Is serum Osteopontin a predictor of carotid atherosclerosis severity among prevalent hemodialysis patients? / ¿Es la osteopontina sérica un factor predictivo de la gravedad de la aterosclerosis carotídea en los pacientes prevalentes en hemodiálisis?

BACKGROUND AND AIM: Chronic hemodialysis (HD) patients are among the highest population risk for accelerated atherosclerosis. Osteopontin (OPN) is a multifunctional protein that is increased in chronic kidney disease that may play a role in vascular remodelling and intimal proliferation. AIM: To assess the relation between OPN levels and severity of carotid atherosclerosis among prevalent HD patients. METHODS: Eighty chronic HD patients underwent serum OPN levels assessment and were further classified into 3 subgroups according to the OPN tertiles’ levels; sub-group 1 (lower tertile) subgroup 2 (middle tertile) and sub-group 3 (upper tertile), together with the carotid duplex and Transthoracic Doppler Echocardiography examination. RESULTS: The mean carotid intima-media thickness (CIMT) was 0.89±0.14mm. Out of the studied group, 50 (62.5%) patients had atheromatous plaques and 15 patients (18.8%). had significant stenosis. The 3rd group with the upper OPN tertile (78–270ng/dl) had the highest incidence of atherosclerosis. A significant correlation between the OPN levels and the CIMT (r=0.533, p=0.001). OPN values detect atherosclerosis with diagnostic sensitivity of 70%, specificity of 69%, positive predictive value (PPV) 73%, negative predictive value (NPV) 65% with area under the curve (AUC) 0.804 (95% CI: 0.711–0.897). Serum OPN detect carotid stenosis with sensitivity of 66%, specificity of 81%, PPV 45%, NPV 91% with AUC=0.769 and detect the presence of carotid atheroma with sensitivity 70%, specificity 66.67%, PPV 77.8%, NPV 57.1% and AUC=0.767 (p-value<0.001). Moreover, serum levels of OPN were significantly positively correlated with grade of diastolic dysfunction (r=0.312, p=0.005), E/A ratio (r=0.293, p=0.008) and inversely correlated with left ventricular ejection fraction (r=−0.304, p=0.006).

ANTECEDENTES Y OBJETIVO: Los pacientes de hemodiálisis crónica (HD) son una de las poblaciones de mayor riesgo de aterosclerosis acelerada. La osteopontina (OPN) es una proteína multifuncional que se incrementa en la enfermedad renal crónica, y que puede jugar un papel en la remodelación vascular y la proliferación de la íntima. OBJETIVO: Evaluar la relación entre los niveles de OPN y la gravedad de la aterosclerosis carotídea en los pacientes prevalentes en HD. MÉTODOS: Se evaluó el nivel sérico de OPN en 80 pacientes de HD crónica. Seguidamente, se clasificó a dichos pacientes en tres subgrupos con arreglo a los niveles de los terciles de OPN: subgrupo 1 (tercil inferior) subgrupo 2 (tercil medio) y subgrupo 3 (tercil superior), junto con dúplex carotídeo y ecocardiografía Doppler transtorácica. RESULTADOS: El espesor medio de la íntima-media carotídea (CIMT) fue de 0,89 ± 0,14 mm. En el grupo estudiado, 50 (62,5%) pacientes tenían placas ateromatosas y 15 pacientes (18,8%) tenían estenosis significativa. El tercer grupo, con tercil OPN (78-270 ng/dL) reflejó la mayor incidencia de aterosclerosis. Existió una correlación significativa entre los niveles de OPN y CIMT (r = 0,533, p = 0,001). Los valores de OPN detectaron aterosclerosis con una sensibilidad diagnóstica del 70%, especificidad del 69%, valor predictivo positivo (VPP) del 73%, valor predictivo negativo (VPN) del 65% y área bajo la curva (AUC) de 0,804 (intervalo de confianza [IC] 95%: 0,711-0,897). La OPN detectó estenosis carotídea con una sensibilidad del 66%, especificidad del 81%, VPP del 45%, VPN del 91%, y AUC = 0,769 y detectó la presencia de ateroma carotídeo con una sensibilidad del 70%, especificidad del 66,67%, VPP del 77,8%, VPN del 57,1% y AUC = 0,767 (valor p < 0,001). [...]

Is serum Osteopontin a predictor of carotid atherosclerosis severity among prevalent hemodialysis patients?

BACKGROUND AND AIM: Chronic hemodialysis (HD) patients are among the highest population risk for accelerated atherosclerosis. Osteopontin (OPN) is a multifunctional protein that is increased in chronic kidney disease that may play a role in vascular remodelling and intimal proliferation. AIM: To assess the relation between OPN levels and severity of carotid atherosclerosis among prevalent HD patients. METHODS: Eighty chronic HD patients underwent serum OPN levels assessment and were further classified into 3 subgroups according to the OPN tertiles' levels; sub-group 1 (lower tertile) subgroup 2 (middle tertile) and sub-group 3 (upper tertile), together with the carotid duplex and Transthoracic Doppler Echocardiography examination. RESULTS: The mean carotid intima-media thickness (CIMT) was 0.89±0.14mm. Out of the studied group, 50 (62.5%) patients had atheromatous plaques and 15 patients (18.8%). had significant stenosis. The 3rd group with the upper OPN tertile (78-270ng/dl) had the highest incidence of atherosclerosis. A significant correlation between the OPN levels and the CIMT (r=0.533, p=0.001). OPN values detect atherosclerosis with diagnostic sensitivity of 70%, specificity of 69%, positive predictive value (PPV) 73%, negative predictive value (NPV) 65% with area under the curve (AUC) 0.804 (95% CI: 0.711-0.897). Serum OPN detect carotid stenosis with sensitivity of 66%, specificity of 81%, PPV 45%, NPV 91% with AUC=0.769 and detect the presence of carotid atheroma with sensitivity 70%, specificity 66.67%, PPV 77.8%, NPV 57.1% and AUC=0.767 (p-value<0.001). Moreover, serum levels of OPN were significantly positively correlated with grade of diastolic dysfunction (r=0.312, p=0.005), E/A ratio (r=0.293, p=0.008) and inversely correlated with left ventricular ejection fraction (r=-0.304, p=0.006). CONCLUSIONS: Serum Osteopontin is of clinical value as a predictor biomarker of the severity of carotid atherosclerosis, presence of atheroma and carotid stenosis with high diagnostic sensitivity and specificity in chronic hemodialysis patients. Increased Osteopontin level is associated with left ventricular diastolic and systolic dysfunction in those patients.

Prevalence of non-alcoholic fatty liver disease among patients with non-diabetic chronic kidney disease detected by transient elastography.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) shares a close relationship with cardiovascular morbidity and mortality. The purpose of this study is to evaluate the frequency of NAFLD in the patients with non-diabetic chronic kidney disease (CKD). METHODS: This cross-sectional study included 80 patients with non-diabetic CKD, of which, 50 patients were on hemodialysis (HD) and 30 patients had CKD stage G3-5 not on dialysis. These patients were randomly selected from Ain Shams University Hospitals, Cairo, Egypt. Patients with diabetes mellitus, obesity, alcohol intake, viral hepatitis, or drug-induced liver steatosis were excluded from this study. Importantly, the controlled attenuation parameter (CAP) (dB/m) of liver steatosis (S0-S3) and liver stiffness/fibrosis measurement (F0-F4) were measured using transient elastography (Fibroscan®). Other evaluations included complete blood count, routine blood chemistry, and C-reactive protein (CRP) titer. RESULTS: In total, 45 (56.25%) (30 males, 15 females) out of total 80 studied patients were reported to have NAFLD. There were 29 patients with end-stage renal disease who were on regular HD and 16 patients with pre-dialysis CKD G3-5. The mean CAP values of hepatic steatosis in the patients with CKD on dialysis and patients with pre-dialysis CKD were 265.41 ± 52.73 and 259 ± 44.8 dB/m, respectively. A significant association between the severity of hepatic steatosis degree with decreased glomerular filtration rate and increased CKD stage was observed in this study. The degree of liver stiffness was significantly related to an increased hepatic steatosis grade. A significant positive correlation was found between the degree of NAFLD and serum levels of alanine aminotransferase, aspartate transaminase, total cholesterol, triglycerides, low-density lipoprotein, and CRP titer (P < 0.05). Importantly, NAFLD was significantly associated with an evident history of cardiovascular disease (CVD) among the studied patients. CONCLUSION: A high frequency of NAFLD (56%) was observed among the patients with non-diabetic CKD on hemodialysis and patients with pre-dialysis CKD. NAFLD may be associated with an increased liver stiffness grade and CVD among those patients.

Cardiovascular risk of circulating endotoxin level in prevalent hemodialysis patients.

BACKGROUND: Cardiovascular diseases (CVDs) are a major cause of morbidity and mortality in patients with end stage renal disease (ESRD). Circulating endotoxins may have toxic effect on myocardial functions and are speculated as pathogens of accelerated atherosclerosis and hemodialysis (HD) patients. OBJECTIVE: We aimed to assess the possible relation between circulating endotoxin levels and left ventricular functions parameters, common carotid artery intimal media thickness (CIMT) in prevalent HD patients. PATIENTS AND METHODS: Forty stable prevalent HD patients with mean age (47.97 ± 14.42) year using regular conventional hemodialysis sessions in Ain shams university hemodialysis unit, Cairo, Egypt were randomly selected. Diabetics, congestive heart failure and those with history of myocardial infarction or coronary artery disease were excluded from the study. All patients were studied by CBC and routine chemistry, as well as hs CRP, Intact PTH, lipid profile and endotoxin level by ELISA before and after the HD session, Delta change of endotoxin (pre dialysis endotoxin-post dialysis endotoxin) was calculated, resting Doppler echocardiographic and carotid duplex. RESULTS: Mean of Pre-HD session serum endotoxin level was (0.356 ± 0.090) EU/mL and the mean of post -HD endotoxin levels was (0.367 ± 0.110) EU/mL. Significant positive correlation between post dialysis endotoxin, MV E/A ratio and grades of left ventricular diastolic dysfunction (P < 0.05) and significant correlation between delta change in endotoxin and EF% (r = -0.36,P = 0.02). By stepwise linear regression analysis for determinants of MVE/A post -HD endotoxin level independently associated with MV E/A ratio (ß = 0.350, P = 0.027). We did not detect any significant correlation between CCA atherosclerosis and neither pre nor post- HD endotoxin level nor with delta change of pre and post HD endotoxin levels. CONCLUSION: Acute increase in post dialytic circulating endotoxin level in prevalent HD patients may be associated with both left ventricular systolic and diastolic dysfunction and that attempts to reduce endotoxin level may have a positive impact on cardiovascular complications in HD Patients.

Value of immunohistochemical expression of podocalyxin in active lupus nephritis / Valor de la expresión inmunohistoquímica de la podocalixina en la nefritis lúpica activa

Podocalyxin is an electronegative sialoglycoprotein that prevents the podocyte foot process from collapsing. The aim of this study was to detect an association between the glomerular immunohistochemical (IHC) expression of podocalyxin and the degree of podocyte effacement detected by electron microscopy, and to evaluate the role of podocalyxin IHC expression as a novel marker for disease activity in lupus nephritis (LN). Methods: Thirty-two renal biopsies of active lupus nephritis patients were studied. Clinical assessment by the systemic lupus activity measure (SLAM-R) score and laboratory data were included [serum creatinine, 24-h urinary protein, antinuclear antibodies (ANA), anti-double-strand DNA antibodies (anti-dsDNA), C3 and C4]. Light (L/M) and electron microscopic (E/M) examination was conducted. Podocyte loss was evaluated by immunohistochemistry with monoclonal anti-podocalyxin antibodies by means of a semiquantitative score that was graded from 0 to 4+ according to the percentage of glomerular involvement. Results: 22 cases (68.8%) with LN class IV, 6 (18.8%) with class III and 4 (12.5%) with class V. The mean age was (25.41±10.13) years. There was a significant negative correlation between IHC podocalyxin score and LN class, and NIH activity parameters such as leukocyte infiltration, endocapillary proliferation, fibrinoid necrosis and cellular crescent and disease activity index but not chronicity index. There was a highly significant negative correlation between IHC podocalyxin and podocyte effacement by E/M (rs=−0.903, P=0.000), and E/M immune deposits (r=−0.53, P=0.001), and a significant association with degree of proteinuria, ANA and SLAM score (P<0.05). Conclusions: Podocyte loss indicated by podocalyxin immunohistochemical expression reflects the degree of activity and severity of LN and the degree of podocyte effacement by E/M (AU)

La podocalixina es una sialoglicoproteína electronegativa que evita el colapso del proceso podocitario. Nuestro objetivo fue detectar una asociación entre la expresión inmunohistoquímica (IHQ) glomerular de la podocalixina y el grado de borramiento podocitario detectado mediante microscopia electrónica, además de evaluar la función de la expresión IHQ de la podocalixina como un nuevo marcador de la actividad de la enfermedad en la nefritis lúpica (NL). Métodos: Se evaluaron 32 biopsias renales de pacientes con NL activa. Se incluyeron la evaluación clínica mediante la puntuación de la determinación de la actividad del lupus sistémico (systemic lupus activity measure, SLAM-R) y datos analíticos (creatinina sérica, proteína en la orina de 24h, anticuerpos antinucleares [AAN], anticuerpos anti-ADN de doble cadena [anti-ADNdc], C3 y C4). Evaluación mediante microscopio de luz (M/L) y microscopio electrónico (M/E). La evaluación de la pérdida podocitaria se realizó mediante inmunohistoquímica con anticuerpos antipodocalixina monoclonales, por medio de una puntuación semicuantitativa que se clasificó de 0 a 4+ en función del porcentaje de afectación glomerular. Resultados: Encontramos 22 (68,8%) casos con clase IV de NL, 6 (18,8%) con clase III y 4 (12,5%) con clase V. La media de edad fue de 25,41±10,13 años. Se observó una asociación negativa significativa entre la puntuación de la podocalixina en la IHQ con la clase de NL y los parámetros de actividad del NIH, como la infiltración leucocitaria, la proliferación endocapilar, la necrosis fibrinoide y los drepanocitos y el índice de actividad de la enfermedad, pero no el índice de cronicidad. Se observó una correlación negativa muy significativa entre la podocalixina en la IHQ y el borramiento podocitario mediante M/E (rs=−0,903; p=0,000), depósitos inmunes mediante M/E (r=−0,53; p=0,001) y una asociación significativa con el grado de proteinuria, AAN y puntuación en el índice SLAM (p<0,05). Conclusiones: La pérdida podocitaria indicada mediante la expresión IQH de la podocalixina refleja el grado de actividad y la intensidad de la NL, así como el grado de borramiento podocitario mediante M/E (AU)

Value of immunohistochemical expression of podocalyxin in active lupus nephritis.

Podocalyxin is an electronegative sialoglycoprotein that prevents the podocyte foot process from collapsing. The aim of this study was to detect an association between the glomerular immunohistochemical (IHC) expression of podocalyxin and the degree of podocyte effacement detected by electron microscopy, and to evaluate the role of podocalyxin IHC expression as a novel marker for disease activity in lupus nephritis (LN). METHODS: Thirty-two renal biopsies of active lupus nephritis patients were studied. Clinical assessment by the systemic lupus activity measure (SLAM-R) score and laboratory data were included [serum creatinine, 24-h urinary protein, antinuclear antibodies (ANA), anti-double-strand DNA antibodies (anti-dsDNA), C3 and C4]. Light (L/M) and electron microscopic (E/M) examination was conducted. Podocyte loss was evaluated by immunohistochemistry with monoclonal anti-podocalyxin antibodies by means of a semiquantitative score that was graded from 0 to 4+ according to the percentage of glomerular involvement. RESULTS: 22 cases (68.8%) with LN class IV, 6 (18.8%) with class III and 4 (12.5%) with class V. The mean age was (25.41±10.13) years. There was a significant negative correlation between IHC podocalyxin score and LN class, and NIH activity parameters such as leukocyte infiltration, endocapillary proliferation, fibrinoid necrosis and cellular crescent and disease activity index but not chronicity index. There was a highly significant negative correlation between IHC podocalyxin and podocyte effacement by E/M (rs=-0.903, P=0.000), and E/M immune deposits (r=-0.53, P=0.001), and a significant association with degree of proteinuria, ANA and SLAM score (P<0.05). CONCLUSIONS: Podocyte loss indicated by podocalyxin immunohistochemical expression reflects the degree of activity and severity of LN and the degree of podocyte effacement by E/M.

Relationship of serum haemojuvelin and hepcidin levels with iron level and erythropoietin requirement in prevalent hepatitis C virus positive haemodialysis patients.

AIM: Iron overload is frequently reported in haemodialysis (HD) patients particularly those with chronic hepatitis C virus (HCV) infection. Soluble haemojuvelin (sHJV) has recently emerged as one of the significant regulators of iron homeostasis and hepcidin expression. The aim of the present study was to evaluate the potential associations of sHJV and hepcidin with inflammation, iron parameters and erythropoietin requirement in prevalent HD patients with HCV. METHODS: Serum sHJV and hepcidin were measured in 60 prevalent HD patients with [group I (n = 30)] and without [group II (n = 30)] HCV, and controls (n = 30) by enzyme-linked immunosorbent assay. Parameters related to anaemia, iron metabolism, inflammation, sHJV and hepcidin were measured. RESULTS: Serum hepcidin in HCV positive versus negative groups was 89.40 ± 46.08 ng/mL and 224.1 ± 72.36 ng/mL, P = 0.000, respectively, while sHJV was 245 ± 1.338 ng/mL and 254 ± 0.762 ng/mL, P = 0.147, respectively in positive versus negative patients. In group I, hepcidin correlated with serum ferritin (r = -0.512 P = 0.005) and transferrin saturation (TSAT%) (r = 0.572, P = 0.000) and sHJV correlated with ferritin (r = 0.40, P 0.000), TSAT% (r = 0.450, P = 0.002) and a significant correlation also existed between sHJV and hepcidin (r = -0.259, P = 0.045). In the regression analysis, ferritin and TSAT% were able to predict sHJV; (standardized ß = 0.52, P 0.001) and (standardized ß = 0.48, P 0.010). Ferritin and sHJV were also able to predict hepcidin (standardized ß = 0.627, P = 0.006) and (standardized ß = 0.300, P = 0.007) in group I. CONCLUSION: Soluble haemojuvelin levels seem to be associated with iron overload parameters and hepcidin levels in HCV positive HD patients.

Value of Foxp3 expressing T-regulatory cells in renal tissue in lupus nephritis; an immunohistochemical study.

BACKGROUND: Forkhead box P3 (Foxp3) functions as a master regulator in the development and function of T-regulatory (Treg) cells. Recent studies have shown that autoimmune diseases including systemic lupus erythematosus (SLE) are associated with an imbalance with the Treg cells and T helper (Th) subtypes. OBJECTIVES: To evaluate immunohistochemical expression of Foxp3 positive Treg cells in lupus nephritis (LN) and analyze its association with clinicopathologic parameters. MATERIALS AND METHODS: Renal biopsy specimens of 50 patients with LN were studied. Specimens were divided into; group A; 25 LN cases without proliferative activity (Class II and V) and group B: 25 cases with proliferative activity (Class III and IV). Immunohistochemical staining for anti-human Foxp3 antibody and grading from grade 0 to grade 3 was done. RESULTS: Foxp3 expression in group A was (grade 0 in 14 [56.0%], grade +1 in 11 [44.0 %]) in comparison to group B (grade +1 in 6 [24.0%], grade +2 in 11 [44.0%] and grade +3 in 8 [32.0%]) (P < 0.001). Foxp3 expression was significantly correlated to National Institutes of Health (NIH) activity and chronicity indices (P < 0.05), as well as serum creatinine (P < 0.01) in both groups A and B and there was a highly significant correlation with proteinuria (P < 0.01) in group B with proliferative LN. CONCLUSIONS: Immunohistochemical Foxp3 expression in renal tissue was higher in proliferative versus non-proliferative LN and is associated with activity and severity of LN. Further studies are needed to determine its prognostic value in LN.

Relationship between asymmetric dimethylarginine plasma level and left ventricular mass in hemodialysis patients.

Left ventricular hypertrophy (LVH) and left ventricular dysfunction are highly prevalent in patients with end-stage renal disease (ESRD). Several studies suggest that left ventricular mass and function is strongly modulated by the nitric oxide (NO) system. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial-based NO synthase, is emerging as an important cardiovascular risk factor in ESRD patients. Our objective is to evaluate the relationship between plasma ADMA level and LVH among hemodialysis (HD) patients. Plasma ADMA measurements by enzyme-linked immunesorbent assay and echocardiographic evaluation were performed for 40 patients on regular HD, 20 patients with pre-dialysis chronic kidney disease, 20 hypertensive patients with left ventricular hypertrophy and normal kidney function and 20 healthy age and sex-matched subjects as a control group. Residual renal function (RRF) was measured in HD patients by urea clearance from a urine collection. Mean values of plasma ADMA level were significantly high in all patient groups when compared with the control group (P < 0.001). However, there was no significant difference between groups I, II and III as regards mean values of plasma ADMA (P >0.05) and between ADMA and RRF in HD patients (r = -0.20, P = 0.60). It was also seen that plasma ADMA was not correlated with left ventricular mass index; however, there could be an association between ADMA level and diastolic dysfunction. The plasma ADMA level was found to be high in the three studied patient groups in comparison with the control group. HD is not an effective procedure for adequate removal of ADMA.