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.

The impact of hepatitis C virus infection on long-term outcome in renal transplant patients.

BACKGROUND/AIMS: The aim of this study was to determine the effect of hepatitis C virus infection on patient and graft survival and liver function in renal transplant patients. METHODS: 1811 renal transplant patients were included in this study. One hundred renal transplant patients (5.5%) were anti-hepatitis C virus-positive. We evaluated demographic, clinical, biochemical, and serological data of patients and compared patient and graft survivals between hepatitis C virus-positive and -negative renal transplant patients. RESULTS: The median follow-up period was 35.7 months. One hundred (5.5%) patients were anti-hepatitis C virus-positive. There were no differences between anti-hepatitis C virus-positive and -negative renal transplant patients regarding age, etiology of renal disease, number of pre-transplant blood transfusions, and hepatitis B virus coinfection rate. Rate of graft loss in anti-hepatitis C virus-positive renal transplant patients was significantly higher than in anti-hepatitis C virus-negative patients (16.0% vs. 9.2%, p=0.026). Survival analysis revealed that patient survival was similar between anti-hepatitis C virus-positive and -negative renal transplant patients. Graft survival was lower in the anti-hepatitis C virus-positive group than in anti-hepatitis C virus-negative patients, especially after the fifth year of renal transplant (p<0.001). Thirty-three percent of anti-hepatitis C virus-positive patients were positive for hepatitis C virus RNA. Twenty-seven percent of anti-hepatitis C virus-positive patients had persistent alanine aminotransferase elevation. None of the patients developed cirrhosis during the follow-up period. CONCLUSION: Our findings suggest that hepatitis C virus infection in renal transplant patients does not adversely affect patient survival. Long-term graft survival seems to be lower in hepatitis C virus-positive compared to hepatitis C virus-negative renal transplant patients. Nevertheless, renal transplant can be considered as a safe and effective treatment modality in anti-hepatitis C virus-positive patients with end-stage renal disease.

Effects of diet and gemfibrozil on posttransplant hyperlipidemia in renal transplant recipients.

BACKGROUND: Posttransplant hyperlipidemia increases cardiovascular morbidity and mortality rate in renal transplant recipients. It also leads to graft loss due to atherosclerosis and glomerular damage. It is essential to control hyperlipidemia in renal transplant recipients to prevent these events. METHODS: In our study, we determined lipid profiles in 59 renal transplant recipients. Twenty of the recipients had hyperlipidemia; 9 had type IV, and 11 had type II hyperlipoproteinemia. Randomly selected 14 of 20 hyperlipidemic patients consisted of the diet group and were treated with American phase 3 diet for 1 month. Randomly selected 6 of the 20 hyperlipidemic patients received their regular diet as the control group. Five diet-resistant patients in the American phase 3 diet group were given diet plus placebo for another 1 month and then they were given diet plus Gemfibrozil (600 mg twice a day) for 2 months. RESULTS: Lipid profile was normalized in 9 of the 14 patients on American phase 3 diet. The lipid profile of 5 patients in the American phase 3 diet group did not change significantly after 1-month diet. These 5 diet-resistant patients were given diet plus placebo for another 1 month, and their lipid levels again did not change significantly. Afterward, they were treated with Gemfibrozil (600 mg twice a day) plus American phase 3 diet for 2 months. At the end of this therapy period, their cholesterol level and triglyceride level decreased significantly. No change was observed in low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels. CONCLUSIONS: We conclude that American phase 3 diet and/or Gemfibrozil are effective in controlling posttransplant hyperlipidemia in renal transplant recipients.

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. METHODS: Fifty-two non-diabetic PD patients without known atherosclerotic disease as well as 30 age- and sex-matched 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 EF as described by Celermejer et al. in all subjects. RESULTS: TBARS, MDA, AOPP, AGE, pentosidine and ADMA levels were significantly higher in PD patients than in controls (P < 0.001). Flow-mediated dilatation (FMD)% and nitrate mediated dilatation (NMD)% in PD patients were lower than in the control group (7.7 +/- 4.0% vs 11.70 +/- 5.50%, P < 0.01 and 17.6 +/- 8.3% vs 26.4 +/- 4.6%, P < 0.01). Additionally, it was found that AOPP are independently correlated with FMD% and NMD% in PD patients (beta = -463, P < 0.01 and beta = -420, P < 0.05). CONCLUSION: This study shows that PD patients without known atherosclerotic disease can also be characterized by endothelial dysfunction and AOPP levels independently predict endothelial function level in PD patients.

The spectrum of diseases causing fever of unknown origin in Turkey: a multicenter study.

OBJECTIVE: The purpose of this trial was to determine the spectrum of diseases with fever of unknown origin (FUO) in Turkey. METHODS: A prospective multicenter study of 154 patients with FUO in twelve Turkish tertiary-care hospitals was conducted. RESULTS: The mean age of the patients was 42+/-17 years (range 17-75). Fifty-three (34.4%) had infectious diseases (ID), 47 (30.5%) had non-infectious inflammatory diseases (NIID), 22 (14.3%) had malignant diseases (MD), and eight (5.2%) had miscellaneous diseases (Mi). In 24 (15.6%) of the cases, the reason for high fever could not be determined despite intensive efforts. The most common ID etiologies were tuberculosis (13.6%) and cytomegalovirus (CMV) infection (3.2%). Adult Still's disease was the most common NIID (13.6%) and hematological malignancy was the most common MD (7.8%). In patients with NIID, the mean duration of reaching a definite diagnosis (37+/-23 days) was significantly longer compared to the patients with ID (25+/-12 days) (p=0.007). In patients with MD, the mean duration of fever (51+/-35 days) was longer compared to patients with ID (37+/-38 days) (p=0.052). CONCLUSIONS: Although infection remains the most common cause of FUO, with the highest percentage for tuberculosis, non-infectious etiologies seem to have increased when compared with previous studies.

Effect of renal transplantation on endothelial function in haemodialysis patients.

BACKGROUND: Haemodialysis patients (HD) have been characterized by a high incidence and prevalence of atherosclerotic cardiovascular disease. Based on the traditional cardiovascular risk factors in this population, we cannot explain this high incidence and prevalence. One of the mechanisms contributing to cardiovascular risk in HD patients may be to uraemic toxins. Cardiovascular risk factors and uraemic toxins themselves may cause endothelial dysfunction, which may play a pivotal role in the development and progression of atherosclerosis in this population. We hypothesized that elimination of uraemic toxins in response to renal transplantation (RTx) can improve endothelial function as assessed by flow-mediated dilatation of brachial artery in haemodialysis (HD) patients. METHODS: Endothelial function measured by flow-mediated dilatation of the brachial artery (FMD) and glyceryltrinitrate-induced dilatation of the brachial artery (NMD) were assessed twice, during haemodialysis treatment and after RTx in 30 chronic haemodialysis patients. All patients were characterized by absence of known atherosclerotic disease and traditional cardiovascular risk factors. We also studied age- and gender-matched 20 normotensive healthy controls. RESULTS: FMD values significantly improved after RTx (6.69+/-3.1% vs 10.50+/-3.0%, P<0.001) in HD patients. FMD of patients both during haemodialysis and after RTx was lower than in healthy controls (6.69+/-3.1%, 10.50+/-3.0% vs 14.02+/-2.3%, P<0.001 and P<0.01, respectively). There was no change in NMD values after RTx in HD patients (16.27+/-1.9% vs 16.30+/-1.8%, P>0.05). Also, NMD values in all patients were similar to healthy control values. CONCLUSIONS: There is an improvement of endothelial function as assessed by FMD of the brachial artery after RTx in HD patients. This may be attributed to the elimination of uraemic toxins by successful RTx.

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.

Effect of hemodialysis on the oxidative stress and antioxidants.

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.

Low calcium dialysate increases cardiac relaxation in CAPD patients.

OBJECTIVE: To establish whether changes in serum calcium affect left ventricular (LV) function in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: This study was conducted on 28 clinically stable CAPD patients (11 females, 17 males). Left ventricular relaxation and systolic function were echocardiographically examined in all patients during standard dialysate (containing 1.75 mmol/L calcium) treatment. All patients were then changed to low calcium dialysate (1.25 mmol/L calcium) for 1 month and all patients were re-examined echocardiographically. Decrement in isovolumic relaxation time (IVRT) and deceleration time (DT), and increment in the ratio of peak early to peak late diastolic velocities (E/Amax) were admitted as indexes showing improvement in LV relaxation. 17 age- and sex-matched controls were also echocardiographically examined. RESULTS: Deceleration time, interventricular septal thickness at systole (IVSTS) and diastole (IVSTD), and posterior wall thickness at systole (PWS) and diastole (PWD) were higher in CAPD patients using standard dialysate than in normal controls. With the use of low calcium dialysate, DTs were similar but IVSTS, IVSTD, PWS, and PWD values remained higher. In normal controls, E/Amax values were higher than those in CAPD patients using standard dialysate (p < 0.001) and low calcium dialysate (p = 0.009). Serum intact parathyroid hormone level, weight, clinical volume status, and blood pressure were similar throughout the study period. Serum ionized calcium levels were decreased significantly during low calcium dialysate treatment. The changes in IVRT, DT, and E/Amax suggest improvement in LV relaxation during low calcium dialysate treatment. CONCLUSION: Left ventricular relaxation is increased with the use of low calcium dialysate compared with standard dialysate treatment. The idea of possible beneficial effects of increment in LV relaxation on cardiovascular morbidity and mortality deserves further studies.