Increased Blood Pressure in Adult Offspring of Families With Balkan Endemic Nephropathy: A Prospective Study

Plamen S. Dimitrov; Valeri A. Simeonov; Svetlana D. Tsolova; Angel G. Bonev; Rossitza B. Georgieva; Wilfried J. Karmaus


BMC Nephrology 

In This Article


Of the 201 participants in the first investigations (2003/04), 189 participated in the follow-up (2004/05, 94%). Two were deceased, one moved out of the area, two could not be contacted, and 7 decided not to participate further. Of the 12 lost, 9 were offspring of BEN patients. Potential risk factors show similar distributions in each of the two investigations ( Table 1 ). One participant had newly developed diabetes. Comparison offspring were about 1.5 to 2 cm taller than BEN offspring; however, the latter were on average 1.5 kg heavier. Blood pressure seems to be higher in BEN offspring: 30.4% were classified as having moderate hypertension (systolic blood pressure ≥140 and/or diastolic ≥90 mm Hg) in the investigation in 2003/04 and 33.3% in 2004/05 ( Table 1 ). The prevalence of moderate hypertension in our rural sample, with a mean age of 50 years, is only marginally lower than the proportion reported in another study of urban population of the same age in Bulgaria.[25] Also, offspring of BEN patients reported more antihypertensive treatment in the year before the investigation.

Figure 1 shows the agreement between the two systolic blood pressure measurements one year apart. The intraclass correlation coefficient (ICC) of 0.68 (lower 5% limit: 0.61) was good for systolic blood pressure, but lower for diastolic blood pressure (ICC = 0.49, lower 5% limit: 0.39). For the minimal cortex width, the ICC was 0.66 (lower 5% limit: 0.58) and 0.92 for kidney length (lower limit: 0.89). Blood lead concentration also showed good agreement (ICC = 0.65, lower limit: 0.57).

Figure 1.

Comparisons of systolic blood pressure measurements in 2003/04 and 2004/05.

The study population consists of 201 subjects that provided 388 observations (two measurements for most participants, one year apart). When analyzing blood pressure differences while controlling for confounders, cortex width and parental BEN status had significant effects on systolic and pulse pressure, but not on diastolic blood pressure. A decrease in the minimal kidney cortex of 1 mm was linearly related to an increase in systolic blood pressure of 1.4 mm Hg (p = 0.005) and an increase of pulse pressure of 1.1 mm Hg (p = 0.002).

Figure 2 shows the scatter plot of minimal cortex width and pulse pressure using a cubic regression with 95% confidence limits. A cubic regression fitted the observations best when no other predictors were taken into consideration. Within the boundaries of our measurements of the cortex width there was no decrease in blood pressure once the minimal kidney cortex width was 16 mm or larger. Blood pressure started to increase when the width was smaller than 16 mm.

Figure 2.

Scatterplot of minimal kidney cortex width with pulse pressure in the 2004/05 investigation (crude association; for adjusted effects, see Table 2 ). The straight line shows the estimated cubic association, the dotted lines show the 95% confidence limits.

A maternal history of BEN was associated with an increased systolic blood pressure in offspring of 6.7 mm Hg (p = 0.03), and when both parents had BEN, an increased systolic blood pressure of 9.9 mm Hg (p = 0.002). There was no statistically significant effect of a paternal history of BEN.

To investigate whether the use of antihypertensive medication had distorted our findings, we repeated the model excluding those observations with antihypertensive drug use. This reduced the number of repeated observation from 388 to 322 (176 subjects), but did not change our findings.


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