FAVORABLE EFFECTS OF SOMATOSTATIN ANALOGUES AND MTOR INHIBITORS ON LV FUNCTION IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: AN ECHOCARDIOGRAPHIC STUDY

INTRODUCTION

Autosomal dominant polycystic kidney disease (ADPKD) is associated with early onset hypertension and left ventricular (LV) hypertrophy (Schrier RW. 2009 [1] (full text)). Novel therapies for ADPKD are somatostatin analogues, octreotide (S) and mammalian target of rapamycin inhibition (mTORi), rapamycin or everolimus (RE)(Colao A. 2009 [2] (full text)(Paoletti E. 2009 [3]). This study assesses the effects of S and RE on LV mass and function as compared with conventional therapy (P).

METHODS

57 ADPKD patients (mean age 38±8; male gender, 29; mean GFR 70.1±28.2 mL/min) were randomly assigned to group P(25), S (17) or RE(15). Patients underwent a clinical and echocardiography assessment at baseline and at 24 to 30 months follow up (mean, 26±3). LV mass was calculated according to Devereux formula and LV volumes and ejection fraction (EF) according to biplane Simpson’s algorithm. LV filling was assessed by the analysis of diastolic mitral flow velocity curves and pulmonary vein flow velocity curves. By tissue Doppler imaging mitral annulus early diastolic velocity peak (Ea) was also measured.

RESULTS AND CONCLUSIONS

The 80% of P group, 52% of S, 93%of RE had hypertension; the 80% of P group, 40% of S and 87% of RE were under treatment with ACEi or ARBs. At baseline, blood pressure and heart rate were comparable among groups (Figura 1). S patients had lower (p<0.01) LV mass than the other two groups (P,105± 17g/m2; S,94± 16 g/m2, R, 118± 24 g/m2) while there were not differences between groups in EF and parameters of LV diastolic function. In each group there was no change in LV mass and EF as compared with baseline. Patients of P group exhibited an increase in the ratio between mitral early diastolic flow velocity peak and Ea (p <0.001) and a longer duration of pulmonary vein reverse flow at atrial contraction (P<0.001), indicative of a worsening in LV diastolic function (Figure 2). This study suggest that a deterioration in LV diastolic function occurs over time in patients with ADPKD. Both octreotide and mTORi seem to have a protective role.