IgA nephropathy: long-term prognosis for pediatric patients.

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.

Regional variation in C4 phenotype in patients with IgA nephropathy.

The relationship between complete deficiency for either isotype of the fourth component of complement, C4A or C4B, and glomerulonephritis was initially examined in white patients from Kentucky with either IgA nephropathy or Schönlein-Henoch purpura. Subsequently, C4B deficiency was found to be associated with IgA nephropathy for pediatric patients followed in Cincinnati, Ohio. We later reported that at least 60% of the original patients from Kentucky were related to at least one other patient with the disease. This finding raised the possibility that the C4 phenotype frequencies for these patients may have been biased by the fact that they were based on a sample of related patients. In our study, C4 phenotyping was performed for 52 related and 63 unrelated patients from Kentucky, 81 unrelated patients from the Mid-South region of the United States, and 39 unrelated patients from the Puglia region of southeastern Italy. In addition, data from patients with IgA nephropathy from Spain were available for comparative studies. Neither C4A deficiency nor C4B deficiency was significantly increased for groups of unrelated patients from the Mid-South, Italy, Spain, or Kentucky in comparison with regional control subjects. In fact, C4A and C4B deficiencies did not occur in any of the Italian patients. With the exception of C4A.6, frequencies for the most common C4A and C4B alleles did not differ among the unrelated patient and control groups from Kentucky and the Mid-South. In addition, no significant differences in C4A and C4B allelic frequencies were observed in comparisons of pediatric patients (diagnostic biopsy before age 18 years) and adult patients with IgA nephropathy in either U.S. population. Italian control subjects had a significantly lower frequency for C4A null alleles in comparison with control subjects from both Kentucky and the Mid-South; a significantly higher frequency of C4B null alleles was found among Kentucky control subjects than in Mid-South, Italian, and Spanish control samples. The importance of recognizing the ethnic background of study subjects and of eliciting a good family history to minimize unsuspected sampling of related patients should be considered in future disease association studies.

The relationship of oral rehydration solution to hypernatremia in infantile diarrhea.

PIP: A major criticism of the use of oral rehydration solution (ORS) in the treatment of diarrhea has been that the high sodium content of the solution might predispose the development of hypernatremia in infants not allowed access to additional free water and in whom glomerular filtration rate and urinary concentrating ability may be low. A study was undertaken in 1980 in Cairo, Egypt to assess the use of ORS. The study included 100 children under age 1, mean age 6.7 months, with dehydration secondary to diarrhea, and 17% were hypernatremic on admission, 27% hyponatremic and 56% isonatremic; the hypernatremic infants were found to be more dehydrated than the others. 24% of the hypernatremic infants had taken Rehydran whereas only 5% of the others had taken it and none had been given the medication in a proper fashion. Of the 17 with hypernatremia 16 completed the course of oral rehydration therapy and 63% had normal serum sodium values by 6 hours of therapy. It was found that the treatment of hypernatremic infants with ORS was successful while with the unsupervised use of Rehydran the risk of this condition was enhanced; errors made in the home included prolonged use of the solution and failure to use water. It is believed that because of widespread illiteracy sole reliance upon written instructions is potentially dangerous.^ieng

Prevalence of antibody to the Norwalk virus in various countries.

Serum samples from children and adults from several countries were tested by radioimmunoassay for antibody to the Norwalk virus. Antibody was commonly found in adults from all the countries tested. Antibody appears to be acquired more rapidly in children from underdeveloped countries than in children from the United States.

Idiopathic rapidly progressive glomerulonephritis with C3 nephritic factor and hypocomplementemia.

A 7-year-old boy with mild renal failure and signs and symptoms of acute poststreptococcal glomerulonephritis including severe hypocomplementemia had, by renal biopsy, numerous crescents but no deposits in the glomerular capillary loops. Instead, deposits identical in location and composition to those described for children with idiopathic rapidly progressive glomerulonephritis were present. The severe hypocomplementemia was found to be due to high levels of C3 nephritic factor; niether nephritic factor nor hypocomplementemia has been reported in rapidly progressive glomerulonephritis of the idiopathic type. Following prompt therapy with methylprednisolone intravenously, serologic abnormalities disappeared and renal function greatly improved, but a later biopsy showed 50% of the glomeruli obliterated by scarring. The case is of importance not only in indicating that severe hypocomplementemia does not rule out idiopathic rapidly progressive glomerulonephritis but also in adding to the list of diseases in which nephritic factor can be found.

Diarrhea associated with rotavirus in rural Guatemala: a longitudinal study of 24 infants and young children.

A population of 24 infants and young children followed prospectively during the first 3 years of life was studied for the occurrence of rotavirus infection by using enzyme-linked immunosorbent assay to detect virus in stools. Infection with rotavirus was associated with 26 (14.2%) of 183 selected diarrheal episodes. Twenty of the 24 infants and young children had diarrhea associated with rotavirus on at least one occasion and six had two such episodes. Rotavirus infection was documented in over 50% of the dehydrating episodes studied, thus further indicating the importance of rotavirus in this population.

Secretory antibody directed against rotavirus in human milk--measurement by means of enzyme-linked immunosorbent assay.

Human milk contains antibodies to a variety of enteropathic agents. We utilized the method of enzyme-linked immunosorbent assay to investigate anti-rotavirus secretory IgA in 113 human milk and colostral specimens from a rural area in Guatemala, 32 colostral specimens from an urban area of Costa Rica, and 12 from an urban area of the United States. Anti-rotavirus SCIgA was found in all colostral samples and in 94% of the milk specimans. Both the absolute concentration of anti-rotavirus SCIgA and concentration relative to total SCIgA were highest in colostrum, falling to lower but detectable levels from one week to two years after birth. No significant differences were noted in the results from the specimens from the three different geographic areas. The possible role of this antibody in immunity to rotavirus infections is discussed.

Epidemiology of human rotavirus Types 1 and 2 as studied by enzyme-linked immunosorbent assay.

To determine the relative importance of two known serotypes of human rotavirus, we developed an enzyme-linked immunosorbent assay to differentiate serotype-specific rotavirus antigen and antibody. Using this technic, we studied the epidemiology of the two serotypes in acute gastroenteritis. Seventy-seven per cent of 414 rotavirus isolates were Type 2, and the remainder were Type 1. The serotype distribution was similar in specimens from children in Washington, D.C., and other parts of the world. Sero-epidemiologic studies revealed that most children living in the Washington, D.C., area acquired antibody to both types by the age of two years. An analysis of children who were reinfected indicated that sequential infections usually involved different serotypes and that illness caused by one serotype did not provide resistance to illness caused by the other serotype. These results suggest that, to be completely effective, a vaccine must provide resistance to both serotypes.

Oral theophylline dosage for the management of chronic asthma.

Theophylline dosage requirements to maintain serum concentrations of 10 to 20 microgram/ml among asthmatic patients were examined in 156 children, ages 2 1/2 months to 16 years, and 33 otherwise health adults. Using 100% bioavailable preparations, low doses were used initially and increased, if tolerated, at three-day intervals. Final dosage was based on serum theophylline measurements which were subsequently repeated after six or more months of therapy. Dosage standardized by weight averaged 24.1 +/- 5.5 mg/kg/day (mean +/- SD) among the 77 children under age 9 years. Age-related variability of weight-adjusted doses were not observed for younger children, but average dose requirements decreased progressively beyound age 9 years to 13 mg/kg/day for patients beyoung 16 years of age. Although interpatient variability in dosage was confirmed at all ages, intrapatient variability in requirements over an average eight-month interval were small; dosage changes to maintain therapeutic serum concentration were primarily associated with growth. These data allow age-specific guidelines for dosage recommendations based on the likelihood of optimally effective and potentially toxic serum theophylline concentrations.

Clinical features of acute gastroenteritis associated with human reovirus-like agent in infants and young children.

Between January, 1974, and June, 1975, infection with a human reovirus-like agent was detected in 47% of 152 infants and children hospitalized with acute gastroenteritis. Certain epidemiologic, clinical, and laboratory findings appear to be helpful in distinguishing gastroenteritis due to HRVLA from other causes in those children sick enough to require hospitalization. Age: 76% of infants and children seven through 12 months of age and 76% of those 13 through 24 months of age had infection with the HRVLA, whereas such infection was found in only 21% of infants under six months of age and 23% of children 25 through 60 months of age. Time of Year: 61% of patients studied during the cooler months had HRVLA infection and such infection was not found from June to October. Frequency of vomiting and dehydration: Twice as many patients infected with HRVLA as those who were not had vomiting (92%) and significant dehydration (83%).