Biomedical subjects
F B Stapleton
Publications and source records attributed to F B Stapleton.
Removal of methotrexate, leucovorin, and their metabolites by combined hemodialysis and hemoperfusion.
This article documents the case of a patient with severe renal failure immediately after having been given high-dose methotrexate; the patient was effectively treated with repeated hemodialysis, charcoal hemoperfusion, leucovorin, and thymidine. The methotrexate plasma concentration was reduced from 390 mumol/L to 7 mumol/L as a result of 24.5 hours of hemodialysis along with 39.5 hours of hemoperfusion. Although a rebound in the plasma methotrexate concentration occurred the first three times that hemodialysis and/or hemoperfusion was stopped, reinstitution of the procedure was always effective in further lowering methotrexate concentrations. The patient was subsequently managed with leucovorin and thymidine rescue. Simultaneous measurements before and after the hemodialysis-hemoperfusion apparatus and before and after the hemoperfusion device alone revealed a percent decrease in the concentration of d-leucovorin of 36% and 79%; 1-leucovorin, 82% and 75%; 5-methyltetrahydrofolate, 52% and 64%; methotrexate, 73% and 37%; and 7-hydroxymethotrexate, 21% and 24%, respectively. Gastrointestinal and hematologic toxicities were completely prevented, and serum creatinine normalized within 24 days.
Beneficial effect of second courses of cytotoxic therapy in children with minimal change nephrotic syndrome.
Therapeutic guidelines are not available for children with minimal change nephrotic syndrome (MCNS) who experience frequent relapses or develop steroid resistance after a course of cytotoxic therapy. The records of nine children with biopsy-proven MCNS who received two courses of cytotoxic therapy with either chlorambucil or cyclophosphamide were reviewed to evaluate the length of remission, associated side-effects and long-term outcome. Initial cytotoxic therapy was given to five frequent-relapsing patients and four steroid-resistant patients 2-48 months (mean 16 months) following diagnosis of nephrotic syndrome. The second drug was given 4-85 months (mean 27 months) after the first. Steroid-resistant patients attained remissions of 0-81 months (mean 23 months) following the first agent and 13-67 months (mean 32 months) following the second. Frequent-relapsing patients experienced remissions of 0.5-24 months (mean 7.4 months) following the first cytotoxic drug and 3-72 months (mean 22 months) after the second. Remissions following the second agent were equal to or longer than those following the first in the seven patients who received both chlorambucil and cyclophosphamide. In the 19- to 128-month follow-up (mean 66 months), all four steroid-resistant patients experienced infrequent relapses which responded to prednisone. One frequent-relapsing patient remains in remission, three have chronic proteinuria and one still has a frequent-relapsing course. For the select group of patients who become frequent relapsing or steroid resistant after one course of cytotoxic therapy, a second course of cytotoxic therapy may allow time for catch-up growth, as well as improve steroid responsiveness once relapses occur.
Renal function in children with idiopathic hypercalciuria.
Abnormalities in renal tubular function have been reported in adult patients with idiopathic renal hypercalciuria. To determine if such abnormalities are present early in the natural history of renal hypercalciuria, we evaluated renal tubular function in ten children with idiopathic renal hypercalciuria, aged 5-17 years. Seven of the children presented with urolithiasis and three with hematuria. Urinary calcium excretion ranged from 4 to 9 mg/kg per day, (5.2 +/- 0.5, mean +/- SEM) with a mean fasting urinary calcium to creatinine ration of 0.31 +/- 0.03. Studies described in this report were performed after 1 week of ingesting a diet containing 1,000 mg calcium, 3,000 mg sodium, and 100 mg purine. Clearance of creatinine ranged from 84 to 159 ml/min per 1.73 m2. Tm phosphate (mg/100 ml GFR) was normal in each child (mean 4.66 +/- 0.06 mg/100 ml GFR). Fractional excretion of uric acid, sodium and beta-2-microglobulin were also normal in each child. Serum bicarbonate concentrations ranged from 21.5 to 27 mEq/l with a mean of 24.4 +/- 0.5 mEq/l and all patients lowered urinary pH to less than 5.5. Hypotonic diuresis demonstrated normal free water clearance with a mean of 12.8 ml/min per 100 ml Cin. Distal sodium delivery and fractional distal sodium reabsorption were normal with a mean of 13.6 +/- 1.2% and 92.7 +/- 0.5%, respectively. Water deprivation studies demonstrated a range of maximum urinary osmolality from 711 to 1,020 mosmol/kg H2O with a mean of 864 +/- 34 mosmol/kg H2O. Seven healthy children, ingesting an identical study diet, concentrated their urine to a mean of 1,059 +/- 31 mosmol/kg h2O.(ABSTRACT TRUNCATED AT 250 WORDS)
Digital subtraction angiography in the evaluation of renal vascular hypertension in children.
Twenty children were evaluated with digital subtraction angiography (DSA) for renal vascular hypertension. IV DSA from a basilic vein approach was performed in four patients and femoral vein approach in two patients. Intraarterial DSA was performed in 14 patients with suspected renal vascular hypertension. Renal vein renin samples were obtained from 17 patients. Two renal artery angioplasties were performed in association with intraarterial DSA. IV DSA was diagnostic in five of six patients with one false-negative result for fibromuscular dysplasia of the tertiary vessels. Intraarterial DSA images were diagnostic in 14 of 14 patients, and renal vein renin results correlated well with DSA results. In 11 patients, DSA was performed as an outpatient (hospital day-care unit) procedure. Of the 20 patients evaluated, 13 patients had abnormal DSA findings which included a hypoplastic but functioning kidney in three patients, distal small vessel abnormalities in five patients, unilateral or peripheral renal artery stenosis in four patients, and middle aortic syndrome in one patient. DSA with renal vein renin samples can be used as a diagnostic procedure for the evaluation of renal vascular hypertension in children as well as adult patients. In addition, it is a useful tool for therapeutic vascular procedures in children.
Acute renal failure at onset of therapy for advanced stage Burkitt lymphoma and B cell acute lymphoblastic lymphoma.
Aggressive therapeutic maneuvers to reduce the risk for acute renal failure are routine in the management of children receiving therapy for advanced stage Burkitt lymphoma and B cell acute lymphoblastic leukemia. The case histories of 40 children entered into a prospective treatment protocol for high-risk disease revealed that ten of 40 patients (25%) had acute renal failure, two at the time of hospital admission and eight in whom renal insufficiency developed 12 to 132 hours following initiation of cytotoxic chemotherapy. Admission values for serum lactic dehydrogenase and serum uric acid were not statistically different between patients with and without subsequent renal failure. Urine output in the 12 hours prior to antineoplastic therapy was 2.9 +/- 0.8 mL/kg/h in the eight children in whom renal failure developed and 5.3 +/- 0.4 mL/kg/h in the patients who did not (P less than .01). The urinary flow rate in the 24 hours following initiation of chemotherapy was significantly lower in children in whom renal impairment developed (1.0 +/- 0.2 mL/kg/h, mean +/- SE) compared with those who did not (3.7 +/- 0.3 mL/kg/h, P less than .001). Renal failure could not be attributed to hyperuricemia or hyperphosphatemia in the majority of patients with renal failure. One to four hemodialysis treatments (2.5 +/- 0.3) were required for the ten patients. Serum creatinine concentrations returned to normal in the nine survivors. Response to initial antineoplastic therapy was not affected by the presence of renal failure. Renal failure continues to be a major clinical problem in children with Burkitt lymphoma and B cell lymphoblastic leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunoregulatory studies in patients with IgA nephropathy.
Numerous studies have evaluated T cell subsets and in vitro IgA synthesis in patients with IgA nephropathy. These reports have resulted in the hypothesis that defective regulation of IgA synthesis is important in the pathogenesis of IgA nephropathy. Baseline immunologic measurements were performed in a clinically well characterized group of 19 pediatric and 13 adult (greater than or equal to 18 years) patients with no macrohematuria or intercurrent infection at the time of study. Mean percentages of OKT3 and OKT4 subsets were significantly decreased for the patients as compared to healthy adult controls. Mean T4:T8 ratios were similar for control and patient groups although 7 patients had T4:T8 ratios greater than 2 SD above the control mean. Unstimulated and pokeweed mitogen stimulated in vitro IgA synthesis was similar for patients and controls. During six episodes of macrohematuria in five patients no significant changes occurred for T cell subset percentages, while mean T4:T8 ratios decreased from baseline. Mean serum concentration of IgA increased during these episodes, although in vitro IgA synthesis remained normal. Our data fail to demonstrate a consistent immunoregulatory abnormality for patients with IgA nephropathy.
Focal segmental glomerulosclerosis in children: comparison of nonedematous and edematous patients.
Persistent proteinuria without edema, associated with focal segmental glomerulosclerosis (FSGS), has been increasingly observed in our pediatric population. The clinical and pathological features and long-term outcome of these patients are poorly understood and less frequently reported. Ten nonedematous children (10.3 +/- 1.4 years) with proteinuria and FSGS are compared with 16 children (9.0 +/- 0.4 years) with FSGS and nephrotic syndrome (NS). Urinary protein excretion and serum cholesterol were statistically higher and serum albumin statistically lower in the children with FSGS-NS. The percentage of glomeruli with sclerosis was similar in the two groups. Mesangial proliferation was observed more frequently in the nephrotic children and focal or diffuse tubular atrophy more often in the nonedematous children with FSGS. Followup serum creatinines are more than 1 SD above the mean for age in 3 of 10 nonedematous patients with FSGS and 9 of 16 patients with FSGS-NS. Of 10 nonedematous patients with FSGS, 1 progressed to renal failure 20 months after diagnosis, while 3 of 16 patients with FSGS-NS progressed to renal failure. We conclude from these data that NS is a poor prognostic sign in FSGS in children and that neither the percentage of glomeruli with sclerosis nor the presence of tubular atrophy is predictive of NS in our patients.
Acute renal failure in neonates: incidence, etiology and outcome.
Acute renal failure (ARF) occurs in as many as 8% of neonates admitted to neonatal intensive care units. Most often, ARF is recognized because of oliguria (urinary flow rate less than 1 ml/kg per hour) although nonoliguric neonatal ARF is being detected with increasing frequency. Among urinary indices utilized to differentiate oliguric neonatal ARF from prerenal oliguria, a fractional excretion of sodium greater than 3% or a renal failure index (RFI) greater than 3 are helpful in confirming ARF. Such indices must be viewed with caution in very premature infants who may have a physiologically high sodium excretion rate and in neonates with the nonoliguric form of ARF. The mortality of oliguric neonatal renal failure may be as high as 60% in medical ARF and even higher in neonates with congenital heart disease, or with anomalies of the genitourinary system. In contrast, nonoliguric renal failure in neonates has an excellent prognosis. Long-term abnormalities in glomerular filtration rate and in renal tubular function are common in survivors of neonatal ARF.
Increased serum concentrations of 1,25(OH)2 vitamin D in children with fasting hypercalciuria.
Inappropriately elevated concentrations of 1,25(OH)2 vitamin D in serum appear to be responsible for excessive gastrointestinal absorption of dietary calcium in patients with absorptive hypercalciuria. We have examined serum 1,25(OH)2 vitamin D concentrations in another group of children with hypercalciuria in whom urinary calcium excretion was excessive after an overnight fast. Eleven children with idiopathic fasting hypercalciuria (IH) (urinary calcium excretion greater than 4 mg/kg/24 hr and fasting urinary calcium/urinary creatinine ratio greater than 0.21) and seven healthy children were observed while they were eating a diet containing 1 gm calcium per day. Fasting serum 1,25(OH)2 vitamin D concentrations were elevated in children with IH compared with control values (35.3 +/- 3.2 vs 21 +/- 2 pg/ml, P = 0.003), whereas fasting serum parathyroid hormone, 25-OH vitamin D, phosphorus, and ionized calcium concentrations were similar in the two groups. These data suggest that disordered 1,25(OH)2 vitamin D metabolism occurs in children with fasting IH. Absorptive and fasting IH may represent a spectrum of a single disorder characterized by excessive urinary calcium excretion and inappropriately elevated serum concentrations of 1,25(OH)2 vitamin D.
Polycystic kidney disease in the first year of life.
To determine the frequency of autosomal recessive and autosomal dominant polycystic kidney disease (PKD) in infants and to compare the rate of progression of these conditions, we conducted a retrospective survey of 48 patients who were seen with PKD before 1 year of age and who survived the first month of age. Seventeen patients had recessive PKD; six had dominant PKD. Eighteen patients had insufficient data to categorize the type of PKD with certainty. Seven patients were classified as "other"; three had glomerulocystic disease and the remainder had multiple malformation syndromes or tuberous sclerosis. Renal ultrasonography and excretory urography accurately detected 15 of 17 patients with recessive PKD, but only one patient with dominant PKD was correctly diagnosed by excretory urography. The majority of patients in all groups required antihypertensive therapy. The 17 children with recessive PKD have been followed up for 6.1 +/- 4.3 (SD) years. Eight patients are doing well. Two patients have died; five others have required treatment for renal failure. Only one patient has an estimated glomerular filtration rate within the normal range after 6 years of age. Long-term evaluation of most of the patients with dominant PKD is not yet available; however, by age 42 months one patient has required dialysis. To provide optimum genetic counseling and accurate diagnosis for patients with PKD, a combination of careful family evaluation, radiography, and liver or kidney biopsy is required. The outcome of patients who survive the neonatal period appears not to be so grim as previously feared, underscoring the importance of aggressive supportive care and the need for physician and family education.
Morphology of urinary red blood cells: a simple guide in localizing the site of hematuria.
The determination of whether urinary red blood cells originate from the kidneys or bladder allows the practitioner to evaluate children with hematuria more efficiently and economically. Recently, examination of the morphology of urinary red blood cells has proven to be a promising adjunct in the evaluation of hematuria. The application of this new office procedure is discussed.
Hypocomplementemic glomerulonephritis in an infant and mother. Evidence for an abnormal form of C3.
A mother developed hematuria during the fourth month of pregnancy, and her nursing infant son from this otherwise uncomplicated pregnancy developed hematuria at 3.5 months of age. Both had a mild glomerulonephritis characterized by mesangial prominence, focal thickening and mottling of the glomerular basement membrane and electron-dense deposits, predominantly in the intramembranous and subendothelial positions. Immunofluorescence studies revealed striking accumulations of C3 and other complement components associated with alternative complement pathway activation within glomeruli, and the presence of small or equivocal amounts of immunoglobulin. C1q, C4 and factor B were not detectable. The glomerular lesion was accompanied by hypocomplementemia. Sera of both mother and infant displayed half normal levels of C3 and factor B, increased levels of C4, and normal levels of 12 other complement proteins. High normal or slight elevation in nephritic factor-like activity was observed in serial serum samples. Studies suggested that this mother and son represent the second kindred having an abnormal form of C3 which produces an alternative complement pathway C3 convertase, C3b, Bb, resistant to control by factor H. No additional affected family members were identified. The course of the nephritis over 7 years without drug therapy has been mild with resolving hematuria and no abnormal proteinuria or decrease in creatinine clearance.
Urolithiasis and enteric hyperoxaluria in a child with steatorrhea.
Malabsorptive states are frequently associated with increased urinary oxalate excretion. The authors describe a 10-year-old girl with steatorrhea, hyperoxaluria, and a renal calculus in a single functioning kidney. Successful management of steatorrhea corrected both the chronic diarrhea and hyperoxaluria. Enteric hyperoxaluria is a well-known etiology of calcium oxalate urolithiasis in adults. Pediatricians caring for children with malabsorptive conditions should be aware of the risk of urinary calculus formation as a result of increased dietary oxalate absorption.
Urolithiasis in children: the role of hypercalciuria.
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Sweet's syndrome with multifocal sterile osteomyelitis.
Sweet's syndrome is a rare condition characterized by fever, leukocytosis, dense dermal infiltration of leukocytes, and painful indurated cutaneous plaques. We describe a 23-month-old male infant with the typical cutaneous manifestations of Sweet's syndrome and painful extremities that limited ambulation. Evaluation revealed multifocal sterile osteomyelitis of both tibia. After the institution of systemic corticosteroid therapy, the patient's symptoms resolved, and bone scans normalized. After one year of follow-up, the patient has intermittent recrudescences that resolve during corticosteroid therapy. Sterile multifocal osteomyelitis represents another clinical manifestation of Sweet's syndrome.
Ultrasonographic features of glomerulocystic disease in infancy: similarity to infantile polycystic kidney disease.
Glomerulocystic kidney disease (GCD) is an unusual condition characterized pathologically by cystic dilatation of Bowman's space and the first portion of the proximal convoluted tubule. We report the serial ultrasound findings in an asymptomatic infant with GCD which were initially confused with infantile polycystic kidney disease. We emphasize the nonspecificity of ultrasonographic findings in cystic renal disease in early infancy and suggest a protocol for the diagnostic work-up of bilateral renal cystic disease in children.
Unilateral presentation of adult-type polycystic kidney disease in children.
Adult polycystic kidney disease is characterized by autosomal dominant inheritance, diffuse bilateral cystic kidney disease and onset during the young adult years. Relatively few cases of adult-type polycystic kidney disease in children have been reported. We describe a 4-year-old girl who appeared to have multiple, unilateral simple renal cysts by excretory urography and ultrasonography. There was no known familial renal cystic disease. When renal histology was consistent with adult-type polycystic kidney disease, screening nephrosonograms revealed that the mother also had the disease. We review 10 published cases of unilateral presentation of adult-type polycystic kidney disease in children. This report emphasizes the necessity of screening studies in parents of children with diffuse unilateral or bilateral cystic renal disease. Awareness of the unexpected unilateral presentation of adult-type polycystic kidney disease in children may allow a nonoperative diagnosis to be made.