Differences in Serum Amino Acid Phenotypes Among Patients with Diabetic Nephropathy, Hypertensive Nephropathy, and Chronic Nephritis

Abstract

BackgroundWe assessed levels of circulating amino acids in different etiologies of chronic kidney disease (CKD) and the association of amino acids with risk factors of CKD progression.Material/MethodsHigh-performance liquid chromatography-based analysis was used to determine amino acid profiles in patients with diabetic nephropathy (DN, n=20), hypertensive nephropathy (HN, n=26), and chronic nephritis (CN, n=33), and in healthy controls (HC, n=25).ResultsAll 3 types of CKD patients displayed decreased serum levels of serine, glycine, GABA, and tryptophan compared with healthy controls. Moreover, serine and tryptophan were positively correlated with glucose in DN cohorts. Total cholesterol was positively correlated with tryptophan levels in the DN cohort and negatively correlated with serine levels in the CN cohort. In the HN cohort, glycine was negatively correlated with triglyceride levels, and systolic blood pressure (SBP) was negatively correlated with GABA levels.ConclusionsPatients with different etiologies of CKD have significantly different amino acids profiles, and this indicates specific supplementary nutritional needs in CKD patients.

Extracellular serine and glycine are required for mouse and human skeletal muscle stem and progenitor cell function

“…Systemic serine and/or glycine levels are reduced in various pathologies and with advanced age [ [12] , [13] , [14] , 16 , 17 ], and these conditions are also associated with impaired skeletal muscle regeneration [ [2] , [3] , [4] , [5] , [6] ]. Using skeletal muscle biopsy tissue of healthy older and younger adults, we identified serine as the only measured amino acid that was reduced in the skeletal muscle with age in our human cohort ( Figure 6 A and Figure S6A ); a similar analysis in young and old mice on an amino acid-defined diet identified glycine as the only amino acid that decreased with age ( Figure S6B ) and the levels were not influenced by sex ( Figure S6C ).…”

“…Currently, dietary serine and glycine standardization or supplementation are not a part of standard care post-skeletal muscle trauma/surgery despite the observation that the availability of endogenous serine and potentially glycine is strongly influenced by the diet [ 44 , 45 ]. Standardization or supplementation of dietary serine/glycine is important to consider given that aged adults and adults with various pathologies are unable to maintain endogenous serine and glycine levels [ [12] , [13] , [14] , 16 , 17 ]. While the source of age- and disease-related decreases in serine/glycine availability in circulation/skeletal muscle tissue remains an open question, it may be due to increased metabolic demand [ 69 ].…”

“…Accelerated proliferation, such as that needed by MuSC/MPCs at the onset of regeneration, has been associated with increased nutrient uptake from cell-extrinsic sources in other cell types [ 15 ]. Interestingly, circulating levels of serine and/or glycine, two nutritionally non-essential amino acids, are reduced systemically in human cohorts of aged individuals [ 16 ] and those with CKD [ 17 ], diabetes [ 14 ], and muscle dystrophies [ 12 ]. These findings are pertinent as serine is readily interconverted to glycine via a one-step reaction catalyzed by serine hydroxymethyltransferase (SHMT) enzymes, and serine and/or glycine are essential for proliferation in some types of cancer cells [ [18] , [19] , [20] ] and T cells [ 21 ].…”

The Effect of Mild Renal Dysfunction on the Assessment of Plasma Amino Acid Concentration and Insulin Resistance in Patients with Type 2 Diabetes Mellitus

“…CKD causes changes in different amino acids depending on the disease that caused it. For example, DN has been reported to reduce levels of serine, glycine, GABA, and tryptophan [ 45 ]. The positive correlation between 1/CysC and GABA in this study confirms this, but it is not true for other amino acids.…”

Serum and Fecal Amino Acid Profiles in Cats with Chronic Kidney Disease

“…Compared to nonessential AAs, essential AAs cannot be synthesized by the organism and require dietary intake. Humans, dogs, and cats with kidney disease, even those with early disease, were previously reported to have a deranged profile of circulating AAs [9][10][11][12][13][14]. In addition, fecal AA profiles were shown to be altered in people receiving hemodialysis and in a rodent CKD model when compared to healthy controls [6,15].…”