Abstract
BackgroundDiabetic 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.ObjectiveThis study analysed the relationship between changes in amino acid ratios and estimated glomerular filtration rate (eGFR) decline in diabetic and non-diabetic patients.MethodsUrine 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.ResultsAmong 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.ConclusionAmino 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.
Highlights
Diabetic nephropathy or chronic kidney disease (CKD), resulting from both type 1 and type 2 diabetes, is one of the leading causes of death in the world among non-communicable diseases.[1,2] Diabetic nephropathy usually develops about 10 years after the onset of diabetes.[3]
The ornithine/arginine and tyrosine/ phenylalanine ratios increased as the estimates the GFR (eGFR) decreased (Table 2)
The concentrations of ornithine, isoleucine, tyrosine and phenylalanine decreased with decreasing renal function and this was confirmed by statistically significant correlations ([R = 0.83; p = 0.17], [R = 0.94; p = 0.06], [R = 0.94; p = 0.06] and [R = 1.00; p = 0.004])
Summary
Diabetic nephropathy or chronic kidney disease (CKD), resulting from both type 1 and type 2 diabetes, is one of the leading causes of death in the world among non-communicable diseases.[1,2] Diabetic nephropathy usually develops about 10 years after the onset of diabetes.[3]. Chronic kidney disease patients are most likely to die from cardiovascular disease than progress to end-stage renal failure.[4]. The diagnostic criteria based on the A/C ratio are as follows: normal range ≤ 3.5 mg/mmol (female) and ≤ 2.5 mg/mmol (male); microalbumin range 2.6 mg/mmol – 25.0 mg/mmol (female) and 3.6 mg/mmol – 35.0 mg/mmol (male); macroalbumin range 26.0 mg/mmol – 100.0 mg/mmol (female) and 36.0 mg/mmol – 100.0 mg/mmol (male).[5] the A/C ratio is a good indicator of CKD, the detected value needs to be sustained in the patient over 3 months to accurately diagnose CKD.[6] It lacks specificity and sensitivity during a progressive decline in renal function and can give false results, where patients with CKD could appear normal.[7]. The microalbuminuria test is used to monitor renal function; it does not detect albumin until progressive loss of renal function has occurred
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