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.

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.