Tularemia is a rare zoonosis caused by the gram-negative coccobacillus Francisella tularensis. We describe a pediatric patient with chronic renal insufficiency who presented with high fever and regional lymphadenopathy caused by tularemia. This case highlights the fact that F. tularensis infection must be considered when investigating a fever of unknown origin, especially in the presence of a history of animal exposure.

A retrospective cohort study was conducted by the Southwest Pediatric Nephrology Study Group (SPNSG) to address whether a longer initial course of corticosteroids in patients with idiopathic nephrotic syndrome (INS) provides superior protection against relapse without increased adverse effects. In order to be included in the evaluation, patients with INS must have responded to an initial steroid course, either standard or long regimen as defined here, and completed at least 1 year of follow-up. The standard regimen consisted of prednisone 2.0±0.3 mg/kg per day or 60±10 mg/m2 per day for 28±4 days, followed by alternate-day prednisone for 4–12 weeks. The long regimen consisted of daily prednisone 2.0±0.3 mg/kg per day or 60±10 mg/m2 per day for 42±6 days, followed by alternate-day prednisone for 6–14 weeks. The primary outcome measure was relapse of NS within 12 months of discontinuing the initial course of prednisone. There were 151 children who met the criteria for the study; 82 received the standard regimen and 69 the long regimen. The two groups did not differ in age, race, blood pressure, serum albumin, or serum cholesterol prior to the initial steroid course. The cumulative prednisone dose was 49% higher in the long regimen group than in the standard regimen group. Relapse within 12 months was reported in 72.5% of patients who received the long regimen versus 84.1% of those who received the standard regimen. The odds ratio for relapse within 12 months was 0.496 (95% confidence interval 0.22, 1.088), long versus standard regimen. This did not reach statistical significance (χ 2=3.058, P=0.08). The odds ratio of experiencing at least one side effect was 3.76, long relative to standard regimen (n=133, P<0.001). Our data suggest that prolongation of the steroid treatment for the initial episode of steroid-sensitive NS may have a beneficial effect, but at the cost of increased side effects. However, definitive conclusions are limited by the retrospective design of the study and the number of patients. This may have caused failure to achieve statistical significance on the basis of a type II error.

Dr. Elena Panchenko, an IPNA councilor from Moscow, Russia, died in Memphis on 15 May 1999, where she was being treated for complications of gastric carcinoma. Elena was a fellow in Memphis, sponsored by IPNA and Le Bonheur Children’s Medical Center, for 4 months in 1991. She was a tireless worker during her fellowship with us and was successful in publishing an article, based upon work done in 1991, in Volume 8 of Pediatric Nephrology entitled, “The differential diagnostic value of urinary enzyme and amino acid excretion in children with nephrotic syndrome”. Elena was instrumental in helping to establish the Russian Society of Pediatric Nephrology and served as its executive vice president in Moscow. She was also actively involved in clinical research concerning IgA nephropathy. Elena was buried in Memorial Park Cemetery in Memphis and is survived by her husband Vladimir Orechova, daughters Katherine and Dasha and her father, Dr. Leonid Feudorovitch Panchenko of Moscow. Elena was 40 years of age and will be missed by all her many friends and colleagues in the nephrology community.

A 9-year-old white girl was referred for evaluation of asymptomatic persistent hematuria that was noted initially at 3 years of age. Gross hematuria, with symptoms of cystitis and a negative urine culture, occurred once. Family history revealed a 41-year-old father who is deaf, has had renal failure for 9 years, has had a failed kidney transplant, and currently is on hemodialysis. He has not had a renal biopsy. A 16-year-old brother is healthy and has no abnormal renal findings. Two of the father’s brothers have hematuria and one also is hearing impaired.The patient’s blood pressure, growth,and other findings on physical examination were normal. Urinalysis revealed red blood cells (RBCs) that were too numerous to count, RBC casts, and trace proteinuria. Other laboratory findings included: blood urea nitrogen,15 mg/dL; serum creatinine, 0.7 mg/dL;C3, 144 mg/dL; normal complete blood count; creatinine clearance, 115 mL/min per 1.73m2; and urinary protein excretion, 3.6 mg/m2 per hour.A renal biopsy was performed because no histologic data were available on any family members, and Alport syndrome (hereditary glomerulonephritis with nerve deafness) was suspected. Light microscopic examination of 38 glomeruli showed normal cellularity and no scarring. Immunofluorescence microscopy was negative. Electron microscopy showed variation in glomerular basement membrane width, thinning and splitting of the lamina densa, focal effacement of epithelial foot processes, and absence of electron-dense deposits.The pathologic findings and family history strongly favor a diagnosis of Alport syndrome. After discussion with the family, annual follow-up of the child to measure renal function, urinary protein excretion, blood pressure, and hearing acuity was recommended.Recognition, definition, differential diagnosis, and orderly evaluation of hematuria in infants and children are frequent and important issues in pediatric office practice. Hematuria is one of the most common renal abnormalities referred from pediatricians to pediatric nephrologists at my institution.An extensive school screening study of well children for hematuria in Helsinki, Finland, revealed that 3.4% had a positive dipstick test on one occasion and 0.9% had two or more positive tests. Because these tests are more sensitive than ones in the past, it is estimated that between 0.5% and 1% of all children may have microhematuria persisting for at least 1 month.Isolated hematuria is unaccompanied by proteinuria. The initial evaluation of a child who has isolated hematuria should rest with the primary physician. The patient who has hematuria that is complicated by persistent proteinuria (>1+ by urinary dipstick) should be referred to a pediatric nephrologist for evaluation. Hematuria is defined as more than 5 to 10 RBCs per high-power microscopic field from a centrifuged midstream voided urine sample.The urine may be yellow, pink,red, brown, or smoky on gross examination. A urine dipstick will change from yellow to graded colors of speckled green, homogeneous green, light blue, and dark blue with increasing amounts of hematuria. Hemoglobin and myoglobin will produce the same color changes on the dipstick as intact RBCs. A false-positive test for blood can result from the presence of drugs such as ascorbic acid, sulfonamides, iron sorbitol,metronidazole, and nitrofurantoin.Therefore, each urine sample that tests positive for blood by dipstick must be examined microscopically to confirm the presence or absence of intact RBCs. The microscopic urinalysis should be performed by the best qualified person available to the primary care physician.If microscopic hematuria has been present for 1 month or more, further investigation for the cause is indicated. A careful patient history,family history, physical examination, and urinalysis are helpful in organizing the evaluation (Table 1). Vigorous exercise such as jogging,bike riding, or snow boarding can cause hematuria. Abdominal, back,or flank pain, especially when associated with bruising, suggests child abuse as a possible etiology. Dysuria, urinary frequency, and suprapubic pain or tenderness suggests a urinary tract infection,cystitis, or hypercalciuria. Abdominal pain may be associated with an abdominal mass, nephrolithiasis,or Henoch-Schönlein purpura. A thorough history of drug ingestion should be sought; aspirin,nonsteroidal anti-inflammatory agents,antibiotics, methyldopa, and other drugs can cause hematuria.A history of edema, hypertension,skin rash, pallor, objective joint findings, abdominal pain, or bloody diarrhea suggests a diagnosis of parenchymal renal disease such as postinfectious glomerulonephritis,Henoch-Schönlein purpura, lupus nephritis, hemolytic uremic syndrome, or immunoglobulin (Ig) A nephropathy. If sore throat or pyoderma precedes the hematuria by 7 to 30 days, poststreptococcal acute glomerulonephritis must be ruled out. Hematuria with a concurrent upper respiratory infection strongly suggests IgA nephropathy. Each of these forms of glomerulonephritis usually is associated with proteinuria and RBC casts on microscopic urinalysis (Table 2). A family history of hematuria without renal failure may be seen with thin basement membrane disease. A family history of hematuria,chronic renal failure, dialysis, or renal transplantation with bilateral deafness at an early age and ocular abnormalities strongly suggests Alport syndrome, as illustrated in the case history. An audiogram is indicated for children suspected of having Alport syndrome because high-tone hearing loss may not be apparent on the initial examination. A family history of nephrolithiasis raises the diagnostic possibility of nephrolithiasis or hypercalciuria. A family history of autosomal dominant polycystic kidney disease demands that this disease be ruled out by appropriate radiologic examination. Sickle cell disease or sickle cell trait in the patient’s family may suggest this diagnosis. As these findings suggest, a screening urinalysis in available first-degree relatives is an important test.The initial urinalysis is helpful in directing further evaluation of the cause of hematuria. RBCs from areas of the urinary tract other than glomeruli will be normal in size or slightly small, with smooth or irregular edges (eumorphic). Nonglomerular bleeding usually is associated with normal urinary protein excretion and an absence of RBC casts. Preliminary tests of urine and blood should include a urine culture,sickle cell preparation in African-American children, urinary calcium:urinary creatinine ratio, serum creatinine, C3, and streptozyme titer. Ultrasonography of the kidneys and urinary bladder is recommended to rule out polycystic kidney disease, tumor, ureteropelvic junction obstruction, and stones.The presence of proteinuria(>1+ on dipstick) strongly suggests glomerulonephritis or intrinsic renal disease as the etiology of the hematuria. The diagnosis of glomerulonephritis demands careful microscopic inspection of the urinary sediment for the presence of RBC casts (Figure).Demonstration of RBCs that have bizarre shapes,blebs, or burrs (dysmorphic RBCs)by phase-contrast microscopy closely correlates with a glomerular origin of the RBC.A definitive diagnosis is more likely to be made in the child who has RBC casts and/or proteinuria than when isolated hematuria is present. Urinary protein excretion should be measured by a timed 12- or 24-hour urine collection or a urine protein:urine creatinine ratio on a single voided sample. Protein excretion of less than 4 mg/m2 per hour is normal; more than 40 mg/m2 per hour is considered in the nephrotic range. A urine protein:urine creatinine ratio(mg/mg) greater than 0.2 is abnormal; above 1.0 is nephrotic range proteinuria. A complete blood count,C3, C4, antistreptolysin-O titer,streptozyme titer, serum electrolytes,blood urea nitrogen, serum creatinine, serum albumin, test for lupus erythematosus, hepatitis B screen,and antinuclear cytoplasmic antibody titer are indicated to clarify further the type of glomerulonephritis. A screening urinalysis on first-degree family members is also important. When confirmatory serologic tests are nondiagnostic,a renal biopsy usually is indicated.A frequent cause of isolated hematuria, especially in the southwestern United States, is idiopathic hypercalciuria (urinary calcium:urinary creatinine ratio of > 0.21 and 24-hour urinary calcium excretion of >4 mg/kg). Approximately 30%of children referred to our pediatric nephrology clinic for evaluation of isolated hematuria have idiopathic hypercalciuria as the etiology. Other conditions that may cause hypercalciuria include hyperparathyroidism,immobilization, vitamin D intoxication, and furosemide use. Renal ultrasonography and plain abdominal radiography are helpful in ruling out the presence of nephrocalcinosis or nephrolithiasis.Two studies have described children who had idiopathic hypercalciuria in whom painless hematuria preceded the formation of calcium oxalate renal stones by 1 to 6 years. A subsequent study identified increased urinary calcium excretion in 23 of 83 children (28%) who were referred for evaluation of isolated hematuria. Two of the 23 children who had idiopathic hypercalciuria developed renal stones within 18 months of evaluation for hematuria. In a multicenter study (Southwest Pediatric Nephrology Study Group), 76 of 215 children (35%)referred for isolated hematuria were shown to have idiopathic hypercalciuria (urinary calcium excretion of >4 mg/kg per day). Compared with children in this study who had hematuria and normal urinary calcium excretion, a greater number of those who had hematuria and idiopathic hypercalciuria exhibited gross hematuria, calcium oxalate crystalluria, a family history of urolithiasis,and/or a family history of hematuria.The finding of hypercalciuria in a child who has hematuria should not exclude consideration of other etiologies of hematuria. In the previously noted multicenter study,factitious hematuria was demonstrated in one child, minor vesicoureteral reflux in three children, and evidence of glomerular pathology in two children who had idiopathic hypercalciuria. Approximately 15%of children who have idiopathic hypercalciuria will develop a renal stone within 5 years of diagnosis.The reported incidence of gross hematuria is approximately 1 in 1,000 visits to a pediatric emergency facility. A cause for the gross hematuria is usually found; it was identified in 58% of children in one prospective study. Urinary tract infection was the most frequent cause in this prospective study,followed by perineal irritation,meatal stenosis with ulceration,trauma, recent surgical procedure,clotting abnormalities,nephrolithiasis, and glomerulonephritis. In a retrospective study of 56 adolescents undergoing a renal biopsy because of gross hematuria, the most common (52%) pathologic diagnosis was IgA nephropathy. Other mesangial lesions of the glomerulus were present in the remainder of the patients.Gross hematuria in patients who have IgA nephropathy usually is associated with viral upper respiratory tract infections or gastroenteritis. The presence of RBC casts and proteinuria in this patient group requires a diagnostic renal biopsy. It is estimated that approximately 15% of children who have isolated,persistent hematuria for more than 12 months’ duration will have IgA nephropathy. A recent study of the long-term prognosis in pediatric patients who have IgA nephropathy concluded that the outcome is as serious as that reported in adults. African-American ethnicity and the severity of histologic findings were associated with a poor outcome. In the previously noted retrospective study of adolescents, multiple complex urologic tests and procedures were performed in some of these patients before considering a renal biopsy. Investigators emphasized that close attention to the details of history, physical examination,and urinalysis findings suggesting a glomerular source of bleeding could lead to an earlier diagnosis and prevent unnecessary urologic studies in most children who have gross hematuria.Less frequently observed causes for gross hematuria, such as pelvocalyceal or urethral diverticulae,bladder stones or tumors, polyps,foreign bodies, and other developmental genitourinary abnormalities,must be considered(Table 4). Intravenous pyelography, renal scan,computed tomography, magnetic resonance imaging, renal arteriography, renal biopsy, and cystoscopy may be required in patients who have unexplained gross hematuria to make a diagnosis.After significant pathologic causes of isolated hematuria have been ruled out, it is important to follow patients at 6- to 12-month intervals for several years. Assessment of linear growth and blood pressure,a urinalysis to document persistent microhematuria or the development of proteinuria, and measurement of renal function are recommended. As many as 10% to 50% of children who have persistent hematuria may develop progressive renal disease,according to some observers. Most of the pediatric literature, however,predicts a good prognosis. If isolated hematuria persists for 1 year or more, consultation with a pediatric nephrologist to determine the adequacy of the prior evaluation, to reassure the family, and to assess the need for a renal biopsy may be in order (Table 5).Isolated microscopic hematuria that persists for more than 1 month requires further investigation. Hematuria that is associated with proteinuria, RBC casts, edema,hypertension, or decreased renal function requires immediate evaluation. Idiopathic hypercalciuria is the etiology of isolated microscopic hematuria in approximately 30%of patients referred to pediatric nephrologists. Evaluation of these children should include a thorough family history, which often will yield clues to the etiology, and urinalysis in first-degree family members. A thorough microscopic examination of a centrifuged urine sample by a trained professional is essential for planning further evaluation of the child who has hematuria; cystoscopy is rarely of diagnostic benefit.

AA renal transplant (RT) recipients tend to have a much lower graft survival than white recipients. At the University of Tennessee, Memphis, for 20 AA pediatric first RT recipients before use of induction therapy, one and 3 year predicted graft survival (PGS) was 60% and 35%, respectively. Of these 20, eight were cadaveric (CAD) and 12 living related donor (LRD). The 1995 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) found that AA CAD and LRD recipients had 60% and 72% three year PGS, respectively. In a large population of predominantly adult CAD RT recipients Gaston et al (Transplantation 53: 103, 1992) showed that early treatment with Minnesota anti-lymphocyte globulin resulted in similar PGS for AA and whites. The 1995 NAPRTCS report indicated that 65% of all CAD pediatric recipients received induction therapy. Since 1990 induction therapy with either OKT3 or antithymocyte globulin (ATGAM) has been used for all pediatric RT recipients in our program. Thirteen AA first RT recipients received induction therapy: 10 CAD (9 with OKT3, one with ATGAM) and 3 LRD (all ATGAM). One CAD recipient also received a liver transplant with the RT. Age at RT ranged from 2.1 to 17.5 years (mean = 12.0 years). Subsequent immunosuppression was with prednisone, azathioprine and cyclosporine A. PGS was estimated by Kaplan-Meier method. PGS for 13 AA patients was 92% at one and 3 years. Ten CAD recipients had PGS of 90% at one and 3 years. Based upon our limited experience, induction therapy appears to provide excellent renal allograft survival for AA pediatric recipients. In conclusion, we suggest that AA pediatric patients should not be transplanted without benefit of such therapy. A larger study is needed to determine whether OKT3 or ATG/ALG preparation is the better therapy.

To investigate possible mechanisms of increased urinary calcium excretion and increased prevalence of urolithiasis in 16- to 20-year-old children, oral calcium loading and diuretic tests were performed in 120 normal children in three age groups (7-8, 12-13, and 17-18 years of age). Urinary calcium/creatinine ratios and 24-h urinary calcium excretion were significantly increased following the oral calcium loading test in 17- to 18-year-olds compared with the two younger age groups. Oral furosemide resulted in increased urinary calcium excretion in the 17- to 18-year age group, while hydrochlorothiazide was less effective in reducing urinary calcium excretion in this age group. These results suggest that increased intestinal calcium absorption and decreased renal tubular reabsorption of calcium in 17- to 18-year-olds may be contributing factors in the increased prevalence of nephrolithiasis in older Taiwanese children.

Children with nephrotic syndrome are susceptible to the development of invasive bacterial infections, particularly those caused by Streptococcus pneumoniae. Recently, penicillin-resistant pneumococcal infections in children have occurred in increased frequency in some regions. We have seen two children with nephrotic syndrome who developed penicillin-resistant pneumococcal bacteremia and/or peritonitis. A change in the initial therapy from penicillin in the usual dose in these patients must be considered.

Objective: The determination of the ultimate prognosis for patients with IgA nephropathy diagnosed in childhood requires long-term follow-up of identified patients. The purpose of this study was to obtain such follow-up for patients from two centers where the disease has been diagnosed for more than 20 years. Methods: Clinical data at the apparent onset of symptoms and renal histologic data were obtained for 103 patients in whom IgA nephropathy was diagnosed before age 18 years. Clinical status at last follow-up was obtained from office records or from direct contact with the patient. Predicted kidney survival was determined by the Kaplan-Meier method. Follow-up of more than 10 years from the time of biopsy was available for 40 of the patients. Results: Fourteen of the patients have progressed to end-stage renal disease; three others have progressive chronic renal insufficiency as defined by an estimated creatinine clearance of less than 50 ml/min per 1.73 m2. Severity of the renal histologic findings and the degree of proteinuria at the time of biopsy were associated with poor outcome. For all patients, predicted kidney survival from the time of apparent onset was 94% at 5 years, 87% at 10 years, 82% at 15 years, and 70% at 20 years. Age at clinical onset and gender were not associated with poor outcome, but black race and severity of renal histologic findings were. Conclusion: With follow-up into adulthood, the outcome for pediatric patients with IgA nephropathy appears to be as serious as that reported in adult patients. Follow-up of a pediatric patient with persistent clinical findings should be maintained after the patient's care is transferred to a physician caring for adults. (J PEDIATR 1995;127:913-9)

Because controlled trials in adults have shown accelerated deterioration of renal function in a small number of patients receiving calcitriol for renal osteodystrophy, we initiated a prospective, randomized, double-blind study of the use of calcitriol versus dihydrotachysterol in children with chronic renal insufficiency. We studied children aged 1 1/2 through 10 years, with a calculated glomerular filtration rate between 20 and 75 ml/min per 1.73 m2, and with elevated serum parathyroid hormone concentrations. Ninety-four patients completed a mean of 8.0 months of control observations and were randomly assigned to a treatment period; 82 completed the treatment period of at least 6 months while receiving a calcitriol dosage (mean +/- SD) of 17.1 +/- 5.9 ng/kg per day or a dihydrotachysterol dosage of 13.8 +/- 3.3 micrograms/kg per day. With treatment the height z scores for both calcitriol- and dihydrotachysterol-treated groups showed no differences between the two groups. In relation to cumulative dose, there was a significant decrease in glomerular filtration rate for both calcitriol and dihydrotachysterol; for calcitriol the rate of decline was significantly steeper (p = 0.0026). The treatment groups did not differ significantly with respect to the incidence of hypercalcemia (serum calcium concentration > 2.7 mmol/L (> 11 mg/dl)). We conclude that careful follow-up of renal function is mandatory during the use of either calcitriol or dihydrotachysterol because both agents were associated with significant declines in renal function. There was no significant difference between calcitriol and dihydrotachysterol in promoting linear growth or causing hypercalcemia in children with chronic renal insufficiency. Dihydrotachysterol, the less costly agent, can be used with equal efficacy.

Urinary enzymesN-acetyl-β-d-glucosaminidase (NAG) and γ-glutamyl transpeptidase (γ-GT) are sensitive markers of specific renal cell damage. Excessive urinary amino acid excretion may also be an indicator of renal tubular damage. We have evaluated urinary excretion of NAG,γ-GT and 37 amino acids, phospholipids and dipeptides in 30 children (aged 2.3–18.1 years) with nephrotic syndrome (NS), 23 with minimal change nephrotic syndrome (MCNS), 7 with focal segmental glomerulosclerosis (FSGS) and 16 healthy age-matched controls. Nine MCNS patients were in relapse and 14 in remission. Enzyme activity is expressed as micromoles per milligram urinary creatinine. In FSGS, NAG excretion correlated with the following: blood urea nitrogen (BUN) (r=0.8), serum protein (r=0.57), serum cholesterol (r=0.85), serum albumin (r=−0.68) and proteinuria (r=0.56). In FSGS the γ-GT excretion was not significantly different from MCNS in remission or in relapse. In FSGS, γ-GT excretion correlated with the following: BUN (r=0.48), serum creatinine (r=−0.66), serum protein (r=−0.54), serum albumin (r=−0.68) and serum cholesterol (r=0.87). Compared with controls, the urinary excretion of 5 amino acids was increased in FSGS patients as a possible indicator of tubular damage. The value for 7 amino acids was reduced in MCNS patients. Urinary amino acid excretion was not different from controls for the other amino acids in either FSGS or MCNS. These data suggest that urinary enzyme excretion, particularly NAG excretion, and amino acid excretion may be useful in the diagnosis and degree of disease in these histological forms of NS in children.

Prompted by a large population of children with renal stones seen in 20 of our country's teaching hospitals over the past 10 years, this study of urinary mineral excretion in normal children was performed. Fasting urine from 1,072 normal Taiwanese school children and 24-h urine collections from 125 children separated into three age groups were analysed for calcium (Ca), phosphate, magnesium (Mg), uric acid, sodium (Na) and creatinine (Cr). Fasting Ca/Cr ratios were not different between the sexes. Ca/Cr ratios were higher in the 17- to 18-year age group as were 24-h urinary Ca excretions. Urinary Mg/Cr ratios were higher in girls than boys and 24-h urinary Mg excretion was highest in the younger age groups. Urinary Mg excretion in Taiwanese children is 54%-86% lower than previously reported in Caucasian children. Both uric acid/Cr ratios and 24-h urinary uric acid excretion were highest in the youngest children. Urinary Na/Cr ratios and 24-h urinary Na excretion were higher in the two younger age groups. There was no correlation between 24-h urinary Ca and Na excretion.

This report describes an infant with congenital nephrotic syndrome and cytomegalovirus infection whose renal biopsy was consistent with the pathological diagnosis of diffuse mesangial sclerosis along with intrarenal cytomegaloviral inclusions.

Changing perspectives in 95 children with poststreptococcal acute glomerulonephritis (PSAGN) in our hospital between 1979 and 1988 are reported. Between 1961 and 1970 an average of 31±6.3 patients/year with PSAGN were treated and 70% had antecedent pyoderma. In the present study antecedent pharyngitis was observed in 59 children und pyoderma in 36. In comparison to the decade ending in 1970 our data show: (1) a marked decline in the prevalence of PSAGN (P=<0.0005), (2) a predominance of antecedent pharyngeal infection (P=0.044), (3) a decline in urban and an increase in rural patients with PSAGN (P=0.0483); and in the last decade: (1) a predominance of antecedent pharyngeal infection in children over 6 years of age (P=0.0009) and (2) a predominance of antecedent pyoderma in black children (P=0.0004).

THE interferons are a group of glycoproteins with antiviral, immunomodulatory, and antitumor activities. There are three major types: alfa (leukocyte or lymphoblastoid), beta (fibroblast), and gamma (immune) interferon. Alfa interferon has proved efficacy in treating various human cancers.1 , 2 The gene for gamma interferon has been cloned more recently, and Phase I and II studies in adults have demonstrated it to be capable of producing antitumor effects.3 , 4 Interferon-induced renal toxicity is quite unusual, although acute renal failure with interstitial nephritis has been reported in one woman receiving alfa interferon for mycosis fungoides.5 We describe a 12-year-old child in whom acute renal . . .

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)

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.