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After transplantation, diarrhea may be caused by infectious agents, drug-specific effects, metabolic conditions, or mechanical complications of surgery. Determining the cause helps to determine whether to initiate antimicrobial therapy and the duration of treatment. In this study we aimed to determine the causes of diarrhea in kidney or liver recipients. Fifty-two diarrhea episodes among 43 solid organ recipients were evaluated. The cause of diarrhea was detected in 43 patients (82.6%). Infectious etiologies accounted for 33 out of the 43 episodes (76.7%) in which a specific cause was determined: Giardia lamblia in 9, Cryptosporidium parvum in 7, cytomegalovirus (CMV) in 6, Clostridium difficile in 3, Campylobacter jejuni in 2, Shigella sonnei in 2, Salmonella enteritidis in 1, rotavirus in 1, Entamoeba histolytica in 1, and Blastocystis hominis in 1. Non-infectious etiologies were found for 10 episodes (23.3%): mycophenolate mofetil-associated diarrhea in 5, antibiotic-associated diarrhea in 2, colchicine-associated diarrhea in 2, and laxative drug-associated in 1. Non-infectious etiologies seem to be relatively common causes of diarrhea among transplant recipients. Therapy was adjusted in 5 patients because of mycophenolate mofetil-associated diarrhea. CMV and C. parvum, which are seldom seen in the normal population, were frequent causes of diarrhea in this group. Evaluating the transplant recipients for non-infectious causes of diarrhea is important in prompt diagnosis and treatment. [ABSTRACT FROM AUTHOR]

An increased frequency of infections has been reported in patients with chronic liver disease. The tendency of patients in this population to acquire UTI is not completely understood. We aimed at investigating the incidence of UTI in children with cirrhosis, before liver transplantation. Twenty-six children (9 girls, 17 boys; mean age, 7.66 ± 5.73 yr) with chronic liver disease who had undergone liver transplantation between 2002 and 2004 were included. On admission for liver transplantation, patients were examined for presence of UTI. Serum biochemistry, complete blood cell count, urinalysis and culture, glomerular filtration rate, and abdominal ultrasonography were performed prior to liver transplantation. Ten of 26 patients (38.5%) were found to have symptomatic UTI. Urine cultures revealed E. coli in five (50%), Klebsiella pneumoniae in three (30%), Enterococcus faecalis in one (10%), and Enterobacter aeruginosa in one (10%) patient(s), respectively, as etiologic factors. The etiologies of chronic liver disease in our patients with UTI were BA in five, PFIC in three, Wilson's disease in one, and alpha-1 antitrypsin deficiency in one patient. We found a significantly greater number of UTIs in patients with biliary atresia than in those without biliary atresia (p < 0.05). The mean age of the patients with UTI was 2.75 ± 3.49 yr, which was significantly lower than in those without UTI (9.75 ± 4.86 yr, p < 0.05). Levels for white blood cells, thrombocytes, ALT, and alkaline phosphatase were significantly higher in patients with UTI than in those without UTI. There were no significant differences between the groups with regard to serum albumin, bilirubin, AST, GGT, BUN, or creatinine levels, glomerular filtration rate, duration of disease, and PELD scores. In patients with bacteriuria, renal USG revealed normal findings in all, but except one patient who had pelvicalyceal dilatation. Scintigraphic findings demonstrated acute pyelonephritis in six (60%) patients with UTI. VCUG demonstrated vesicoureteral reflux in two patients. In conclusion, symptomatic UTI is common in children with cirrhosis. It occurs more frequently in patients with biliary atresia than it does in patients with other types of chronic liver disease. In febrile children with chronic liver disease, UTI should be considered in the differential diagnosis. [ABSTRACT FROM AUTHOR]

To investigate the influence of HLA match on graft survival, we evaluated 878 live-donor and 183 cadaver-donor kidney transplantations performed at our hospital between October 1985 and November 2001. In the 878 live-donor cases, 273 of the donors were mothers, 131 were fathers, 281 were siblings, 28 were offspring, 89 were second-degree relatives, and 76 were unrelated (68 spouses and eight emotionally attached friends). The 1-, 3-, and 5-year graft survival rates in the first-degree living-related transplantation group were 90%, 76%, and 66%, respectively. The corresponding rates in the second-degree living-related group were 90%, 75%, and 70%, respectively; and in the living-unrelated group were 80%, 70%, and 60%, respectively. The 1-, 3-, and 5- year graft survival rates for the cadaveric kidney transplantations carried out at our center during this same time period were 78%, 60%, and 48%, respectively. These rates were significantly lower than those for each of the live-donor transplantations. We analyzed graft survival in relation to HLA mismatch, and a comparison of the findings showed that 0-mismatched cases had a statistically significant graft survival advantage over those with 1, 2, 3,4 and 5 mismatches; however, there were no significant differences between the groups with 1, 2, 3, 4 and 5 mismatches. In conclusion, even kidneys from live donors in transplantations with suboptimal donor-recipient HLA matching show better 5-year survival than cadaveric grafts in transplantations. These results from a single centre suggest that immunological as well as nonimmunological factors are associated with the pathogenesis of late graft loss. [ABSTRACT FROM AUTHOR]

Immunosuppressive therapy for organ transplant recipients is complicated by high rates of malignant diseases, one of these being Kaposi's sarcoma (KS). We reviewed the records of 1075 patients who underwent kidney transplantation at our center between October 1985 and May 2002. A total of 52 malignant diseases were observed in 50 patients (4.7%), during the post-transplantation period. Kaposi's sarcoma was identified in 16 of these 50 individuals. Of the 16 recipients, six were male and 10 were female. The mean age in the group was 39±9 years (range: 10–62 years). At the time of the KS diagnosis, 14 of the recipients were taking triple-drug immunosuppressive therapy consisting of cyclosporine A, azathioprine, and prednisolone. The other two individuals were receiving azathioprine and prednisolone. The mean time from transplantation to diagnosis with KS was 24±15.2 months (range: 8–74 months). One recipient had concomitant lymphoma and KS. The lesions of seven patients were limited to the skin, five cases involved the skin and gastrointestinal tract, and four patients had disseminated disease. After KS was confirmed, the first-line of treatment was to withdraw cyclosporine A and azathioprine, and taper the prednisolone. The tumors were managed with appropriate surgical and/or medical therapy. At the time of writing, nine individuals were still alive: four had normal renal function and five had lost their grafts as a result of chronic rejection. We have found the combination of immunosuppressive drug withdrawal and chemotherapy to be very effective in patients with limited disease, but the results in cases of generalized disease have been poor. [ABSTRACT FROM AUTHOR]

Chronic allograft dysfunction (CAD) is a complex phenomenon caused by underlying kidney disease and superimposed environmental and genetic factors. We investigated the relationship between polymorphism in the gene encoding for angiotensin-converting enzyme (ACE) and CAD in renal transplant recipients. The study included 125 patients who underwent transplantation over a 5-year period. The following information was collected for each case: date of transplantation, age and sex of donor and recipient, donor type, cold ischemia time, number of HLA mismatches, number of acute-rejection episodes, and laboratory findings at discharge from hospital and annual rechecks. Blood pressure was measured at yearly intervals throughout the follow up. DNA isolated from mononuclear cells in peripheral blood was used as a template for amplification of insertion/deletion (I/D) polymorphism in the ACE gene by polymerase chain reaction. The proportions of patients with the different genotypes were DD=54.4%, ID=33.6%, and II=12%. Chronic allograft dysfunction was detected in 36 (52.9%) of the recipients with DD genotype and 15 (26.3%) of those with ID or II genotypes (P <0.003). Analysis of the major risk factors for CAD showed that the serum creatinine level at the time of hospital discharge, the cadaveric donor type, the ACE DD genotype, and the level of proteinuria at 1 year post-transplantation were associated with poorer renal function ( P <0.05). These findings suggest that the DD variant of ACE I/D gene polymorphism is associated with an increased risk of developing CAD. [ABSTRACT FROM AUTHOR]

Research on renal biopsies has shown that HLA class I antigens are distributed throughout the renal parenchyma, but that the distribution of HLA-DR varies greatly. We investigated HLA-DR expression in the biopsies of 90 renal transplants, and also semiquantitatively assessed the proportions of CD68-, CD3-, and HLA-DR-positive infiltrating cells by immunohistochemistry. The relationships between tubular DR expression and interstitial lymphocyte and macrophage infiltration were examined. Forty of the biopsies showed acute rejection (AR), 33 showed chronic rejection (CR), 10 showed suspected rejection (SR), and seven showed no evidence of rejection (NR). HLA-DR expression was noted in 35/40 (87.5%) of the AR cases, 22/33 (66.6%) of the CR cases, and 6/10 (60%) of the SR cases. Only one (14.3%) of the NR cases exhibited HLA-DR antigen expression in the renal tubules. The proportions of lymphocyte and macrophage infiltration observed in the interstitium were significantly correlated with the tubular DR expression in all cases (P <0.01). Six months after the biopsies were carried out, 24/35 (68.6%) of the AR patients with tubular DR expression showed second-episode rejection or deteriorated renal function. The remaining 11 AR cases with tubular DR expression had stable renal function at this stage. The cases that had no significant tubular DR expression had no problems with rejection or functional deterioration. These findings are consistent with the theory that expression of HLA-DR antigens on renal tubular cells may be a marker of rejection and poor graft outcome. [ABSTRACT FROM AUTHOR]

To determine the prevalence of joint pain and arthritis in renal transplant recipients, and to investigate relationships with various laboratory and clinical parameters. Eighty-two patients who underwent renal transplantation (RT) and had a joint examination reported on their level of joint pain and arthritis by questionnaire. The patients were then followed for a year, with repeated joint examinations and laboratory tests every 3 months. Thirty-one of 82 patients (37.8%) complained of joint pain before the RT, and seven of these 31 individuals reported continued pain after the operation. Seventeen of the 82 (20.7%) began to suffer joint pain after the RT. Six (7.3%) and three (3.7%) of the 82 patients developed arthritis before and after the transplantation, respectively. We found no statistical association between the joint pain and sex, age, cause of renal failure, dialysis duration, time since transplantation, bone mineral density, human leukocyte antigen type, serum levels of urate, parathormone, calcium, alkaline phosphatase, phosphorus, C-reactive protein, erythrocyte sedimentation rate, donor source (living-related or cadaveric), or presence of HCV infection. However, levels of serum cyclosporine higher than 200 ng/ml were significantly correlated with the joint pain. This study shows that joint pain is common before and after RT. In renal transplant recipients, joint pain is significantly correlated with serum cyclosporine levels. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of HLA-matching and donor type on recurrence of amyloidosis after renal transplantation. Thirty patients with systemic amyloidosis who received kidney transplants between 1985 and 2001 were included. Donor source and HLA tissue typing of the donor and recipient were evaluated in each case. Twenty of the 30 patients developed biopsy-confirmed recurrence of amyloidosis in their allografts. The time from transplantation to diagnosis of amyloidosis in the graft ranged from 18 months to 10 years. Eighteen of the 20 patients with recurrence had received their grafts from living-related donors (LRDs), and two had received their grafts from cadaveric donors. There was a strong correlation between amyloidosis recurrence and degree of HLA-DR matching (P <0.05). Further, in the recipients of the LRD grafts, the risk of amyloidosis recurrence was significantly higher when the donor-recipient pair were HLA-identical than when they were not perfectly matched ( P <0.01). The incidence of amyloidosis recurrence in our cases was significantly higher than the rates reported for other series. Most of the cases in previous reports involved cadaveric grafts. The higher rate of amyloidosis recurrence in our cases may be explained by the high proportion of LRD grafts, and by genetic susceptibility. [ABSTRACT FROM AUTHOR]

Although renal transplant recipients tend to exhibit similar clinical and immunological changes over time, some allograft biopsies show early interstitial fibrosis (IF). To evaluate the relationship between HLA-antigens and IF in renal allografts, we reviewed the HLA-A, -B, -DQ, and -DR antigens in 88 renal transplant recipients. For each antigen type, we determined the number of patients who did and did not possess the antigen. We then determined the mean time to onset of IF for each of these two groups, and statistically compared the means. In the second part of the analysis, we divided the 88 patients into those who did and did not show IF at 6 months post-transplantation, and then calculated the prevalence of each antigen type in the IF(+) and IF(–) groups. This same procedure was repeated with the patients grouped according to the presence of IF at 12 months post-transplantation. The groups of patients with HLA-B8, -B27, -DQ2, -DQ5, -DQ6, -DQ7, -DR4, -DR13, and -DR15, had significantly shorter times to IF onset after transplantation than the corresponding groups without these antigens (P <0.05). The groups that were IF(+) at 6 and 12 months post-transplantation had significantly higher frequencies of HLA-B8, -B27, -DQ2, and -DR4 than the corresponding IF(–) groups at these two timepoints ( P <0.05). The results indicate that any kidney recipient with these antigens is predisposed to developing diffuse IF in their graft relatively soon after transplantation. We conclude that although there is multiple etiological agents in the pathogenesis of IF one can not exclude a HLA association in such cases. [ABSTRACT FROM AUTHOR]

In this study, we retrospectively evaluated our long-term results of the recipients who received a second allograft. Between 3 November 1975 and 31 December 2001, our transplantation team performed 1365 kidney transplantations. Fifty (3.6%) of these patients underwent retransplantations. Forty-seven received their second transplantation and the remaining three received their third transplantation. The same low-dose triple drug immunosuppression protocol with prednisolone, azathioprine and cyclosporine A was used in both groups. There were two study groups: the patients in Group 1 (n =19) underwent allograft nephrectomy, while those in Group 2 ( n =31) did not. Demographic properties, rejection rates throughout the follow up period, serum creatinine levels within 12 months, graft and patient survival rates, postoperative complications, time interval between the transplantations, and HLA matchings were studied. For statistical analysis the Student's t and Kaplan–Meier tests were used, and P -values <0.05 were accepted as significant. Forty-one patients who underwent re-transplantation received kidney from living related donors and remaining 9 patients from cadaveric donors. Mean interval between first and second transplantations was 50 months (range, 1–192 months). Mean blood creatinine levels was 1.8 mg/dL (range, 0.8–6.5 mg/dL). HLA-AB and HLA-DR mismatches were 1.92±1.1 and 0.9±0.7, respectively. Acute rejection rates were significantly different between Group 1(9/19,47%) and Group 2(12/31,38%) (P =0.03). Graft loss was found to be lower in Group 1 (6/19, 32%) than that in Group 2 (11/31 35%), though these values were not statistically different ( P >0.05). The average interval between first and second transplantations was 32,1±21 months in Group 2 and 61,5±46 months in Group 1 ( P =0.018). The duration of hemodialysis before second transplantation were 17±9 months in Group 2 and 27±11 months in Group 1 ( P... [ABSTRACT FROM AUTHOR]

Our transplantation team performed 1061 kidney transplantations from October 1985 to November 2001. Sixty-nine of these were interspousal transplantations. In 61 cases the wife donated her kidney to the husband, and in the remaining eight cases the husbands were the donors. The average number of HLA-A, -B, and -DR mismatches were 3.5, despite the fact that the HLA matching was better for the transplants performed from the first-degree relatives (average number of HLA-A, -B, and -DR mismatches was 2.1). Ten-year graft survival rates were 55% for the former and 60% for the latter. HLA -A, -B, and -DR typing showed one antigen mismatch in one patient, two mismatches in nine, three mismatches in 17, four mismatches in 33, and more than four mismatches in eight patients. The mean recipient follow-up period was 90 months (range: 5–170 months). Mean ratio of donor body weight (DBW) to recipient body weight (RBW) was 0.9±0.1 (0.7–1.2). Median serum creatinin levels and creatinin clearance values were 1.9 mg/dl (1.1–3.6 mg/dl), 58.1 ml/min (25–106 ml/min), respectively. Statistically significant relationship between the DBW/RBW ratio and both the creatinin levels and the creatinin clearance values was observed. Eighteen rejection episodes were observed in the wife-to-husband transplantations and two in the husband-to-wife group. Ten recipients died in the follow-up period; the DBW/RBW ratio may have an important role for post-transplant graft functions. We conclude that although HLA matching is not ideal in these cases, graft spouses offer a good alternative to cadaveric kidneys, which are in critically short supply in Turkey. [ABSTRACT FROM AUTHOR]

In this study, we aimed to clarify the factors that may effect long-term graft and patient survivals. We retrospectively evaluated the outcome of 112 renal transplant recipients who shared paired cadaveric kidneys between 1985 and July 2001. There were two study groups, each with 56 patients, according to the timing of the operations. The operations were performed by the same transplant team, so Group 1 represents the recipients of the first kidney and Group 2, the second. The same low-dose triple drug immunosuppression protocol with prednisolone, azathioprine and cyclosporine A was used in both groups. Cyclosporine A was converted to tacrolimus in seven patients in Group 1 and in five patients in Group 2. Demographic properties, number of acute-rejection episodes, serum creatinine levels, creatinine clearance values, graft and patient survival rates, postoperative complications, recipient body weights, cold ischemia times, and de novo malignancies were studied. To analyze our results the Chi-square and Wilcoxon Signed Ranks tests were used, differences, with P <0.05 were accepted as significant. Regarding the HLA matchings, the groups were similar. Mean cold ischemia times were 22.1±8.7 and 23.3±9.1 h in Groups 1 and 2, respectively (P >0.05). Acute-rejection rates within the first month following the transplantation were also similar in both groups. Serum creatinine levels and creatinine clearance values at 30 days post-transplantation showed no significant difference between the groups ( P >0.05). One, 2 and 5 years' graft survival rates (Group 1 vs. Group 2) were 97% vs. 92%, 74% vs. 77% and 27% vs. 24%, respectively. No statistically significant difference was observed on returning to the hemodialysis rates (10/56 vs. 13/56). In Group 2, the rate of proteinuria (over 200 mg/day) throughout the follow-up period was significantly higher than that in Group 1 (Chi-square, P =0.03). Three patients underwent re-transplantation: one in Group 1 and two in... [ABSTRACT FROM AUTHOR]

The number of patients with end-stage renal disease increases, with kidney transplantation remaining the treatment of choice for this dismal disease. From January 1 to December 31, 2001, 48 kidney transplantations were performed at Baskent University Faculty of Medicine. Thirty-nine of the recipients were male and nine were female, and the average age of the patients was 31.8. Thirty-seven of these transplantations were performed from living donors, and 11 were from cadaver organs. Of these 48 patients, one died during the post-operative period as a result of septicemia. Graft nephrectomy was performed in one patient because of massive bleeding. There were 16 acute-rejection episodes in 12 patients during follow up, and all patients recovered. At the end of the year, the overall patient and graft survival rates were 98% and 95.8%, respectively. Despite these good results, there is an increasing number of patients on the waiting list and we are not able to use the full capacity of our center because of continued organ shortages. [ABSTRACT FROM AUTHOR]

Vaccination against hepatitis B virus (HBV) infection is very important for hemodialysis (HD) patients, as these individuals are at high risk because of intravenous interventions and therapies. The aim of this study was to examine how genetic factors may be related to the response of HD patients to the HBV vaccination. This was carried out by investigating the frequencies of HLA class I and II alleles in responders and nonresponders. The study included 256 (171 male and 85 female) HD patients who tested negative for antibodies to the hepatitis B surface antigen in pretransplantation evaluations performed at our center between 1986 and 1999. Each patient received four doses of 40 μg DNA-recombinant hepatitis B vaccine at 0, 1, 2 and 6 months. Group I consisted of the 166 patients who responded to the vaccination (anti-HBsAg >10 SI U/l) and Group II consisted of the 90 nonresponders (anti-HBsAg <10 SI U/l). The frequency of the HLA-A3 allele was significantly higher in Group I than in Group II (P =0.02). One hundred and seven of the 256 patients underwent renal allograft transplantation, and 14 recipients lost their grafts at a mean of 1326±1394 days. There was no significant difference in graft outcome between the responders and the nonresponders ( P >0.05). In conclusion, this was a preliminary study showing that HLA alleles may have immunomodulatory effects in end-stage renal failure patients. The response to hepatitis B vaccination is affected multifactorially and HLA-A3 may be a genetic predictor for responders, but further studies and larger series are required. [ABSTRACT FROM AUTHOR]

Many researchers are now focusing on ways in which the renin-angiotensin system (RAS) and RAS gene polymorphism affect progressive renal damage, hypertension, cardiac complications, and renal allograft function. In this study, we investigated the frequency of polymorphism in the genes for angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type 1 and 2 receptors (AT1 and AT2), and endothelial nitric oxide synthase (ec-NOS) in Turkish renal transplant recipients. Angiotensin-converting enzyme insertion/deletion (I/D) polymorphism was assessed in 125 patients. M235T polymorphism of the angiotensinogen gene, 1166 A/C polymorphism of the AT1 receptor gene, and 3123C/A polymorphism of the AT2 receptor gene, and intron 4 VNTR polymorphism in the ec-NOS gene were assessed in 40 of the patients. The latter list was also investigated in 50 healthy controls from the general Turkish population. DD/ID/II genotypes of the ACE gene were detected in 56%, 34%, and 10% of the kidney recipient group, respectively. In the 40 recipients who were tested for the other polymorphisms, the corresponding figures for the AGT TT/TM/MM genotypes were 0%, 82.5%, and 17.5%, respectively; for the AT1 CC/CA/AA genotypes were 0%, 2.5%, and 97.5%, respectively; for the AT2 AA/CA/CC genotypes were 0%, 0%, and 100%, respectively; and for the ec-NOS intron 4 aa/ab/bb genotypes were 0%, 12%, and 88%, respectively. The results revealed that Turkish renal transplant recipients exhibit a wide-range of RAS gene and ec-NOS polymorphisms. [ABSTRACT FROM AUTHOR]

Chronic allograft nephropathy (CAN) is a major problem after renal transplantation, and chronic inflammation is an important element of this condition. C-reactive protein (CRP) is an important marker of inflammation and atherosclerosis. This retrospective study analyzed the value of post-transplantation CRP monitoring in the prediction of CAN and graft failure in kidney transplantation. The study included 125 renal transplant patients whose CRP levels were in the normal range (<10 mg/l) at the time of transplantation. Serum CRP levels before transplantation, at 1 month and at 1 year post-transplantation, at the time of CAN diagnosis, and the mean level throughout follow up in patients without CAN were recorded. The CRP findings were compared in patients grouped according to whether or not they developed CAN. Chronic rejection was diagnosed in 40.8% of the patients, and 82.4% of this group progressed to graft failure at a mean of 45.8±30.4 months after the diagnosis of CAN. When the group CRP results were compared, the levels before transplantation were similar, but at 1 month post-transplantation the levels in the group with CAN were significantly higher (P <0.04). The mean CRP level at 1 year was also higher in the CAN group, but this difference was not significant. The mean level at the time of the CAN diagnosis was significantly higher than the mean level during follow up in the group without CAN ( P <0.01). Thus, the CRP levels were significantly higher in CAN group than in the group without CAN at two of the timepoints tested: immediately after trans plantation and at the time of CAN diagnosis. Regression analysis showed that the high CRP level at 1 month post-transplantation and at the time of the CAN diagnosis significantly influenced the allograft failure ( P <0.005 and P <0.01, respectively). In conclusion, post-transplantation CRP monitoring provides important information concerning the risks of CAN and graft failure. Testing of CRP levels should... [ABSTRACT FROM AUTHOR]

Pre and postrenal transplantation panel reactive antibody (PRA) screening is associated with increased rates of hyperacute or acute-graft rejection and graft loss. It has been suggested that phenotypic HLA-antigens are involved in PRA sensitization. This study investigated the relationships between HLA-specific antibody frequencies and PRA sensitization in Turkish patients with end-stage renal disease (ESRD). Three hundred and forty patients on the renal transplantation waiting list participated. We determined the level of PRA sensitization and the candidates' class I and II HLA-antibody profile. Panel reactive antibody levels greater than 30% were accepted as positive. The frequencies of the different antibodies in the sensitized group were calculated. Twenty-four (7%) of the 340 patients showed PRA-ABC positivity and 34 (10%) showed DR positivity. Thirty-nine (11.5%) of the candidates were PRA-positive. The most frequent class I HLA-antibodies in this group were A2, A34, and B56, and the most frequent class II antibodies were DR1, DR7, DR10, DR11, DR14, DR52, DQ1, DQ4, DQ6, and DQ7. Analysis showed that the presence of each of these HLA class II antibodies was significantly correlated with PRA positivity. Apart from the presence of HLA-A2, A24, and DR11 antibodies, the HLA profile for the PRA-positive candidates differed from that of the general Turkish population. In conclusion, identification of the associated HLA-specific antibodies and correlation with the Turkish population HLA-antigen distribution will identify high-risk patients as candidates for transplantation. [ABSTRACT FROM AUTHOR]

Pruritus is a common problem among hemodialysis (HD) patients, and the etiopathogenesis of uremic pruritus is still unclear. This study evaluated the relationships between pruritus and human leukocyte antigen (HLA) types in individuals on HD. Seventy-nine HD patients (32 females and 47 males; mean age: 38.76±14.04 years; age range: 9–70 years) were studied. The HD duration in the group ranged from 9 to 142 months (mean: 52.53±32.48 months). Subjects were assigned to one of two groups, one with pruritus (n =45) and one without pruritus ( n =34). Demographic and laboratory parameters were compared in patients with and without pruritus. There were no significant differences between the groups with respect to age, sex, or HD duration. There were also no significant differences in the groups' serum levels of Hb, ferritin, BUN, creatinine, Ca, P, PTH, uric acid, AST, ALT, GGT, total bilirubin and ALP ( P >0.05 for all). There were also no differences between the two groups according to the presence of HbsAg and anti-HCV ( P >0.05). The frequency of the HLA-B35 allele was significantly higher in the pruritus group than in the group without pruritus ( P <0.05). The pruritus group also had higher frequencies of HLA-A3 and -DR4, but these differences were not significant ( P >0.05). The results of this preliminary study indicate that the HLA-B35 antigen may contribute to pruritus in HD patients. Further studies are needed to clarify the role that the HLA system plays in pruritus in this patient group. [ABSTRACT FROM AUTHOR]

The graft survival rates of sensitized kidney recipients have been shown to be lower than those of nonsensitized patients. Therefore, panel reactive antibody (PRA) and cross-match determination is accepted as mandatory screening for renal transplantation candidates. Our recent previous study showed that simvastatin has a significant immunosuppressive effect in PRA-positive and/or crossmatch-positive patients. We present the long-term pre and post-transplantation outcomes of simvastatin treatment in highly sensitized dialysis patients. Thirty patients were followed for a mean period of 22 months. The PRA and flow cytometric measurements were performed at monthly intervals. Ten patients underwent successful kidney transplantation (eight living-related and two cadaveric). None of the patients developed hyperacute or acute rejection, and there was no graft loss during the 16.1±8.2 months of post-transplantation follow up. Of the 18 patients who stayed on dialysis throughout the study with PRA-positivity, six were lost to follow up and three spontaneously stopped taking the simvastatin. In the latter three cases, the PRA levels rose significantly after the drug was discontinued. Eight of the remaining nine PRA-positive patients showed significant drops in mean PRA level over the study period, and entered the range considered acceptable for transplantation. Only one patient showed persistently high PRA levels throughout the study. In one patient, the drug had to be discontinued because of acute toxic hepatitis. In conclusion, the results indicate that long-term continuous simvastatin therapy is effective in immunized and highly sensitized dialysis patients. Meanwhile, it has a beneficial effect on 1-year graft survival rates in sensitized renal transplantation patients. [ABSTRACT FROM AUTHOR]

Tacrolimus has been known as an effective immunosuppressive drug since 1987, and in our clinic we have used this agent since November 1999. Our transplantation team has performed 1359 kidney transplantations since 1975. Until November 1999, all of these recipients received a standard low-dose triple-drug immunosuppressive regimen of prednisolone, azathioprine, and cyclosporine A. Since November 1999, cyclosporine A was replaced by tacrolimus in 95 kidney recipients. In this study, our early results are analyzed. The mean follow-up period after alteration of the immunosuppressive protocol was 12 (1–24) months. The mean time interval between the transplantation and the tacrolimus replacement was 34±11.4 months (1–158 months). Chronic allograft nephropathy in 16 (17%) patients, nephrotoxicity related to cyclosporine A in 22 (23%) patients and steroid-resistant acute rejection in 57 (58%) were the indications of tacrolimus conversion. One acute-rejection episode in 30 patients, two in 17, and three in 10 patients were observed before starting the tacrolimus. After the drug conversion, one acute rejection in 17 and two acute rejections in four patients were observed. Graft loss was seen in 15 (15%) patients after the drug conversion. Tacrolimus was withdrawn because of diabetes mellitus in seven patients, epilepsy in four, and severe Nocardia sepsis, lymphoma and Kaposi sarcoma in one patient each. Decreases of serum creatinin levels and also increases in blood glucose levels showed a statistically significant association with the tacrolimus doses (P =0.0004, P =0.04, respectively). The decrease in creatinin clearance values was closely related to the increase in tacrolimus levels. The target range with maximum efficacy and minimum toxicity seems to be 10–15ng/ml. Tacrolimus conversion can be successful in cases of rejection and nephrotoxicity, but dose-dependent blood glucose elevations must be followed closely in these patients. [ABSTRACT FROM AUTHOR]

Elevated levels of intact parathyroid hormone (iPTH) are not uncommon after renal transplantation, and this disturbance may affect renal allograft function. This study investigated whether iPTH levels were related to histopathological findings of acute rejection in kidney graft biopsies. Thirty-eight renal transplant recipients (29 males, nine females; mean age 29.5±10.3years) were studied. Renal allograft biopsy was performed in each case to investigate increased creatinine levels. Lymphocyte and macrophage infiltration of the interstitium was evaluated immunohistochemically with monoclonal antibodies to CD3 and CD68. Expression of HLA-DR and fibronectin were also studied. The proportion of interstitial cell staining was graded semiquantitatively. Serum calcium, phosphorus and iPTH levels before and after the renal transplantation were compared. Patients were grouped according to their stabilized iPTH levels at 3 months post-transplantation. Group I (n =13) exhibited persistently elevated iPTH levels (levels elevated since surgery), and Group II ( n =25) showed persistently low-normal iPTH levels. The mean age of the Group I patients was significantly lower, and their serum calcium levels post-transplantation were significantly higher than those in Group II ( P =0.02 and P =0.03, respectively). Persistent elevation of iPTH was strongly associated with interstitial T-cell density, macrophage density, and glomerular fibronectin expression in the renal allograft biopsies ( P <0.05). Also, the time to fibrosis was significantly shorter in Group I ( P =0.02). The study revealed that PTH has a potent immunomodulatory effect, and that persistent hyperparathyroidism has a significant impact on renal allograft outcome. The data indicate that the serum iPTH level is a valuable indicator of immune response, and that regular monitoring of serum iPTH levels is essential after renal transplantation. [ABSTRACT FROM AUTHOR]

Abstract:Intravenous ascorbic acid administration (IVAA) could override recombinant human erythropoietin (rHuEPO) resistance in hemodialysis patients with iron overload. We investigated the hematopoietic response to IVAA in iron-overloaded hemodialysis patients. We included 36 patients whose ferritin levels were higher than 500 μg/L and who needed more than 100 U/kg/week of rHuEPO. The study included an initial phase (500 mg IVAA twice weekly was administered to all of the patients for 8 weeks) and a maintenance phase (patient groups were formed; Group 1 received IVAA 500 mg/week for 8 weeks and Group 2 received no therapy). We observed a significant increase in hematocrit and transferrin saturation and a decrease in the percentage of hypochromic red cells and ferritin levels at the end of the initial phase. The total weekly-required rHuEpo dose and rHuEpo/hemoglobin also fell significantly after the initial phase. The response remained stable in patient groups during the maintenance phase. In 6 nonresponders, the hypochromic red cells were <10%. In conclusion, IVAA effectively overrides rHuEPO resistance in iron-overloaded hemodialysis patients. [ABSTRACT FROM AUTHOR]

Abstract: Biliary atresia is defined as partial or total obliteration of the extra-hepatic bile ducts. In advanced cases, liver transplantation (LTx) is considered the most appropriate treatment. This report describes a female patient whose biliary atresia and subsequent cirrhosis required LTx at 1 yr of age. Macroscopic inspection of the hilar region of the native liver post-Tx revealed the formation of a pouch in the hepatic duct and a stone in the lumen of the portal vein. X-ray diffraction analysis showed that the stone was composed of cholesteryl cinnamate, gluconic acid phenylhydrazide, Na β broma-allyl mercaptomethyl penicillinate, and Al2O3 crystals. While the cholesterol component is a known element of gallstones, we attributed the Na β broma-allyl mercaptomethyl penicillinate to the patient's drug therapy. Our literature search revealed no previous record or crystallographic analysis of portal vein phlebolithiasis. In this report we describe this rare finding. [ABSTRACT FROM AUTHOR]

In order to assess certain aspects of pediatric kidney transplantation (Tx) in Turkey, we retrospectively analyzed the results of 56 of these pediatric procedures performed at our center. From January 1986 to January 1998, 56 pediatric renal Tx (29 males, 27 females; 0–17 yr of age) were carried out at Başkent University Hospital. All were first-time Tx. Fifty-one (91%) patients were on hemodialysis and four (7.3%) were on peritoneal dialysis prior to Tx. Pre-emptive Tx was performed for only one patient. Living-related donors (LRD) provided 47 (84%) of the transplanted organs and cadaver sources were utilized for nine (16%) patients. The mean cold ischemia time (CIT) for cadaveric donors (CD) was 38.6 h (range 23–56 h). Among living-related graft (LRG) recipients, the average waiting time for Tx was 4 months for Tx performed after 1990 and 8 months for those prior to 1990 (p< 0.05). Median length of hospital stay for Tx was 17±1.1 and 18±1.4 days for LRG and cadaveric graft (CG) recipients, respectively. Fifteen of 47 (33%) LRG recipients and six of nine (67%) CG recipients received anti-rejection treatment within 30 days following the Tx surgery. Graft failure developed in 16 (12 LRG, four CG) recipients. Two patients developed Kaposi's sarcoma, 17 and 3 months after Tx. There were total of six deaths (four with functioning grafts). The 1-, 3-, and 5-yr graft survival rates were 93%, 75%, and 63%, respectively, and corresponding patient survival rates were 96%, 92%, and 77%. The social and educational status of 27 patients with functioning grafts were also evaluated. Our results showed that 56% of patients ended their education before high school and only three patients have been married. The high rate of school drop-out and unemployment among pediatric renal transplant recipients in our population underline the need for a more intensive rehabilitation program. [ABSTRACT FROM AUTHOR]

- Ten urological complications (2.9%) were found in 350 kidney transplants performed in this centre. These included obstructive uropathy (20%), urinary leaks (40%), distal uretic fistulas (necrosis) (30%) and renal calculi (10%). Two grafts were lost due to chronic rejection 9 and 30 months post-operatively. The remaining 8 patients have stable renal function (mean creatinine 1.5 mg%). It was concluded that meticulous surgical technique may reduce the number of urological complications and early diagnosis and prompt surgical treatment may help to save the grafts. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on orogenital ulcers in a liver transplant recipient.

Disseminated Nocardia infection has a high mortality and morbidity rate in solid organ transplant recipients, even when appropriate antibiotics are given. In this report a renal transplant recipient is described, who developed disseminated Nocardia asteroides infection with lung, eye, and brain involvement, in addition to coinfection with Trichophyton rubrum . [ABSTRACT FROM AUTHOR]

There are limited data on demographics, long-term follow-up, and iron/rHuEPO requirements of hemodialysis(HD) patients in Turkey. The aim of the study was to analyze the effects of the HD duration, primary illness, blood pressure, and age on serum albumin, CRP, blood pressure, iron/rHuEPO requirements, PTH, and HCV positivity of HD patients. 703 patients(280 women, 423 men, aged 47.8 ± 15.5 years) from 4 HD units were included and grouped according to the duration on HD. The demographic, clinical, and biochemical data of the last 3 months for each patient were recorded retrospectively. When the groups were compared, patients with a longer HD duration were younger and percentage of diabetic patients decreased as the duration increased. Serum albumin and CRP levels were similar between the groups. When the groups were compared according to the blood pressure profiles, after the 5th year, a decline in the systolic blood pressures was observed. Diastolic blood pressures were similar across the years. There was no significant difference in need of antihypertensive medicines. Iron requirements showed a fall after the 5th year, and an increase in after the 10th year. There was a decline in the hematocrit levels by the duration on HD but there was no change in rHuEPO requirements over the years. Parathyroid hormone levels and HCV positivity tended to increase across the years. Our results revealed that during the first 10 years, age, etiology(diabetes, hypertension), and blood pressure control seemed to be important factors affecting survival. Whereas, after the 10th year, patients seemed to be more prone to the long-term complications of HD, such as HCV infection, anemia, secondary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

The presence of persistently high C-reactive protein (CRP) levels is well known to be associated with a state of inflammation, malnutrition, and erythropoietin resistance in hemodialysis (HD) population. Meanwhile, a substantial group of patients present with intermittent elevations of CRP levels, and its clinical consequences are unclear. We designed this study to compare the inflammatory and nutritional parameters and erythropoietin requirements in HD patients with persistent or intermittent CRP elevation and those with CRP levels in without. We included 100 HD patients [age: 48.4 ± 14.3 years; HD duration: 69.3 ± 49.0 months (minimum 12 months)]. The 6-month retrospective clinical and laboratory data were retrieved from the patient records, and those with chronic inflammatory disease, malignancy, infectious complications, and surgery were excluded. The monthly determined CRP levels (at least 6 for each patient) were reviewed, and the patients were grouped according to their CRP levels as those with persistent (group 1), intermittent (at least one level of CRP 10 mg/L) (group 2), and those with CRP in normal ranges set by the laboratory (group 3). We compared the fibrinogen, ICAM-1, VCAM-1, albumin, prealbumin, normalized protein catabolic rate (nPCR), interdialytic weight gain (IDWG), and rHuEPO/kg/Hct results of the patient groups. The patient groups revealed significant differences in terms of fibrinogen (p < 0.001), albumin (p < 0.0001), prealbumin (p < 0.007), ICAM-1 (p < 00.2) levels and nPCR (p < 0.03), IDWG (p < 0.02), and rHuEPO/kg/Hct (p < 0.03) values. Group 2 presented to be in risk of inflammation and malnutrition with a decrease in albumin levels and nPCR and presence of rHUEpo resistance when compared to patients in group 3. We conclude that, similar to HD patients with persistently high CRP levels, those with intermittent elevation of CRP must also be considered to be in a state of chronic inflammatory response associated with malnutrition and erythropoietin resistance. This signifies the importance of regulatory monitoring of CRP in HD population. [ABSTRACT FROM AUTHOR]

Vascular access thrombosis is a frequent complication in hemodialysis (HD) patients. Genetic mutations, inflammation, and changes in the vascular wall are some factors that are thought to increase thrombosis risk. In this study, we tested for possible relationships between vascular thrombosis and some known thrombophilic mutation/polymorphisms in coagulation factors [factor V Leiden (FVL), prothrombin (Pt) G20210A, methylene tetrahydrofolate reductase (MTHFR C677T), factor XIII (F-XIII) Val34Leu, alpha-fibrinogen (AF) Thr312Ala, factor VII (F-VII) R353Q] and angiotensin I converting enzyme (ACE) gene in our HD patients. Patients who had experienced at least 3 episodes of AVF thrombosis composed of the study group, and patients who had never encountered this complication composed of the control group. None of the patients in either group had a history of diabetes mellitus, atherosclerosis, dialysis-related amyloidosis, or vasculitis. In order to find the frequency of F-XIII Val34Leu, AF Thr312Ala, and F-VII R353Q polymorphisms in our population, we also searched persons without renal disease or history of thrombosis (normal group). Results are summarized in Table. There was a tendency toward thrombotic mutation/polymorphisms in the study group for FVL, Pt G20210A, ACE I/D, and AF Thr312Ala. We suggest that patients who develop recurrent AVF thrombosis should be screened for the above-mentioned factors and investigated for other possible risk factors. This screening would allow more effective focus on prophylaxis. [ABSTRACT FROM AUTHOR]

Background/Aim: Clinical presentation and complications of end-stage renal disesase(ESRD) patients are under influence of many enviromental and genetic factors. In this study we aimed to define frequencies of BsmI and TagI Vitamin D receptor(VDR) gene polymorphisms and possible influences on clinical presentations in Turkish ESRD population.Methodology and Patients: 186 patients(111 male, 75 female) who are being maintained on hemodialysis were included. Genotyping was performed for the insertion/deletion BsmI(B→b, restriction site, exon VIII→IX), TagI(T→t, 352 exon IX) VDR gene polymorphisms. Last 12 months’ laboratory values(C-reactive protein, intact parathyroid hormone, albumin, calcium, phosphorus, Ca x P product) and clinical findings(vitamin D requirement, body weight) were recorded and analysed retrospectively.Results: Mean age and follow-up period lengths were 42.1 ± 12.6 years and 76.3 ± 43.9 months, respectively. Polymorphism percentages were as follows: BsmI; BB/Bb/bb: 28.9/65.3/5.8%, TagI; TT/Tt/tt: 36.7/60.5/2.8%, respectively. Further analysis revealed that TT variant of TagI was related with hyperparathyroidism(p < 0.05). Analysis of data after regrouping patients according to iPTH levels(0–249, 250–499, 500 + pg/mL) and hemodialysis duration(<60 vs≥60 months) revealed that influence of TT variation on hyperparathyroidism became more frequent in case of increased hemodialysis duration and iPTH levels(p < 0.005).Conclusion: TT variation of TagI VDR gene influences the development of hyperparathyroidism in HD patients. This influence becomes more evident in patients with longer HD duration. [ABSTRACT FROM AUTHOR]

Hepatitis C virus(HCV) infection affects survival and morbidity of end-stage renal disease patients and also increases treatment costs. Aim of this study is to define prevalence of HCV infection in our hemodialysis(HD) units and documenting past interventions and clinical status of patients. 711 patients were included. Patient data were collected from 4 HD units of Baskent University. Patient records were examined for demograpic findings, anti-HCV, HCV RNA, liver biopsy, interferon treatment information, last 12 months’ laboratory values(serum transaminases, albumin, lipid profiles, hemoglobin, C-reactive protein), and current clinical status, retrospectively. 143 patients(3%) were anti-HCV positive. These patients’ alanine transferase levels(23.5 ± 20.5 vs 15.5 ± 12.8 U/L, p < 0.0001) and HD duration(97.9 ± 58.6 vs 46.3 ± 35.6 months, p < 0.0001) were significantly higher. No other significant difference could be identified between the groups. Analysis of HD duration of anti-HCV positive patients revealed that prevalance was increasing as the duration increased. Anti-HCV positivity was known for a mean of 60.4 ± 38.8 months while 44 patients(30.7%) were already infected at initiation of HD. HCV RNA analysis was positive in 26.7% and a liver biopsy was performed in 23% of patients after 19.8 ± 23.3 months following positive anti-HCV identification. Minimally active chronic hepatitis C was the most common pathological diagnosis(70, 3%). Only 18 patients(12.5%) recieved interferon therapy. None of the patients had chronic liver disease clinical and physical findings by the time this study was done. HCV infection is a common problem in HD patients that increases the need for medical interventions and treatment. [ABSTRACT FROM AUTHOR]

Poor patient compliance is common during dialysis therapy. We aimed to study incidence of noncompliance, contributing factors, and effects on quality of life(QOL) among cadaveric renal transplantation waiting list patients. We included 86 renal transplantation waiting list patients(56M/30F). Dialysis duration, previous renal transplantation history, comorbid conditions, interdialytic weight gain, predialysis BUN, creatinine, potassium, and phosphate were recorded. Noncompliance criteria were skipping>1 dialysis session or shortening a dialysis session>10 min in 1 month, interdialytic weight gain>5.7% of body weight, predialysis serum potassium>6 mEq/L, and phosphate level>7.5 mg/dl. There were 49 noncompliant(age: 46.8 ± 21.8 years, HD duration: 83.9 ± 48.7 months) and 37 compliant(age: 42.8 ± 12.1 years, HD duration: 96.5 ± 45.2 months) patients. QOL was evaluated by short form 36 and depression levels by Beck Depression Inventory. Previous renal transplantation was present in 24.4% and comorbid diseases in 31.3% of all patients. In depressed patients, 77.8% had comorbid diseases. No difference was found between the groups considering age, gender, dialysis duration, previous transplantation history, and comorbid diseases(p > 0.05). Noncompliant patients had lower QOL(p < 0.04). Noncompliant patients had higher degree of depression(p = 0.01). QOL and Beck scores were negatively correlated(p = 0.001, r = −0.561). Noncompliance to diet and dialysis therapy is associated with depression, which further decreases QOL in renal transplantation waiting list patients. Early diagnosis of depression, is possible by monitoring noncompliance, and therapeutic intervention may benefit during the transplantation-waiting period. [ABSTRACT FROM AUTHOR]

The rate of certain malignancies in renal transplant recipients is 14 to 500 times higher than the rate in the general population. The reported prevalence rates for malignant tumors in various kidney recipient series range from 4% to 18% with an average of 6%. The tumors occur in patients who are younger than individuals affected in the general population, and the incidence rates rise with each year after transplantation. Since 1975, we have recorded 52 cases of malignancy development in 50 (3.7%) patients who were treated with P + AZA, P + CsA + AZA, or P + CsA + MMF therapy (P, prednisolone; AZA, azathioprine; CsA, cyclosporin A; MMF, mycophenolate mofetil). In this article, 50 renal transplant recipients who developed malignancy and were followed by the Transplantation Center at Başkent University Faculty of Medicine were analyzed. Analysis revealed that patients who received CsA had a higher incidence of Kaposi's sarcoma than those who received the standard regimen. Regarding other tumor types, our results showed no statistical differences among the incidence rates in the different treatment groups.

While it has been reported that myocardial infarction and cerebrovascular disease are more common in continuous ambulatory peritoneal dialysis (CAPD) patients than in hemodialysis patients, some studies have not supported these results. The aim of this study was to compare CAPD and hemodialysis patients with regard to atherosclerotic changes and to assess which factors might be responsible for atherosclerosis in dialysis patients. Group 1 consisted of 65 CAPD patients, and Group 2 consisted of 109 hemodialysis patients who were age-, gender-, and duration-of-dialysis-matched with CAPD patients. We used ultrasonographic measurement of carotid artery intima media thickness to identify atherosclerosis. Known risk factors for atherosclerosis including hypertension, smoking, serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, lipoprotein (a) [Lp(a)], albumin, intact parathormone, fibrinogen, and C-reactive protein were determined in all patients. More atherosclerotic changes were seen in CAPD than in hemodialysis patients. Of all the atherosclerosis risk factors, only serum total cholesterol, LDL-C, and Lp(a) levels were significantly higher in patients on CAPD.

To evaluate the histologic changes in the livers of renal transplant candidates who were infected with hepatitis viruses, we performed a percutaneous liver biopsy in each of 74 regular hemodialysis patients. Forty percent of them were seropositive for the antibody to hepatitis C virus (anti-HCV) whereas 29.7% had anti-HCV and antibody to hepatitis B surface antigen (anti-HBs) concomitantly. Seven (9.5%) were seropositive for only hepatitis B surface antigen HBsAg. Histopathological examination revealed that 30% of patients had chronic active hepatitis (CAH), 11% had chronic persistent hepatitis (CPH), and 3% displayed histopathological evidence of cirrhosis. Eleven of 22 patients with CAH were positive for only anti-HCV, and 2 of 22 were positive for only HBsAg. One patient had HBsAg and anti-HCV together, and 8 of 22 had anti-HBs and anti-HCV concomitantly. None of the anti-HBs positive patients exhibited abnormal histopathological changes. We found no statistically significant difference in histopathological findings between the HBsAg positive and anti-HCV positive patients. As 32 of 74 patients (43%) had some degree of chronic liver disease, we concluded that it is prudent to evaluate liver histology in HBsAg and anti-HCV seropositive renal transplant candidates before transplantation.