Relationship between amino acid ratios and decline in estimated glomerular filtration rate in diabetic and non-diabetic patients in South Africa

Abstract

Background: Diabetic kidney disease is a major complication resulting from type 1 and type 2 diabetes. Currently, the microalbuminuria test is used to monitor renal function; however, it does not detect albumin until progressive loss of renal function has occurred. Objective: This study analysed the relationship between changes in amino acid ratios and estimated glomerular filtration rate (eGFR) decline in diabetic and non-diabetic patients. Methods: Urine samples were collected from participants between February 2019 to April 2019 and analysed from November 2020 to January 2021. Diabetic (glycated haemoglobin 6.4%) and non-diabetic patients (glycated haemoglobin ≤ 6.4%) from Chris Hani Baragwanath Hospital, South Africa, were further categorised based on the degree of renal function predicted by the eGFRs. Amino acids were quantified using tandem mass spectrometry to determine the concentrations and ratios of tyrosine/phenylalanine, ornithine/arginine, arginine/citrulline and citrulline/ornithine at different stages of the chronic kidney disease. Results: Among diabetic patients, the tyrosine/phenylalanine ratio showed a statistically significant increase (p = 0.04) as the eGFR declined from stage 1 to stage 4; the ornithine/arginine ratio showed a strong negative correlation with eGFR. The citrulline/ornithine ratio differed between the diabetic and non-diabetic patients in stage 1 of chronic kidney disease. Conclusion: Amino acid ratios (ornithine/arginine and tyrosine/phenylalanine) are affected by the progression of diabetes and can be correlated to renal function. The citrulline/ornithine ratios differ between the studied groups in stage 1 of the disease and may be utilised to predict the onset of chronic kidney disease.

Keywords

• diabetic nephropathy
• albuminuria
• amino acids
• lc-ms/ms
• chronic kidney disease
• glomerular filtration rate