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Authors

Background:

Renal function declines according to age and vascular risk factors, whereas few data are available regarding genetically-mediated effects of anti-hypertensives over renal function.

Objective:

To estimate urea and creatinine variations in dementia due to Alzheimer disease (AD) by way of a pharmacogenetic analysis of the anti-hypertensive effects of angiotensin-converting enzyme inhibitors (ACEis).

Methods:

Consecutive outpatients older than 60 years-old with AD and no history of kidney transplant or dialytic therapy were recruited for prospective correlations regarding variations in fasting blood levels of urea and creatinine in one year, considering ACE genotypes of rs1800764 and rs4291 and their respective haplotypes, and treatment with ACEis along with blood pressure variations.

Results:

For 190 patients, 152 had arterial hypertension, and 122 used ACEis. Minor allele frequencies were 0.492 for rs1800764-C and 0.337 for rs4291-T, both in Hardy-Weinberg equilibrium. There were no overall significant yearly variations in levels of urea and creatinine, but their concurrent variations were positively correlated (ρ <0.0001). Each A allele of rs4291 led to an yearly urea increase of 3.074 mg/dL, and an yearly creatinine increase of 0.044 mg/dL, while the use of ACEis was protective regarding creatinine variations. The use of ACEis was also protective for carriers of rs1800764-CT/rs4291-AA, while carriers of rs1800764-CT/rs4291-AT had steeper reductions in creatinine levels, particularly when they were treated with ACEis.

Conclusions:

Effects of ACEis over creatinine variations are genetically mediated and independent of blood pressure variations in older people with AD.

Fabricio Ferreira de Oliveira, Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil

Fabricio Ferreira de Oliveira, MD, MSc, PhD, is a post-doctoral fellow at the Department of Neurology and Neurosurgery of the Federal University of São Paulo – UNIFESP.

Juliana Marília Berretta, Department of Medicine, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil

Juliana Marília Berretta, MD, is an assistant geriatrician at the Department of Medicine of the Federal University of São Paulo – UNIFESP.

Elizabeth Suchi Chen, Department of Morphology and Genetics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil

Elizabeth Suchi Chen, MSc, PhD, is a professor at the Department of Morphology and Genetics of the Federal University of São Paulo – UNIFESP.

Marilia Cardoso Smith, Department of Morphology and Genetics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil

Marilia Cardoso Smith, MSc, PhD, is a full professor at the Department of Morphology and Genetics of the Federal University of São Paulo – UNIFESP.

Paulo Henrique Ferreira Bertolucci, Department of Neurology and Neurosurgery, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil

Paulo Henrique Ferreira Bertolucci, MD, MSc, PhD, is an associate professor at the Department of Neurology and Neurosurgery of the Federal University of São Paulo – UNIFESP.
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Received 2016-01-18
Accepted 2016-05-31
Published 2024-06-07