Relationship between carotid artery intima-media thickness and brachial artery flow-mediated dilation in peritoneal dialysis patients.

BACKGROUND AND AIM: Carotid artery intima-media thickness (CIMT) and brachial artery flow-mediated dilation percentage (FMD%) are two commonly used parameters for detecting subclinical atherosclerosis. However, studies investigating the relationship between CIMT and brachial artery FMD% in different populations have produced conflicting results. The aim of this study was to determine the relationship between CIMT and brachial artery FMD% in patients on peritoneal dialysis (PD) METHODS: Fifty-two PD patients without known cardiovascular disease and 30 age-gender matched controls were included in the study. Endothelial function was determined using ultrasonography (US) to measure the FMD of the brachial artery, and this parameter was expressed as the percentage change from the baseline diameter of the brachial artery (FMD%). We also measured CIMT by US and analysed the relationship between CIMT and brachial FMD%. RESULTS: The CIMT was significantly higher in patients than in the control group (0.84 +/- 0.08 vs. 0.75 +/- 0.06 mm, P < 0.01), whereas brachial artery FMD% was lower in patients than in the controls (8.2 +/- 5.0 vs. 11.7 +/- 5.5%, P < 0.01). There was no significant correlation between CIMT and FMD% (r = -0.004, P = 0.94). CONCLUSION: Although PD patients are known to be characterized by an impaired flow-mediated vasodilatation of brachial artery and increased in CIMT, we did not find a significant correlation between FMD% and CIMT in our PD patient cohort. One possible explanation for our results is that each method measures a different aspect and stage of atherosclerosis.

Oxidative stress and asymmetric dimethylarginine is independently associated with carotid intima media thickness in peritoneal dialysis patients.

BACKGROUND: 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 (beta = 0.33, p < 0.01), MDA (beta = 0.27, p < 0.01), AOPP (beta = 0.22, p < 0.02), AGE (beta = 0.45, p < 0.01), pentosidine (beta = 0.56, p < 0.01) and ADMA (beta = 0.54, p < 0.01). CONCLUSIONS: OS markers and serum ADMA levels independently predict the CIMT level in PD patients.

Assessment and comparison of endothelial function between dialysis and kidney transplant patients.

Dialysis and kidney transplant patients display endothelial dysfunction. Previous studies concerning comparisons of endothelial function in dialysis and kidney transplant patients included subjects with cardiovascular risk factor(s) that alone may lead to endothelial dysfunction. In this study, we compared endothelial function between dialysis and transplant patients who did not show known cardiovascular risk factors that lead to endothelial dysfunction. We studied age- and gender-matched cohorts: 30 hemodialysis (HD), 30 peritoneal dialysis (PD), and 30 kidney transplant patients. We also included 20 age- and gender-matched healthy controls. We assessed the endothelial function of patients and controls by a noninvasive technique. Serum biochemistry profiles of patients were also similar to controls in terms of lipid profile and fasting blood glucose level. Although mean FMD% levels of HD and PD patients were similar (6.6% +/- 3.1% vs 6.8% +/- 3.0%, P > .05), the mean percent of flow-mediated endothelium-dependent dilatation (FMD%) level in transplant patients was higher than those in HD or PD patients (10.50% +/- 3.0% vs 6.6% +/- 3.1% and 6.8% +/- 3.0%, respectively; P < .01). In addition, the mean FMD% level in healthy controls was higher than those in HD, PD, and transplant patients (14.0% +/- 2.3% vs 6.6% +/- 3.1%, 6.8% +/- 3.0% and 10.50% +/- 3.0%; P < .01, respectively). In conclusion, endothelial functions in transplant patients were better than those in dialysis patients.

Sirolimus as primary immunosuppression agent in kidney transplant recipients: Akdeniz University experience.

OBJECTIVES: Recently usage of sirolimus as the primary immunosuppressant is widening among kidney transplant recipients. We reviewed the clinical follow-up of patients transplanted at our center using sirolimus protocols. METHODS: Sirolimus including primary immunosuppressive treatment protocols were begun in February 2002. Among the 21 patients (15 men, six women) who received sirolimus, six patients were prescribed sirolimus + prednisolone; seven, sirolimus + mycophenolate mofetil + prednisolone; and eight, sirolimus + cyclosporine + prednisolone. The mean age of the patients was 32.9 +/- 7.3 years and the mean posttransplantation follow-up, 13.2 +/- 4.5 months. RESULTS: Three patients experienced acute rejection episodes, which were treated successfully with steroids. None of the patients had either hematologic or wound healing problems. Lymphoceles developed in eight patients. Serum creatinine level was 1.4 +/- 0.5 mg/dL at 12 months. There was a serious increase in serum cholesterol and triglyceride levels starting from the first month posttransplant (total cholesterol levels pretransplant and at 1 month, respectively: 159.3 +/- 29.5 and 255.7 +/- 52.3 mg/dL, P = .0001; triglycerides pretransplant and at 1 month, respectively: 146.9 +/- 89.5 and 215.1 +/- 102.5 mg/dL, P = .001). Despite routine antihyperlipemic treatment those high levels were maintained for 12 months. CONCLUSIONS: We achieved 100% graft and patient survival rates for 1 year among patients who were using sirolimus. But the most important role in defining the morbidity and mortality in this group of patients is cardiovascular events; for this reason the abnormalities in the lipid profile must be taken seriously.

Tacrolimus plus low-dose mycophenolate mofetil in renal transplant recipients: better 2-year graft and patient survival than with a higher mycophenolate mofetil dose.

OBJECTIVES: Mycophenolate mofetil (MMF) has become more widely prescribed in recent years, but its adverse effects on the gastrointestinal system and bone marrow restrict its use in certain settings. The aim of this study was to compare the demographic features and clinical data for 173 renal transplant recipients who received tacrolimus (TAC) plus 1 g/d MMF (group I, n = 112) versus TAC plus 2 g/d MMF (group II, n = 61 patients) over a 2-year period. Each patient received similar TAC doses. METHODS: We compared demographic data and clinical data for each case: acute rejection (AR) episodes, chronic rejection (CR) episodes, death, graft loss, development of posttransplantation diabetes mellitus (PTDM), and posttransplantation hypertension rates. RESULTS: Demographic features were similar. There were also no significant differences between groups I and II with respect to number of AR episodes (17/112 vs 12/61, respectively), number of CR episodes (4/112 vs 1/61, respectively), PTDM, and hypertension rate (P > .05). Kaplan-Meier survival analysis revealed 2-year graft survival rates of 94% in group I versus 83% in group II. The corresponding 2-year patient survival rates were 100% in group I versus 91% in group II. The graft survival and patient survival rates in group I were significantly higher than those in group II (log-rank 0.005 and 0.001, respectively). CONCLUSIONS: The 2-year graft and patient survival rates for the renal transplant recipients in this study suggest that the combination of a full TAC dose with 1 g/d MMF is a better choice than 2 g/d MMF.

Effect of cyclosporine, mycophenolate mofetil, and their combination with steroids on apoptosis in a human cultured monocytic U937 cell line.

Transplant patient plasma produces an increased rate of mononuclear cell apoptosis despite a normal serum creatinine value. Immunosuppressive medications may be one factor that causes an altered apoptotic pattern. We evaluated the in vitro effects of various doses of cyclosporine, mycophenolate mofetil, and steroids on apoptosis of a cultured human monocytic U937 cell line, using estimates by fluorescence microscopy and annexin V assays. Increasing cyclosporine concentrations (100 to 800 ng/mL) progressively increased apoptosis rates (16% to 32%). The combination of steroid (0.01 microg/mL) and cyclosporine increased the apoptosis rate to 45%. Mycophenolate mofetil alone (0.3 microg/mL) led to an apoptosis rate of 34%. Therapeutic levels of mycophenolate mofetil from 3 to 7 microg/mL led to apoptosis rates from 56% to 67%. The combination of cyclosporine, steroid, and mycophenolate mofetil increased the rate of apoptosis to 95%. Immunosuppressive therapy may contribute to the high rate of apoptosis observed among mononuclear cells of transplanted patients. This effect may alter patient susceptibility to infections and contribute to a unique mechanism of immunosuppression.

Influence of inflammation on the relation between markers of iron deficiency in renal replacement therapy.

Iron deficiency is an important factor in the management of anemia in both dialysis and transplant patients. Serum ferritin and transferrin saturation (TS) may be influenced by the presence of inflammation. Recently, the soluble transferrin receptor (s-TfR) has been considered to be a marker of functional iron stores. In this study, parameters of the iron state were investigated in terms of agreement (assessed by kappa) with the diagnosis of iron deficiency and with inflammation. The study was performed in 38 hemodialysis, 31 continuous ambulatory peritoneal dialysis, and 21 anemic renal transplant patients. CRP and amyloid A protein (AAP) were studied as markers of inflammation. Iron deficiency was defined as ferritin <100 mg/L, TS <20%, or s-TfR >1.76 mg/mL. We observed that s-TfR levels were significantly related to both dialysis duration (r = 0.28 in dialysis and r = 0.60 in transplant patients, both P <.05) and PTH levels (r = 0.23 in dialysis and r = 0.55 in transplant patients, both P <.05). Among the transplant group, ferritin and TS, as well as TS and s-TfR were significantly related (r = 0.84 and r = -0.64, respectively), but not s-TfR and ferritin. Among the dialysis group, ferritin and TS, and also TS and s-TfR, were significantly related (r = 0.35 and r = -0.30, respectively), whereas s-TfR and ferritin were not. In the transplant group, the kappa value for agreement between ferritin and TS in the diagnosis of iron deficiency was 0.76 (P =.006), and 0.33 (P =.04), respectively. Among patients with CRP levels <0.3 mg/L or AAP levels <6.4 mg/L, the relation between parameters of iron state was more robust. The kappa value for agreement between ferritin and s-TfR was 0.49 (P =.006) in the dialysis group and 1 (P =.002) for that between ferritin and TS in the transplant group. Our results suggest that PTH levels may influence s-TfR levels. Discordance between ferritin, TS, and s-TfR as markers of iron deficiency might be explained by the effects of inflammation.

Seroprevalence of antibodies to legionella pneumophila in hemodialysis patients.

Patients with chronic renal failure are at increased risk for infections because of impaired cellular immunity. This study was designed to determine the prevalence of antibodies to Legionella pneumophila serogroups 1 to 6 and to evaluate the possible risk factors for Legionnaires' disease in hemodialysis patients. Serum samples to be screened for antibodies against L pneumophila and risk factor data were collected from 252 hemodialysis patients. The overall prevalence of L pneumophila antibodies in hemodialysis patients was found to be 5.16% There was no statistically significant difference between L pneumophila seropositivity and potential risk factors. Further studies are needed to determine possible risk factors for Legionnaires' disease in hemodialysis patients.

Cigarette smoking in renal transplant recipients.

Cigarette smoking may adversely influence patient and graft survival. In Europe and the United States the prevalence of cigarette smoking in dialysis patients is 35% to 40% and 25%, respectively. In Turkey, the estimated prevalence of cigarette smoking rate in the normal population is 26%. This study evaluated the rate of smoking in 63 cadaveric, and 158 living-related renal transplant recipients including (150 men, and 76 women of 38 +/- 12 years; range, 8 to 70) who were operated between 1986 and 2001. Demographic data were collected with a questionnaire delivered to patients during their routine outpatient visits. During this time period, 8 patients had died, 4 from hemophagocytic syndrome, 2 from cardiovascular disease, 1 from Kaposi sarcoma and 1 from a cerebrovascular accident. Twenty-three patients have lost their grafts. While at the time of transplantation 97 (42%) were smoking cigarettes, only 29 (12%) continued smoke after transplantation. Male gender significantly correlated with cigarette smoking (P =.000). Twelve smokers were single but 85 out of 97 were married, a statistically significant difference (P =.010). In contrast there was no significant relationship between pretransplant smoking and educational status (P =.354); graft loss and smoking (P =.129); or mortality and smoking (P =.224). There was a significant relationship between pretransplant and posttransplant smoking (P =.000). There was no relationship between pre- and post-transplant smoking and development of diabetes mellitus or hypertension. Interestingly the posttransplant serum albumin level was lower among smokers than nonsmokers (4.44 +/- 0.02 g/dL vs 4.30 +/- 0.02 g/dL; P =.019). There was a close relationship between transplantation duration and smoking.

Is there any effect of compliance on clinical parameters of renal transplant recipients?

Noncompliance with regard to diet, medications and routine physician visits is frequently observed among some patient groups. This results in late graft dysfunction and behavior loss. In the present study, we defined compliance as attendance at 80% or more outpatient visits. The study included 63 cadaveric and 158 living-related renal transplant recipients namely, 150 men and 76 women of 8 to 70 years of age (median 38 +/- 12) who were operated between 1986 and 2001. Demographic data, number of visits attended per month, cigarette smoking, and alcohol intake were probed with a questionnaire that was delivered to the patients, 8 of whom died; hemophagocytic syndrome (n = 4), cardiovascular disease (n = 2), Kaposi' sarcoma (n = 1), and cerebrovascular bleeding (n = 1). Twenty-three patients had lost their graft. Compliance among men was lower than among women, a result that trended toward statistical significance (P =.087). Compliance was not related to marital status (P =.297), but tended to increase with educational background (P =.059). Graft loss (P =.546) and aging (P =.509) were not related to compliance. There was no relationship between compliance and mortality rate (P =.526). Interestingly, living-related kidney transplant recipients showed lower compliance than cadaveric kidney recipients, a result that was statistically significant (P =.04). Noncompliance was also related to cigarette smoking during the pre- and posttransplant periods (P =.008 and P =.03, respectively), as well as alcohol intake (P =.000). In conclusion, male gender and living-related donation are related to noncompliance, but (in contrast with literature) not young age, graft loss, or mortality. Compliance increases with educational status of the patients. Smoking and alcohol intake are closely related to noncompliance.

Plasma homocysteine levels in renal transplant patients on tacrolimus therapy.

Increased plasma total homocysteine levels afford an independent risk factor to assess cardiovascular morbidity in patients with normal and impaired renal function, including stable transplant recipients. The purpose of this study was to evaluate plasma homocysteine levels and factors known to influence homocysteine metabolism (folate and Vitamin B(12)) in renal transplanted patients treated with tacrolimus. Plasma homocysteine, serum folate and serum vitamin B(12) concentrations were measured in 18 cadaveric renal transplant patients with stable function both before and 3 months after the renal transplantation. While the mean plasma homocysteine level in the renal transplant group was significantly higher than in the control group, no significant change was observed following renal transplantation under tacrolimus therapy (16.84 +/- 6.43 micromol/L vs 16.02 +/- 6.54 micromol/L). The levels of folate before and after transplantation were considerably lower than the control group; a significant effect of tacrolimus has not been observed (7.32 +/- 4.68 ng/mL and 7.55 +/- 5.20 ng/mL). Serum vitamin B(12) levels in the transplant group were significantly lower than the control group; a significant decline was seen 3 months after the renal transplantation (448.94 +/- 230.03 pg/mL vs 334.38 +/- 240.61 pg/mL). Consequently, although plasma homocysteine levels of renal transplant recipients are higher, a lowering effect of tacrolimus therapy was not observed on plasma homocysteine levels. The lower levels of folate and Vitamin B(12) in the transplant group compared to a control group supports therapy with folate and Vitamin B(12) to decrease homocysteine concentrations.

Influence of tacrolimus plus mycophenolate mofetil regimens on acute rejection rate and diabetes mellitus development in renal transplant recipients.

In this study we investigated the influence of a tacrolimus (TAC) plus mycophenolate mofetil (MMF) immunosuppressive regimen on the acute rejection rate and side effect profile in renal transplant recipients. The study included 80 living-related and 40 cadaveric donor renal transplant recipients (82 men, 38 women) of mean age 35 +/- 10 years (range, 16 to 58) who were operated between August 1999 and September 2002. The mean HLA mismatches was 3 +/- 1 (range, 0 to 5). All patients received prednisolone, MMF (2 g/d for the first 14 days posttransplant and then 1 g/d) plus TAC (0.2 mg/kg/d). They were followed for the development of rejection attacks and side effects. Diabetes mellitus developed in 13 patients (9 men, 4 women; 10.8%). Initially, patients required insulin therapy but after 6 months, 5 recipients no longer needed insulin therapy and were switched to oral hypoglycermic agents and diet control. Hypertension was diagnosed in 58 patients (48.3%). Neither gender nor donor origin (P =.14; P =.79, respectively) produced a significant difference in diabetes mellitus development. Biopsy proven acute rejection episodes were observed in 16 out of 120 patients (13.3%). Six out of 120 patients lost their grafts throughout the study period including one death because of suicide, one because of cytomegalovirus disease and hemophagocytic syndrome, one due to posttransplant lymphoproliferative disease and two to a cardiac arrhythmia. Only one patient lost his graft due to acute accelerated vascular rejection. Biopsy-proven chronic rejection appeared in one patient. In conclusion, although the incidence of insulin-dependent diabetes mellitus during posttransplant 6 months, seems high it decreased to 1.6% upon reduction of the TAC dosage. TAC plus MMF immunosuppression seems effective and safe in terms of acute rejection rates and side effect profiles.

Chemical peritonitis associated with high dialysate acetaldehyde concentrations.

BACKGROUND: During the standard heat sterilization process of lactate-buffered peritoneal dialysis (PD) solutions, glucose degrades to form compounds called glucose degradation products such as acetaldehyde, formaldehyde, or glyoxal. Despite evidence that these products may be responsible for some in vitro cytotoxic effects induced by commercially available PD fluids, data on their acute or chronic effects on the human peritoneum is scarce. SUBJECTS AND METHODS: This case presentation is based on an observation of 21 aseptic peritonitis cases of unknown aetiology. All cases appeared within one month in a university hospital PD unit that had a peritonitis rate of 1 episode/26 patient months and 55 active patients on CAPD. Acetaldehyde level in the bags was assayed by gas chromatography. RESULTS: Twenty-one patients presented with signs of peritonitis including cloudy dialysate and abdominal tenderness with additional abdominal pain in 11 patients and vomiting in one. In all cases, cultures and Gram stains were negative for micro-organisms. Fever was not observed in any patient. Average dialysate white blood cell count was 1795/mm(3). All patients were free of intraperitoneal medication when symptoms appeared. Patients were using PD solutions from a newly established domestic production plant. Apparently all patients with symptoms of peritonitis used bags with the same lot number and the solution in the bags appeared to be darker in colour than that in bags with other lot numbers. Chemical analysis of the unused PD solution samples revealed acetaldehyde levels of 17-20 p.p. m. in bags containing darker solution, which is very high compared with the usual acetaldehyde level of 6 p.p.m. in heat-sterilized PD solutions. CONCLUSIONS: Based on the above findings, we hypothesize that higher levels of acetaldehyde and possibly other glucose degradation products may have been an aetiological factor in these 21 cases of chemical peritonitis. Our observation suggests that acetaldehyde, in concentrations 3-4 times higher than the usual level in commercially available PD solutions, may induce acute sterile peritonitis in CAPD patients.