Urinary markers for early detection of Diabetic Nephropathy in type 1 Diabetes Mellitus

Background: diabetic nephropathy [DN] is a serious complication of diabetic mellitus associated with increased risk of morbidity and mortality. Diagnostic markers to detect DN at early stage are important as early intervention can slow loss of kidney functions and improve patient outcomes. N-acetyl Beta d-glucosaminidase [NAG] is a lysosomal enzyme, present in high concentrations in renal proximal tubular cells, Gamma-glutamyltransferase [GGT] is an enzyme which located along the proximal tubular brush border, Malondialdehyde [MDA] is a highly toxic product, formed in part by lipid oxidation derived free radicals, Reactive carbonyl derivatives [RCD[S]] is an oxidative stress marker in urine, as a measure of the oxidative modification of proteins and beta-2-microglobulin is filtered by the glomerulus, absorbed and catabolized by the proximal tubules. The aim of this study is to investigate the urinary outcome of these markers as early detectors of diabetic nephropathy in type 1 diabetic children

Subjects and methods: This case-control study included 67 children with type 1 diabetes mellitus [33 male; 34 female], age [11.03 +/- 1.05 years] and thirty one age [10.58 +/- 1.11 years] and sex [13 male; 18 female] matched healthy children [13 male; 18 female]. Type 1 diabetic children were further subdivided into microalbuminuric and normoalbuminuric subgroups according to microalbuminuria concentration [30 mg/ g creatinine]. Age, sex, diabetic duration and the current daily insulin dose, and family history of diabetes, weight, height, body mass index, systolic and diastolic blood pressure were recorded. Fasting plasma glucose, glycated hemoglobin, blood urea nitrogen, plasma creatinine, urinary creatinine, micoalbumin, N-acetyl-B-D glucosaminidase [NAG], Gama glutamyl transferase [GGT], Beta-2-microglobulin, Malondialdehyde [MDA] and Reactive carbonyl groups [RCDS[S]] were measured in all subjects

Results: a significant increase in tubular injury markers of diabetes [NAG, GGT, beta-2-microglobulin] and oxidative stress parameters [MDA, RCDS[S]] as compared to control subjects was found. Microalbuminuric subjects showed a significant elevatation in the urinary markers including NAG, GGT, beta-2-microglobulin, MDA, RCDS[S] as compared to normoalbuminuric subjects. The studied urinary tubular enzymes [NAG, GGT], oxidative stress markers [MDA, RCDS[S]] and Beta-2- microglobulin showed positive correlations with one another

Conclusion: The results of this study introduced the possibility of depending on tubular enzymes [NAG, GGT], oxidative stress markers [MDA, RCDS[S]] and Beta2 microglobulin as early, reliable, and sensitive predictors for diabetic nephropathy. The NAG activity index proved to be the most sensitive biomarker, then beta-2- microglobulin for early discovering the tubule cells damage

Urinary Sodium Excretion Has Positive Correlation with Activation of Urinary Renin Angiotensin System and Reactive Oxygen Species in Hypertensive Chronic Kidney Disease

It is not well described the pathophysiology of renal injuries caused by a high salt intake in humans. The authors analyzed the relationship between the 24-hr urine sodium-to-creatinine ratio (24HUna/cr) and renal injury parameters such as urine angiotensinogen (uAGT/cr), monocyte chemoattractant peptide-1 (uMCP1/cr), and malondialdehyde-to-creatinine ratio (uMDA/cr) by using the data derived from 226 hypertensive chronic kidney disease patients. At baseline, the 24HUna/cr group or levels had a positive correlation with uAGT/cr and uMDA/cr adjusted for related factors (P or =200 mEq/g cr was higher than in patients with or =200 mEq/g cr (P=0.016). During the 16-week follow-up period, an increase in urinary sodium excretion predicted an increase in urinary angiotensinogen excretion. In conclusion, high salt intake increases renal renin-angiotensin-system (RAS) activation, primarily, and directly or indirectly affects the production of reactive oxygen species through renal RAS activation.

Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes

Diabetic nephropathy is the most serious complication in diabetes mellitus. It is known that oxidative stress and inflammation play a central role in the development of diabetic nephropathy. In this study, we investigated that ferulic acid (FA) known as anti-oxidative agent could effect on diabetic nephropathy by anti-oxidative and anti-inflammatory mechanism. We examined the effects of FA in obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats and non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats. We treated FA to experimental rats from 26 to 45 weeks of age. We evaluated ACR, MDA and MCP-1 in 24 h urine and examined renal histopathology and morphologic change in extracted kidneys from rats. Also, we evaluated the ROS production and MCP-1 levels in cultured podocyte after FA treatment. In the FA-treated OLETF rats, blood glucose was significantly decreased and serum adiponectin levels were increased. Urinary ACR was significantly reduced in FA-treated OLETF rats compared with diabetic OLETF rats. In renal histopathology, FA-treated OLETF rats showed decreased glomerular basement membrane thickness, glomerular volume, and mesangial matrix expansion. FA treatment decreased oxidative stress markers and MCP-1 levels in 24 h urine of rats and supernatants of cultured podocyte. In conclusion, it was suggested that FA have protective and therapeutic effects on diabetic nephropathy by reducing oxidative stress and inflammation.

Urinary N-acetyl--D-glucosaminidase and Malondialdehyde as a Markers of Renal Damage in Burned Patients

This study was aimed to evaluate renal dysfunction during three weeks after the burn injuries in 12 patients admitted to the Hallym University Hankang Medical Center with flame burn injuries (total body surface area, 20-40%). Parameters assessed included 24-hr urine volume, blood urea nitrogen, serum creatinine, creatinine clearance, total urinary protein, urinary microalbumin, 24-hr urinary N-acetyl--D-glucosaminidase (NAG) activity, and urinary malondialdehyde (MDA). Statistical analysis was performed using repeated measures ANOVA test. The 24-hr urine volume, creatinine clearance, and urinary protein significantly increased on day 3 post-burn and fell thereafter. The urine microalbumin excretion showed two peak levels on day 0 post-burn and day 3. The 24-hr urinary NAG activity significantly increased to its maximal level on day 7 post-burn and gradually fell thereafter. The urinary MDA progressively increased during 3 weeks after the burn injury. Despite recovery of general renal function through an intensive care of burn injury, renal tubular damage and lipid peroxidation of the renal tissue suggested to persist during three weeks after the burn. Therefore, a close monitoring and intensive management of renal dysfunction is necessary to prevent burn-induced acute renal failure as well as to lower mortality in patients with major burns.