acid-phosphatase and Diabetic-Nephropathies

Renal dysfunction, a major complication of type 2 diabetes, can be predicted from estimated glomerular filtration rate (eGFR) and protein markers such as albumin concentration. Urinary protein biomarkers may be used to monitor or predict patient status. Urine samples were selected from patients enrolled in the retrospective diabetic kidney disease (DKD) study, including 35 with good and 19 with poor prognosis. After removal of albumin and immunoglobulin, the remaining proteins were reduced, alkylated, digested, and analyzed qualitatively and quantitatively with a nano LC-MS platform. Each protein was identified, and its concentration normalized to that of creatinine. A prognostic model of DKD was formulated based on the adjusted quantities of each protein in the two groups. Of 1296 proteins identified in the 54 urine samples, 66 were differentially abundant in the two groups (area under the curve (AUC):

Topics: Acid Phosphatase; Adult; Aged; Biomarkers; Calcium-Binding Proteins; Case-Control Studies; Cathepsin A; Chromatography, Liquid; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Extracellular Matrix Proteins; Female; G(M2) Activator Protein; Humans; Male; Mass Spectrometry; Middle Aged; Mucin-1; Prognosis; Proteomics; Retrospective Studies; Support Vector Machine; Urine

To protect the kidney effectively with medication in type 2 diabetics, it is crucial to identify such at-risk patients early for treatment. We investigated whether peptiduria precedes proteinuria (the earliest urinary marker in our model), and thereby serve as an early predictor of diabetic nephropathy.. A longitudinal study was performed in a rat model of diabetic nephropathy. Peptides, defined as degradation products of proteins of < 13 kD size, were quantified by a previously validated method using a combination of Lowry and Biorad protein assays. Peptides in urine were also confirmed by chromatographically separating low molecular weight fractions from urine and quantifying albumin fragments in these fractions by enzyme immunoassay. Also, the mechanism of peptiduria was addressed by measuring acid phosphatase, a marker of lysosomal activity, in urine and on kidney sections (histochemically).. In rats with diabetic nephropathy, proteinuria occurred after 12 weeks of diabetes, while peptiduria occurred as early as 2 weeks after diabetes. Peptiduria was confirmed by showing that the chromatographically separated low molecular weight fractions of urine containing albumin fragments is in proportion to the level of peptiduria. The time course of peptiduria paralleled the increase in urinary acid phosphatase suggesting that the mechanism of early peptiduria could be due to upregulation of lysosomal enzyme activity in the tubules.. Our results showing that peptiduria precedes proteinuria in diabetic nephropathy provide a compelling rationale to perform a prospective human clinical trial to investigate whether peptiduria can serve as an early predictor of diabetic nephropathy.

Topics: Acid Phosphatase; Albuminuria; Animals; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Longitudinal Studies; Lysosomes; Male; Molecular Weight; Peptides; Predictive Value of Tests; Proteinuria; Rats; Rats, Sprague-Dawley; Reproducibility of Results

Increased levels of serum undercarboxylated osteocalcin, which were associated with bone metabolism markers, correlated inversely with indices of glucose metabolism (plasma glucose, hemoglobin A1C, and glycated albumin) in hemodialysis patients with abnormalities of bone metabolism.. Undercarboxylated osteocalcin (ucOC), a possible marker of bone metabolism and one of the osteoblast-specific secreted proteins, has recently been reported to be associated with glucose metabolism. We tested the hypothesis that ucOC levels are associated with indices of glucose metabolism in chronic hemodialysis patients with abnormalities of bone metabolism.. Serum ucOC, bone alkaline phosphatase (BAP, a bone formation marker), and tartrate-resistant acid phosphatase-5b (TRACP-5b, a bone resorption marker) were measured in 189 maintenance hemodialysis patients (96 diabetics and 93 non-diabetics), and their relationships with glucose metabolism were examined.. ucOC correlated positively with BAP (ρ = 0.489, p < 0.0001), TRACP-5b (ρ = 0.585, p < 0.0001) and intact parathyroid hormone (iPTH; ρ = 0.621, p < 0.0001). Serum ucOC levels in the diabetic patients were lower than those of non-diabetic patients (p < 0.001), although there were no significant differences in serum BAP or TRACP-5b between diabetic and non-diabetic patients. Serum ucOC correlated negatively with plasma glucose (ρ = -0.303, p < 0.0001), hemoglobin A1C (ρ = -0.214, p < 0.01), and glycated albumin (ρ = -0.271, p < 0.001), although serum BAP or TRACP-5b did not. In multiple linear regression analysis, log [plasma glucose], log [hemoglobin A1C], and log [glycated albumin] were associated significantly with log [ucOC] after adjustment for age, gender, hemodialysis duration, and body mass index but were not associated with log [BAP], log [TRACP-5b], or log [intact PTH].. Increased levels of serum ucOC, which were associated with bone metabolism markers, were inversely associated with indices of glucose metabolism in hemodialysis patients.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Biomarkers; Blood Glucose; Bone Diseases, Metabolic; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Isoenzymes; Kidney Failure, Chronic; Male; Middle Aged; Osteocalcin; Renal Dialysis; Serum Albumin; Tartrate-Resistant Acid Phosphatase

Topics: Acid Phosphatase; Adult; Aged; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Diabetic Nephropathies; Female; Fructose-Bisphosphate Aldolase; Humans; Isoenzymes; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Male; Middle Aged; Proteinuria

Topics: Acid Phosphatase; Animals; Basement Membrane; Collagen; Culture Techniques; Diabetic Nephropathies; Glucosephosphate Dehydrogenase; Histological Techniques; Hypertrophy; Kidney; Kidney Glomerulus; L-Lactate Dehydrogenase; Oxygen Consumption; Protein Biosynthesis; Proteinuria; Rats

Topics: Acid Phosphatase; Adrenal Cortex Hormones; Chymotrypsin; Diabetic Nephropathies; Diabetic Retinopathy; Humans; Hyaluronoglucosaminidase; Hypoglycemic Agents