''What is going to happen to my child?'' is one of the most common questions asked by parents of children with renal disease. Unfortunately, the answer is relatively easy in patients who present with advanced chronic renal insufficiency, but it is considerably more difficult in those who have milder lesions - particularly when conflicting data regarding patient outcome exist in the literature. This situation is well exemplified by a sampling of the current literature dealing with prognosis and prognostic indicators in children with IgA nephropathy [1-15]. Depending on one's bias, it is possible to quote references supporting the thesis that most children with this condition are destined to live a normal and full life or that they must be monitored indefinitely because of the risk of insidious progression of disease. It is likewise possible to quote contradictory statements on the prognostic importance of many different features, such as age at presentation, episodes of gross hematuria, glomerular filtration rate (GFR) at presentation, presence of peripheral glomerular capillary staining.with IgA, and a variety of acute and chronic lesions by light microscopy. Why do such discrepancies exist? How can they be avoided? How can we get at the truth? The outcome of patients reported in the papers by Berg et al. in this issue of Pediatric Nephrology [15] and the 1991 report by Linne et al. in the same journal [14] provide an excellent focal point to examine some of these issues in children with IgA nephropathy. Berg et al. state correctly from their data that ''juvenile IgA nephropathy is not a harmless disease''. This conclusion was based on the clinical course seen in 36 children followed in their medical clinic in Huddinge, Sweden, for periods of at least 3 years (mean 6.3 years) after the diagnostic renal biopsy. At last follow-up, 39% of the patients had reduced renal function (GFR <mean -2SD), 25% were hypertensive, and 11% had progressed to end-stage renal disease (ESRD). Berg et al. have also provided accurate measurements of renal function and protein excretion in this paper. However, the current ''outcome'' findings of Berg et al. [15] contrast sharply with the previous report by Linne et al. [14] which described the outcome of 34 patients who had been followed for at least 8 years in three Swedish clinics - including Huddinge. At the time of follow-up, only 1 (3%) of these patients had a mild decrease in GFR, 10% had hypertension, and none had progressed to ESRD. Although Berg et al. proposed that their more pessimistic outcome in individual patients reflected a longer period of follow-up, it is noteworthy that the minimum and average follow-up periods in the study of Berg et al. [15] were less than those in the study of Linne et al. [14]. In addition, it is relevant to point out that 2 of Berg's patient developed ESRD within 3 years of their diagnostic biopsies. Although it is certainly reasonable to conclude that outcome data are more likely to be accurate when the follow-up period is longer, it is also important to stress the importance of a second factor, namely the influence of ''chance,'' when dealing with such small numbers of patients. ''Prognostication'' is further compromised by the fact that most reports dealing with outcome indicators in children with IgA nephropathy have involved patients who have follow-up periods varying from 0 to many years. Clearly, the inclusion of patients with little or no follow-up reduces the credibility of statements regarding percentages of patients showing a poor outcome and makes it difficult to interpret any statistical analysis of specific risk factors. It would seem more appropriate to restrict this form of analysis to patients who have had at least 3-5 years follow-up and to provide confidence bands for the information that is provided. For example, if the ''true'' incidence of ESRD in IgA nephropathy patients is 15% after 4 years of follow-up, we would not really expect to see a 15% frequency of ESRD unless we were incredibly ''lucky'' or had access to a very large patient population. In fact, the observed frequency of ESRD would be expected to be within the following approximate limits in 95% of the studies (with the indicated number of patients): 20 patients, 0%-30%; 40 patients, 4%-26%; 80 patients, 7%-23%; 160 patients, 9%-21%; 320 patients, 11%-19%. If the true incidence were 25%, the incidence values would vary between: 20 patients, 6%-44%; 40 patients, 11%-39%; 80 patients, 15%-35%; 160 patients, 18%-32%; 320 patients, 20%-30%. The closer the true incidence is to 50%, the broader are the intervals. Although it is impractical to accumulate long-term follow-up data on larger numbers of patients in single-center studies of pediatric patients, such data can be generated by multicenter collaborative groups or networks. This underscores the increasing importance of the established and evolving regional and national study groups that exist around the world. However we do not wish to undermine the importance of single-center reports to draw attention to illustrative examples of progressive disease; rather it emphasizes the fact that prognostic information should not be elicited from such reports. Since the level of enthusiasm for developing and testing therapeutic trials for children with IgA nephropathy is influenced greatly by the ''outcome data'' available in the literature, it is important that the inherent risk of underestimating (or overestimating) the potential risk of progressive disease in small numbers of patients be stated clearly. The present report by Berg et al. [15] has brought some ''balance'' to the Swedish experience. It confirms the concerns of many pediatric nephrologists that indeed IgA nephropathy is anything but a ''harmless disease'' and that we must now devote our resources to the exploration of some of the therapeutic options that have been advocated for this disease.
