Hemoglobin is inversely related to flow-mediated dilatation in chronic kidney disease

The microcirculation is regulated by oxygen gradients and by endothelial release of nitric oxide, which can react with hemoglobin to form S-nitroso derivatives. Here we induced flow-mediated dilatation of the brachial artery in response to ischemia in 141 non-diabetic patients with stage 3–4 chronic kidney disease who had no history of smoking, cardiovascular events or use of erythropoietin-based agents. Patients with hemoglobin concentrations above the cohort median of 11.6 g/dl were found to have significant reductions in flow-mediated dilatation compared to those below the median. This inverse relationship remained significant after adjustment for potential confounders, including insulin sensitivity, glomerular filtration rate, proteinuria, body mass index, serum urate, etiology of underlying renal disease, treatment with anti-hypertensive drugs, and traditional Framingham risk factors. Given that hemoglobin can act as an important nitric oxide carrier and buffer, our studies suggest that the mechanism by which hemoglobin influences the endothelium-dependent microcirculation requires its nitrosylation; however, more direct studies need to be performed

FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease

Studies in animals show that fibroblast growth factor (FGF)-23 interferes with vascular reactivity induced by the nitric oxide (NO) system. To investigate the relationship between circulating FGF-23 levels and the response of forearm blood flow to ischemia (flow-mediated vasodilatation, FMD) and nitroglycerin, we tested 183 patients with stage 3-4 chronic kidney disease (CKD). None of them had cardiovascular complications or were taking drugs interfering with vascular function. Patients with FGF-23 levels above the median had significantly lower glomerular filtration rate, FMD, and fetuin-A levels (an anti-inflammatory molecule and potent inhibitor of calcification). They also had higher proteinuria and phosphate levels when compared to patients whose FGF-23 levels were below the median. The response to nitroglycerin was not different between the two groups. Multiple regression analysis showed that the relationship between FGF-23 and FMD was only modestly sensitive to adjustment for classical risk factors, biomarkers of bone mineral metabolism, high-sensitivity C-reactive protein, and homeostatic model assessment index. Adjustment for asymmetrical dimethyl arginine (ADMA) weakened the strength of this link; however, it remained highly significant. There was no independent association between FGF-23 and nitroglycerin. Thus, attenuation of FMD by ADMA suggests that this endogenous inhibitor of NO synthase may, in part, mediate the vascular effects of FGF-23 in patients with CKD. © 2010 International Society of Nephrology

Antibody response following hepatitis B vaccination in dialysis patients: Does depression and life quality matter?

WOS: 000270469900022PubMed: 19654067Previously, it was demonstrated that antibody production against hepatitis B virus (HBV) surface antigen (anti-HBs) achieved in hemodialysis patients is suboptimal. Decreased health-related quality of life (HRQOL) and depression is common among hemodialysis patients. This study evaluated whether HRQOL and depressive behavior are associated with antibody response against HBV surface antigen in hemodialysis patients. Depressive symptoms and HRQOL were assessed by Beck Depression Inventory (BDI) and Medical Outcomes Study Short Form (SF-36), respectively. Patients were separated into non-seroconversion (anti-HBs antibody titers 10 IU/L) groups. Among 188 patients, 37 (19.7%) were diagnosed as nonresponsive to vaccination (anti-HBs antibody titers <101 U/L). Anti-HBs response is positively associated with Physical Component Summary Score of SF-36 (odds ratio: 1.44; P: 0.009) and albumin (odds ratio: 10.615, P: 0.007), and negatively with BDI score (odds ratio: 0.903, P: 0.007). We concluded that HRQOL and depression is closely related with antibody response following HBV vaccine in hemodialysis patients. (C) 2009 Elsevier Ltd. All rights reserved

Simple renal cysts and circadian blood pressure: are they related to each other in patients with hypertension?

WOS: 000288558900022PubMed: 20390353Previous studies have shown that the presence of simple renal cysts was related to hypertension. However, the relationship between simple renal cysts and circadian blood pressure was not studied before. Our study population comprised of newly diagnosed patients with essential hypertension. Medical history, physical examination and office blood pressure measurements, laboratory analysis, ambulatory blood pressure measurements, renal ultrasonography, and 24-h urine specimens were collected. In total, the study included 190 patients (male/female ratio 77/113; mean age 50.3 +/- A 11.3). Overall, 127 (66.8%) patients were dippers and 92 (48.4%) had at least one simple renal cyst. Thirty-five patients had solitary cysts and 57 patients had multiple cysts. Cysts were bilateral in 47 of patients. Most of ambulatory blood pressure recordings were higher in patients with at least one simple cyst when compared to patients without cysts. In multivariate logistic regression analysis, serum uric acid (P: 0.047, OR: 1.287, CI: 1.011-1.658), lower creatinine clearance (P: 0.001, OR: 1.030, CI: 1.012-1.049), presence of diabetes (P: 0.029, OR: 2.451, CI: 1.094-5.491), and presence of at least one cyst in each kidney (P: 0.002, OR: 3.087, CI: 1.533-6.212) were found to be independently related to nocturnal non-dipping. In conclusion, the presence of simple renal cysts is related to higher ambulatory BP and is associated with non-dipping phenomenon in patients with essential hypertension

Short-Term Treatment with Sevelamer Increases Serum Fetuin-A Concentration and Improves Endothelial Dysfunction in Chronic Kidney Disease Stage 4 Patients

Background and objectives: Vascular calcification and endothelial dysfunction contribute to the development of cardiovascular disease in patients with chronic kidney disease (CKD). Sevelamer, a non–calcium-based phosphate binder, has been shown to attenuate cardiovascular calcification in CKD patients, although the exact mechanism has not been clarified. This study was designed to investigate the effect of short-term sevelamer treatment on both serum fetuin-A concentrations and endothelial dysfunction seen in CKD patients

Effect of Renin Angiotensin System Blockade on Pentraxin 3 Levels in Type-2 Diabetic Patients With Proteinuria

Background and objectives: Long pentraxin 3 (PTX3) is a multimeric inflammatory mediator. Increased serum PTX3 levels have been reported among end-stage renal disease patients. Moreover, PTX3 has been suggested to represent a novel mortality risk factor, and elevated PTX3 levels have been shown to accompany increased albuminuria among patients with chronic kidney disease (CKD)

ADMA Levels Correlate with Proteinuria, Secondary Amyloidosis, and Endothelial Dysfunction

Asymmetric dimethyl-arginine (ADMA), a residue of the proteolysis of arginine-methylated proteins, is a potent inhibitor of nitric oxide synthesis. The increased protein turnover that accompanies proteinuric secondary amyloidosis may increase circulating levels of ADMA, and this may contribute to endothelial dysfunction. We performed a cross-sectional study of 121 nondiabetic proteinuric patients with normal GFR (including 39 patients with nephrotic-range proteinuria and secondary amyloidosis) and 50 age-, sex-, and BMI–matched healthy controls. The proteinuric patients had higher levels of serum ADMA, symmetric dimethyl-arginine (SDMA), high-sensitivity C-reactive protein (hsCRP), and insulin resistance (homeostasis model assessment index) than controls. Compared with controls, brachial artery flow-mediated dilatation (FMD), serum L-Arginine, and the L-Arginine/ADMA ratio were significantly lower among proteinuric patients, suggesting greater endothelial dysfunction. When patients with secondary amyloidosis were compared with patients with glomerulonephritis who had similar levels of proteinuria, those with amyloidosis had higher ADMA and SDMA levels and lower L-Arginine/ADMA ratios and FMD measurements (P < 0.001 for all). Finally, even after adjusting for confounders, ADMA level correlated with both proteinuria and the presence of secondary amyloidosis, and was an independent predictor of FMD. We propose that ADMA synthesis may be increased in chronic kidney disease, especially in secondary amyloidosis, and this may explain part of the mechanism by which proteinuria increases cardiovascular morbidity and mortality

The Relationship between Hemoglobin Levels and Endothelial Functions in Diabetes Mellitus

Background and objectives: Hemoglobin (Hb) is the main carrier and buffer of nitric oxide. Evidence has been produced that Hb concentration is inversely related with endothelial function in human diseases. Testing whether this association exists also in diabetic patients stage 1 to 2 chronic kidney disease (CKD) is important because anemia in these patients starts at an earlier stage than in other renal diseases. The relationship was investigated between Hb and flow-mediated dilation (FMD) levels of the patients with diabetic nephropathy in a cross-sectional design