Adiponectin and cardiovascular outcomes among hemodialysis patients.

BACKGROUND: Adiponectin (ADPN) levels are consistently elevated among patients with advanced chronic kidney disease, but its relationship with cardiovascular outcomes in this population remains controversial. The aim of our study was to measure the plasma levels of ADPN in patients with end-stage renal disease on maintenance hemodialysis (HD) and we studied its correlates to cardiovascular outcomes and mortality. METHODS: Our study included 133 HD patients (79 male and 54 female patients) with a mean age of 54.6 ± 17.3 years who had been receiving regular HD for at least 6 months in the nephrology units of Theodor Bilharz Research Institute, Cairo, Egypt. The clinical and biochemical correlates of plasma ADPN levels were investigated and the predictive power of ADPN levels with respect to cardiovascular events and mortality was prospectively tested in HD patients, who were monitored for 24 ± 9 months. Plasma ADPN levels were measured by using a sensitive enzyme-linked immunosorbent assay. RESULTS: Plasma ADPN levels were 3 times higher (p < 0.0001) among HD patients (18.1 ± 6.8 µg/ml) than among healthy subjects (6.2 ± 1.8 µg/ml). Plasma ADPN levels were lower (p < 0.007) among patients who experienced new cardiovascular events (13.9 ± 6.4 µg/ml) than among event-free patients (18.6 ± 8.4 µg/ml). The relative risk of cardiovascular events was 1.96 times (95% confidence interval 1.290-2.977, p = 0.0016) higher among patients in group 1 (ADPN <15.1 µg/ml), compared with those in group 2 (ADPN ≥15.1 µg/ml). Plasma ADPN levels were inversely related to BMI, insulin levels, homeostatic model assessment index values, triglyceride and LDL-C, CRP and left ventricular mass index. Furthermore, plasma ADPN levels were directly related to HDL-C. CONCLUSION: Plasma ADPN is an independent (inverse) predictor of cardiovascular events and mortality among HD patients. The directions of the RELATIONSHIPS between ADPN and several metabolic risk factors indicate that ADPN has a protective role in prevention of CVD.

Value of troponin T as a screening test of cardiac structure and function in chronic kidney disease.

BACKGROUND: Cardiovascular disease starts early in the course of chronic kidney disease (CKD) and is the leading cause of death in patients with end-stage renal disease. Since high-sensitivity cardiac troponin T (hs-cTnT) can detect much lower levels of myocardial injury than conventional assays, it may be useful for studying the earliest stages of heart disease in patients with CKD. OBJECTIVE: To evaluate the association of circulating hs-cTnT with LV structural and functional abnormalities detected by echocardiography among dialysis dependent and non-dialysis dependent CKD patients. METHODS: This study was conducted on 107 subjects divided into three groups. Group I consisted of CKD patients on conservative treatment (n = 42), Group II: hemodialysis patients (n = 42), Group III: control group: age and sex matched healthy volunteers (n = 23). All subjects were subjected to clinical examination, biochemical evaluation including estimation of hs-cTnT and Echo-Doppler study of cardiac structure and function. RESULTS: There was a significant increase in LAV (p < 0.01), LVM (p < 0.01) in both patient groups compared to the control group. Mitral annular plane systolic excursion (MAPSE) was significantly decreased in both patient groups compared to the control group (p < 0.01, p < 0.05) and in group I compared to group II (p < 0.05) with a significant decrease in S velocity in group I compared to groups II and III (p < 0.01). There was a significant decrease in Vp (p < 0.01) with a significant increase in AEF (p < 0.01) in both patients' groups compared to the control group and AEF was significantly increased in group II compared to group I (p < 0.01). Ea velocity and Ea/Aa decreased significantly (p < 0.01) with significant increase in Aa velocity (p < 0.05, p < 0.01), E/Ea (p < 0.01) and E/Vp (p < 0.05) in both patient groups compared to the control group. There was a significant increase in hs-cTnT levels in both patient groups compared to the control group (P < 0.01). We found a positive correlation between hs-cTnT levels and LAV (r = 0.291, p < 0.03), IVST (r = 0.374, p < 0.004), PWT (r = 0.309, p < 0.02), LVM (r = 0.282, p < 0.03), A wave velocity (r = 0.271, p < 0.04), E/Ea (r = 0.506, p < 0.0001), PCWP (r = .507, p < 0.0001) and a negative correlation between hs-cTnT and MAPSE (r =  - 0.300, p < 0.02), S wave velocity (r =  - 0.259, p < 0.05), Ea (r =  - 626, p < 0.0001), Ea/Aa (r =  - 0.543, p < 0.0001). Troponin at the cut-off value of >5 ng/L, revealed 100% sensitivity and 95% specificity with areas under curve (AUC) of 0.998 and accuracy of 95.65% (P < 0.01) for discrimination of Group I vs control group and 76.2% sensitivity and 95.7% specificity with AUC 0.796 and accuracy 71.84% (P < 0.01) for discrimination of group II vs control group. CONCLUSION: Structural and functional cardiac abnormalities are common in CKD patients. Serum hs-cTnT levels increased in CKD patients and was associated with LVH, LAV and some of the echocardiographic parameters of LV systolic and diastolic dysfunction. Our research suggests that hs-cTnT levels may be important for early screening of cardiac structure and function in CKD patients to provide evidence for early intervention.

Association of chitotriosidase enzyme activity and genotype with the risk of nephropathy in type 2 diabetes.

OBJECTIVE: The immune-inflammatory system has been implicated in the pathogenesis of diabetic nephropathy; however, many of the mechanisms involved remain unclear. Chitotriosidase enzyme is an active human chitinase and a major protein product of activated macrophages. Although playing an important role in innate and acquired immunity, chitotriosidase involvement in the development of diabetic nephropathy is unknown. DESIGN AND METHODS: Chitotriosidase enzyme activity and the presence of the functional 24-bp duplication mutation of the chitotriosidase gene (CHIT1) were assessed in 262 Egyptian type 2 diabetic patients with and without nephropathy and 90 non-diabetic controls. In diabetic patients, multiple linear regression models were adapted to assess the association of chitotriosidase activity with two important measures of renal disease progression: urinary albumin/creatinine ratio and eGFR, while the association of the CHIT1 genotype with the incidence of nephropathy was evaluated by multiple logistic regression. RESULTS: In diabetic patients, chitotriosidase enzyme activity showed a statistically significant elevation as compared to controls and correlated positively with the progression of nephropathy. A significant association of chitotriosidase activity with both urinary albumin/creatinine ratio and eGFR was detected after adjusting for age, gender, duration of diabetes, body mass index, hypertension status, total cholesterol, triglycerides and HbA1c levels, P<0.001. We also identified a protective association between the CHIT1 mutated genotype and diabetic nephropathy after adjusting for the same confounders (odds ratio: 0.517, 95% CI: 0.289-0.924, P=0.026). CONCLUSIONS: This study demonstrates for the first time that the immunomodulatory effects of chitotriosidase enzyme could be implicated in the development of nephropathy in type 2 diabetes.

IL10 in Lupus Nephritis: Detection and relationship with disease activity.

INTRODUCTION: Glomerulonephritis is a major determinant of the course and prognosis of systemic lupus erythematosus (SLE) and is evident in 40%-85% of patients. IL10, a cytokine produced by monocytes and-to a lesser extent-lymphocytes, has pleiotropic effects in immune regulation and inflammation. It enhances B cell survival, proliferation, differentiation, and antibody production; these effects play a role in autoimmune diseases. Among identified polymorphisms in the IL10 promoter, three linked single nucleotide polymorphisms (SNPs) of -1082 G/A, 819 T/C, and -592 A/C have been shown to influence the IL10 gene expression. Compared with the -592 C allele, the 592 A is associated with lower IL10 production in vitro. The objectives of this study were to investigate the -592 A/C polymorphism in patients with and without lupus nephritis and to assess its influence on IL10 secretion in vivo and its role in pathogenesis and clinicopathological characteristics of lupus nephritis. METHODS: This case control study was conducted on 40 SLE patients recruited for the study from those attending the nephrology department of the Theodor Bilharz Research Institute (outpatient clinic and inpatient ward) in 2013. Patients were divided into two groups, group I (SLE patients without evidence of nephritis) and group II (SLE patients with lupus nephritis). Data were analyzed using SPSS (version 12), a t-test, Chi square, ANOVA, and the Pearson product-moment correlation coefficient. RESULTS: Our study found an increase in IL10 serum in lupus nephritis patients compared to those without renal involvement (without statistical significance). No significant differences emerged in the level of IL10 serum among different pathological classes. CONCLUSION: The IL10 gene (-592 A/C) polymorphism, though not associated with lupus nephritis's susceptibility in the present study, does play a role.

Novel troponin-like biomarkers of acute kidney injury.

Acute kidney injury (AKI) is a common and serious condition in both the inpatient and outpatient settings, and its diagnosis depends on serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers has limited our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has realized a number of potential biomarkers. For example, neutrophil gelatinase-associated lipocalin is emerging as an excellent stand alone troponin-like biomarker in the plasma and urine for predicting and monitoring clinical trials and in the prognosis of AKI. In recent years, a number of new biomarkers of AKI with more favorable test characteristics than creatinine have been identified and studied in a variety of experimental and clinical settings. This review will consider the most well-established biomarkers of AKI.

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 & 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.