INTRODUCTION AND AIMS: Chronic Kidney Disease (CKD) is associated with early atherosclerosis, micro-inflammation and cardiovascular disease (CVD). Protein carbamylation resulting in urea-derived cyanate compounds, implied in many pathophysiological events in nephrology, could represent a potential link between CKD and CVD.The aim of the study was to verify the hypothesis that reducing serum urea by dietary treatments poor in animal proteins could result in reduced carbamylation products. METHODS: We enrolled 60 (46 males, mean age 67 years) CKD 3b-4 patients in a pilot cross-over randomized controlled trial.The enrolled patients were divided into 2 arms of 30 patients each by a software randomization. Arm A alternatively underwent 3 dietary schemes as follows: 3 months free diet (FD - proteins (p.) 1 gram/body weight/day (g/bw/d), animal proteins (a.p.) 78%), 6 months Very Low Protein Diet supplemented with ketoacids (VLPD - p. 0.3-0.5 g/bw/d + 0.05 g/bw/d supplementation, a.p. 0%), 3 months FD, 6 months Mediterranean Diet (MD - p. 0.7-0.8 g/bw/d, a.p. 44%); Arm B: 3 months FD, 6 months MD, 3 months FD, 6 months VLPD.We measured blood pressure, serum and urine routine markers. Homocitrulline (Hcit) and Hcit/Lysin (Lys) ratio, used as markers of protein carbamylation, were measured by LC-MS/MS. Differences between variables were tested with parametric (t-Student) or non-parametric (Wilcoxon) tests, as opportune, while Spearman test was used to correlate serum urea with Hcit, Lys and Hcit/Lys. All analyses were conducted as intention-to-treat. P-values < 0.05 were considered statistically significant. RESULTS: MD and VLPD decrease serum urea by 20.5% and 58.3% as compared with FD (p<0.001), respectively. VLPD decreases Hcit and Hcit/Lys by 41.4% and 28.9% as compared with FD (p<0.001). MD lowers Hcit by 27.6% (p<0.001) and Hcit/Lys by 10.5% compared with FD (ns). VLPD was more effective than MD in lowering both carbamylation markers (p<0.001). VLPD lowers diastolic blood pressure and serum levels of Na, P, PTH, homocysteine and increases serum bicarbonate and hemoglobin as compared to FD (p<0.05).Moreover, Hcit, Lys and Hcit/Lys significantly correlate with serum urea (r=0.7, r=0.7 and r=0.6, respectively; p < 0.0001). CONCLUSIONS: In conclusion, our study demonstrates that dietary regimens characterized by a reduced intake of animal proteins, such as VLPD and MD, are effective in reducing the levels of cyanates through urea reduction in CKD patients. Moreover we demonstrate, for the first time in our knowledge, that MD is capable of reducing urea and the cyanates, although to a minor extent than VLPD.These findings suggest to consider urea as another therapeutic target in CKD, susceptible of modifications by a dietary approach.

DIETARY REGIMENS POOR IN ANIMAL PROTEINS DECREASE CYANATES PRODUCTION THROUGH UREA REDUCTION IN CHRONIC KIDNEY DISEASE

Marzocco, Stefania;Dal Piaz, Fabrizio;
2017-01-01

Abstract

INTRODUCTION AND AIMS: Chronic Kidney Disease (CKD) is associated with early atherosclerosis, micro-inflammation and cardiovascular disease (CVD). Protein carbamylation resulting in urea-derived cyanate compounds, implied in many pathophysiological events in nephrology, could represent a potential link between CKD and CVD.The aim of the study was to verify the hypothesis that reducing serum urea by dietary treatments poor in animal proteins could result in reduced carbamylation products. METHODS: We enrolled 60 (46 males, mean age 67 years) CKD 3b-4 patients in a pilot cross-over randomized controlled trial.The enrolled patients were divided into 2 arms of 30 patients each by a software randomization. Arm A alternatively underwent 3 dietary schemes as follows: 3 months free diet (FD - proteins (p.) 1 gram/body weight/day (g/bw/d), animal proteins (a.p.) 78%), 6 months Very Low Protein Diet supplemented with ketoacids (VLPD - p. 0.3-0.5 g/bw/d + 0.05 g/bw/d supplementation, a.p. 0%), 3 months FD, 6 months Mediterranean Diet (MD - p. 0.7-0.8 g/bw/d, a.p. 44%); Arm B: 3 months FD, 6 months MD, 3 months FD, 6 months VLPD.We measured blood pressure, serum and urine routine markers. Homocitrulline (Hcit) and Hcit/Lysin (Lys) ratio, used as markers of protein carbamylation, were measured by LC-MS/MS. Differences between variables were tested with parametric (t-Student) or non-parametric (Wilcoxon) tests, as opportune, while Spearman test was used to correlate serum urea with Hcit, Lys and Hcit/Lys. All analyses were conducted as intention-to-treat. P-values < 0.05 were considered statistically significant. RESULTS: MD and VLPD decrease serum urea by 20.5% and 58.3% as compared with FD (p<0.001), respectively. VLPD decreases Hcit and Hcit/Lys by 41.4% and 28.9% as compared with FD (p<0.001). MD lowers Hcit by 27.6% (p<0.001) and Hcit/Lys by 10.5% compared with FD (ns). VLPD was more effective than MD in lowering both carbamylation markers (p<0.001). VLPD lowers diastolic blood pressure and serum levels of Na, P, PTH, homocysteine and increases serum bicarbonate and hemoglobin as compared to FD (p<0.05).Moreover, Hcit, Lys and Hcit/Lys significantly correlate with serum urea (r=0.7, r=0.7 and r=0.6, respectively; p < 0.0001). CONCLUSIONS: In conclusion, our study demonstrates that dietary regimens characterized by a reduced intake of animal proteins, such as VLPD and MD, are effective in reducing the levels of cyanates through urea reduction in CKD patients. Moreover we demonstrate, for the first time in our knowledge, that MD is capable of reducing urea and the cyanates, although to a minor extent than VLPD.These findings suggest to consider urea as another therapeutic target in CKD, susceptible of modifications by a dietary approach.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/4704854
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