الفهرس 
Diabetic NephropathyOnly 14 pages are availabe for public view
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Abstract
Our study aimed to evaluate the possible relationship of Serum Monocyte Chemoattractant Protein-1 (MCP-1) with early stages of diabetic nephropathy in Egyptian patients. We conducted this study on 75 patients with Diabetes Mellitus. They were randomly selected from outpatient clinics of Ain Shams University Hospitals and 20 healthy volunteers as a control group. Patients were divided into 3 groups: Group (1) composed of 25 patients with normoalbuminuria (spot U Alb/Cr <30μg/mg) and normal renal functions (eGFR > 90 ml/min/1.73 m² estimated by MDRD equation). Group (2) composed of 25 patients with microalbuminuria (spot U Alb/Cr between 30 & 300 μg/mg) and normal renal functions while Group (3) composed of 25 patients with macroalbuminuria (as detected by dipstick and confirmed by spot U Alb/Cr > 300 μg/mg) and normal renal functions.
All studied patients were subjected to medical history and clinical examination including estimation of Body Mass Index (BMI) and mean arterial blood pressure, estimation of degree of albuminuria (using albumin dipsticks, urinary microalbumin by ELISA and spot U Alb/Cr in morning urine sample), estimation of glomerular filtration rate (GFR) using Modification of Diet in Renal Disease (MDRD) equation, estimation of serum (calcium, phosphorus, sodium, potassium, creatinine and blood urea nitrogen), glycosylated hemoglobin (HbA1c), serum high-sensitivity C-reactive protein (hs-CRP) by ELISA and estimation of serum monocyte chemoattractant protein-1(MCP-1) by ELISA.
Our study showed that serum MCP-1 was significantly higher in each of the three diabetic groups compared to the control group. Also, it was significantly higher in macroalbuminuric compared to normoalbuminuriac group.
We found that our results agreed with some authors’ results and disagreed with others. Some studies found that only urinary levels but not serum levels of MCP-1 were significantly elevated in diabetic patients with proteinuria. These studies suggest that locally produced MCP-1 may be involved in the development of advanced diabetic nephropathy, especially in the formation of tubulointerstitial lesions possibly through monocytes/macrophages recruitment and activation and suggests that facilitated MCP-1 production by mesangial cells in diabetic milieu contributes to the initiation and progression of diabetic nephropathy. Moreover, up-regulation of MCP-1 may be a common pathway involved in the progressive tubulointerstitial damage in diabetic nephropathy.
As the role of MCP-1 in relation to the development of diabetic nephropathy is not clearly defined, data from previous studies have raised the question as to whether MCP-1 is a cause or consequence of the vascular damage associated with microalbuminuria. In our study, the significant higher MCP1 levels in diabetic patients compared to control and also the significant higher MCP1 levels in macroalbuminuric patients compared to normoalbuminuric patients raises the possibility that MCP-1 is a cause rather than consequence of vascular damage.
In the whole diabetic patients group, there were significant positive correlations for serum MCP-1 with age, HbA1c, spot U Alb/Cr but not with hs-CRP, BMI or diabetic duration.
Also, there was significant positive correlation for MCP-1 with age in microalbuminuric group and significant positive correlation for MCP-1with HbA1c in macroalbuminuric group.
Many studies and ours noticed the positive correlation for serum MCP-1 levels with both blood glucose control as assessed by HbA1c and stage of diabetic nephropathy.These data supports the hypothesis that upregulation of MCP-1 gene expression by persistent hyperglycemia in diabetic patients’ results in the recruitment of monocytes into the kidney possibly contributing to the development of diabetic nephropathy.
Some studies disagreed with us and noticed that systemic MCP-1 levels are not significantly regulated by hyperglycaemia and not significantly related to diabetic nephropathy and hypothesized again that the possible local MCP-1 produced by mesangial cells in the diabetic milieu may have a role on the infiltration and activation of monocytes/macrophages into glomerulus, and may contribute to the initiation and progression of diabetic nephropathy and may not be reflected by increased systemic levels of MCP-1. These and previously published data highlight the need for large prospective studies in different populations to explore the contribution of elevated MCP-1 concentrations to the development of diabetes.
Regarding hs-CRP in our study, it was significantly higher in each of the three patients groups compared to control group, but there was no significant difference when comparing hs-CRP among the three patients groups.
We found that our results disagreed with some authors’ results but agreed with other study which noticed that hs-CRP levels were not different between microalbuminuric and normoalbuminuric subjects. However, differences were detected when hs-CRP levels were analyzed in relation to time of microalbuminuria onset. The results of this study support that inflammation is related to microalbuminuria onset rather than a predicting risk for its development and this may explain the absence of significant difference of hs-CRP among the patients groups in our study.
In the whole diabetic patients group, there was no significant correlation for hs-CRP with any parameter. But, there was significant positive correlation for hs-CRP with serum U Alb/Cr in macroalbuminuric group only.
Many studies reveal that blood sugar control is an important factor associated with elevated urinary albumin level. But, in our study, blood glucose control as assessed by HbA1c was not significantly correlated with spot U Alb/Cr regarding the whole diabetic patients group. Strangely, there were significant negative correlations for spot U Alb/Cr with HbA1c in both normo and microalbuminuric groups.
Although it is known that poor glycemic control is correlated with the development of early diabetic nephropathy, but the difference of the correlation between HbA1c and AER in many studies may be explained by another study noticed that discordances between HbA1c and other measures of glycemic control are common in clinical practice and remain unexplained. The study developed a measure of discordance between HbA1c and fructosamine (FA) termed the glycosylation gap (GG). The study noticed that GG correlated better with nephropathy than did either HbA1c or FA alone in this population and proposed that the glycosylation gap will be useful as a research probe quantitating variation between the two underlying tests of glycemic control to identify sources of population variation in diabetic complications beyond glycemic control per se.
In our study, we found no association between BMI and microalbuminuria. This might be due to the relatively narrow range of BMI in the study subjects most of who were overweight. However, the correlation between microalbuminuria and BMI is still a myth that needs further complete assessment.
Regarding diabetic duration in our study, it was not correlated with any parameter. Although this disagreed with several studies that noticed correlation of diabetic duration with albuminuria, but agreed with others. The discrepancy probably indicates longer duration of prior undiagnosed diabetes and that the known duration is underestimated and not likely to accurately date the onset of type 2 diabetes and this may explain our results regarding duration of diabetes. This raises the fact that screening for asymptomatic diabetes and defining newer risk factors to identify those at risk for complications are essential to reduce the socioeconomic burden of diabetes.