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Nephron Clin Pract. 2012;121(3-4):c174-9. doi: 10.1159/000346404. Epub 2013 Jan 23.

Gene polymorphisms as clinical tools in chronic glomerulopathies: a prospective study.

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1
Division of Nephrology, Hôpital du Sacré-Coeur de Montréal, University of Montreal, Montreal, Que., Canada.

Abstract

BACKGROUND/AIMS:

Studies have proposed various polymorphisms of genes implicated in the physiopathology of chronic kidney disease as risk factors of progression and potential clinical tools. We sought to validate and simultaneously compare their predictive value in a prospective cohort of chronic glomerulopathies receiving recommended antihypertensive and antiproteinuric therapies.

METHODS:

Using PubMed, we identified 9 polymorphisms previously associated with progression. These were mostly of the renin-angiotensin-aldosterone and inflammation pathways: MCP-1 A2518G, TGF-β1 T869C and C-509T, ACE I/D, AGT M235T, AT1R A1166C, TSC-22 A-396G, eNOS 4b/a and CYP11β2 C-344T. We hypothesized that their determination would identify individuals at higher risk of progression.

RESULTS:

We recruited 93 predominantly male and Caucasian patients with a mean age of 63 and baseline eGFR of 33 ml/min/1.73 m(2) followed prospectively over a median of 36 months. 61% of patients had diabetic nephropathy, almost all received RAA blockade (90%) and none immunosuppressive therapy. The average blood pressure during follow-up was 140/72 mm Hg, the urinary protein to creatinine ratio 0.15 g/mmol and the rate of renal function decline -3.2 ± 4.1 ml/min/1.73 m(2)/year. Proteinuria and blood pressure strongly predicted progression. However, under recommended therapy, none of the proposed polymorphisms predicted renal function decline. In addition, none showed simple or partial correlations with the severity of proteinuria or blood pressure. Finally, summation variable of risk polymorphisms did not predict progression.

CONCLUSION:

This study does not validate the use of these 9 polymorphisms as individual clinical tools in patients with chronic glomerulopathies on recommended antihypertensive and antiproteinuric therapies.

PMID:
23344084
DOI:
10.1159/000346404
[Indexed for MEDLINE]
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