The Effect of Convective Dialytic Modalities on Arterial Stiffness in End-Stage Renal Disease Patients

Among end-stage renal disease (ESRD) patients receiving hemodialysis, increased arterial stiffness is an independent cardiovascular risk predictor. Over the past few years, arterial stiffness attenuation has been increasingly recognized as a novel therapeutic target toward cardiovascular risk reduction in the dialysis population. Structural alterations related to the long-term arteriosclerotic process are difficult to modify; with the exception of blood pressure (BP)-lowering, there are no other therapeutic interventions with well-documented benefits in delaying the progression of arteriosclerosis among dialysis patients. Enhanced clearance of middle-to-high molecular weight solutes by combining convective and diffusive transport through hemodiafiltration and the associated benefits on microvascular endothelial function have generated the hypothesis that convective dialytic modalities may be advantageous in improving large-artery stiffness. This notion is supported by some clinical studies showing that switching ESRD patients from low-flux hemodialysis to high-efficiency on-line hemodiafiltration was associated with significant reduction in arterial stiffness. These beneficial effects, however, were not confirmed in a recent subanalysis of the CONvective TRAnsport STudy (CONTRAST) trial. In this chapter, we summarize the currently available evidence on the effect of hemodiafiltration versus hemodialysis on arterial stiffness, discussing also the potential clinical implications of this effect

Oxidative Stress and Acute Kidney Injury in Critical Illness: Pathophysiologic Mechanisms—Biomarkers—Interventions, and Future Perspectives

Acute kidney injury (AKI) is a multifactorial entity that occurs in a variety of clinical settings. Although AKI is not a usual reason for intensive care unit (ICU) admission, it often complicates critically ill patients’ clinical course requiring renal replacement therapy progressing sometimes to end-stage renal disease and increasing mortality. The causes of AKI in the group of ICU patients are further complicated from damaged metabolic state, systemic inflammation, sepsis, and hemodynamic dysregulations, leading to an imbalance that generates oxidative stress response. Abundant experimental and to a less extent clinical data support the important role of oxidative stress-related mechanisms in the injury phase of AKI. The purpose of this article is to present the main pathophysiologic mechanisms of AKI in ICU patients focusing on the different aspects of oxidative stress generation, the available evidence of interventional measures for AKI prevention, biomarkers used in a clinical setting, and future perspectives in oxidative stress regulation

Oxidative Stress in Patients Undergoing Peritoneal Dialysis: A Current Review of the Literature

Peritoneal dialysis (PD) patients manifest excessive oxidative stress (OS) compared to the general population and predialysis chronic kidney disease patients, mainly due to the composition of the PD solution (high-glucose content, low pH, elevated osmolality, increased lactate concentration and glucose degradation products). However, PD could be considered a more biocompatible form of dialysis compared to hemodialysis (HD), since several studies showed that the latter results in an excess accumulation of oxidative products and loss of antioxidants. OS in PD is tightly linked with chronic inflammation, atherogenesis, peritoneal fibrosis, and loss of residual renal function. Although exogenous supplementation of antioxidants, such as vitamins E and C, N-acetylcysteine, and carotenoids, in some cases showed potential beneficial effects in PD patients, relevant recommendations have not been yet adopted in everyday clinical practice

Simultaneous clinical resolution of focal segmental glomerulosclerosis associated with chronic lymphocytic leukaemia treated with fludarabine, cyclophosphamide and rituximab

<p>Abstract</p> <p>Background</p> <p>Although renal involvement in advanced haematological malignancies is common, glomerulonephritis associated with lymphoproliferative disorders is rare, and the related pathogenetic mechanisms are still poorly understood. We present a rare case of chronic lymphocytic leukaemia(CLL)-associated focal segmental glomerulosclerosis with nephrotic-range proteinuria.</p> <p>Case presentation</p> <p>A 53-year-old Caucasian man, previously healthy, with no history of hypertension, alcohol use or smoking presented with rapid weight gain, massive peripheral oedema, and hypertension. Laboratory findings included a white blood cell count of 49,800 cells/mm³with an absolute lymphocyte count of 47,000 cells/mm³, serum albumin of 2.3 g/dL, urea 65 mg/dL, and creatinine 1.5 mg/dL. A 24-hour urine collection contained 7.1 g protein and significant haematuria. A peripheral blood smear showed mature lymphocytosis and smudge cells. Diagnostic imaging showed mild paraaortic lymphadenopathy with no renal abnormalities. Bone marrow aspiration and trephine biopsy showed diffuse and focal infiltration with B-CLL lymphocytes. Percutaneous renal biopsy revealed total sclerosis in 3/21(14%) of the glomeruli and focal and segmental solidification and sclerosis in 4/21 (19%) glomeruli. A regimen of fludarabine, cyclophosphamide and rituximab was successful in inducing remission of the CLL and clinical resolution of the nephritic-range proteinuria.</p> <p>Conclusions</p> <p>A multidisciplinary approach to monitor both the malignancy and the glomerular lesions is crucial for the optimal management of paraneoplastic glomerulonephritis. Although chemotherapy with fludarabine, cyclophosphamide and rituximab successfully treated CLL-associated nephrotic syndrome in our patient, further studies are required to confirm efficacy in this setting.</p

Coronary artery bypass surgery in a patient with Kartagener syndrome: a case report and literature review

Kartagener syndrome consists of congenital bronchiectasis, sinusitis, and total situs inversus in half of the patients. A patient diagnosed with Kartagener syndrome was reffered to our department due to 3-vessel coronary disease. An off-pump coronary artery bypass operation was performed using both internal thoracic arteries and a saphenous vein graft. We performed a literature review for cases with Kartagener syndrome, coronary surgery and dextrocardia. Although a few cases of dextrocardia were found in the literature, no case of Kartagener syndrome was mentioned

Cytochrome c as a potentially clinical useful marker of mitochondrial and cellular damage

Mitochondria are evolutionary endosymbionts derived from bacteria. Thus they bear molecules, such as mitochondrial DNA that contains CpG DNA repeats and N-formyl peptides, found in bacteria. Upon cell necrosis or apoptosis these molecules are released into the interstitial space and the circulation and recognized by the immune cells through the same receptors that recognize pathogen associated molecular patterns, leading to inflammation. Other mitochondrial molecules are not of bacterial origin, but they may serve as danger associated molecular patterns (DAMPs) when due to cell injury are translocated into inappropriate compartments. There they are recognized by pattern recognition receptors of the immune cells. Cytochrome c is such a molecule. In this review experimental and clinical data are presented that confirms cytochrome c release into the extracellular space in pathological conditions characterized by cell death. This indicates that serum cytochrome c, which can be easily measured, may be a clinically useful marker for diagnosing and assessing the severity of such pathological entities. Reasonably, detection of high cytochrome c level into the circulation means release of various other molecules that serves as DAMPs when found extracellularly, the mitochondrial DNA and N-formyl peptides included. Finally, because the release of this universally found compound into the extracellular space makes cytochrome c an ideal molecule to play the role of a DAMP per se, the available experimental and clinical data that support such a role are provided

Association of the Inactive Circulating Matrix Gla Protein with Vitamin K Intake, Calcification, Mortality, and Cardiovascular Disease: A Review

Matrix Gla Protein (MGP), a small Gla vitamin K-dependent protein, is the most powerful natural occurring inhibitor of calcification in the human body. To become biologically active, MGP must undergo vitamin K-dependent carboxylation and phosphorylation. Vitamin K deficiency leads to the inactive uncarboxylated, dephosphorylated form of MGP (dpucMGP). We aimed to review the existing data on the association between circulating dpucMGP and vascular calcification, renal function, mortality, and cardiovascular disease in distinct populations. Moreover, the association between vitamin K supplementation and serum levels of dpucMGP was also reviewed

Crystalline silica activates the T-cell and the B-cell antigen receptor complexes and induces T-cell and B-cell proliferation

Silicosis is an occupational fibrotic lung disease, which is associated with an increased incidence of autoimmune diseases. The effect of crystalline silica on the immune system is thought to be mediated by the antigen presenting cells. However, the direct effect of silica on T-cells and B-cells has not been evaluated adequately. For this purpose, CD4(+)T-cells and B-cells from 10 healthy individuals were isolated and cultured with or without Min-U-Sil 5. Cell proliferation was assessed with BrdU assay. In cell proliferation experiments, tacrolimus, an inhibitor of the signal transduction derived from the activation of the T-cell or the B-cell antigen receptor (BCR) complex, was also used. The levels of phosphorylated zeta and phosphorylated Igα, indicative of the T-cell and BCR complex activation respectively, and of the transcription factor c-Myc, required for cell proliferation, were assessed by Western blotting. Crystalline silica triggered CD4(+)T-cell and B-cell proliferation, while tacrolimus significantly decreased the silica-induced proliferation in both cell types. Crystalline silica enhanced the level of phosphorylated zeta and phosphorylated Igα in CD4(+)T-cells and B-cells, respectively. In both cell types, treatment with silica increased c-Myc expression. Thus, crystalline silica may induce T-cell and B-cell proliferation by activating T-cell and BCR complexes. It is likely that the direct activation of CD4(+)T-cells and B-cells by silica crystals detected in this study circumvents many self-tolerance check-points and offers a mechanistic explanation for the crystalline silica-induced autoimmune diseases

Antioxidant Supplementation in Renal Replacement Therapy Patients: Is There Evidence?

The disruption of balance between production of reactive oxygen species and antioxidant systems in favor of the oxidants is termed oxidative stress (OS). To counteract the damaging effects of prooxidant free radicals, all aerobic organisms have antioxidant defense mechanisms that are aimed at neutralizing the circulating oxidants and repair the resulting injuries. Antioxidants are either endogenous (the natural defense mechanisms produced by the human body) or exogenous, found in supplements and foods. OS is present at the early stages of chronic kidney disease, augments progressively with renal function deterioration, and is further exacerbated by renal replacement therapy. End-stage renal disease patients, on hemodialysis (HD) or peritoneal dialysis (PD), suffer from accelerated OS, which has been associated with increased risk for mortality and cardiovascular disease. During HD sessions, the bioincompatibility of dialyzers and dialysate trigger activation of white blood cells and formation of free radicals, while a significant loss of antioxidants is also present. In PD, the bioincompatibility of solutions, including high osmolality, elevated lactate levels, low pH, and accumulation of advanced glycation end-products trigger formation of prooxidants, while there is significant loss of vitamins in the ultrafiltrate. A number of exogenous antioxidants have been suggested to ameliorate OS in dialysis patients. Vitamins B, C, D, and E, coenzyme Q10, L-carnitine, a-lipoic acid, curcumin, green tea, flavonoids, polyphenols, omega-3 polyunsaturated fatty acids, statins, trace elements, and N-acetylcysteine have been studied as exogenous antioxidant supplements in both PD and HD patients

Dietary Antioxidant Supplements and Uric Acid in Chronic Kidney Disease: A Review

Increased serum levels of uric acid have been associated with the onset and development of chronic kidney disease (CKD), cardiovascular disease, and mortality, through several molecular pathogenetic mechanisms, such as inflammation and oxidative stress. Oxidative stress is present even in the early stages of CKD, progresses parallelly with the deterioration of kidney function, and is even more exacerbated in end-stage renal disease patients undergoing maintenance hemodialysis. Although acting in the plasma as an antioxidant, once uric acid enters the intracellular environment; it behaves as a powerful pro-oxidant. Exogenous intake of antioxidants has been repeatedly shown to prevent inflammation, atherosclerosis and oxidative stress in CKD patients. Moreover, certain antioxidants have been proposed to exert uric acid-lowering properties. This review aims to present the available data regarding the effects of antioxidant supplements on both oxidative stress and uric acid serum levels, in a population particularly susceptible to oxidative damage such as CKD patients