Incidence and predictive factors of Balkan endemic nephropathy: a longitudinal study.

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.

The role of a parental history of Balkan endemic nephropathy in the occurrence of BEN: a prospective study.

Balkan endemic nephropathy (BEN) is a chronic kidney disease that affects persons living in the Balkans. Despite the unique geographical specificity of this disease, its etiology has remained unclear. Even if a positive family history of BEN has been identified, it is still uncertain how the disease develops in offspring. In this paper, we examine clinical mechanisms related to the onset of BEN in individuals who have a parental history of BEN to identify early detection of the disease and formulate interventions. We conducted a 5-year prospective study, using markers in years one and three to predict new cases of BEN in year five. New cases of BEN were defined based on three criteria: parental history of BEN, reduced kidney size, and reduced kidney function. Incident cases were divided into (1) probable, (2) definite, and (3) combined labeled total incidence. We evaluated parental history in relation to BEN and tested the potentially intervening effects of kidney length, kidney cortex width, ß(2)-microglobulin, C-reactive protein, and creatinine clearance, using path analyses. The findings of the path analyses suggested that parental history of BEN had both direct and indirect effects. The direct effect was significant for all three modes of parental history (biparental, maternal, and paternal; odds ratios 71.5, 52.3, and 50.1, respectively). The indirect effects of maternal BEN acted via kidney length and creatinine clearance. Biparental BEN was mediated by (1) kidney length and creatinine clearance, and (2) creatinine clearance alone. Paternal BEN had three indirect effects: (1) through kidney length and creatinine clearance, (2) via kidney cortex width and creatinine clearance, and (3) via kidney cortex width only. In conclusion, a family history of BEN led to reduced kidney length and cortex width, and a decline in creatinine clearance, which in turn predicted the onset of BEN.

Reduced kidney size in adult offspring of Balkan endemic nephropathy patients and controls: a prospective study.

INTRODUCTION: Reduced kidney size has been proposed as a criterion for clinical diagnosis of Balkan endemic nephropathy (BEN). Some studies suggest that smaller kidneys are found in advanced stages of BEN, whereas others reported them in earlier stages. To investigate the clinical course of kidney sizes in the offspring of BEN and non-BEN parents, we followed up a cohort of adult offspring over 5 years. We hypothesized that parental history affects kidney dimensions. METHODS: Four repeated ultrasound measurements of kidney length and cortex width were conducted in 121 offspring of BEN and 98 offspring of non-BEN parents. Repeated measurements were analyzed using mixed models adjusting for gender and time-dependent information on other kidney diseases, diabetes, age, height and year of follow-up. RESULTS: A reduction of kidney length was associated with maternal BEN (-4 mm, P = 0.001). We detected a parallel decline in kidney length in the various offspring groups. However, kidney cortex width was significantly smaller when both parents or the mother had BEN and offspring age > or =60 years (-1.88 mm, P = 0.0003; -1.03 mm, P = 0.05). In the 5th year of follow-up, 37 participants developed BEN (14 confirmed, 23 suspected). Kidney cortex width at baseline was smaller in offspring who developed BEN (P = 0.0001). CONCLUSIONS: The development of kidney dimensions depends on the parental BEN status and offspring age. In BEN offspring, ultrasound measurements of the kidney cortex width seem to have a prognostic value.