Evaluation the Effects of Alpha-tocopherol in Comparison with N-acetylcystein for Prevention of Contrast Induced Nephropathy (CIN) in CKD Patients.

INTRODUCTION: Contrast induced nephropathy (CIN), a well-known complication of using radio contrast media, dramatically increases the likelihood of patient morbidity and mortality following coronary angiography. As there is no specific treatment for CIN, prevention could be the best strategy to address this issue. Since now, the only approved preventing strategy was hydration with normal saline while antioxidant agents as a new yet unapproved remedy for this purpose could be applied .The present study was conducted to examine the effect of alpha tocopherol in CIN prevention. METHODS: This prospective controlled trial was carried out on 201 patients with chronic kidney disease (eGFR < 60 cc/min) underwent coronary angiography. We assigned three groups of CKD patients: 72 patients who received prophylaxis administration with isotonic saline (Group A), 66 patients with isotonic saline plus N-acetylcysteine (1200mg twice a day) for 2 days (Group B) and 63 patients who received isotonic saline plus daily alpha tocopherol (600 IU once daily from one day before till 2 days after angiography) for 4 days (Group C). The contrast media in all three groups was nonionic iso-osmolal agent, Visipaque. RESULTS: Even though CIN didn't developed in any of the three aforementioned groups but there was statistically significant reduction in eGFR from baseline in all three groups (P < .001). Moreover, We found no statistically significant difference in GFR reduction between three studied groups. CONCLUSION: Administration of alpha tocopherol has no additive beneficial effect over isotonic saline in CIN prevention in CKD patients.

Correlation between serum leptin and bone mineral density in hemodialysis patients.

INTRODUCTION: For diagnosing of specific types of bone lesions in hemodialysis (HD) patients, it is necessary to conduct a bone biopsy as the gold standard method. However, it is an invasive procedure. While different markers have been suggested as alternative methods, none of them has been selected. The frequency of hip fractures is 80 fold in HD patients who have two-fold mortality as compared with general population. OBJECTIVES: Recently, serum leptin has been suggested as a bone density marker. This study tries to confirm this proposal. PATIENTS AND METHODS: In this study about 104 HD patients (53.8% male and 46.2% female) were enrolled. The average age was 38.28±7.89 years. Serum leptin, bone alkaline phosphatase, intact parathyroid hormone (iPTH), 25(OH)D, calcium, phosphorus and bone mineral density (BMD) (at the femoral neck and lumbar spine, as measured by dual-energy x-ray absorptiometry [DXA]) were assessed. RESULTS: Analysis by polynomial regression revealed no correlation between BMD Z-score at two points and serum leptin level. According to the thresholds of 25 ng/mL and 18-24 ng/mL in some studies, we detected 25 ng/mL as the threshold in our patients. Under this threshold, the leptin effect on bone mass was negative, and above the threshold of 25 ng/mL, we found leptin had positive effect on bone mass. CONCLUSION: In this investigation, we found, leptin has a bimodal effect on bone mass. Cortical bones assessment may be a better option for assessment.

RIFLE criteria for acute kidney injury in the intensive care units.

BACKGROUND: Acute kidney injury (AKI) is commonly occurred in intensive care unit (ICU) patients. The aim of the study was a comparison of RIFLE (Risk of renal injury/Injury to the kidney/Failure of kidney function/Loss of kidney function/End stage disease) classification with other scoring systems in the evaluation of AKI in ICUs. MATERIALS AND METHODS: We performed a retrospective study on 409 ICU patients who were admitted during the 5 years period. RESULTS: At the 1(st) day of admission and time of discharge, the total and non-renal Acute Physiology and Chronic Health Evaluation II and sequential organ failure assessment scores were compared to max RIFLE criteria. In this assessment, there was concordance among the results (P < 0.05). CONCLUSION: The RIFLE classification can be used for detection of AKI in ICU patients.

Graft function based on two hours peak level monitoring of cyclosporine A during the first six months of renal transplantation.

Inadequate cyclosporine blood levels may cause acute rejection in transplanted renal graft, and its increase is accompanied with graft toxicity. Cyclosporine has variable bioavailability and pharmacokinetics among patients at different times after transplantation. In this study, we compared the effects of cyclosporine blood levels (trough versus 2-hour peak, C2) on renal graft function during the first six months after transplantation in order to find better methods for drug levels assessment in our patients. We studied 50 patients who received grafts at Mashhad transplant centers from October 2006 to May 2007. Drug levels were monitored seven times during the study; in each assessment, more than 80% of the patients did not reach the therapeutic C2 levels. There was no significant correlation between age, sex, times of transplantation and acute rejection with drug C2 levels. There was no difference between graft function in patients with therapeutic C2 level and those with inadequate C2 levels. However, we found a significant correlation between trough levels and acute rejection (P <0.05). Only during the 6 th month after transplantation was the drug dosage significantly higher in patients with therapeutic C2 level than that in other patients (P >0.05). Apparently, peak levels were not a suitable method in drug monitoring in our patients, or peak levels might have occurred at a different time (like 1.5 or 3 or 4 h after ingestion of the drug) in our population. Based on this study, trough level may be a better method of evaluation of cyclosporine effects on renal allografts than 2-h peak levels in our patients.

Incidence of malignancy after living kidney transplantation: a multicenter study from iran.

Malignancy is a common complication after renal transplantation. However, limited data are available on post-transplant malignancy in living kidney transplantation. Therefore, we made a plan to evaluate the incidence and types of malignancies, association with the main risk factors and patient survival in a large population of living kidney transplantation. We conducted a large retrospective multicenter study on 12525 renal recipients, accounting for up to 59% of all kidney transplantation in Iran during 22 years follow up period. All information was collected from observation of individual notes or computerized records for transplant patients. Two hundred and sixty-six biopsy-proven malignancies were collected from 16 Transplant Centers in Iran; 26 different type of malignancy categorized in 5 groups were detected. The mean age of patients was 46.2±12.9 years, mean age at tumor diagnosis was 50.8±13.2 years and average time between transplantation and detection of malignancy was 50.0±48.4 months. Overall tumor incidence in recipients was 2%. Kaposis' sarcoma was the most common type of tumor. The overall mean survival time was 117.1 months (95% CI: 104.9-129.3). In multivariate analysis, the only independent risk factor associated with mortality was type of malignancy. This study revealed the lowest malignancy incidence in living unrelated kidney transplantation.

Evaluation of the effects of simvastatin in reduction of panel-reactive antibody (PRA) levels in patients with end-stage renal disease awaiting renal transplantation.

This study was undertaken to assess the effect of simvastatin in the reduction of panel-reactive antibody (PRA) levels in patients with end-stage renal disease (ESRD) awaiting renal transplantation. During the 1-year period from September 2007 to August 2008, 60 ESRD patients with PRA levels more than 30% were enrolled into the study. Each patient was given oral simvastatin 10 mg/day as the initial dose. After one month, in those patients who did not respond, the dose was increased to 20 mg/day. Again, at the end of two months, if there was no response, the dose was further raised to 40 mg/day of simvastatin. The appropriate response to the treatment was defined as serum PRA levels getting reduced to less than 30%. Among the 60 patients who were enrolled in the study, three cases were excluded due to side-effects of the drug and 57 patients remained in our study. The mean age was 42.8 ± 28.2 years (range 18-75). Among these, 34 (59.6%) were females. Before the study, the PRA levels were between 30 and 100 (mean ± SD: 60.4% ± 20%). After the administration of simvastatin, a significant decrease in PRA levels was seen in our patients (P < 0.0001). In patients who had baseline PRA less than 40%, the PRA dropped to below 30% in 69.2% of the cases with 10 mg simvastatin. In those who had baseline PRA more than 40%, a similar reduction was seen only in 15.9% of the cases. However, in those who did not respond initially to 10 mg of simvastatin, statistically significant reductions were seen after the administration of 20 mg and, if needed, 40 mg of simvastatin (P = 0.001). In conclusion, simvastatin can be a useful drug in ESRD patients to lower the PRA levels.

Patient outcome in primary peritoneal dialysis patients versus those transferred from hemodialysis and transplantation.

BACKGROUND: According to the concept of integrated care, renal transplantation, peritoneal dialysis (PD), and hemodialysis (HD) should be considered three complementary methods of renal replacement therapy. This study tried to evaluate patient outcomes in three different groups of PD patients, namely primary PD patients, those transferred to PD with failing kidney transplant, and those transferred to PD from HD. METHOD: From January 1, 1995, to end of 2006 from 26 PD centers, 1,355 patients including demographic, clinical and laboratory data, which were monthly collected through questionnaires, were enrolled in the study. We compared patients' characteristics, factors affecting patient survival, and patient outcomes between primary PD patients (group 1, n = 1,067), patients transferred from transplantation (group 2, n = 43) and those transferred from HD (group 3, n = 245), which had been on HD for at least 3 months before switching to PD. RESULTS: There was no difference in the proportion of patients with diabetes in the three groups. Overall, 238 patients (17.5%) were transferred to HD but there was no significant difference in PD technique survival on between the three groups. Death occurred in 256 (24%), 3 (7%) and 65 (26.5%) subjects in groups 1, 2 and 3, respectively. Most patients (81.5%) in group 2 underwent re-transplantation. The Kaplan-Meier survival rates were not different between the three groups. In the Cox multiple regression model, age, presence of diabetes and serum albumin level significantly influenced patient survival. CONCLUSION: We concluded that PD could be considered safe for patients experiencing complications on HD, as well as for those with renal transplantation.

Epidemiology of culture-negative peritonitis in Iranian patients on continuous ambulatory peritoneal dialysis.

INTRODUCTION: Culture-negative peritonitis is a major challenge in the treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD). This study aimed to evaluate the culture-negative peritonitis in patients from the Iranian CAPD Registry. MATERIALS AND METHODS: Data of 1472 patients from 26 CAPD centers were analysed. Peritonitis was defined as any clinical suspicion together with peritoneal leukocyte count of 100/mL and more. RESULTS: The patients had been on PD for a mean of 500 ± 402 days. There were a total of 660 episodes of peritonitis observed among 299 patients (peritonitis rate of 1 episode in 34.1 patient-months). Excluding patients with both negative and positive culture results, there were 391 episodes of peritonitis in 220 patients (174 culture-positive episodes in 97 patients and 217 culture-negative episodes in 123). The 1- to 4-year patient survival rates were 85%, 75%, 69%, and 59% for the patients with culture-positive peritonitis, and 92%, 78%, 73% and 63% for the patients with culture-negative peritonitis, respectively (P = .34). The technique survival rates were 90%, 57%, 42%, and 27% and 95%, 85%, 74%, and 40%, respectively (P = .001). On follow-up, there were higher rates of active PD patients, lower rates of PD dropouts, and higher rates of kidney transplantation in patients with culture-negative peritonitis compared to those with culture-positive peritonitis. CONCLUSIONS: In our patients, the prevalence of culture-negative peritonitis was high (55.9%). Patient survival with culture-negative peritonitis was comparable to those with culture-positive peritonitis and technique survival was higher among those with culture-negative peritonitis.

Prognosis of HTLV-1 positive renal transplant recipients in Iran.

The human T lymphocyte virus-1 (HTLV-1) is the responsible pathogen for diseases such as HTLV-1 associated myelopathy (HAM) and adult T-cell leukemia (ATL). Mashhad, in northeast Iran, with high instances of this infection, has a noticeable number of infected renal failure patients. Since immunosuppressive drugs might decrease the latency period of HTLV-1 or increase its complications, the question arises whether HTLV-1 positive renal failure patients are suitable candidates for kidney transplants. To answer this, HTLV-1 positive recipients were evaluated in our study. Patients were divided into two groups. First group consisted of patients at the Imam Reza Hospital dialysis center. Second group had 20 kidney transplantation recipients consisting of ten infected and ten uninfected recipients as control from Imam Reza. Medical history of these patients was recorded and evaluated. The follow-up periods were between one and six years. Among them, 3.8% of patients undergoing dialysis were infected. The most important fact resulting from this study is that none of the infected recipients suffered from HAM or ATL during the follow-up period. In addition, it did not show any significant difference in the incidence of post-transplant complications between the infected and non-infected groups. Our study indicates that HTLV-1 positive patients may undergo kidney transplant without fear of increased incidence of side effects than those found in uninfected recipients. Because of short-term follow-up, probable long latency period of the virus, and the limited number of infected recipients, further work on this issue would be prudent.

Serum triiodothyronine level as an indicator of inflammation in patients undergoing dialysis.

INTRODUCTION. It has been shown that inflammation affects thyroid function. In patients with end-stage renal disease, low plasma triiodothyronine (T3) may be an unsuspected expression of the inflammatory state of these patients. This study evaluated the correlation between T3 and high-sensitivity C-reactive protein (HSCRP) levels in patients on peritoneal dialysis (PD) and hemodialysis. MATERIALS AND METHODS. This is a cross-sectional study aiming at the correlation between T3 and HSCRP levels among 30 patients on PD, 30 patients on hemodialysis, and 20 healthy individuals. Serum levels of HSCRP, T3, thyroxine (T4), thyroid stimulating hormone, T3 resin uptake, and free T3 index (FT3I) and free T4 index (FT4I) were compared between the three groups. RESULTS. There were no significant differences between hemodialysis and PD patients in respect to T3, T4, FT3I, and FT4I. In PD and hemodialysis patients, T3 and FT3I were lower than in controls (P < .001), but there was no significant difference between PD and hemodialysis patients. T3 resin uptake and thyroid stimulating hormone differed significantly between PD and hemodialysis patients. There was a significant inverse correlation between HSCRP and T3 and FT3I among hemodialysis patients (P = .04); however, there was no such correlations in PD patients. CONCLUSIONS. The relationship between T3 and HSCRP suggests that inflammation might be involved in the low T3 syndrome in hemodialysis patients, but we did not find a significant correlation between T3 and HSCRP levels in patients on peritoneal dialysis.

Gender disparity in kidney transplantation.

Gender discrimination in benefiting from medical treatment is a worldwide problem. Kidney transplantation, as the ideal treatment for patients with end-stage renal disease (ESRD), is not an exception. Considering the unique kidney donation patterns and different family styles in the Middle East, studying this problem in Iran seemed justifiable and necessary. In addition to comparing the numbers of female and male recipients, which has been done in other similar studies, considering the critical effect of waiting time on the outcome, we assessed and compared the waiting times also. The data of age, gender, nationality, donor type and waiting time before transplantation of 1426 (61.85% male, 38.14% female) recipients who underwent transplantation in Imam Reza Hospital in the northeast of Iran from 1990 to 2003, was analyzed. Recipients were categorised into three groups based on donation patterns: those receiving kidney from live unrelated, live related and cadaver donors. The number of patients in each group was 1057 (61.96% male, 38.03% female), 232 (67.24% male, 32.75% female) and 137 (51.82% male, 48.17% female) respectively. The mean overall waiting time was 708 days. Comparing waiting time of male and female recipients in each of these groups did not show significant difference. In all categories of donors, females were less likely than males to be recipients. Furthermore, waiting time for females was longer than males when receiving kidney from sisters and children. For spousal donations, males were recipients more frequently than females although female recipients in this group waited less than their male counterparts to receive the kidney. Generally, our results are in accordance with results of similar researches. In all three mentioned groups, males comprised the majority while the waiting time does not show significant difference between genders. We suggest some reasons for this phenomenon, of which the two main ones are: fewer females are suffering from ESRD and/or females have less chance to find a potential donor in the family, which can be attributed to their lower socio-economic status.

Influence of renal graft function on mycophenolic acid pharmacokinetics during the early period after kidney transplant.

OBJECTIVES: Mycophenolate mofetil, the prodrug of mycophenolic acid, is widely used for maintenance immunosuppressive therapy in renal transplant recipients. The effect of renal graft function on mycophenolic acid pharmacokinetics parameters is still controversial. The aim of this study is to investigate the impact of renal graft function on mycophenolic acid pharmacokinetics during the early posttransplant period. MATERIALS AND METHODS: Our study was done on 13 patients with severe renal impairment (glomerular filtration rate < 30 mL/min, impaired group) and 13 patients with normal graft function (glomerular filtration rate < 70 mL/min, control group), at a steady mycophenolic acid plasma level, during the first month after transplant. All patients received a fixed dose of mycophenolate mofetil (1 g twice daily) in combination with cyclosporine and steroids. Mycophenolic acid plasma levels were determined by a validated high-performance liquid chromatography method. Mycophenolic acid area under the time concentration curve from 0 to 12 hours and apparent mycophenolic acid plasma clearance (CL/f) were measured for each patient. RESULTS: Mycophenolic acid area under the time-concentration curve (0-12 h), mycophenolic acid area under the time-concentration curve (6-10 h), first peak concentration (Cmax1), and secondary peak concentration (Cmax2) were higher in the impaired group, while mycophenolic acid plasma clearance was higher in the control group (P < .05). Trough levels (C0) were similar for both groups (P < .05). There was a negative correlation between glomerular filtration rate and area under the time-concentration curve (r=-0.422, P = .04), while there was a positive correlation between glomerular filtration rate and mycophenolic acid plasma clearance (r=0.463, P = .02). CONCLUSIONS: Mycophenolic acid pharmacokinetics parameters in normal renal function patients and severe renal impairment patients are different, and renal graft function correlates with total mycophenolic acid area under the time-concentration curve and apparent mycophenolic acid plasma clearance. However, the necessity of dosage adjustment based on renal graft function requires further studies.

Kidney transplantation in elderly Iranian patients.

The population of elderly people with chronic renal insufficiency is increasing around the world. It has been shown that renal transplantation (RT) may be the best treatment for these patients. However, it has been observed that older patients who have received a RT have a higher mortality rate than those who are younger. The aim of this study was to evaluate the outcome of RT in recipients over 50 years of age. During the period between 1988 and 2002, 650 renal transplantations were performed at the Imam Reza Hospital in Mashad, Iran, of which 83 were performed in patients older than 50 years (50 to 66 years). We studied the one, three, and five-year patient and graft survival rates as well as the prevalence of urinary tract infection (UTI) after transplantation in these patients. We also evaluated the effect of the recipient's age and sex and the type of donor (related or unrelated) on patient survival as well as the prevalence of UTI. Patient survival at one, three, and five years after RT were 92.4%, 84.7%, and 75.6%, respectively. The graft survival at one, three, and five years after RT were 91.1%, 79.7%, and 66.7%, respectively. UTI occurred in 67.1% of patients after transplantation. The patient and graft survival rates were not related to the age and sex of the recipients and the type of donors. Also, there was no correlation between the prevalence of UTI and the age and sex of the recipients. Our study suggests that RT can be performed safely and with acceptable prognosis in elderly patients after appropriate clinical evaluation.

Factors affecting length of hospitalization in kidney transplant recipients.

OBJECTIVES: Owing to improvements in surgical techniques and clinical care, many of the earlier difficulties surrounding kidney transplants have been overcome and so, the number of operations performed has increased dramatically. Resource utilization and costs are now cited as problems for some transplant centers. Because length of hospitalization accounts for the largest portion of the total cost of the treatment process, we sought to determine and assess the factors that might reduce its length. MATERIALS AND METHODS: We retrospectively studied the medical histories of 115 kidney transplant recipients and donors whose operations were performed between May 2000 and April 2002. Collected information for the recipients included sex, age, reason for kidney failure, weight, height, blood group, length of pretransplant dialysis, number of prior transplants (1 or 2), immunosuppressive regimen, postoperative complications (ie, lymphocele, wound infection, urinary tract infection, graft rejection), and hospitalization after the first discharge owing to postoperative complications. For donors, these demographics included age, sex, blood group, type of donor (deceased or living), and relationship to the recipient. RESULTS: Length of pretransplant dialysis and relationship of the donor to the recipient were independently associated with predicting an increased length of hospitalization (and consequently, increased costs). CONCLUSIONS: By reducing the length of pretransplant dialysis (wait time) and performing more operations between related donors and recipients, the length of hospitalization as well as the cost of treatment can be significantly reduced. Given the results of this study and owing to the increasing number of transplant surgeries occurring globally, future research should focus on analyzing other factors that affect length of hospitalization and associated costs.

Pharmacokinetics of mycophenolic acid during the early period after renal transplant.

OBJECTIVES: Mycophenolic acid, the active metabolite of mycophenolate mofetil, is administered with cyclosporine and oral steroids to prevent acute rejection after renal transplant. The aim of this study was to investigate correlations among time after transplant, subjects' demographics, and mycophenolate mofetil dosage according to body weight withmycophenolic acid pharmacokinetics during the early posttransplant period. PATIENTS AND METHODS: Mycophenolic acid plasma levels of 19 patients were determined by a validated high-performance liquid chromatographic method at the steady state soon after transplant when graft function was good (glomerular filtration rate = 70 mL/min). All patients received a fixed dosage of mycophenolate mofetil (1 g b.i.d.) in combination with cyclosporine and steroids. The area under the time-concentration curve (AUC) and mycophenolic acid plasma clearance were measured for each patient. RESULTS: The AUC from zero to 12 hours and trough levels increased as the time after transplant increased (P < .05), but mycophenolic acid plasma clearance decreased over time (P = .02). There was a correlation between total body weight and the AUC (P = .01, r2 = -0.627) as well as between total body weight and mycophenolic acid clearance (P = .04, r2 = 0.555). No statistically significant differences were found regarding mycophenolic acid plasma level, AUC, and mycophenolic acid plasma clearance with regard to sex or age of the subjects (P > .05). The mycophenolate mofetil dosage according to body weight correlated positively with the AUC (P = .01, r2 = 0.628), but there was a negative correlation between total body weight and mycophenolic acid plasma clearance (P = .02, r2 = -0.604). CONCLUSIONS: Our results demonstrate that total body weight, time after transplant, and mycophenolate mofetil dosage according to body weight affect mycophenolic acid pharmacokinetics. We suggest that mycophenolic acid pharmacokinetics monitoring is necessary to individualize mycophenolate mofetil dosing during the early posttransplant period.