Evaluating the association of interleukin-10 gene promoter -592 A/C polymorphism with lupus nephritis susceptibility

BACKGROUND: Interleukin-10 (IL-10) is an important immunoregulatory cytokine. There are few studies evaluating the association between IL-10 and lupus nephritis (LN). The aim of this study was to evaluate the association of IL-10 gene promoter -592 A/C with LN susceptibility. METHODS: The study was conducted on 84 patients with systemic lupus erythematosus (SLE). Patients were divided into LN group (Group I, 48 patients) and non-LN group (Group II, 36 patients). The -592 A/C polymorphisms in IL-10 promoter gene were determined by polymerase chain reaction and restriction fragment length polymorphism in both groups. IL-10 was determined by enzyme-linked immunosorbent assay. Frequencies of the genotypes were compared between LN and non-LN patients and among LN patients with different pathologic classes. RESULTS: There was a significant increase in serum level of IL-10 (P = 0.001) in Group I compared with Group II and significant positive correlation between serum IL-10 and SLE disease activity index (r = 0.466, P = 0.001) in Group I. There were no significant differences in the distribution of the IL-10 gene promoter -592 A/C genotypes or the allele frequencies between Groups I and II. There was no significant difference between AC/CC and AA genotypes with SLE disease activity index, proteinuria, hematuria, anti-double-stranded DNA, and IL-10 in Group I. There was no significant difference in the distribution of AC and CC genotypes among different pathologic LN classes. CONCLUSION: IL-10 suggested to play a role in pathogenesis and development of LN. However, the promoter -592 A/C of IL-10 gene suggested to be not associated with serum IL-10 levels or LN susceptibility. In addition, it appears that promoter -592 A/C of IL-10 gene not associated with LN activity or the pathologic classes of LN.

Experimental rat model of diabetic nephropathy: RAGE detection and effect of spironolactone monotherapy

The glycation process results in formation of advanced glycation end products [AGEs], which accumulate in different organs at an accelerated rate in diabetes, resulting in alteration of both structure and function. This effect is via the receptor for AGES [RAGE], which is a signaling receptor leading to profibrotic reactions. The renin angiotensin aldosterone system [RAAS] is activated in diabetic nephropathy [DN] and leads to more renal damage. This is inhibited by angiotensin converting enzyme inhibitors [ACEIs] and angiotensin receptor blockers [ARBs] and mineralocorticoid receptor blockers [MRBs]. To show the monotherapeutic effect of spironolactone in diabetic nephropathy and to detect RAGE. Diabetes was induced in rats by streptozotocin. Three weeks after,spironolactone [SPL] was given for 4 weeks. Then, control, diabetic and treated rats were sacrificed. The results of blood chemistry at the end of 4 weeks showed statistical increase in serum sodium, potassium and urea with no effect on serum creatinine or blood glucose. Kidney pathological injuries were attenuated by SPL also, RAGE deposition compared to the diabetics. The study showed RAGE deposition in the experimental DN and confirmed the beneficial effects of MRB in DN

Carotid intima media thickness, left ventricular hypertrophy and weekly averaged blood pressure in hemodialysis patients

Undoubtedly, cardiovascular complications are the leading cause of mortality and morbidity in haemodialysis [HD] patients, and hypertension plays an important role in development of cardiovascular disorders in them. The present study evaluated the weekly averaged blood pressure with its relation to carotid intima media thickness and left ventricular mass index in HD patients. The study included 112 HD patients [85 males and 27 females]. We used daily home blood pressure [HBP] monitoring to record a total of 20 points of BP over a period of 1 week, including measurements of the wake-up and night BPs; in addition to the BP recorded before and after each HD session that occurred three times a week. The average of 20 BP measurements was defined as the weekly averaged blood pressure [WAB]. Also, the relationship between WAB and left ventricular hypertrophy [LVH] or carotid intima media thickness and carotid intima media thickness and left ventricular hypertrophy were evaluated. The results showed that systolic WAB [144.26 +/- 7.39 mmHg] and diastolic WAB [75.84 +/- 5.15 mmHg] were almost consistent with the wake-up BP on the day after the midweek dialysis session [R2=0.628 and 0.684, respectively]. The WAB showed significant positive correlations with the left ventricular mass index [LVMI] [R=0.387, P<0.0003] and carotid intima media thickness [R=0.226, P<0.0034], whereas the predialysis systolic BP showed a significant positive correlation with the CIMT and non-significant correlation with LVMI. There was a significant positive correlation between CIMT and LVMI

Diagnostic relevance of pyuria in haemodialysis patients [renal tuberculosis as an A etiology of sterile pyuria]

This study was designed to assess the significance of pyuria as a marker of urinary tract infections [UTIs] in haemodialysis patients and renal tuberculosis as a common a etiology of sterile pyuria. The study was conducted on 50 patients with end stage renal disease [ESRD] on regular haemodialysis [group I], as well as 10 healthy controls [group II]. Fresh urine samples were cultured, examined microscopically for pyuria and tested by Bayer reagent strips for protein, blood, nitrite and leucocyte esterase [LE]. Gram stain of colonies and their identification to the species level using API 20 E system were performed. Ziehl-Neelson [ZN] staining for acid alcohol fast bacilli and Polymerase chain reaction [PCR] for detection of Mycobacterium tuberculosis [MTB] DNA were performed on 24 hours collected urine samples. All patients had pyuria [>/= 5 WBCs/hpf]. Protein, blood, LE and nitrite were significantly higher in patients than in controls [P value <0.01, <0.01, <0.001 and <0.05 respectively]. A significant correlation was found between patients' symptoms and bacterial growth [p<0.1]. Thirty one patients had sterile pyuria; three out of them [10%] were proved to be tuberculous by ZN or PCR. To conclude, pyuria is a common finding in haemodialysis patients and is proved to be a valuable parameter of UTIs in these patients. In symptomatic patients with sterile pyuria, renal tuberculosis should be excluded by ZN staining and/or PCR. In asymptomatic patients, periodic urine culture should be performed to confirm presence or absence of UTIs

Independent, non-traditional risk factors for cardiovascular events and atherothrombosis in chronic kidney disease and in hemodialysis-dependent patients

This study aimed at evaluating the role of the emerging non-traditional risk factors, their impact on Cardiovascular Disease [CVD] prediction-together with traditional RFs-in Chronic Kidney Disease [CKD] and end-stage renal disease [ESRD] patients. Total homocysteine [tHcy], plasma fibrinogen [Fbg], plasma factor VII activity [FVIIc], anaemia [HCT] and C-reactive protein [CRP], were studied in 37 Egyptian patients classified into chronic kidney disease group [10 cases] and hemodialysis [HD] group [27 cases] in addition to 10 healthy age and sex-matched controls. This study showed that tHcy, fbg CRP and FVIIc demonstrated highly significant increase in the total patient group and in the HD group compared to the normal controls. These values showed a progressive increase with the disease approaching hemodialysis dependence. Among the 37 patients, 21 showed evidence of ischemic heart disease [IHD]. A statistically significant elevation of the previous factors was found in IHD when compared to non-ischemic group of patients. Multivariante analysis showed CRP as the most predictive risk factor for CVE in CKD and ESRD patients. Therefore, it was concluded that the emerging non-traditional factors studied could explain to a great extent-together with traditional RFs- the high rate of CVD in these patients and that CRP is the most fulfilling for being recommended in clinical practice. Alterations of these factors will aid prevention of coronary heart disease [CHD], thus benefiting the patient from risk factor modification

Impact of renal functional impairment on serum tumor markers levels

The objective of this work was to study the impact of renal functional impairment on the circulating levels of alpha-fetoprotein [AFP], carcinoembryonic antigen [CEA], and cancer antigen 19-9 [CA-19-9]. Fifty-one subjects were enrolled in this study. They were divided into three groups. The first group consisted of 13 apparently healthy volunteers [five males and eight females] as a control group. The second group included 17 patients with end stage renal failure [ESRF] [eight males and nine females]. The third group comprised 21 patients [12 males and nine females] with ESRF maintained on hemodialysis [HD]. Tumor marker determinations were performed using enzyme-linked immunosorbent assay. Data management and analysis were performed using Statistical Analysis Systems. Data were summarized using means and standard deviations. Comparisons between groups were done using Kruskall-Wallis, nonparametric analysis of variance. To measure the strength of the association between two numeric variables, Pearson's correlation coefficient was computed. All p-values are two-sided. P-values <0.05 were considered significant. The results suggested that renal functional impairment should be added to the list of benign conditions associated with high serum CEA and CA-l9-9 levels. Before interpreting a tumor marker result in a patient with compromised renal function, it was showed that renal impairment might induce a misleading tumor marker elevation. The lack of significant correlation between elevated serum tumor marker values and serum creatinine and/or urea, and the observed normal serum AFP values raises many questions about the exact mechanisms responsible for increased some tumor markers levels in uremia. The recorded conflicting results of serum tumor markers in uremia indicated that the study of tumor marker kinetics in uremic patients deserves a more considerable attention

Up regulation of angiogenic growth factors is associated with renal dysfunction in type 2 diabetes mellitus

TYPE 2 diabetes mellitus has reached epidemic proportions, and one of its ominous complications, diabetic nephropathy [DN], represents today the leading cause of end-stage renal failure [ESRF]. A large amount of evidence supports the hypothesis that a panel of growth factors, are involved in the development of diabetic nephropathy through a complex intra renal system. This study was applied to study the changes in the blood levels of transforming growth factor-beta [TGF-beta], vascular endothelial growth factor [VEGF], and basic fibroblast growth factor [bFGF] in diabetic patients with and without nephropathy, and to investigate whether they were associated with renal impairment. Such information is crucial to determining the optimal approach to the treatment and prevention of the disease

Methods: 51 subjects were enrolled in the study, and were divided into three groups; the first group consisted of 12 healthy subjects; the second of 17 patients with type 2 diabetes without nephropathy [normoalbuminuric]; and the third group of 22 patients with type 2 diabetic nephropathy [macroalbuminuric]. Growth factors determination was performed using enzyme-linked immunosorbent assay [ELISA]

Results: Serum TGF-beta and bFGF values showed significant elevation in both diabetic groups as compared to healthy subjects [P<0.001], with insignificant difference between both diseased groups. Serum VEGF levels, on the other hand, were significantly elevated in patients with DN as compared to both healthy subjects and diabetics without renal impairment [P<0.001]. Serum VEGF showed significant direct correlation with serum creatinine [r= 0.490, P= 0.006], serum urea [r= 0.537, P= 0.0004], and serum bFGF [r=0.372, P=0.02]. Significant direct correlation was also recorded between serum TGF-beta and both serum creatinine [r=0.401, P=0.011], and serum VEGF [r=0.341, P=0.034]

Conclusions: Our results support the hypothesis that a network of growth factors may participate in the development of renal functional impairment in patients with type 2 diabetes. Further insight into the complex processes that regulate this network may be useful in the future development of new antagonists useful in the treatment of diabetic Kidney disease