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.

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.

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.

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.

Tc-99m-HMDP bone uptake quantification and plasma osteocalcin levels in hemodialysis patients--a preliminary study.

In this preliminary study plasma osteocalcin levels and Tc-99m-HMDP (Technetium 99m hydroxymetylene diphosphonate) bone uptake (BU) were measured in 10 chronic end-stage renal failure patients who were on maintenance hemodialysis. The aim of this study was to determine the correlation between bone uptake and osteocalcin-a sensitive and specific marker of osteoblastic activity. There was a statistically significant increase in both 20 and 180 minute uptake in the patient group (36 +/- 2.7 and 39 +/- 3.6) when compared to the normal volunteers (32 +/- 3.1 and 19 +/- 2.7). Plasma osteocalcin levels were also significantly high (24.5 +/- 5.6 ng/ml) when compared with normal values (6.5 +/- 2.3 ng/ml). The correlations between osteocalcin and 20 and 180 min BU were high (r = 0.62 and 0.72 respectively). In conclusion, our preliminary study suggests that, in hemodialysis patients, Tc-99m-HMDP bone uptake quantification is a sensitive and non-invasive method for showing increased osteoblastic activity.

Transfer of native insulin through the peritoneal membrane during CAPD in non-diabetic and diabetic patients.

Because of its relatively small molecular size of 5800 daltons, insulin is a transperitoneally diffusable substance. Insulin is also known to be a mitogenic coadjuvant for mice fibroblasts, and safety of its long-term intraperitoneal use has been questioned because of the potential risk for peritoneal fibrosis. For similar reasons native insulin content of the peritoneal effluent should also not be neglected. To our knowledge, no sufficient data are available about native insulin transfer to dialysate during continuous ambulatory peritoneal dialysis (CAPD). In this study we measured plasma and dialysate immune-reactive insulin levels during a 4 hour peritoneal exchange in 9 nondiabetic and 4 type II diabetic end-stage renal disease patients on CAPD. In both plasma and dialysate, insulin levels were higher in diabetic patients. At hour 4 of dwell time, plasma insulin was 37.5 +/- 7.9 microU/mL in non-diabetics and 64.2 +/- 34.1 microU/mL in type II diabetics. In both groups, dialysate insulin was 1.5 to 2 x higher than their simultaneous peripheral vein insulin levels and was measured as 88.1 +/- 26.8 microU/mL in nondiabetic group and 101.7 +/- 52.6 microU/mL in the diabetic group at hour 4 (p < 0.005 vs 4 hour plasma level). In conclusion, in both diabetic and nondiabetic CAPD patients, native insulin was present in the dialysate in amounts exceeding simultaneous plasma levels. Equilibration with high portal vein insulin content through hepatic capsule may explain higher insulin concentrations measured in the dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cefodizime on peritoneal mononuclear- and polymorphonuclear-cell chemotaxis.

In this study, a third-generation cephalosporin with proposed immunomodulatory properties, cefodizime, was investigated to see if it has any effect on the chemotactic activity of human peritoneal monocyte and polymorphonuclear cell populations ex vivo. Ten continuous ambulatory peritoneal dialysis patients with peritonitis were entered in the study. Monocytes and polymorphonuclear cells were isolated from the patients' peritoneal effluent prior to initiation of any antibiotic therapy. Chemotaxis was measured by the Boyden chamber method before and after 2-hour incubation with cefodizime (200 mg/2L). Following 2-hour incubation with 200 mg/2L cefodizime, monocyte chemotaxis was increased from 36.8 +/- 5.6 microns to 50.2 +/- 6.6 microns (P = 0.0005). A similar increase was observed in polymorphonuclear cells from 42.0 +/- 8.8 microns to 48.7 +/- 10.3 microns (P = 0.02). We conclude that cefodizime acts as a priming agent on peritoneal polymorphonuclear cells, particularly on monocytes, and increases their chemotactic movements.

Response to triple treatment with omeprazole, amoxicillin, and clarithromycin for Helicobacter pylori infections in continuous ambulatory peritoneal dialysis patients.

In this study, the response to triple treatment with omeprazole, amoxicillin, and clarithromycin was investigated in continuous ambulatory peritoneal dialysis (CAPD) patients with Helicobacter pylori (Hp) infections. The study enrolled 20 CAPD patients (11 male, 9 female) who had dyspeptic complaints. The mean age of the patients was 46 (range: 21-65). The study also enrolled, as a control group, 124 patients (66 male, 58 female) who had no systemic disease, but who had upper gastrointestinal endoscopy for dyspeptic complaints. The mean age of the patients in the control group was 47 years (range: 20-74 years). Upper gastrointestinal endoscopy, rapid urease test (CLO test), and direct histologic examination were carried out to detect Hp infection. Hp infection was detected in 10 cases (50%) in the CAPD group and in 53 cases (43%) in the control group. In both groups, patients with Hp infection received the triple treatment of omeprazole 20 mg twice daily for 30 days, amoxicillin 500 mg thrice daily for 15 days, and clarithromycin 500 mg thrice daily for 15 days. To assess response to treatment, upper gastrointestinal endoscopy, CLO test, and direct histologic examination were repeated 3 months after initiation of the treatment. Hp was eradicated in all of the 11 CAPD patients (100%), and in 42 of the control patients (92%). Our results suggest that the triple treatment with omeprazole, amoxicillin, and clarithromycin for Hp infection is as effective in CAPD patients as in the normal population.

[Fulminant meningococcemia]. / Fulminant meningokoksemia.

Fulminant meningococcemia is a rare clinical form of meningococcal disease which has been frequently fatal. In this case report, two patients with fulminant meningococcemia which have been cured completely were presented and the related literature was examined.