Gulsen Yakupoglu

Effect of hemodialysis on the oxidative stress and antioxidants

Abstract Oxidative stress plays a role in many disease states. These diseases have an increased incidence in uremia, and particularly in hemodialysis (HD) patients. This suggests an increased exposure to oxidative stress. An imbalance between oxidants and antioxidants has been suggested in uremic patients on HD. However, the respective influence of uremia and dialysis procedure has not been evaluated. It is postulated that antioxidant capacity in uremic patients is reduced, yet the mechanism remains unclear. We have determined the levels of lipid peroxidation expressed as thiobarbituric acid-reactive substances. We assessed oxidative protein damage by carbonyl content and activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in predialysis uremic patients and in end-stage renal disease (ESRD) patients before and after hemodialysis. Vitamin E and vitamin C levels, reduced glutathione and sulfhydryl content were also studied. We found enhanced oxidative stress in ESRD patients undergoing HD and in predialysis uremic patients. This was mostly due to defective antioxidant enzyme levels. Preventive modalities, including use of biocompatible membranes, ultrapure dialysate, exogenous supplementation of antioxidant vitamins, extracorporeal removal of reactive oxygen species (ROS) and oxidatively modified substances, would appear highly desirable to reduce complications in the long-term dialysis patients.

Advanced oxidative protein products are independently associated with endothelial function in peritoneal dialysis patients

Aim:  Oxidative stress (OS) and asymmetric dimethylarginine (ADMA) are accepted as non‐classical cardiovascular risk factors in end‐stage renal disease patients. To clarify the role of these factors in the atherosclerotic process, we investigated if OS and ADMA are associated with endothelial function (EF) in peritoneal dialysis (PD) patients.

Reviews: Uremic Toxins: A New Focus on an Old Subject

The uremic syndrome is characterized by an accumulation of uremic toxins due to inadequate kidney function. The European Uremic Toxin (EUTox) Work Group has listed 90 compounds considered to be uremic toxins. Sixty‐eight have a molecular weight less than 500 Da, 12 exceed 12,000 Da, and 10 have a molecular weight between 500 and 12,000 Da. Twenty‐five solutes (28%) are protein bound. The kinetics of urea removal is not representative of other molecules such as protein‐bound solutes or the middle molecules, making Kt/V misleading. Clearances of urea, even in well‐dialyzed patients, amount to only one‐sixth of physiological clearance. In contrast to native kidney function, the removal of uremic toxins in dialysis is achieved by a one‐step membrane‐based process and is intermittent. The resulting sawtooth plasma concentrations of uremic toxins contrast with the continuous function of native kidneys, which provides constant solute clearances and mass removal rates. Our increasing knowledge of uremic toxins will help guide future treatment strategies to remove them.

Oxidative Stress and Asymmetric Dimethylarginine Is Independently Associated with Carotid Intima Media Thickness in Peritoneal Dialysis Patients

Backgrounds: Oxidative stress (OS) and asymmetric dimethylarginine (ADMA) are accepted as nonclassical cardiovascular risk factors in end-stage renal disease patients. To clarify the role of these factors in the atherosclerotic process, we investigated if OS and ADMA are associated with common carotid artery intima media thickness (CIMT) in peritoneal dialysis (PD) patients. Methods: Thirty PD patients without known atherosclerotic disease and classical cardiovascular risk factors as well as age- and gender-matched 30 healthy individuals were included. We measured serum thiobarbituric acid-reactive substances (TBARS), malondialdehyde (MDA), advanced glycation end product (AGE), pentosidine, advanced oxidation protein products (AOPP), ADMA and CIMT in each subjects. Results: TBARS, MDA, AOPP, AGE, pentosidine and ADMA levels were significantly higher in PD patients than in controls (p < 0.001). CIMT in patients was higher than in the control group (0.83 ± 0.09 vs. 0.77 ± 0.06 mm; p < 0.01). CIMT was independently correlated with TBARS (β = 0.33, p < 0.01), MDA (β = 0.27, p < 0.01), AOPP (β = 0.22, p < 0.02), AGE (β = 0.45, p < 0.01), pentosidine (β = 0.56, p < 0.01) and ADMA (β = 0.54, p < 0.01). Conclusions: OS markers and serum ADMA levels independently predict the CIMT level in PD patients.

The cost effectiveness of mycophenolate mofetil in the first year after living related renal transplantation.

REJECTION of transplanted organs results from the ability of lymphocytes to proliferate for the destruction of foreign tissue. Like all human somatic cells, lymphocytes proliferate by mitotic division and need purine and pyrimidine nucleotides for DNA synthesis. There are two major pathways in purine nucleotide synthesis: the de novo pathway and the salvage pathway. Most of human cell types can use salvage pathway for the proliferation if de novo synthesis is blocked; whereas, T and B lymphocytes depend mainly on de novo pathway. Mycophenolate Mofetil (MMF) selectively inhibits the proliferation of T and B lymphocytes because it acts as a reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), a rate limiting enzyme in the de novo pathway of guanosine nucleotide synthesis. Depletion of guanosine nucleotides with MMF results in impaired DNA synthesis and exerts antiproliferative effect. Since lymphocytes rely on de novo purine synthesis, this antiproliferative effect is selectively on lymphocytes. It is different from azathioprine because of its selective antiproliferative effect on lymphocytes. MMF has also two other effects on immune response: It suppresses antibody formation by B lymphocytes and inhibits the glycosylation of lymphocyte and monocyte glycoproteins. In some studies, MMF, in combination with corticosteroids and cyclosporine, reduced the incidence of renal allograft rejection within the first 6 months after transplantation when compared with triple drug protocols with azathioprine (AZA). In this study, we assessed the cost effectiveness of triple immunosuppressive regimen including MMF in the first year after living related renal transplantation.

Changes in urine levels of substance P, vasoactive intestinal peptide and calcitonin-gene-related peptide in patients with urinary tract infections.

Urinary tract infections (UTI) are important health problems and predisposing causes of UTI are not entirely known. Neuro-immune interactions play an important role in human health and disease. Capsaicin-sensitive sensory nerves which in nerve bladder extensively regulate immune system through neuropeptides such as substance P (SP), calcitonin-gene related peptide (CGRP) and vasoactive intestinal peptide (VIP). In addition these neuropeptides also have anti-bacterial effects. To determine how the levels of these peptides changes during UTI, 67 patients (50-90 years-old) diagnosed with UTI in Akdeniz University Faculty of Medicine Hospital were compared with 37 healthy people 50 years or older as the control group. Additionally, 7 patients with UTI symptoms (dysuria, urgency) but with sterile pyuria were also included in the study. Urine samples from 15 patients, whose symptoms regressed with control urine cultures being sterile, were taken after completion of the treatments. Urine neuropeptide levels were determined by ELISA. CGRP levels are significantly higher in patients with UTI, but did not associate with pyuria whereas SP and VIP levels were significantly lower in patients with sterile pyuria, indicating sensory nerve deficiency. Since CGRP exerts immunosuppressive effects, increased levels of the peptide may predispose to UTI. Furthermore, the connection between the observed sensory nerve deficiency and sterile pyuria warrants further studies.

Reviews: Uremic Toxins: A New Focus on an Old Subject: UREMIC TOXINS

The uremic syndrome is characterized by an accumulation of uremic toxins due to inadequate kidney function. The European Uremic Toxin (EUTox) Work Group has listed 90 compounds considered to be uremic toxins. Sixty‐eight have a molecular weight less than 500 Da, 12 exceed 12,000 Da, and 10 have a molecular weight between 500 and 12,000 Da. Twenty‐five solutes (28%) are protein bound. The kinetics of urea removal is not representative of other molecules such as protein‐bound solutes or the middle molecules, making Kt/V misleading. Clearances of urea, even in well‐dialyzed patients, amount to only one‐sixth of physiological clearance. In contrast to native kidney function, the removal of uremic toxins in dialysis is achieved by a one‐step membrane‐based process and is intermittent. The resulting sawtooth plasma concentrations of uremic toxins contrast with the continuous function of native kidneys, which provides constant solute clearances and mass removal rates. Our increasing knowledge of uremic toxins will help guide future treatment strategies to remove them.