In HD patients, carotid atherosclerosis is associated with inflammation and circulating levels of soluble adhesion molecules ICAM-1 and VCAM-1. The correlations between serum ICAM-1 and IMT and ICAM-1 and survival may indicate that this molecule could be a marker of a process that contributes to the high mortality of HD patients.
Approximately 85% of hemodialysis patients are hypertensive, but less than 30% achieve adequate blood pressure (BP) control. Reduction of volume overload is fundamental for BP control, but clinical criteria to estimate dry-weight are inaccurate. In the present study we examined the effect of dry-weight reduction with a lung-ultrasound-guided strategy on ambulatory BP in 71 clinically euvolemic hemodialysis patients with hypertension. Patients were equally randomized into an active group, following a strategy for dry-weight reduction guided by pre-hemodialysis lung ultrasound, and a control group with standard-of-care treatment. All patients underwent 48-hour ambulatory BP monitoring (ABPM) at baseline and after eight weeks. Overall, more patients in the active than in the control group had dry weight reduction, 54.3% compared to 13.9%, respectively. The ultrasonographic-B line change during follow-up was significantly different (-5.3±12.5 in active versus D2.2±7.6 in control group), which corresponded to significant differences in dry weight changes between the groups. The magnitude of reductions in 48-hour systolic BP (-6.61±9.57 vs.-0.67±13.07) and diastolic BP (-3.85±6.34 vs.-0.55±8.28) was significantly greater in the active group. Similarly, intradialytic BP, 44-hour BP, and daytime or night-time systolic/diastolic BP during both days of the interdialytic interval were significantly reduced in the active group but remained unchanged in the control group. The percentage of patients experiencing one or more intradialytic hypotensive episodes was marginally lower in the active group (34.3% vs. 55.6%). Thus, a lung-ultrasound-guided strategy for dry-weight reduction can effectively and safely reduce ambulatory BP levels in hemodialysis patients. Clinical implementation of this simple technique can help increase BP control in this population.
Urinary MCP-1, IL-6 and EGF levels may represent histology in IgAN. EGF excretion can be a predictive marker and its serial measurements may give information about disease outcome and the effect of treatment.
Background
Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population.
Methods
Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses.
Results
Mean baseline CCA-IMT amounted to 0.74mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072mm for fibrinogen (p < 0.001); and 0.0025mm for leucocyte count (p = 0.033). ‘Inflammatory load’, defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest ‘inflammatory load’ had a greater CCA-IMT progression (p = 0.015).
Conclusion
Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for ‘inflammatory load’ suggest important combined effects of the three inflammatory markers on early atherosclerosis.
This study suggests that 12-month therapy with CyA (+/-prednisolone) is effective in inducing remission in most nephrotic patients with MN and well-preserved renal function. Longer treatment with lower doses is a useful approach to maintain remission. Relapses occur more frequently in the monotherapy group and usually are associated with CyA trough levels<100 ng/ml.
Nephrotic patients with FSGS may benefit from a more prolonged course of Pred. Nephrotic patients responding to treatment have a significantly better renal survival than non-responders. Age and plasma creatinine at biopsy are independent risk factors leading to ESRD. The severity of tubulointerstitial fibrosis is predictive of response to therapy.
Immunoglobulin A nephropathy (IgAN) is a worldwide disease characterized by the presence of galactose-deficient IgA1 deposits in the glomerular mesangium. A kidney biopsy for diagnosis is required. Here, we measured two miRNAs (let-7b and miR-148b), previously identified as regulators of the O-glycosylation process of IgA1, in serum samples from patients with IgAN and healthy blood donors (controls) recruited in an international multicenter study. Two predictive models, based on these miRNAs, were developed and the diagnostic accuracy of the combined biomarkers was assessed by the area under the receiver operating characteristic (ROC) curve (AUC) carried out in three steps. In a training study, the combined miRNAs were able to discriminate between 100 patients with IgAN and 119 controls (AUC, 0.82). A validation study confirmed the model in an independent cohort of 145 patients with IgAN and 64 controls (AUC, 0.78). Finally, in a test study, the combined biomarkers were able to discriminate patients with IgAN from 105 patients affected by other forms of primary glomerulonephritis, supporting the specificity (AUC, 0.76). Using the same study design, we also performed two subgroup analyses (one for Caucasians and one for East Asians) and found that race-specific models were the best fit to distinguish IgAN patients from controls. Thus, serum levels of the combined miRNA biomarker, let-7b and miR-148b, appears to be a novel, reliable, and noninvasive test to predict the probability of having IgAN.
Aim. Recent evidence suggests that chronic subclinical inflammation plays a key role in the pathogenesis and progression of diabetic nephropathy. Aim of the present study was to investigate possible correlation between the presence and degree of microalbuminuria and markers of inflammation in patients with type 2 diabetes mellitus (DM). Patients-Methods. Eighty patients were enrolled and clinical and laboratory data were recorded. Albumin-creatinine ratio (ACR) was calculated in first-morning urine samples. Serum and urinary tumor necrosis factor-α (TNF-α) levels were determined by ELISA. Results. Forty-five patients had normoalbuminuria, 33 microalbuminuria, and 2 macroalbuminuria. Patients with microalbuminuria were older, with higher glycosylated hemoglobin levels (HbA1c) and they more frequently had diabetic retinopathy, neuropathy, and cardiovascular disease and were on treatment with angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARBs). ACR was significantly correlated with the presence of cardiovascular disease, hypertension, and HbA1c levels and the administration of clopidogrel and ACEi or ARBs. ACR was not correlated with C-reactive protein, fibrinogen, or serum TNF-α levels but had a strong correlation with urinary TNF-α levels. Conclusions. In patients with type 2 DM, urinary, but not serum, TNF-α levels are associated with the presence and severity of microalbuminuria.
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