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The kidney is susceptible to a wide range of nephrotoxins which vary in their e¡ect from mild renal dysfunction to severe damage and end-stage renal failure. The identi¢cation of the presence of early renal damage, and also of individuals at risk of developing renal dysfunction, is important in order that corrective therapies can be applied at an early stage. However, glomerular ¢ltration rate (GFR) is unlikely to fall until 50% of nephrons have ceased to function. A major challenge is to provide measurements, both qualitative and quantitative, that give an early indication of the initial site of renal damage before gross deterioration in kidney function has occurred. Nephrotoxic exposure results in a cascade of events of gradually increasing severity. Initially, functional changes occur which, if exposure continues, then progress past a point of no return leading ultimately to renal failure. Most biomarkers measure the e¡ect of a toxin on the kidney, but some are insensitive, making it di⁄cult to measure accurately the extent to which the kidney has been exposed. Used selectively, biomarkers are able to give information on the stage and severity of the damage/disease process. To be useful, a biomarker should be easily measured by robust inexpensive procedures, which can be carried out on random or timed urine samples. The e¡ect of nephrotoxic agents is best assessed with a small battery of tests that can be followed by more specialized tests to con¢rm the severity and type of renal damage that has occurred.

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We set out to study how anti-filarial IgG4 and IgE, which have been studied extensively in adult populations, are influenced by gender and by the degree of filarial endemicity during childhood. Development of specific IgG4 and IgE was examined in 502 children aged 3 months to 12 years, who were resident in 3 villages in South-Sulawesi with microfilaria prevalences of 6, 23 and 42 %. Specific IgG4 and IgE could be detected as early as 18 months after birth, in low amounts, and increased to levels comparable to those produced by adults at the age of 3 years. A higher prevalence of anti-filarial IgG4 in boys, indicating higher filarial infection compared to girls, became apparent after the age of 7. The specific IgG4 response was strongly influenced by the degree of filarial endemicity and production of this antibody was considerably delayed in the low transmission village. With respect to IgE, it was noted that specific IgE was consistently higher in boys from infancy onwards indicating a predisposition for high IgE production in males. The influence of filarial endemicity was less profound on IgE thaon on IgG4. In conclusion, reactivity to filarial antigens begins early in life and is differentially influenced by gender and transmission intensity.

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