Nutritional therapy reduces protein carbamylation through urea lowering in chronic kidney disease

Oct 10, 2017Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

Nutritional therapy may lower harmful protein changes by reducing urea in chronic kidney disease

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Abstract

Nutritional treatments that significantly decrease serum levels of urea are associated with reduced protein carbamylation.

Lower diastolic blood pressure and decreased serum levels of urea, sodium, phosphorus, and parathyroid hormone were observed with the Mediterranean diet (MD) and very low protein diet (VLPD).
Higher serum levels of bicarbonate and hemoglobin were noted with MD and VLPD.
Both MD and VLPD led to significant decreases in serum homocitrulline levels and homocitrulline/lysine ratios compared to free diet.
Reductions in urea levels correlated with substantial reductions in homocitrulline levels, indicating a potential link between urea levels and protein carbamylation.

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BACKGROUND: Protein carbamylation is one of the non-enzymatic reactions involved in protein molecular ageing. We sought to investigate the relationship between urea levels and protein carbamylation, and whether a Mediterranean diet (MD) and a very low protein diet (VLPD) reduce protein carbamylation through reduction in urea levels in patients with chronic kidney disease (CKD).

METHODS: This is a prospective, randomized, crossover controlled trial that investigated 60 patients with CKD grades 3B-4 (46 males, mean age of 67 years). The enrolled CKD patients were randomly assigned (1:1) to two different nutritional treatment arms: (i) 3 months of free diet (FD), 6 months of VLPD, 3 months of FD and 6 months of MD; and (ii) 3 months of FD, 6 months of MD, 3 months of FD and 6 months of VLPD. Blood levels of lysine (Lys) and homocitrulline (Hcit) and their ratio were used as markers of cyanate levels. Due to a lack of pre-existing data on the potential effects of different dietary regimens and in light of the exploratory nature of the study, no formal sample size estimation was carried out.

RESULTS: At study completion, lower diastolic blood pressure and decreased serum levels of urea, sodium, phosphorus and parathyroid hormone, but higher serum levels of bicarbonate and haemoglobin, were noted with MD and VLPD. When compared with FD, both MD and VLPD were also associated with a decrease in serum Hcit levels and Hcit/Lys ratios (P < 0.001). Notably, reductions in urea levels correlated with substantial reductions in Hcit levels (R2 = 0.16 and 0.17 for VLPD and MD, respectively).

CONCLUSION: In conclusion, nutritional treatments that significantly decrease serum levels of urea are associated with reduced protein carbamylation.

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Nutritional therapy reduces protein carbamylation through urea lowering in chronic kidney disease

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