Cytoskeleton Alteration And Kidney Damage: The Role Played By The Alpha Adducin Polymorphism In The Onset And Progression Of Chronic Kidney Failure In The Autosomic Dominant Polycystic Kidney Disease

Introduction and Aims: Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic nephropathy and an important cause of ESRD, End Stage Renal Disease, accounting for about 5% of patients requiring dialysis. The number of cysts and their complications are variable among single patients as well as the renal outcome. Adducin is a heterodimeric cytoskeleton protein consisting of an alphasubunit and either a beta- or gamma-subunit. It is involved in cohesion of renal cells. In rats and humans, mutation of the a-adducin subunit leads to the stimulation of the sodium (Na(+)), potassium (K(+)) adenosine triphosphate (ATP)-ase activity in renal tubular cells, increased renal Na(+) reabsorption, and, subsequently, hypertension.

Methods: We analyzed the genetic background of a sample of 154 patients affected by ADPKD, in order to evaluate the influence of α-adducin gene polymorphism in renal outcome. ΔGFR (Glomerular Filtration Rate loss) was evaluated at the follow-up (every 6 months). Statistical analysis has been performed by Cox Regression corrected for sex, age, blood pressure, comorbid conditions, therapy and previous renal function.

Results: ADPKD patients carrying at least a mutated allele (GW and WW) present a significant loss of renal function vs wild type ones. We observed a GFR loss of 30% vs basal value in 77 months in mutated pts and in 90 months in wild type ones (p=0.03). Mean of follow up 45.5 months in the entire sample (min 6 max 169.73).

Conclusions: α-adducin genotype is associated with loss of renal function in ADPK. As mutated genotype is known to be also associated with hypertension and renal handling of sodium it could contribute to our understanding of the pathogenetic mechanisms that lead in renal failure progression for ADPKD patients.