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Balkan endemic nephropathy (BEN) is a chronic kidney disease that progresses slowly. There are no known clinical markers to identify an early disease development. We evaluated the relationship between parental history of BEN and clinical markers as predictors of new occurrences of BEN. A 5-year prospective study in the offsprings of BEN and control patients was conducted in Vratza, Bulgaria, between 2003 and 2009 using markers in years one and three to predict new cases of BEN in the year five. We defined incident cases of BEN based on parental history, reduced kidney size and reduced kidney function, distinguishing probable and definite BEN, both combined as total incidence. The data were analyzed by Cox regression models using age as time scale and controlling for gender. We estimated hazard ratios and their 95% confidence intervals. The incidence of BEN was 17.4%. Paternal history was strongly associated with all three incidence groups (hazards ratio: 27-68, P <0.05). A reduction of kidney size of 1 mm resulted in a 5% increased hazard. However, taking parental history of BEN into account, these associations lost their significance. No kidney function measures were associated with new onset of BEN. A parental history of BEN is more important than clinical markers predicting the incidence of BEN. Without this information, kidney length forecasts probable BEN and the total incidence, while none of any clinical markers was related to definite BEN.