Blood pressure (BP) is hardly controlled in chronic kidney disease (CKD). We compared the effect of very low protein diet (VLPD) supplemented with ketoanalogs of essential amino acids (0.35 g/kg/day), low protein diet (LPD, 0.60 g/kg/day), and free diet (FD) on BP in patients with CKD stages 4 and 5. Vegetable proteins were higher in VLPD (66%) than in LPD (48%). LPD was prescribed to 110 consecutive patients; after run-in, they were invited to start VLPD. Thirty subjects accepted; 57 decided to continue LPD; 23 refused either diet (FD group). At baseline, protein intake (g/kg/day) was 0.79+/-0.09 in VLPD, 0.78+/-0.11 in LPD, and 1.11+/-0.18 in FD (P<0.0001). After 6 months, protein intake was lower in VLPD than LPD and FD (0.54+/-0.11, 0.78+/-0.10, and 1.04+/-0.21 g/kg/day, respectively; P<0.0001). BP diminished only in VLPD, from 143+/-19/84+/-10 to 128+/-16/78+/-7 mm Hg (P<0.0001), despite reduction of antihypertensive drugs (from 2.6+/-1.1 to 1.8+/-1.2; P<0.001). Urinary urea excretion directly correlated with urinary sodium excretion, which diminished in VLPD (from 181+/-32 to 131+/-36 mEq/day; P<0.001). At multiple regression analysis (R2=0.270, P<0.0001), BP results independently related to urinary sodium excretion (P=0.023) and VLPD prescription (P=0.003), but not to the level of protein intake. Thus, in moderate to advanced CKD, VLPD has an antihypertensive effect likely due to reduction of salt intake, type of proteins, and ketoanalogs supplementation, independent of actual protein intake.

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This work is aimed at providing a description of the complex world of drug carriers, starting from the description of this particular market in terms of revenue. Then, a brief overview of several types of conventional and innovative drug carrier systems has been included. The types of administration routes were also analyzed, with a critical and qualitative comment on drug release kinetics and drug profile shapes. Carriers were classified according to their ability to provide a prolonged and targeted release. The concept of the therapeutic window has been presented, providing advantages of having pulsed drug release to avoid side effects to target tissues. A critical comment on the use of conventional and innovative techniques for the production of drug carriers by large industrial companies has been proposed. As a final attempt for this work, an overall unique schematization of a drug carrier production process has been added, highlighting the necessity to create a strong double link among world-requested versatility of drug carriers for human applications and the newly developed industrial processes.