s-adenosylhomocysteine and Renal-Insufficiency--Chronic

To determine whether urine S-adenosylmethionine (SAM) might be an indicator of chronic kidney disease (CKD).. We investigated urine levels of SAM and related metabolites (S-adenosylhomocysteine and homocysteine cysteine) in 62 patients (average age, 65.9 years) with CKD (stages II-V).. Patients with stages III-V CKD stages have significantly decreased urine levels and SAM/S-adenosylhomocysteine ratio and also cysteine/homocysteine ratio in blood plasma (P <.05), compared with patients with stage II CKD. Urine SAM levels allowed us to distinguish patients with mildly decreased kidney function from those with moderate to severe renal impairment (AUC, 0.791; sensitivity, 85%; specificity, 78.6%).. Our study results demonstrate that urine SAM is a potent biomarker for monitoring renal function decline at early CKD stages. Urine SAM testing confers an additional advantage to healthcare professionals in that it is noninvasive.

Topics: Adult; Aged; Aged, 80 and over; Female; Glomerular Filtration Rate; Homocysteine; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; S-Adenosylhomocysteine; S-Adenosylmethionine

To evaluate the association of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) in urine with chronic kidney disease (CKD).. Case-control study including 50 patients with CKD and 20 healthy volunteers.. SAM level and SAM/SAH ratio in urine were significantly lower in patients than in control individuals (P <.001 and P = .01, respectively). The estimated glomerular filtration rate was associated with the SAM level (P = .04) and the SAM/SAH ratio in urine (P = .01).. CKD is associated not only with the decline in the SAM level but also with the decrease in the SAM/SAH ratio in urine. Thus, use of the urinary SAM/SAH ratio as a noninvasive diagnostic indicator of renal function seems promising.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; S-Adenosylhomocysteine; S-Adenosylmethionine

Human monocytes are a heterogeneous cell population consisting of 3 subsets: classical CD14++CD16-, intermediate CD14++CD16+ and nonclassical CD14+CD16++ monocytes. Via poorly characterized mechanisms, intermediate monocyte counts rise in chronic inflammatory diseases, among which chronic kidney disease is of particular epidemiologic importance. DNA methylation is a central epigenetic feature that controls hematopoiesis. By applying next-generation Methyl-Sequencing we now tested how far the 3 monocyte subsets differ in their DNA methylome and whether uremia induces DNA methylation changes in differentiating monocytes. We found that each monocyte subset displays a unique phenotype with regards to DNA methylation. Genes with differentially methylated promoter regions in intermediate monocytes were linked to distinct immunological processes, which is in line with results from recent gene expression analyses. In vitro, uremia induced dysregulation of DNA methylation in differentiating monocytes, which affected several transcription regulators important for monocyte differentiation (e.g., FLT3, HDAC1, MNT) and led to enhanced generation of intermediate monocytes. As potential mediator, the uremic toxin and methylation inhibitor S-adenosylhomocysteine induced shifts in monocyte subsets in vitro, and associated with monocyte subset counts in vivo. Our data support the concept of monocyte trichotomy and the distinct role of intermediate monocytes in human immunity. The shift in monocyte subsets that occurs in chronic kidney disease, a proinflammatory condition of substantial epidemiological impact, may be induced by accumulation of uremic toxins that mediate epigenetic dysregulation.

Topics: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cell Differentiation; DNA Methylation; fms-Like Tyrosine Kinase 3; Gene Expression Regulation; GPI-Linked Proteins; Healthy Volunteers; High-Throughput Nucleotide Sequencing; Histone Deacetylase 1; Humans; Lipopolysaccharide Receptors; Monocytes; Receptors, IgG; Renal Insufficiency, Chronic; Repressor Proteins; S-Adenosylhomocysteine; Uremia