Kawasaki disease complicated by renal artery stenosis.

We report the case of a child who developed severe renovascular hypertension six months after acute Kawasaki disease. The hypertension was well controlled with enalapril, but there was a gradual decrease in function of the affected kidney. The lesion, an ostial stenosis of the right main renal artery, was not amenable to percutaneous balloon angioplasty, so was treated with bypass surgery. Vasculitis is an important cause of renovascular hypertension in children. This case highlights the importance of regular blood pressure monitoring in children with a history of systemic vasculitis.

Effective therapy for severe Henoch-Schonlein purpura nephritis with prednisone and azathioprine: a clinical and histopathologic study.

OBJECTIVES: To validate a scoring system to assess the severity of renal lesions and to correlate histology with clinical findings. We also examined the efficacy of treatment with prednisone (1 to 2 mg/kg/d) and azathioprine (1 to 2 mg/kg/d) for severe Henoch-Schonlein purpura (HSP) nephritis. METHODS: Twenty patients were evaluated retrospectively. All underwent biopsy before treatment, and 13 underwent biopsy after therapy. We developed a scale based on glomerular, tubulointerstitial (TI), and vascular changes and assigned all specimens acuity, chronicity, and TI scores. The outcomes of 17 patients were compared with those of a historical control group. RESULTS: Chronicity score at initial biopsy increased with increasing delay between onset of renal involvement and first biopsy (rho = 0.55, P =.016) but did not progress after treatment was initiated. Both acuity (rho = 0.57,P =. 016) and TI (rho = 0.69, P =.003) scores correlated with clinical severity at first biopsy. The TI score correlated negatively with serum albumin (rho = -.60, P <.01). Significantly more patients in the study group than in the control group had a favorable outcome (15 [88%] of 17 vs 32 [54%] of 59, P =.011). CONCLUSIONS: Our scale reflects disease activity and highlights the importance of TI changes in severe HSP nephritis. Outcome comparisons indicate that early treatment with prednisone and azathioprine prevents progression of chronic changes and improves outcome.

Infusion clearance of subcutaneous iothalamate versus standard renal clearance.

Accurate, timed urine collections for the measurement of glomerular filtration rate (GFR) may be impractical in infants or in patients with urological abnormalities. GFR may be measured without urine collection using a constant subcutaneous infusion of iothalamate. We compare the infusion clearance with conventional renal clearance in 14 children and young adults. The mean clearance ratio (infusion clearance/renal clearance +/- 1 SD) was 0.99 +/- 0.1 and the mean discrepancy between the two methods was 8.5% +/- 4.7%. The 95% limits of agreement for the ratio of the two methods are 0.83-1.23. These data indicate that subcutaneous infusion of iothalamate is a practical method for measuring GFR in children without a urine collection.

Urine testing in young febrile children: a risk-benefit analysis.

OBJECTIVE: To assess the relative risks and benefits of 10 potential urine testing strategies (compared with no testing) involving urinalysis and urine culture for children aged 3 to 24 months with fever but no focus of bacterial infection. DESIGN: Decision analysis based on the literature. The 10 testing strategies consist of five pairs; within each pair of strategies, one calls for urinalysis and urine culture of a clean-voided (bag) specimen, and urine culture, and in the other, the urine specimen is sent for culture only if the result of the urinalysis is abnormal. The five pairs differ in selectivity for testing: all children, girls only, temperature > or = 39 degrees C only, fever only (no respiratory or gastrointestinal symptoms), or temperature > or = 40 degrees C only. The results of the decision analysis are expressed as the preventive fraction (the proportion of cases prevented) for end-stage renal disease (ESRD) and hypertension, and as two risk/benefit (RB) ratios: the number of children tested per case of ESRD prevented (RB1), and the number of children with false-positive diagnosis and treatment of urinary tract infection per case of ESRD prevented (RB2). RESULTS: On the basis of the available evidence, none of the testing strategies succeeds in preventing the majority of cases of ESRD and hypertension (preventive fraction = 0.10 to 0.50), and all are associated with high ratios of children tested (RB1 = 4167 to 12,500) and false-positive diagnosis and treatment (RB2 = 563 to 1800) per case of ESRD prevented. A strategy of combined urinalysis and urine culture in children with temperature > or = 39 degrees C is associated with the most favorable RB profile: preventive fraction = 0.45, RB1 = 5556; RB2 = 776. Sensitivity analyses indicate that the relative ranking of the strategies is relatively robust in regard to alterations in the estimates of the sensitivity or specificity of the urinalysis, the relative risk of renal scarring associated with delayed diagnosis and treatment, and the risk of scarring-induced hypertension or ESRD. CONCLUSIONS: Up to 50% of the long-term sequelae of occult urinary tract infections in young febrile children appear preventable by urine testing, but even the most favorable strategies require testing of thousands of children, and unnecessarily treating hundreds, for every case prevented. Our analysis reveals those strategies with more favorable RB profiles and emphasizes the need for rapid and convenient urine tests with much higher sensitivity and specificity or the need for less aggressive management strategies for febrile infants and young children with urinary tract infection.

Parents' versus physicians' values for clinical outcomes in young febrile children.

OBJECTIVE: To compare how parents and physicians value potential clinical outcomes in young children who have a fever but no focus of bacterial infection. METHODS: Cross-sectional study of 100 parents of well children aged 3 to 24 months, 61 parents of febrile children aged 3 to 24 months, and 56 attending staff physicians working in a children's hospital emergency department. A pretested visual analog scale was used to assess values on a 0-to-1 scale (where 0 is the value of the worst possible outcome, and 1 is the value for the best) for 22 scenarios, grouped in three categories according to severity. Based on the three or four common attributes comprising the scenarios in a given group, each respondent's value function was estimated statistically based on multiattribute utility theory. RESULTS: For outcomes in group 1 (rapidly resolving viral infection with one or more diagnostic tests), no significant group differences were observed. For outcomes in groups 2 (acute infections without long-term sequelae) and 3 (long-term sequelae of urinary tract infection or bacterial meningitis), parents of well children and parents of febrile children had values that were similar to each other but significantly lower than physicians' values for pneumonia with delayed diagnosis, false-positive diagnosis of urinary tract infection, viral meningitis, and unilateral hearing loss. For bacterial meningitis with or without delay, however, the reverse pattern was observed; physicians' values were lower than parents'. In arriving at their judgment for group 2 and 3 scenarios, parents gave significantly greater weight to attributes involving the pain and discomfort of diagnostic tests and to diagnostic error, whereas physicians gave significantly greater weight to attributes involving both short- and long-term morbidity and long-term worry and inconvenience. Parents were significantly more likely to be risk-seeking in the way they weighted the attributes comprising group 2 and 3 scenarios than physicians, ie, they were more willing to risk rare but severe morbidity to avoid the short-term adverse effects of testing. CONCLUSIONS: Parents and physicians show fundamental value differences concerning diagnostic testing, diagnostic error, and short- and long-term morbidity; these differences have important implications for diagnostic decision making in the young febrile child.

Role of the complete blood count in detecting occult focal bacterial infection in the young febrile child.

Previous studies of the value of the complete blood count (CBC) in distinguishing viral from bacterial infection in young febrile children have failed to exclude children with clinically evident bacterial infection and thus have inflated the positive predictive value of the test for occult focal infection. We prospectively studied 2492 children 3-24 months of age who presented to a children's hospital emergency department between March 1989 and August 1990 with fever (> or = 38.0 degrees C) of acute (< or = 4 days) onset but no evident bacterial focus of infection, 433 (17.4%) of whom received a CBC. We also carried out an 8-year retrospective analysis to estimate prior, or pre-test, probabilities (prevalences) and examine CBC results for rare occult bacterial infections (meningitis, osteomyelitis, and septic arthritis). Estimated prior probabilities for the four most common categories of infection that can be diagnosed at the initial visit were: non-pneumonitic viral infection, 88.6% in boys and 86.0% in girls; pneumonia, 8.5% in both sexes; urinary tract infection (UTI), 3.0% in boys and 5.5% in girls; and bacterial meningitis, 0.0066% in both sexes. The likelihood (sensitivity) of a total white blood cell (WBC) count > or = 15,000/mm3 was 25.5, 64.5, 62.5, and 50.0% for viral infection, pneumonia, UTI, and meningitis, respectively. Among children with a high total white blood cell count, neither a total polymorphonuclear count > or = 10,000/mm3 nor a band count > or = 500/mm3 was associated with significantly elevated likelihoods for occult pneumonia or UTI, a finding confirmed by multiple logistic regression analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Muscle extract infusion in rabbits. A new experimental model of the crush syndrome.

Previous studies provide inconclusive data concerning the nephrotoxicity of myoglobin following muscle injury. We investigated the possibility that released muscle constituents other than myoglobin may be associated with renal damage, and studied accompanying hematological and coagulation changes. An extract of homologous or autologous muscle was infused intravenously in rabbits in a dose of 100 mg of muscle extract protein/kg; equine myoglobin was given to control animals. Experimental animals developed proteinuria, cylindruria, and a 50% reduction in glomerular filtration rate. Leukopenia, thrombocytopenia and evidence of intravascular coagulation also were seen. The muscle extract was shown to have thromboplastic activity; however inhibition of this by phospholipase C did not prevent the changes induced by muscle extract infusion possibly because the intrinsic changes coagulation pathway still was activated. Although moderate hypotension and ECG changes developed in some rabbits, these were not consistent and the renal functional changes appeared to be independent of these factors. Pulmonary and glomerular microthrombi were seen in experimental animals and there was vacuolation of the renal proximal tubular cells. The studies indicate that a number of biological systems are activated following muscle extract infusion and that these may be more important than the nephrotoxicity of myoglobin in the pathogenesis of the renal injury.

Friedreich's ataxia with nephrotic syndrome and convulsive disorder: clinical and neurophysiological studies with renal and nerve biopsies and an autopsy.

In a sibship of four, Friedreich's ataxia and minimal lesion nephrotic syndrome occurred in two siblings, a third sibling had Friedreich's ataxia, but no evidence of nephrotic syndrome; the fourth sibling had neither condition. The chance of Freidreich's ataxia and minimal lesion nephrotic syndrome occurring in two siblings is small, and suggested a common immunological abnormality. High dose prednisone and antimetabolites given for the nephrotic syndrome did not appear to affect the course of Friedreich's ataxia. The two siblings with Friedrich's ataxia and nephrotic syndrome developed epilepsy at age 15 years. All three children with Friedreich's ataxia had abnormal electroencephalograms (EEGs). These epileptiform EEG abnormalities were probably inherited from the mother, who had spike wave epilepsy. The neurologic deficits of Friedreich's ataxia, in turn, may have allowed the EEG trait to be expressed as a seizure disorder. The progressive ataxia and epileptic, sometimes myoclonic, seizures in these patients and the dentate nucleus changes in the autopsied patient were consistent with the diagnosis of dyssynergia cerebellaris myoclonica. This suggested that the latter disorder may represent a coincidence of two genetic entities: Friedreich's ataxia and spike wave epilepsy.

Red cell membrane phospholipid abnormalities in the hemolytic uremic syndrome.

Eight patients with the hemolytic uremic syndrome had depression of percentage of red cell phosphatidyl ethanolamine content. Five patients also had subnormal plasma tocopherol levels. In addition all patients had significant increases in total plasma lipids which could contribute to peroxidative damage. The association of depressed red cell phosphatidyl ethanolamine and plasma tocopherol levels is suggestive of peroxidative damage, and may contribute to the hemolysis in this syndrome.

Abnormalities of carbohydrate metabolism in idiopathic Fanconi syndrome.

Various metabolic studies were performed in a patient with the idiopathic Fanconi syndrome in whom constant ketonuria suggested that organic acidemia might contribute to the metabolic acidosis. Glucose intolerance with a diminished insulin release was found after PO or IV glucose loads and after glucagon administratio. An insulinopenic "diabetes-like" state has not previously been described in such patients. The patient had impaired galactose-glucose interconversion, elevated blood lactate levels, reduced pyruvate levels, and an increased lactate:pyruvate ratio. Hepatomegaly and hypoglycemia were not present, and liver and muscle biopsies revealed no enzymatic evidence of glycogenosis. The erythrocyte UDP galactose transferase activity was normal. The patient failed to convert fructose to glucose and had a rise in blood lactate after ethanol administration. Further studies revealed no production of glucose after alanine or glycerol administraion, each test being associated with elevated blood lactate levels and, after alanine, an increased lactate:pyruvate ratio. The lactate:pyruvate ratio was elevated after glucagon administration with increased lactate and reduced pyruvate concentrations.

Renal injury after muscle extract infusion in rats: absence of toxicity with myoglobin.

A crude muscle extract infused into rats produced oliguria, a precipitous drop in total hemolytic complement, and in circulating white cell and platelets counts. A mild vaso-depressor effects was noted. These changes were not produced by myoglobin or saline infusion. Muscle constituents other than myoglobin are responsible for the systemic and renal nephrotoxic effects observed.

The nephrotic syndrome and renal vein thrombosis.

In recent years, there has been a shift away from the concept that renal vein thrombosis is a cause of the nephrotic syndrome. A careful analysis of this subject favors the opposite contention that nephrotic syndrome is a cause of renal vein thrombosis when these two conditions occur in the same patient.

Hemolytic uremic syndrome with hypocomplementemia, serum C3NeF, and glomerular deposits of C3.

A 4-year-old boy had hemolytic uremic syndrome (HUS) associated with depression of serum C3 level, a B-hemolytic streptococcal throat infection, and an elevated level of antistreptolysin O titer. In addition to the characteristic histologic changes associated with this syndrome, substantial infiltration of polymorphonuclear leukocytes and nodular deposits of C3 globulin were seen in the glomeruli of the first biopsy specimen. Two months after clinical remission, he had a recurrence of hemolytic anemia, thrombocytopenia, and acute renal failure. The serum C3 concentration had decreased again, and serum C3NeF was detected in the serum. The typical changes associated with HUS were still present on electron microscopy. Bilateral nephrectomy and renal transplantation were done because of the development of uncontrollable severe hypertension and increasing azotemia. This patient had three manifestations of HUS, but because of several differences, such as hypocomplementemia, serum C3NeF, a recurrence, and persistent glomerular deposits of C3 globulin, he appears to have had a different form of the syndrome.

Electrolyte and acid-base disturbances in the management of leukemia.

Electrolyte disturbances in leukemia can be the result of the disease process or drug therapy. One group of electrolyte abnormalities is related to the stage of the leukemic process. Included in this group are newly diagnosed patients who may show elevated serum potassium, phosphorus, and magnesium--a result of their release from malignant cells after cytotoxic therapy or their accumulation due to urate nephropathy. Patients in remission usually have normal serum electrolyte concentrations, but acute leukemia patients during relapse may have hypokalemia, hypophosphatemia, and hypomagnesemia. This imbalance may be related to cellular uptake of these electrolytes in the presence of inadequate dietary intake. Other factors contributing to electrolyte derangements, and related to the leukemic process, include hyponatremia and hypochloremia secondary to the SIADH, hypokalemia in acute monocytic or acute myelomonocytic leukemia due to lysozyme-induced tubular damage, hypercalcemia possibly secondary to leukemic infiltration of bone or parathyroid glands (with PTH release), or production of a PTH-like substance by leukemic cells. Nonspecific factors related to the disease process which may aggravate the electrolyte imbalance include gastrointestinal loss through nausea, vomiting, and malnutrition. The drug-related electrolyte abnormalities include cyclophosphamide- and vincristine-induced SIADH; decreased serum sodium, chloride, potassium, and calcium concentrations as a result of polymyxin B nephrotoxicity; hypokalemia and hypomagnesemia secondary to amphotericin B; hypocalcemia, hypophosphatemia, and hyperphosphaturia due to L-asparaginase-induced hypoparathyroidism; hypokalemia due to a nonreabsorbable anion effect of antibiotics in the distal tubule or changes in membrane ionic transport of all cells by large doses of antibiotics. Electrolyte disturbance in leukemia thus have a multifactorial pathogenesis which can best be delineated according to the stage of the leukemic process and the drugs being used. Recognition of the cause or causes in a particular patient is essential for an effective approach to management. This review emphasizes the need for routine measurement of serum electrolytes during all phases of the leukemic process.