SP383
LOW PROTEIN DIET REDUCES MICROBIAL AND INFLAMMATORY TOXINS IN ADVANCED RENAL FAILURE

INTRODUCTION: Chronic kidney disease (CKD) is characterized by a burden of atherosclerotic toxins. Gut Microbiota generates the “uremic microbial toxins”, such as total and free p-cresol (t-PC. f-PC) and total and free indoxyl-sulphate (t-IS, f-IS), resulting from the metabolism of tyrosine-phenylalanine and tryptophan, respectively. Lipoprotein-associated phospholipase A2(Lp-PLA2) is produced by inflammation cells, enters into atherosclerotic plaques, making them instable. PC, IS, and Lp-PLA2are correlated with cardiovascular disease and mortality. Low protein diet (LPD) is useful to reduce the uremic syndrome, but its role in reducing the microbial and inflammatory toxins is not clear. The aim of our perspective study is to evaluate whether the LPD can reduce PC, IS, and Lp-PLA2.

METHODS: We enrolled 28 subjects, 19 male, aged 63±14 years, with MDRD<25 ml/min/m2 afferent to our outpatient Nephrology Unit, from March 2017-to March 2018, to receive a LPD schedule (daily intake of protein <0,6 g/kg/day). Lp-PLA2activity, measured as enzymatic assay, and PC and IS, measured as mass spettrometry, such as the routinary biochemical and bioimpedentiometric parameters were compared before (T0) and after two months (T2) of LPD. All patients signed the informed consent.

RESULTS: The renal function, measured as the mean of creatinine and urea clearance and MDRD equation was 19.4±6.7 and 18.9±4.3 ml/min respectively at T0 and remained stable, so did the proteins urine excretion (1.3±1.5 g/24h).

After only 2 months of LPD, we observed a significant decrease in total cholesterol (188±48 mg/dl vs 177±40 mg/dl, p=0.02) and a clinically even if not statistically significant decrease in triglycerides (224±189 vs 169±69 mg/dl, p= 0.07) and blood urea nitrogen (52±16 vs 47±15 mg/dl, p=0.08), while the most common biochemical parameters, did not change. Interestingly, the doses of epoietin Z and furosemide significantly decreased (1464±3108 to 893±2330 UI per week, p =0.019, and 40±72 to 31±42 mg per day, p=0.007, respectively). Also the bio-impedentiometric values remained stable. LPD significantly reduced the levels of Lp-PLA2(161±51 to 151±50 nmol/mil/min, p=0.02), t-PC (141.7±69.7 vs 122.3±70.7 mcMol, p=0.04) and f-PC (5.3±3.2 to 4.3±3.3mcMol, p=0.03). Overall, t-IS and f-IS did not change (32.6±13.9 vs 32.2±13.6 and 1.6 mcMol and 0.7 vs 1.6±0.7 mcMol), but in subjects (n 13) with protein urine excretion<0.5g/day t-IS significantly decreased (34.1±13.6 to 27.9±9.6 mcMol, p=0.03) when compared to proteinuric subjects (31.3±14.5 to 35.9±15.7 mcMol, p=NS).

CONCLUSIONS: Our study demonstrated that the LPD reduces Lp-PLA2, PC and partially IS in patients with advanced renal failure. LPD seems a good and low cost strategy to remodulate the gut microbiota and the atherosclerosis in CKD