagged metaiodobenzylguanidine (MIBG) showed tumors only in the region of the right renal hilum, thus indicating that they were primary lesions. At surgery, except for lymph node metastases noted microscopically in one patient, tumors were found only near the right renal hilum. The adrenal glands seemed normal on inspection, palpation, and computed tomography. In another family, a mother and son had primary pheochromocytomas arising from the urinary bladder. We suggest that primary extra-adrenal pheochromocytoma is a syndrome in which specific genetic abnormalities determine sites of tumor development.

Pediatric renal transplantation with an emphasis on the prognosis of patients with chronic renal insufficiency since infancy.

In this report recent experience with renal transplantation in 43 children who were 17 days to 16 years old was reviewed. One-year patient survival rate was 98%, and overall one-year graft survival rate was 68%. One-year graft survival rate was 73% for cyclosporine-treated patients and 78% for recipients of related donor kidneys. A subpopulation of patients affected with renal insufficiency since infancy was analyzed separately to evaluate the prognosis of these patients, who have previously been reported to be a high risk for permanent neurologic, developmental, and growth retardation. All 16 such patients underwent transplantation. Gross motor delay that was noted in 31% of patients before surgery resolved in all patients after transplantation. No evidence of severe developmental delay was noted after transplant and seven of 11 patients with successful transplants had evidence of catch-up growth. Overall renal transplantation is a safe and effective procedure for children with renal failure, and even the patients at highest risk for growth and developmental failure caused by renal insufficiency show potential for rehabilitation after transplantation.

Fragmentation and polymeric complexes of albumin in human urine.

Analysis of urine proteins of some individuals with proteinuria by SDS-PAGE and silver staining revealed protein bands in urine which did not appear to be present in plasma. The bands migrated with apparent molecular weights of 260 000, 180 000, 110 000, 45 000, 40 000, 30 000, 24 000, 18 000 and 11 000. These bands were shown to be albumin polymer and fragments by using a polyclonal antibody to (a) immunoprecipitate radiolabelled urine proteins, and (b) identify bands blotted from SDS-PAGE gels onto nitrocellulose paper. The specificity of the polyclonal anti-albumin antibody was confirmed by using two mouse monoclonal antibodies raised against human albumin which, between them, recognized the same protein bands on nitrocellulose paper as did the polyclonal antibody. The results of these studies of albumin in human urine confirm that albumin exists as polymer and also show that albumin fragmentation occurs in urine. Fragmentation occurs by proteolysis of the albumin molecule both at sites within and outside disulfide loops. The predominant cleavage site appears to be approximately two-fifths of the distance from one end of the albumin molecule to produce disulfide-linked fragments of about 45 000 and 30 000 molecular weight.

Acetate intolerance during hemodialysis.

Acetate is frequently substituted for bicarbonate in hemodialysis solutions. Plasma acetate and bicarbonate concentrations were measured in nine patients with chronic renal failure undergoing hemodialysis with dialyzate containing acetate. In three patients (2 children and 1 adult) plasma acetate concentrations exceeded 15 mEq/liter during the dialysis. The mechanisms leading to acetate intolerance are probably multiple. It cannot be assumed that dialysis with acetate containing solutions will restore the buffer anion deficit characteristic of chronic renal failure.

Rise in plasma free-norepinephrine during anesthetic induction with ketamine.

Mean plasma free-norepinephrine concentration rose significantly (p less than 0.001) during induction of anesthesia with intravenous ketamine (2.0 mg/kg) in 12 patients. In contrast, no change occurred during induction with thiamylal (5.0 mg/kg) in a control group of 8 patients. No significant rise in plasma free-epinephrine concentration occurred in either ketamine or thiamylal groups. These data support the suggestion that increased venous return mediated by the sympathetic nervous system may be responsible for the increased cardiac output and hypertension known to occur during ketamine anesthesia.

Sonographic standards for normal infant kidney length.

Standards for kidney length in relation to size were derived from measures of 34 normal, full-term, healthy infants aged 2-56 weeks. Of six general size variables (age, weight, length, head circumference, abdominal circumference, and C7 to coccyx length), net kidney length correlated best with a combination of infant length and weight. A nomogram has been generated from these data for use by the radiologist.

"Dilatation" of the left renal vein on computed tomography in children: a normal variant.

Compression of the left renal vein (LRV) between the superior mesenteric artery and the aorta is thought to be a cause of hematuria, periureteral and gonadal varices, and varicocele ("Nutcracker phenomenon"). Previous investigators have suggested that this diagnosis can be made on computed tomography when the LRV ratio greater than or equal to 1.5 (the diameter of the LRV proximal to the aorto-mesenteric angle divided by the diameter of the LRV distal to the aorto-mesenteric angle). This study was designed to establish the normal range for the LRV ratio on CT in children. The LRV ratio was measured in thirty-nine consecutive children undergoing intravenously enhanced CT of the abdomen. None of the children had hematuria on urinalysis immediately before or after the CT. Children with any known abnormality involving the kidneys, adrenal glands, IVC, or renal or gonadal veins were excluded. The patients ranged in age from 3.4 to 18.5 years (mean = 10.6 years). LRV ratio ranged from 0.78 to 2.00 (mean = 1.46; S.D. = 0.312). Twenty of the 39 children (51.3%) had a LRV ratio greater than or equal to 1.50. The conclusion is that the normal range for the LRV ration is too wide for it to be useful in diagnosing LRV entrapment and that a LRV ratio greater than or equal to 1.5 on CT is normal in children.

Recurrent focal segmental glomerulosclerosis in pediatric renal transplant recipients: successful treatment with oral cyclophosphamide.

Focal segmental glomerulosclerosis (FSGS) is the most common glomerulopathy leading to end-stage renal disease in children and transplantation is complicated by recurrent disease in a significant percentage of children. Treatment of recurrent FSGS has included high-dose steroids, high-dose cyclosporine (CSA), plasmapheresis, and ACE inhibitors with mixed results. We have had a consistent approach using oral cyclophosphamide (CTX) to treat recurrent FSGS since 1982. Three patients with ESRD secondary to nephrotic syndrome had recurrent disease. Biopsies in all 3 were consistent with recurrent FSGS. Patients were begun on a 8-12 week course of 1-2 mg/kg/day of CTX and dosage was adjusted for WBC count. Azathioprine was with held during CTX. Patients' dosage at the end of 12 weeks ranged from 0.89-1.75 mg/kg/day. All patients tolerated CTX well. After 8-12 weeks of treatment, 2 patients with nephrotic syndrome normalized their serum albumin and had negative to trace protein on urinary dipstick. One patient with proteinuria decreased his protein excretion from 770 to 340 mg/m2/day. At follow-up at 8, 38, and 125 months post-transplant, these 3 patients have stable graft function and negative to trace protein on urinalysis. The patient followed for 125 months has had 2 additional relapses at 51 and 82 months post-transplant that were treated successfully with pulse intravenous steroids. Three pediatric patients with recurrent focal segmental glomerulosclerosis post-renal transplant were treated with oral CTX and had significant improvement in proteinuria and preservation of graft function. This suggests that oral CTX is a potentially effective and well-tolerated treatment for recurrent FSGS in children.

Renal papillary necrosis in juvenile rheumatoid arthritis.

Three patients who developed renal papillary necrosis while receiving long-term, high-dose aspirin therapy for juvenile rheumatoid arthritis are presented. It appears that aspirin alone or aspirin in combination with other drugs is the causative agent. The incidence and biologic significance of renal papillary necrosis are insufficient to alter the use of aspirin as the drug of choice in management of JRA. It is recommended that all children with JRA be encouraged to drink ample fluids and be followed with periodic urinalysis and blood pressure measurements. Those children who develop hematuria or hypertension should be evaluated by excretory urography.

Suppression of plasma renin activity in a boy with chronic hyperkalemia.

Chronic hyperkalemia (6.8 mmol/L [6.8 mEq/L]) was discovered in a boy, aged 13 years 7 months, with short stature, delayed puberty, and normal blood pressure. Additional studies revealed hyperchloremic metabolic acidosis (serum values: sodium ion, 139 mmol/L [139 mEq/L]; chloride, 113 mmol/L [113 mEq/L]; bicarbonate, 18 mmol/L [18 mEq/L]), a normal glomerular filtration rate, a subnormal renal threshold for bicarbonate reabsorption, and normal serum thyroxine, growth hormone, and cortisol values. Renal excretion of potassium ion was subnormal for the prevailing serum concentration of potassium ion but was increased normally by infusion of sodium sulfate. The serum aldosterone concentration was appropriate for a normokalemic subject, despite marked suppression of plasma renin activity (PRA) (supine/upright: aldosterone, 140/580 pmol/L [5/21 ng/dL]; PRA, 0.0/0.03 ng/L X s [0.0/0.1 ng/mL/h]). Treatment with chlorothiazide and sodium chloride resulted in correction of the abnormal electrolyte concentrations and an increase in linear growth velocity. Serum aldosterone concentrations did not change significantly during treatment, even though the PRA had increased (supine/upright: aldosterone, 110/920 pmol/L [4/33 ng/dL]; PRA, 0.89/2.17 ng/L X s [3.2/7.8 ng/mL/h]). In this patient, we conclude that (1) hyperkalemia was due to inadequate renal excretion of potassium ion; (2) the serum potassium ion concentration was the major stimulus to aldosterone secretion before treatment; (3) suppression of PRA was more likely due to hyperkalemia than to extracellular volume expansion.

Interobserver and intraobserver variations in sonographic renal length measurements in children.

Sonographic measurement of renal length is used commonly to evaluate growth of the kidneys in children. However, no previous studies have been performed to determine the degree of interobserver and intraobserver variability in such determinations. We measured the interobserver and intraobserver error in sonographic measurements of renal length obtained independently by three experienced imagers in 21 children (41 kidneys). The mean interobserver variation between any two imagers ranged from 3.87 to 5.49 mm. The mean intraobserver variation was 0.87 to 3.61 mm. The observed variability in sonographic measurement of renal length is comparable to the expected annual increase in length of the kidneys during childhood (2.2-5.7 mm per year). Therefore, caution is suggested when using sonography to evaluate renal growth in children during a year's time.