الفهرس 
CLAUDINS AND CLAUDIN-1Only 14 pages are availabe for public view
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Abstract
he biology of claudins is a rapidly evolving field, and many intriguing questions remain unanswered. Although it had been assumed that the reason there are ≥24 isoforms of claudin is that each one has distinct permeability properties. There is increasing evidence that many claudins are not only at the tight junction but found along the entire basolateral membrane.
Recent studies have clearly shown that the slit diaphragm is the structure likely to be the barrier of the glomerular capillary wall. Several molecules constituting the slit diaphragm were identified. Among them, nephrin, podocin, CD2AP, FAT and NEPH1 are accepted to be essential in maintaining the barrier function of the slit diaphragm.
The slit diaphragm is a highly developed cell–cell junction. It is now widely accepted that these cell–cell junctions play a critical role in maintaining the balance of water and ions. from this viewpoint, the nephrotic syndrome could be considered as a disease of the cell–cell junction. Upregulation of claudin-1 in the podocyte is able to induce proteinuria. However, it needs to be recognized that diabetic nephropathy is a multifaceted disease affecting the expression and function of many more SD and TJ genes in the podocyte.
In diabetic nephropathy and glomerulonephritis the gene expression of claudin-1, is markedly upregulated in the podocyte, accompanied by a tighter filtration slit diaphragm (cell-cell junction made by the glomerular podocytes) and the appearance of TJ-like structures between the foot processes causing further podocytes injury and proteinuria.
Aim of this study was to assess the level urinary claudin -1 as a marker of podocyte injury in patients with proteinuria.
Our study was conducted on 60 randomly selected patients from Ain Shams University Hospitals and 30 healthy controls similar in age and sex with cases.
We excluded patients with AKI, obstructive uropathy, Patients with estimated glomerular filtration rate (eGFR) less than 15 mL/min/1.73 m2.
All patients and control were subjected to Full history taking including age, gender, using of antiprotienuric agents as ACEI or ARBs, using of immune-suppressive drugs and using of insulin or oral hypoglycemic for diabetic patients, complete physical examination including blood pressure measurement. CBC, KFTs, LFTs, s.albumin, viral markers (HBV,HCV,HIV), GFR calculation according to MDRD equation, alb/creat ratio (uACR).
The study included 38 (42.2%) males and 52 (57.7%) females. The mean of age was 44.97± 6.66 years in diabetic group, 42.23± 9.19 years in GN group and 40.35±5.59 years in control group.
we found that urinary claudin-1 level was significantly higher in diabetic patients than in control group and also found that urinary claudin-1 level was significantly higher in GN patients than in control group.
In comparison between GN group and diabetics group, we found that urinary claudin-1 was higher in GN group than diabetic group but with no statistically significant difference between the two groups.
We found that uACR was significantly higher in GN group than in Diabetics group with highly statistically significant difference between the two groups.
In Diabetics group, we found that there is positive correlation between urinary claudin-1 and uACR. As regard diabetic patients on anti proteinuric measures we found that there is negative correlation between urinary claudin-1 and antiproteinuric measures.
In GN group, we found that there is positive correlation between urinary claudin-1 and uACR. We also found positive correlation between urinary claudin-1 with age and s. creatinine, but it has negative correlation with s. albumin and GFR. We also found positive correlation between uACR with age, BUN and s. creatinine while uACR has negative correlation with s. albumin, HGB and eGFR.
We also found that there is negative correlation between anti-proteinuric measures and uACR and anti-proteinuric measures are statistically significant in reducing albuminuria.
As regard etiology of GN. We found that patients with membranous GN have higher level of uACR than in patients with FSGS which have higher uACR than patients with lupus nephritis and there is highly statistically significant positive correlation between GN and uACR
As regard classes of lupus nephritis we found that patients with LN class IV have higher level of uACR and urinary claudin-1 than in LN class III which have higher level of uACR and urinary claudin-1 than LN class II.
By Logistic regression analysis in Diabetics group, we found that uACR, urinary claudin-1, BUN and s. creatinine are important predictors of DM
By logistic regression analysis in GN group, we found that urinary claudin-1, BUN and s. creatinine are important predictors of GN.
By the multivariate linear regression analysis in GN group we found that age and s.albumin are independent predictors of uACR while s.albumin is the only independent predictor of urinary claudin-1
By univariate linear regression analysis in diabetics group we found that uACR is the only independent predictor of urinary claudin-1.
By the univariate linear regression analysis in GN group we found that age, BUN, s. creat, s. albumin, GFR and claudin-1 are independent predictors of uACR while s. creat, s. albumin, eGFR and uACR are independent predictors of urinary Claudine-1.
According to the ROC curve in diabetics group, the best cut off value for uACR to detect diabetic patients was found > 110 with sensitivity of 100%, specificity of 100% and accuracy of 100% while the best cut off for urinary claudin-1 to detect diabetic patients was found > 6 with sensitivity of 93.33%, specificity of 80% and accuracy of 91.9%.
According to the ROC curve in GN group, the best cut off value for uACR to detect GN patients was found > 110 with sensitivity of 100%, specificity of 100% and accuracy of 100% while the best cut off for urinary claudin-1 to detect patients with GN was found > 8 with sensitivity of 96.67%, specificity of 86.67% and accuracy of 95.9%.