Functional changes in peripheral arterial disease (PAD) could play a role in higher cardiovascular risk in these patients.
123 patients who underwent elective coronary angiography were included. ...Ankle-brachial index (ABI) was measured and arterial stiffness parameters were derived with applanation tonometry.
6 patients (4.9%) had a previously known PAD (Rutherford grade I). Mean ABI was 1.04 ± 0.12, mean subendocardial viability ratio (SEVR) 166.6 ± 32.7% and mean carotid-femoral pulse wave velocity (cfPWV) 10.3 ± 2.4 m/s. Most of the patients (n = 81, 65.9%) had coronary artery disease (CAD). There was no difference in ABI among different degrees of CAD. Patients with zero- and three-vessel CAD had significantly lower values of SEVR, compared to patients with one- and two-vessel CAD (159.5 ± 32.9%/158.1 ± 31.5% vs 181.0 ± 35.2%/166.8 ± 27.8%; p = 0.048). No significant difference was observed in cfPWV values. Spearman's correlation test showed an important correlation between ABI and SEVR (r = 0.196; p = 0.037) and between ABI and cfPWV (r = - 0.320; p ≤ 0.001). Multiple regression analysis confirmed an association between cfPWV and ABI (β = - 0.210; p = 0.003), cfPWV and mean arterial pressure (β = 0.064; p < 0.001), cfPWV and age (β = 0.113; p < 0.001) and between cfPWV and body mass index (BMI (β = - 0.195; p = 0.028), but not with arterial hypertension, dyslipidemia, diabetes mellitus or smoking status. SEVR was not statistically significantly associated with ABI using the same multiple regression model.
Reduced ABI was associated with increased cfPWV, but not with advanced CAD or decreased SEVR.
Largely on the basis of data from patients with type 1 diabetes, the natural history of diabetic renal disease has been classified as a sequence of three stages: normoalbuminuria, microalbuminuria, ...and macroalbuminuria. Progressive decline of glomerular filtration rate (GFR) was thought to parallel the onset of macroalbuminuria (overt nephropathy), whereas glomerular hyperfiltration was deemed a hallmark of early disease. However, researchers have since shown that albuminuria is a continuum and that GFR can start to decline before progression to overt nephropathy. In addition to proteinuria, other risk factors might contribute to GFR deterioration including female sex, obesity, dyslipidaemia (in particular hypertriglyceridaemia), hypertension, and glomerular hyperfiltration, at least in a subgroup of patients. This phenomenon could explain why patients with type 2 diabetes can have renal insufficiency even before the onset of overt nephropathy, and might also suggest why the heterogeneous phenotype of type 2 diabetic renal disease does not necessarily associate with typical histological lesions of diabetic renal disease, unlike in type 1 diabetic renal disease. Patients with renal insufficiency but without albuminuria are usually excluded from randomised clinical trials in overt nephropathy, thus optimum treatment for this group of patients is unknown. The wide inter-patient variability of the disease probably needs individually tailored intervention.
Diabetes prevalence is increasing worldwide, mainly due to the increase in type 2 diabetes. Diabetic nephropathy occurs in up to 40% of people with type 1 or type 2 diabetes. It is important to ...identify patients at risk of diabetic nephropathy and those who will progress to end stage renal disease. In clinical practice, most commonly used markers of renal disease and progression are serum creatinine, estimated glomerular filtration rate and proteinuria or albuminuria. Unfortunately, they are all insensitive. This review summarizes the evidence regarding the prognostic value and benefits of targeting some novel risk markers for development of diabetic nephropathy and its progression. It is focused mainly on tubular biomarkers (neutrophil-gelatinase associated lipocalin, kidney injury molecule 1, liver-fatty acid-binding protein, N-acetyl-beta-d-glucosaminidase), markers of inflammation (pro-inflammatory cytokines, tumour necrosis factor-α and tumour necrosis factor-α receptors, adhesion molecules, chemokines) and markers of oxidative stress. Despite the promise of some of these new biomarkers, further large, multicenter prospective studies are still needed before they can be used in everyday clinical practice.
Background/Aims: Albuminuria is a well-established marker of subclinical organ damage. Pulse-wave analysis (PWA) employs the technique of applanation tonometry to obtain a peripheral pulse pressure ...waveform, from which central hemodynamic data are derived by application of the transfer function. Using PWA we can measure the subendocardial viability ratio (SEVR) and ejection duration (ED). SEVR or the Buckberg index is a non-invasive estimate of myocardial workload, oxygen supply and perfusion and a measure of the ability of the arterial system to meet the heart`s energy requirements. ED is the duration of ventricular ejection. The objective of this study was to evaluate the relationship between albuminuria and PWA parameters in chronic kidney disease (CKD) patients. Methods: We studied 86 CKD patients aged 59.8±13.5 years, 56 (65.1%) were male. PWA analysis and 24-hour ambulatory blood pressure (24hABP) monitoring were performed. The following parameters were calculated: (1) aortic augmentation index with and without correction for a heart rate of 75 (Aix and AIx@ HR75), (2) SEVR, calculated as the ratio of the diastolic pressure time index and the systolic pressure time index, (3) ED, (4) estimated central aortic systolic and diastolic pressure and (5) central aortic pulse pressure calculated as the difference between estimated aortic systolic and diastolic BP. Blood samples and urine albumin-to-creatinine ratio (UACR) were analyzed; UACR values were natural log transformed (lnUACR). Results: Using CKD-EPI creatinine-cystatin C formula the eGFR in patients was 7-130 ml/min/1.73m2 (mean 32.6; SD±24.6). We found statistically significant correlation between lnUACR and cystatin C (r=0.308; P=0.004), eGFR (r=-0.219; P=0.04), hemoglobin (r=-0.255; P=0.02), phosphorus (r=0.222; P=0.04), iPTH (r=0.268; P=0.01), SEVR (r=-0.254; P=0.02) and ED (r=0.315; P=0.003). No statistically significant correlations between lnUACR and cardiac biomarkers TnI, NT-proBNP, central aortic BP and 24h ABP values were found. Using multiple regression analysis statistically significant association was found between SEVR as dependent variable and lnUACR (β=-0.223, P=0.039), sex (β=-0.216, P=0.035), and diabetes (β=0.332, P=0.001). Multiple regression analysis with ED as dependent variable has shown statistically significant association with lnUACR (β=0.242, P=0.031) and diabetes (β=-0.275, P=0.01). Patients were stratified into tertiles according to the lnUACR. Statistically significant differences in serum creatinine (P=0.001), cystatin C (P=0.012), hemoglobin (P=0.03), calcium (P=0.036), iPTH (P=0.008), SEVR (P=0.007) and ED (P=0.004) were found between tertiles. In post hoc analysis we found statistically significant differences between first and third tertile in SEVR (P=0.002; 95% CI:10.5-45) and in ED (P=0.001; 95% CI:-6.89-(-1.87)). Conclusions: Nondialysis CKD patients with higher levels of albuminuria have lower SEVR and higher ED and our results have shown the importance of central hemodynamic parameters like are SEVR and ED as a better or earlier noninvasive hemodynamic indexes in these patients.
Abstract
Renal dysfunction is associated with mortality in patients after ischemic stroke. Cystatin C is a potentially superior marker of renal function compared to creatinine and estimated ...glomerular filtration rate (GFR). In our observational cohort study, 390 Caucasian patients suffered from acute ischemic stroke (mean age 70.9 years; 183 women and 207 men) were included and prospectively followed up to maximal 56 months. Serum creatinine and cystatin C were measured at admission to the hospital; GFR was estimated according to CKD-EPI creatinine and CKD-EPI creatinine/cystatin equations. According to values of serum creatinine, estimated GFR and serum cystatin C patients were divided into quintiles. In the follow-up period, 191 (49%) patients died. For serum cystatin C and estimated GFR based on creatinine and cystatin C, the mortality and the hazard ratios for long-term mortality increased from the first to the fifth quintile nearly linearly. The associations of serum creatinine and estimated GFR categories based on creatinine with long-term mortality were J-shaped. As compared with lowest quintile of serum cystatin C, the fifth quintile was associated with long-term mortality significantly also after multivariate adjustment (age, gender, initial stroke severity, known risk factors for stroke mortality). In contrast, in adjusted analysis serum creatinine and estimated GFR (CKD-EPI creatinine and CKD-EPI creatinine/cystatin) were not associated with long-term mortality. In summary, serum cystatin C was independently and better associated with the risk of long-term mortality in patients suffering from ischemic stroke than were creatinine and estimated GFR using both CKD-EPI equations.
Imbalanced STAT5 phosphorylation in conventional and regulatory CD4 T cell subsets from SLE patients is related to their Bcl‐2 expression, homeostatic‐proliferation differences, and relapsing ...disease.
Activation of the STAT5 signaling pathway up‐regulates antiapoptotic protein Bcl2 and drives proliferation of autoreactive conventional CD4 T cells (Tcons). In systemic lupus erythematosus (SLE), an increased T cell Bcl2 content and perturbed homeostasis of CD45RA−FOXP3hi activated regulatory T cells (aTregs) were described. We assessed Tcon/Treg subsets and phosphorylation of STAT5 (pSTAT5) in blood T cells from patients with SLE by using conventional and imaging flow cytometry. Forty‐one patients with SLE, 33 healthy controls, and 29 patients with rheumatoid arthritis were included. Long‐term monitoring was performed in 39 patients with SLE, which were followed longitudinally for up to 1000 d. Significantly increased Bcl2 protein content in T cells from patients with SLE was associated with IL‐7–dependent STAT5 activation, expressed as increased basal levels and nuclear localization of pSTAT5. pSTAT5 levels were significantly increased in the FOXP3 low‐expressing CD4+ T cell subsets but not in the aTreg subset, which was significantly decreased in patients with SLE. In contrast to aTreg, SLE Tcon displayed significantly increased pSTAT5 and Bcl2 levels. Moreover, the percentage of Tcon‐expressing proliferation marker Ki‐67 was significantly increased in patients with SLE and was positively correlated with CD4 T cell pSTAT5 levels. Finally, a subgroup of patients characterized by an increased Tcon–pSTAT5/aTreg–pSTAT5 ratio experienced a more aggressive‐relapsing disease course and displayed higher time‐adjusted cumulative CD4 T cell pSTAT5 levels during follow‐up, which were positively correlated with time‐adjusted cumulative disease activity. Our results indicate that imbalanced STAT5 phosphorylation, which is related to Bcl2 and Ki‐67 expression, may confer survival and proliferative advantage to Tcon over aTreg and could represent a possible marker of SLE disease severity.
The ten most statistically significant estimated glomerular filtration rate (eGFRcrea)-associated loci from genome-wide association studies (GWAs) are tested for associations with chronic kidney ...disease (CKD) in 208 patients, including dialysis-independent CKD and dialysis-dependent end-stage renal disease (kidney failure). The allele A of intergenic SNP rs2453533 (near
) is more frequent in dialysis-independent CKD patients (
= 135, adjusted
= 0.020) but not dialysis-dependent kidney failure patients (
= 73) compared to healthy controls (
= 309). The allele C of intronic SNP rs4293393 (
) is more frequent in healthy controls (adjusted
= 0.042) than in CKD patients. The Allele T of intronic SNP rs9895661 (
) is associated with decreased eGFRcys (adjusted
= 0.001) and eGFRcrea (adjusted
= 0.017). Our results provide further evidence of a genetic difference between dialysis-dialysis-independent CKD and dialysis-dependent kidney failure, and add the
gene locus to the list of loci associated only with dialysis-independent CKD.
risk allele carriers in the dialysis-independent group may have a genetic susceptibility to higher creatinine production rather than increased serum creatinine due to kidney malfunction, and therefore, do not progress to dialysis-dependent kidney failure. When using eGFRcrea for CKD diagnosis, physicians might benefit from information about creatinine-increasing loci.
Estimating glomerular filtration rate (GFR) in elderly patients is a problem, since they are poorly represented in studies developing GFR equations. Serum cystatin C is a better indicator of GFR than ...serum creatinine in elderly patients. Therefore the aim of our study was to compare frequently used serum cystatin C based GFR equations with a gold standard (51CrEDTA clearance) in elderly chronic kidney disease (CKD) patients. 106 adult Caucasian patients, older than 65 years (58 women, 48 men; mean age 72.5 years), were included. In each patient 51CrEDTA clearance, serum creatinine (IDMS traceable method) and serum cystatin C (immunonephelometric method) were determined. GFR was estimated using the Simple cystatin C, CKD‐EPI cystatin C, CKD‐EPI creatinine‐cystatin C and BIS2 equation. Mean serum creatinine of our patients was 141.4 ± 41.5 μmol/L, mean serum cystatin C 1.79 ± 0.6 mg/L, mean 51CrEDTA clearance was 52.2 ± 15.9 mL/min per 1.73 m2. Statistically significant correlations between 51CrEDTA clearance and all formulas were found (P < 0.0001). In the receiver operating characteristic (ROC) curve analysis (cut‐off for GFR 45 mL/min per 1.73 m2) no significant differences in diagnostic accuracy between all the before mentioned equations were found. Bland‐Altman analysis for the same cut‐off showed that CKD‐EPI creatinine‐cystatin C and BIS2 equation underestimated and CKD‐EPI cystatin C and Simple cystatin C equation overestimated measured GFR. All equations lacked precision. Analysis of ability to correctly predict patient's GFR below or above 45 mL/min per 1.73 m2 showed similar ability for all equations (P = 0.24–0.89). All equations are equally accurate for estimating GFR in elderly Caucasian CKD patients. For daily practice Simple cystatin C equation is most practical.
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