A cohort study of membranous nephropathy, primary or secondary.

BACKGROUND: Although IgG4 deposit against phospholipase A2 receptor (anti-PLA2R) is predominantly presented in the renal biopsy of patients with primary membranous nephropathy (MN), its diagnostic value of this immune complex has not been fully established. METHODS: In this cohort study, 108 biopsy-proven MN patients with proteinuria were evaluated during two years follow up and were divided into primary and secondary groups. Renal biopsy specimens were pathologically assessed for IgG4 and PLA2R depositions by immunohistochemistry (IHC). Therefore, the relationships between staining severity, MN type and total proteinuria in all patients were determined. RESULTS: Of 108 patients, 73.1% had primary MN and 26.9% were diagnosed as secondary form. IHC staining in patients with primary MN was positive for PLA2R in 76 (96.2%) and IgG4 in 68 (86.1%). Cases with positive PLA2R expression had a significantly higher rate among patients with mild to moderate stages (P = 0.03). No significant relationship was found between intensity of PLA2R and IgG4 deposits with proteinuria and serum creatinine. Based on our data, double positivity/negativity of PLA2R and IgG4 expression adds prominent information to the clinical data and were found to be useful and robust biomarkers for detection of primary MN patients with high sensitivity and specificity (97.1 and 96.3% respectively, PPV = 98.5% and NPV = 92.9%). CONCLUSIONS: Simultaneously expression of PLA2R and IgG4 in renal biopsy specimens of patients with MN could possibly be used as a potential diagnostic method to distinguish primary from secondary MN and also pathological severity of the disease.

Effect of omega-3 fatty acids on plasma level of 8-isoprostane in kidney transplant patients.

OBJECTIVE: It has been shown previously that the serum level of F2-isoprostanes acts as an indicator of oxidative stress, which is a risk factor for vascular disease especially in end-stage renal disease. It is not known whether n-3 polyunsaturated fatty acids can decrease oxidative stress in renal recipient patients. DESIGN, SETTING, AND SUBJECTS: In this single blind, randomized, placebo-controlled study, the effect of 3 and 6 months of fish oil administration on 8-isoprostane levels in renal transplant recipients was evaluated. INTERVENTION: Twenty-two renal transplant patients who fulfilled inclusion and exclusion criteria randomly received either fish oil dietary supplementation, 6 g/day (720 mg of DHA and 1,080 mg of EPA) or placebo for 6 months. MAIN OUTCOME MEASURE: Serum 8-isoprostane concentration was measured as markers of oxidative stress. RESULTS: A significant decrease in 8-isoprostane levels was observed only in the placebo group after transplantation compared to baseline (P < 0.05). However, the group receiving fish oil had a significantly lower cholesterol level than that of the placebo group (P < 0.05). CONCLUSION: On the basis of our results, omega-3 fatty acids supplementation decreased the beneficial effects of kidney transplantation on oxidative stress.

Estimation of Abbreviated Mycophenolic Acid Area Under the Concentration- Time Curve during Stable Post-transplant Period by Limited Sampling Strategy.

BACKGROUND: The Area Under the Concentration-time curve (AUC) of Mycophenolic Acid (MPA), is a valid prognosticator of the risk of rejection and the gold standard in its Therapeutic Drug Monitoring (TDM), over time post-transplantation. OBJECTIVE: This study aimed to investigate MPA pharmacokinetic parameters and develop a Limited Sampling Strategy (LSS) to estimate an abbreviated MPA AUC, in the stable phase post-renal transplantation. METHODS: In this study, 19 patients with normal graft function (glomerular filtration rate >70 ml/min) who fulfilled the inclusion and exclusion criteria were involved. Blood samples at various times were taken in the stable phase after transplantation. MPA plasma concentration was measured by reverse-phase high-performance liquid chromatography. MPA AUC0-12h was calculated using the linear trapezoidal rule. Multiple stepwise regression analysis was used to determine the minimal time points of MPA levels that could be used to yield model equations best fitted to MPA AUC 0-12h. The findings of this study were compared with the results of our previous study, which was done similarly in the early phase post-renal transplantation. RESULTS: The results demonstrated that the MPA-AUC and clearance were not affected over time, but MPA-tmax was significantly lower in the stable phase in comparison with the early phase (P=0.001). The best regression equation for AUC estimation in the stable phase was AUC=9.57*C6+27.238 (r2=0.907). The validation of the method was performed using the jackknife method. The mean prediction error of these models was not different from zero (P > 0.05) and had a high root mean square prediction error (7.91). CONCLUSION: In conclusion, the pharmacokinetics of MPA could be affected by time after transplantation, making it essential to develop a limited sampling strategy as an efficacious approach for therapeutic drug monitoring during the stable post-transplant period.

Multivariate Longitudinal Assessment of Kidney Function Outcomes on Graft Survival after Kidney Transplantation Using Multivariate Joint Modeling Approach: A Retrospective Cohort Study.

Background: The performance of a transplanted kidney is evaluated by monitoring variations in the value of the most important markers. These markers are measured longitudinally, and their variation is influenced by other factors. The simultaneous use of these markers increases the predictive power of the analytical model. This study aimed to determine the simultaneous longitudinal effect of serum creatinine and blood urea nitrogen (BUN) markers, and other risk factors on allograft survival after kidney transplantation. Methods: In a retrospective cohort study, the medical records of 731 renal transplant patients, dated July 2000 to December 2013, from various transplant centers in Mashhad (Iran) were examined. Univariate and multivariate joint models of longitudinal and survival data were used, and the results from both models were compared. The R package joineRML was used to implement joint models. P values <0.05 were considered statistically significant. Results: Results of the multivariate model showed that allograft rejection occurred more frequently in patients with elevated BUN levels (HR=1.68, 95% CI: 1.24-2.27). In contrast, despite a positive correlation between serum creatinine and allograft rejection (HR=1.49, 95% CI: 0.99-2.22), this relationship was not statistically significant. Conclusion: Results of the multivariate model showed that longitudinal measurements of BUN marker play a more important role in the investigation of the allograft rejection.

Factors Affecting the Long-Term Survival of Kidney Transplantation in Northeastern of Iran between 2000 and 2015.

BACKGROUND: Graft and patient survival are of great importance after transplantation. This study aimed to determine the long-term survival rate of kidney transplantation and its effective factors among transplanted patients in Mashhad transplantation centers in northeastern Iran. METHODS: Overall, 618 kidney transplant recipients were examined in different transplantation centers during the years from 2000 to 2015 in a historical cohort study. The Kaplan-Meier method and the Log-rank test were used to calculate the survival rate of the kidney transplant, and to check the difference between survival curves respectively. Modeling of effective factors in survival rate was performed using Cox regression model. RESULTS: Overall, 1, 3, 5, 7, 10, and 15-year survival rate of kidney transplantation were 99%, 98%, 97%, 93%, 88 and 70% respectively. The adjusted hazard ratio indicated that variables such as recipient age >40 yr [HR=0.22, 95% CI=(0.071,0.691)], serum creatinine after transplantation >1.6 Mg/dl [HR=3.03, 95% CI=(1.284,7.125)], history of hypertension [HR=6.70, 95% CI=(2.746,16.348)], and BMI [HR (normal weight versus underweight)=0.26, 95% CI=(0.088,0.761), HR (over weight versus underweight)=0.13,95% CI=(0.038,0.442)] were significant factors on kidney transplant survival rate. CONCLUSION: The short-term transplant survival rate was good in transplant patients. What's more, through a consideration of variables such as age, creatinine serum after transplantation, history hypertension and body mass index, as well as proper planning to control their effect, it is possible to improve the long-term graft survival rate.

Effect of silymarin administration on TNF-α serum concentration in peritoneal dialysis patients.

Chronic inflammation in dialysis patients increases the production of cytokines such as TNF-α, IL-1ß and IFN- IFN-γ and there is evidence of a significant mortality rate in dialysis patients due to inflammation. Overproduction of inflammatory cytokines can induce complications such as atherosclerosis, malnutrition and anaemia, which are mostly resistant to erythropoietin treatment. Cardiovascular disease is the leading cause of death in haemodialysis patients and about half of the mortality is attributable to cardiovascular disease. Silymarin modulates the immune system by inhibition of neutrophil immigration, mast cell immobilization, prostaglandin production and leukotriene synthesis. Furthermore, silymarin suppresses the induction of TNF-α and it was hypothesized that silymarin could decrease the serum concentration of TNF-α in peritoneal dialysis patients, and thus treat anaemia. Fifteen peritoneal dialysis patients were enrolled in this study and serum levels of soluble TNF-α were measured using an enzyme-linked immunosorbant assay (ELISA) kit. Serum TNF-α was found to be decreased in some patients and in the response group, the haemoglobin concentration after 8 weeks of silymarin administration was increased significantly (p < 0.05). Based on the results of this study, it is suggested that silymarin may be useful in the treatment of inflammation for peritoneal dialysis patients.

Study of Lophomonas blattarum Infection in Kidney Transplant Patients in Mashhad City, Iran.

BACKGROUND: Lophomonas blattarum is a flagellate protozoan which is known as an emerging parasite in the human respiratory system. Organ transplant recipients are considered as immunocompromised patients due to prescription of immunosuppressive drugs. This group of patients is susceptible to opportunistic infection as well as lophomoniasis. This study aims to investigate the prevalence and clinical manifestation of pulmonary infections caused by L. blattarum in kidney transplant recipients. METHODS: This is a case-control study including 50 kidney transplant recipients and 50 controls. The sputum samples were collected from 50 kidney transplant recipients with bronchopulmonary infection signs suspected to lophomoniasis admitted in Montaserieh and Imam Reza hospitals, Mashhad, Iran. 50 healthy individuals as the control group were matched for sex and age with case ones. The consent form, checklist, and required information were provided for each patient. All samples were microscopically examined for the flagellated protozoan, L. blattarum, using direct smear. RESULTS: Among 50 kidney transplant recipients suspected to lophomoniasis, L. blattarum was identified in sputum samples of 4 (8%) participants of the case group including one female and three males. None of the samples were positive among the control group. Symptoms in patients of this study were high fever (4 out of 4 patients), cough (3 out of 4 patients), and dyspnea (2 out of 4 patients). Three patients showed a positive response to metronidazole treatment. CONCLUSION: The results of this study suggest that L. blattarum should be considered as a pathogenic agent in kidney transplant recipients. It is necessary to examine sputum samples in posttransplant pneumonia patients, especially in those resistant to antibacterial therapy.

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.

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.

Assessment of Circannual Rhythm in Plasma Level of Vitamin D Among Kidney Transplant Recipients in Mashhad.

We studied plasma vitamin D level in 96 kidney transplant recipients and its circannual rhythm. Blood samples were tested for 25-hydroxy vitamin D, parathyroid hormone, creatinine, phosphate, and calcium levels in winter and summer 2014. The mean age was 41 years, and the mean transplant age was 6.1 years. Plasma levels of 25-hydroxy vitamin D were 18.0 ± 15.0 ng/mL in winter and 18.3 ± 14.7 ng/mL in summer (P = .64). Parathyroid hormone was inversely correlated with vitamin D level in both seasons (r = -0.044, P < .001). There was no relationship between vitamin D and other variables. Our study showed vitamin D deficiency is prevalent among kidney transplant recipients both in winter and summer. Also, vitamin D level did not rise from winter to summer. It is recommended to routinely check on kidney transplant recipients' vitamin D status.

Expression of T Helper 17 and Regulatory T Cell Cytokines and Molecules in Glomerulonephritis Class IV Systemic Lupus Erythematosus.

INTRODUCTION: Lupus nephritis is a serious organ involvement with unknown etiology, and glomerulonephritis class IV is one of the most severe forms of the disease which correlates with poor prognosis and death. Immunological abnormalities are implicated in the expression of lupus nephritis. In this study, we examined some T helper 17 and regulatory T-related cytokines and molecules in systemic lupus erythematosus patients with glomerulonephritis class IV. MATERIALS AND METHODS: The study group comprised of 20 glomerulonephritis class IV SLE patients and 20 sex- and age-matched SLE patients without kidney involvement as control group. Blood samples was collected from each participant, lymphocytes were isolated, and RNA was extracted from lymphocytes. Then cDNA was synthesized using reverse transcription enzyme, and finally using specific primers and probes, the expression levels of forkhead box P3 (Foxp3), transforming growth factor (TGF)-ß, interferon (IFN)-γ, interleukin (IL)-6, and IL-17 genes were analyzed by real-time polymerase chain reaction based on the TaqMan method. RESULTS: The expression levels of IL-6, IL-17, IFN-γ, and Foxp3 genes were significantly higher in SLE patients with glomerulonephritis class IV than those with non-nephritis SLE. However, the expression of TGF-ß was not significantly different between the SLE patients with and without glomerulonephritis class IV involvement. CONCLUSIONS: According to our results, it seems that in class IV glomerulonephritis patients, increased Foxp3-producing regulatory T cells has an imperfect capacity to control the pathogenic IL-17- and IFN-γ-producing cells.

The relationship between serology of hepatitis E virus with liver and kidney function in kidney transplant patients.

Although hepatitis E virus (HEV) is well known to cause acute hepatitis, there are reports showing that HEV may also be responsible for progression of acute to chronic hepatitis and liver cirrhosis in patients receiving organ transplantation. In this study, we aimed to evaluate the prevalence of HEV in patients with kidney transplantation. In this study, 110 patients with kidney transplantation were recruited, and anti-HEV IgG, creatinine, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and estimated glomerular filtration rate (eGFR) in the first, third and sixth months after renal transplantation were measured. The mean serum anti-HEV IgG titers in the study participants was 1.36 (range 0.23 to 6.3). Twenty-three patients were found to be seropositive for HEV Ab defined as anti-HEV IgG titer > 1.1. The difference in liver and renal function tests (creatinine, eGFR, AST, ALT and ALP) at different intervals was not significant between patients with HEV Ab titers higher and lower than 1.1 (p > 0.05). However, an inverse correlation was observed between HEV Ab and eGFR values in the first (p = 0.047, r = -0.21), third (p = 0.04, r = -0.20) and sixth (p = 0.04, r = -0.22) months after renal transplantation in patients with HEV Ab < 1.1 but not in the subgroup with HEV Ab > 1.1. Also, a significant correlation between age and HEV Ab levels was found in the entire study population (p = 0.001, r = 0.33). Our findings showed a high prevalence of seropositivity for anti-HEV IgG in patients receiving renal transplants. However, liver and renal functions were not found to be significantly different seropositive and seronegative patients by up to 6 months post-transplantation.

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.

Weight-gain-related factors in renal transplantation.

OBJECTIVES: Previous studies of renal transplant recipients have suggested that weight gain after transplantation is relatively common. The purpose of this study was to define the occurrence, magnitude, and predictors of weight gain in this group. MATERIAL AND METHODS: We conducted a prospective study of 100 renal transplant recipients from 2002 to 2004 at Imam-Reza Hospital in Mashhad, Iran, to identify patterns of weight change attributed to sex, age at transplantation, socioeconomic class, and duration of dialysis. A descriptive study also was made on serum cholesterol and triglyceride levels in renal transplant recipients 12 months after transplantation. Patients' weights were evaluated at 3, 6, 9, and 12 months after transplantation. RESULTS: Univariate analyses at 1 year posttransplantation showed that women had greater weight gains than did men (P = 0.003); older recipients had greater weight gains than did younger recipients (P = 0.009); weight gain was correlated with an increase in serum triglyceride and cholesterol levels (P = 0.000 and P = 0.004); and socioeconomic class was not correlated with weight changes (P = 0.955). CONCLUSIONS: Female sex, older age, and increasing incidences of hypercholesterolemia and hypertriglyceridemia were significantly associated with weight gain 1 year after organ transplantation.

One-Year Multicenter Double-Blind Randomized Clinical Trial on the Efficacy and Safety of Generic Cyclosporine (Iminoral) in De Novo Kidney Transplant Recipients.

OBJECTIVES: Iminoral is the generic microemulsion of cyclosporine. We performed a randomized double-blind multicenter trial to evaluate its efficacy and safety compared with the innovator medication Neoral for preventing acute rejection episodes in adult patients during the first year after renal transplant. MATERIALS AND METHODS: We used 221 de novo renal transplant recipients from 6 transplant centers in Iran enrolled between April 2008, and January 2010. They were randomized to receive either Iminoral or Neoral as the calcineurin inhibitor component of the immunosuppressive regimen in addition to mycophenolate mofetil and oral corticosteroids. They were followed-up for 1 year. The primary endpoint was the rate of acute allograft rejection. Secondary endpoints consisted of 1-year graft survival rates, daily dosages of cyclosporine, trough and C2 cyclosporine blood level, serum creatinine levels, patient death rates, discontinuing the study drug, tolerability, and adverse events. RESULTS: The risk of acute rejection episode during the first month after transplant was 9% for Iminoral and 10% for Neoral; these declined to 4% and 2% during next 11 months. One-year graft survival rate was 0.86 for both groups. Renal function stabilized during the first month. Declination of the creatinine levels was similar between the 2 groups and reached a stable value of 114.9 µmol/L five months after the transplant. The frequency of clinical complications was similar between the groups. CONCLUSIONS: Iminoral is safe and effective when used in de novo kidney transplant patients as an immunosuppressive medication.

Preperitoneal tunneling-a novel technique in peritoneal dialysis catheter insertion.

INTRODUCTION: This study describes a new preperitoneal tunneling (PPT) method for inserting a peritoneal dialysis catheter (PDC), thereby lessening surgical complications and increasing the catheter's survival. METHODS: This new technique was used in 23 cases from December 2005 to January 2007 and followed up until March 2011 (63 months). The procedure was performed laparoscopically under local (16 cases) or general (7 cases) anesthesia by one surgeon. Catheter survival is reported by Kaplan-Meyer analysis. RESULTS: The catheters were mechanically obstructed in 2/23 cases (8.7%); and were withdrawn due to a peritonitis in 2 cases and inadequacy of peritoneal dialysis in 1 case. Ten patients received kidney transplantation and six died before completing this follow-up period. The patients still reaped the benefits of the PDC until receiving a kidney transplant or death. The 5-year survival rate of the catheter was 89%. No incidence of catheter migration, omental wrapping, herniation or leakage was noticed. CONCLUSION: Preperitoneal tunneling is a simple and safe method for insertion of PDC, and can effectively prevent catheter migration, dislocation and omental wrapping.

Evaluation of the effect of pentoxifylline on erythropoietin-resistant anemia in hemodialysis patients.

Use of recombinant human erythropoietin (rh-Epo) improves hemoglobin (Hgb) in 90-95% of the cases of anemia of chronic kidney disease (CKD). However, it is known that pro-inflammatory cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alfa (TNF-α) and interleukin-1 (IL-1) suppress erythropoiesis, resulting in inadequate response to rh-Epo. Pentoxifylline has been shown to have modulatory effects on the immune system. This prospective study to evaluate the effect of pentoxyphylline on erythropoeisis was performed on 15 (eight males, seven females) clinically stable patients who had been on hemodialysis for at least six months with anemia (Hgb of <10.7 g/dL) unresponsive to rh-Epo despite high doses. They were treated with 400 mg pentoxifylline tablets once daily for 12 weeks. Hgb increased after one and two months of drug administration, but significant changes were observed in eight (53%) patients after three months (P <0.05). Our study illustrates a probable new use for an old medicine. Three months treatment with pentoxifylline was seen to increase Hgb significantly in rh-Epo-resistant patients. More prospective studies with a larger sample size are needed to determine the inhibitory role of cytokines on hematopoiesis and exploring new drugs or new drug indications to overcome anemia in advanced renal failure.

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.

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.