Mohamed M. El-Khatib

Correlations of Urinary Biomarkers, TNF-Like Weak Inducer of Apoptosis (TWEAK), Osteoprotegerin (OPG), Monocyte Chemoattractant Protein-1 (MCP-1), and IL-8 with Lupus Nephritis

ObjectiveThis case-controlled study was designed to correlate urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) levels, with renal involvement in a cohort of systemic lupus erythematosus (SLE) patients to examine their diagnostic performance.Patients and MethodsIn 73 SLE patients, and in 23 healthy volunteers, urinary levels of TWEAK, OPG, MCP-1, and IL-8 levels were measured. Disease activity was assessed by total SLE disease activity index, and renal activity by renal activity index (rSLEDAI), and both were correlated with urinary biomarkers. Sensitivity, specificity, and predictive values of individual biomarkers to predict lupus nephritis were also calculated.ResultsSignificantly higher levels of urinary biomarkers were observed in SLE patients with lupus nephritis (LN) compared with those without LN (TWEAK, p < 0.001; MCP-1, p < 0.001; OPG, p < 0.001; IL-8, p < 0.032). Other significantly higher levels were observed in SLE patients with LN compared with control subjects (TWEAK, MCP-1, OPG, and IL-8 p < 0.001). Positive correlations were observed between rSLEDAI and TWEAK (r = 0.612 and p < 0.001), MCP-1 (r = 0.635 and p < 0.001), and OPG (r = 0.505 and p < 0.001).ConclusionsUrinary levels of TWEAK, OPG, and MCP-1 positively correlate with renal involvement as assessed by rSLEDAI with reasonable sensitivity, specificity, and predictive values to detect lupus nephritis while IL-8 was not significantly associated with global or rSLEDAI.

Early Diagnostic Markers for Contrast Nephropathy in Patients Undergoing Coronary Angiography

The present work aimed to prove the usage of neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for kidney injury and to assess the relationship between NGAL and serum creatinine and cystatin C in patients with normal serum creatinine undergoing percutaneous coronary angiography. Thirty patients with normal serum creatinine undergoing coronary angiography were enrolled. Estimation of blood glucose, glycosylated hemoglobin, lipid profile, creatinine, NGAL, and cystatin C were done before coronary angiography for all patients. Serum creatinine, NGAL and cystatin C were evaluated again at 4 and 24 hours after coronary angiography. There was a significant increase in serum NGAL level 4 hours and 24 hours after coronary interventions compared to the baseline value before coronary angiography. Before coronary angiography, serum NGAL was positively correlated with serum creatinine, and cystatin C. Conclusion: Serum NGAL and cystatin C could be valuable in the detection of early renal impairment after coronary angiography.

Relationship of BsmI polymorphism of vitamin D receptor gene with left ventricular hypertrophy and atherosclerosis in hemodialysis patients

Abstract Background. Left ventricular hypertrophy (LVH) is a common manifestation of cardiovascular disease and has an important prognostic value in patients with end-stage renal disease (ESRD). Vitamin D receptor (VDR) has been intensively investigated, and one of these (BsmI) already has been associated with survival in the dialysis population. Objective. The aim of this study was to investigate the role of VDR polymorphism (BsmI) on the development of ventricular hypertrophy and atherosclerosis in hemodialysis patients. Subject and methods. The subjects were 80 patients with end-stage renal disease on maintenance hemodialysis, and 40 healthy controls. Clinical and laboratory parameters, including genetic variation in VDR gene (BsmI), were assessed. In addition, echocardiography and intima-media thickness were performed for all subjects. Results. There was no significant difference in the distribution of BsmI genotypes either in patients or in the control group. The frequency of the B allele of BsmI polymorphism (41.6%) in dialysis patients was similar to that of healthy control subjects (39.2%). Patients with BB genotype had significantly lower serum concentrations of 25-hydroxy vitamin D compared to both Bb and bb genotypes. The number of B alleles was positively correlated with left ventricular mass index (LVMI), but not with intima-media thickness. Conclusion. These results suggest that the B alleles of the BsmI polymorphism could be considered as novel markers of altered vitamin D signaling in ESRD patients, and this alteration in BB genotype produces an increase in left ventricle mass.

Apelin: a potential link between inflammation and cardiovascular disease in end stage renal disease patients.

Abstract Background and objectives. Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients. Increasing evidence suggests a role for apelin in the pathology of the cardiovascular system. In the present study, the plasma level of apelin was studied in patients with hemodialysis to assess the effect of renal transplantation and dialysis session on plasma apelin and whether circulating apelin levels reflect cardiovascular homeostasis and inflammation in these patients. Patients and methods. Plasma apelin, high sensitive CRP (hsCRP) and IL-6 levels were investigated in 30 end stage renal disease (ESRD) patients on maintenance hemodialysis (HD), a group of 15 HD patients scheduled for renal transplantation and a group of 15 HD patients on maintenance HD, as well as ten healthy volunteer subjects who served as controls. An echocardiography was performed for all subjects. Results. Plasma apelin levels were significantly lower in hemodialyzed patients compared to controls. Plasma apelin was also found to be positively correlated with left ventricular end systolic dimension (LVESD), left ventricular end diastolic dimension (LVEDD), interventricular septum (IVS), right ventricle (RV), left atrium (LA), Aorta (Ao), while, it was negatively correlated with hsCRP and IL-6 in ESRD patients. Regarding the effect of hemodialysis on plasma apelin levels, no significant effect was found after a single hemodialysis session, while levels increased significantly in the early post-transplant period. Conclusions. Apelin is related to echocardiographic features and inflammatory markers in hemodialyzed patients. Apelin may provide a mechanism for systemic inflammatory monitoring and adaptive regulation of cardiovascular function.

Association of fetuin-A and cardiac calcification and inflammation levels in hemodialysis patients

Abstract Background. Vascular calcification is commonly found in chronic kidney disease (CKD) patients and it is one of the predictors of cardiovascular death. Recently, several studies have demonstrated that low fetuin-A levels are associated with mortality in uremic patients. Objectives. To investigate the importance of non-traditional risk factors of calcification including fetuin-A, IL-6 and high sensitivity CRP (hsCRP) in hemodialysis patients and their relationship to the extent of cardiac calcification by means of multislice computed tomography (MSCT), and echocardiography. Patients and methods. The study was conducted on 70 hemodialysis patients as well as 20 healthy control subjects. All patients were subjected to MSCT for evaluation of calcium score in the coronary arteries as well as echocardiography for detecting valvular calcification. In addition, the patients were sampled for evaluation of inflammatory markers such as hsCRP and IL-6 and also fetuin-A. Results. Mean serum fetuin-A was significantly lower in hemodialysis patients than controls subjects. By dividing the patients into tertiles of serum fetuin-A, a significant association between low levels of fetuin-A and high calcium score and valvular calcification were found. Multiple regression analysis showed that calcium scoring and IL-6 were the most independent risk factors for serum fetuin-A levels. Conclusion. Serum fetuin-A showed important association with coronary, valvular calcification and inflammation in hemodialysis patients. Assessment of both cardiac calcification and serum levels of fetuin-A may be of value to identify those subjects at higher risk of development and progression of vascular lesion and may be a novel therapeutic approach.

Relationship of increased circulating adrenomedullin with cardiac dysfunction, inflammation, oxidative stress and volume overload in hemodialysis patients

Abstract Adrenomedullin (AM) is a peptide involved in cardiovascular homeostasis. The aim of our study was to investigate whether circulating AM might be related to cardiac function, volume overload, oxidative stress and inflammation in hemodialysis patients. Plasma adrenomedullin, C-reactive protein (CRP), oxidized LDL (ox-LDL), lipoprotein (a), systolic and diastolic cardiac functions were assessed before hemodialysis in 80 patients as well as in 40 healthy control subjects. Plasma adrenomedullin levels were significantly higher in the hemodialysis group compared to the control group. Plasma adrenomedullin levels were negatively correlated with systolic and diastolic blood pressure, S/D ratio, deceleration time, left ventricular ejection fraction, ox-LDL and lipoprotein (a). However, it was positively correlated with CRP, delta body weight, mitral E/A wave, and inferior vena cava diameter. Higher plasma adrenomedullin levels may provide a possible index of cardiac dysfunction, systemic inflammation, and volume overload conditions in haemodialysis patients with concomitant cardiovascular disease. In addition, the negative correlation between ox-LDL, lipoprotein (a) and adrenomedullin may suggest that endogenous AM is an important protective factor in anti-atherosclerosis and might be useful as a new target for prevention and therapy for the disease.

Fibroblast growth factor 23 levels before and after renal transplantation

Background Fibroblast growth factor 23 (FGF23), a novel bone-derived hormone that inhibits phosphate reabsorption and calcitriol production by the kidney, has uncovered primary regulatory pathways and new systems biology governing bone mineralization, vitamin D metabolism, parathyroid gland function, and renal phosphate handling. Aim of the work The aim of the present prospective study was to investigate FGF23 levels in patients with end-stage renal disease before and after a successful renal transplant and their probable association with the markers of bone and mineral metabolism. Patients and methods A total of 40 patients were studied for 6 months and divided into two groups (hemodialysis vs. renal transplant patients). Serum FGF23, calcium, phosphorus, and intact parathyroid hormone (iPTH) were estimated for both groups. We compared the changes in serum FGF23, calcium, phosphorus, and iPTH in renal transplant patients 3 and 6 months after successful renal transplantation. Results The serum FGF23 decreased significantly after renal transplantation. iPTH and P levels also decreased significantly after renal transplant, whereas Ca level increased. Conclusion FGF23 levels were markedly increased in patients with end-stage renal disease associated with an increase in phosphorous and iPTH levels. FGF23 levels decrease dramatically after successful renal transplantation and remain within the normal limits when graft function is good. iPTH and P levels also decrease significantly after renal transplantation, whereas Ca increases.

Evaluation of serum hepcidin in assessment of iron status in renal transplant patients

Background: Hepcidin is a 25 aminoacid peptide that is produced primarily by the liver in response to a variety of stimuli known to modulate tissue iron stores and its serum availability. It circulates in plasma, is filtered by the kidney, and accumulates in urine. The presence of hepcidin in the plasma negatively regulates the egress of iron from the cells and macrophages, involved in transport of iron into the extracellular spaces. Hepcidin binds to ferroportin 1 present on the cell surface leading to the internalization of ferroportin 1 and subsequent degradation. Hepcidin has also been shown to be an acute phase reactant increased by interleukin6 (IL-6) and markedly induced by infection and inflammation. Documentation of the role of hepcidin in the development of anemia in chronic kidney disease and whether it can be used as a marker of iron status in chronic kidney disease (CKD) has been sought in many studies. The aim of this study was to detect the value of hepcidin as a marker of iron status in post renal transplant recipients as compared with chronic renal failure (CRF) patients on hemodialysis. Results: In our study we found the level of serum prohepcidin in the renal transplant recipient group to be comparable to the control group. In the group with CKD the serum prohepcidin was significantly lower than controls as well as the transplant recipients (p-value: 0.00). There was no significant difference between the CKD group with higher hemoglobin and those with lower hemoglobin. From the correlation between the acute phase proteins and prohepcidin we found a positive correlation between serum ferritin, CRP and prohepcidin only in the group with CKD on hemodialysis. -----------------Correspondence and offprint requests to: Dr. Mohamed El-Khatib, Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt. Conclusion: We suggest that serum prohepcidin can be used as a routine measurement in transplant recipients as an indicator of the iron stores in the body. Further dedicated studies on large groups of patients need to be done to verify the usefulness of such a test.