Drug-Drug Interactions among Kidney Transplant Recipients in The Outpatient Setting.

BACKGROUND: Number of patients undergoing kidney transplantation is ever increasing. Drug-drug interactions (DDIs) can complicate transplant patient's treatment course. OBJECTIVE: To investigate patterns and factors associated with potential DDIs in kidney transplant recipients under maintenance immunosuppressive regimen at a referral transplantation center in Shiraz, Iran. METHODS: 390 eligible kidney transplant outpatients referred to Motahhari clinic and one of the attending nephrologist's private office during an18-month period were assessed for DDIs. Using the Lexi-Interact online drug interactions software, the prescribed drugs were assessed for the number and type of potential DDIs. Only type D and X interactions were considered eligible for inclusion. RESULTS: During the study period, 344 DDIs were detected of which, 290 were type D; 54 were type XDDIs. 81% of the detected DDIs were pharmacokinetics. Interaction between cyclosporine + mycophenolic acid (32.3%) was the most frequent DDIs followed by cyclosporine + atorvastatin (11.3%). Immunosuppressant (43.44%) was the most frequently used medication responsible for DDIs. Number of co-administered medications (OR: 1.34, 95% CI: 1.12-1.51) and cyclosporine as main immunosuppressive main drug (OR: 10.43, 95% CI: 6.24-17.42) were identified as independent risk factors for DDIs. CONCLUSION: Major DDIs were common in kidney transplant recipients. Considering the importance of DDIs in kidney transplant patients, more attention is warranted in this regard by health care members, especially physicians and pharmacists.

Comparison of the Effect of Alemtuzumab versus Standard Immune Induction on Early Kidney Allograft Function in Shiraz Transplant Center.

BACKGROUND: Induction therapy regimens classified as conventional immunosuppressive agents and lower doses of conventional agents combined with antibodies against T-cell antigens have been purposed to prevent acute rejection after renal transplantation. Various induction agents with different doses and durations have been suggested based on the risk profile of patients. OBJECTIVE: To assess the acute rejection rate (total rate and based on the type of induction therapy regimen) during the first year after kidney transplantation, the type of acute rejection based on Banff classification and to determine the associations between rate of acute rejection, type of the rejection and induction therapy regimen. METHODS: 249 kidney transplant candidates were divided into two groups-low-risk patients (n=208) who received conventional immunosuppressive agents, and high-risk patients (n=41) who received alemtuzumab-and followed for one year to detect acute rejection first diagnosed clinically, and confirmed by percutaneous kidney biopsy based on Banff criteria. RESULTS: The total incidence of acute rejection was 19.6% (20.7% of the low-risk and 14.4% of the high-risk patients). The most prevalent types of the acute rejection in patients treated with conventional immunosuppressive agents and patients received alemtuzumab as induction therapy were grade IB and grade IA, respectively. The incidence of acute rejection among recipients received a kidney from a deceased donor was 20.6% and grade IA was the most prevalent type (6.9%) whereas the most prevalent grade of acute rejection in patients who received living donor grafts was IB (8.3%). CONCLUSION: Despite the expected greater risk for acute rejection among high-risk patients, no significant difference was observed between low- and high-risk patients, which may be justified by the greater efficacy of alemtuzumab compared with standard triple induction therapy in reducing the rate of acute rejection.

Comparison of health status and quality of life of related versus paid unrelated living kidney donors.

The aim of this cross-sectional study was to assess the health status and quality of life (QOL) of paid unrelated versus related living kidney donors postdonation at Shiraz Transplant Center in Iran. We invited all donors (n = 580, 347 paid unrelated, 233 related) who underwent donor nephrectomy at our center from 2004 to 2010 to participate in a health survey and physical examination. Of 580 donors, 144 consented to participate; participation of paid unrelated donors was significantly lower than related (52/347 vs. 92/233; p < 0.001). Participants underwent a complete physical examination, QOL assessment (using a 36-item short form health survey [SF-36] questionnaire) and laboratory work-up. The paid unrelated donors compared with related donors were younger (34.2 ± 7.2 vs. 40.7 ± 9.7 years, p < 0.001), had shorter time since donation (2.9 ± 1.6 vs. 3.8 ± 2 years, p = 0.004), had higher estimated GFR (72.6 ± 22 vs. 63.8 ± 15.3 mL/min/1.73 m(2), p = 0.006) and had a higher percentage of patients with microalbuminuria (35% vs. 0%, p < 0.001). Additionally, general health and social functioning scores among paid unrelated donors were significantly lower (p < 0.001 and p = 0.02, respectively) than related donors. Other SF-36 scores, although lower in paid unrelated donors, did not reach statistical significance. Iranian paid unrelated donors have lower QOL and higher incidence of microalbuminuria compared with related donors.

Acute renal failure and acute necrotizing pancreatitis after Echis carinatus sochureki bite, report of a rare complication from southern Iran.

Venomous animal bites are a significant health problem for rural populations in many parts of the world. Herein, we report an unusual presentation of Echis carinatus sochureki bite from southern Iran. A 36 year old woman was referred to Shiraz Nemaze Hospital due to anuria, headache, gastrointestinal bleeding, nausea and vomiting and severe abdominal pain after Echis carinatus sochureki bite. According to the clinical and paraclinical evaluations, the patient was admitted with impression of acute renal failure and acute pancreatitis. Acute pancreatitis is a rare complication after snake bite. This article is the first report of acute pancreatitis after Echis carinatus sochureki bite.

Endothelial Nitric Oxide Synthase Gene T-786C Polymorphism in Renal Transplant Recipients.

BACKGROUND: Nitric oxide (NO) is a major mediator in vascular biology, regulating regional blood flow. NO and the enzymes required for its production contribute to ischemia-reperfusion injury. The T-786C functional polymorphism in the promoter region substantially reduces promoter activity of the endothelial nitric oxide synthase (eNOS) gene and compromises endothelial NO synthesis. OBJECTIVE: To examine the association between T-786C (rs 2070744) single nucleotide polymorphism (SNP) in eNOS gene and the development of acute rejection in renal transplant patients. METHODS: 60 renal transplant recipients (30 with episodes of acute rejection (ARs) and 30 without rejection (non-ARs)), between June 2008 and March 2010, were included in this study. The polymorphism was determined by PCR-restriction fragment-length polymorphism analysis. RESULTS: The distribution of the genotypes were TT/TC/CC 60%, 33.4%, 6.6%, and 43%, 46.7%, 13.3% in ARs and non-ARs, respectively (p=0.28). The frequency of T-allele was 76.7% and 66.3%; and for C-allele was 66.6% and 33.3% in ARs and non-ARs, respectively (p=0.09). There were no significant associations between these polymorphisms and acute and chronic kidney allograft rejection. CONCLUSION: We could not detect any significant association between polymorphism in T-786C of eNOS gene and the development of acute rejection.

The effect of simvastatin on lowering panel reactive antibody titer in sensitized dialysis patients: a randomized placebo controlled clinical trial.

BACKGROUND: Patients with panel reactive antibodies (PRA) have many difficulties to find a crossmatch-negative kidney for transplantation and are at a higher risk of post-transplantation rejection. OBJECTIVE: To evaluate the effect of simvastatin on PRA and post-transplant outcome of these sensitized patients. METHODS: 82 patients with end-stage renal disease (ESRD) with a PRA ≥25% were evaluated. In a one-year follow-up, the patients were treated with simvastatin. These patients were compared with 82 matched controls receiving placebo tablets. At the end of the second and 12(th) month, PRA was rechecked in all patients. Those patients who underwent transplantation continued to take simvastatin six months after transplantation. Serum creatinine levels were checked at monthly intervals post-operation. RESULTS: The mean±SD PRA level at the end of the second month was 36.63%±31.14% and 45.34%±24.36% in cases and controls, respectively (P=0.012). Seven patients in the case group and 10 in the control group were lost to follow-up. The remaining patients continued to take simvastatin for 12 month. The mean±SD PRA level at the end of the 12(th) month was 24.02%±31.04% in cases and 43.15%±26.56% in controls (P=0.001). 25 patients underwent renal transplantation and continued to receive simvastatin 6 months after transplantation. These patients were matched with 25 controls treating with placebo. The mean±SD creatinine level 6 months after kidney transplantation was 2.05±1.14 mg/dL and 3.15±1.09 mg/dL in cases and controls consecutively (P=0.02). CONCLUSION: Simvastatin can be safely used to lower PRA and improve post-transplantation outcomes.

Transperitoneal laparoscopic living donor nephrectomy: 2 years' experience.

BACKGROUND: Due to the shortage of organ donations and the rising number of patients with terminal renal insufficiency, living donor kidney donation has become increasingly important during recent years. Hand-assisted laparoscopic living donor nephrectomy (LLDN) is an alternative to the conventional open approach and may decrease the surgical trauma to the donor. The aim of this study was to report our experience with this technique. MATERIALS AND METHODS: We reviewed demographic data, operative duration, hospital stay, and postoperative complications among 100 LLDNs performed from August 2006 to July 2008. We also performed a retrospective analysis of chemical and biochemical data of recipients. RESULTS: Thirty female and 70 male subjects of mean age of 35.88 +/- 12.21 years were operated on during this period. The mean operative time for donor nephrectomy was 138.30 +/- 31.92 minutes (range 60-205) and for recipients, 87.66 +/- 11.79 minutes (range = 75-120), with a mean warm ischemia time of 5.19 +/- 1.76 minutes (range = 2-8). The donors' mean hospital stay was 28.34 +/- 8.31 hours (range = 24-72). Five donor operations were converted to open nephrectomy because of uncontrolled bleeding or abnormal anatomy. There was no need for blood transfusions or reoperations in the donors. Mean hospital stay for the recipients was 9.44 +/- 3.61 days (range = 5-22). Creatinine and blood urea nitrogen decreased from preoperative values of 10.46 +/- 3.73 and 66.10 +/- 25.16 to 1.39 +/- 0.38 and 29.64 +/- 8.83 mg/dL at discharge. The renal graft was rejected in two cases due to immunologic causes without any response to therapy. There was no vascular thrombosis in the transplanted kidneys. CONCLUSION: LLDN is a viable alternative to the standard open nephrectomy. It may have a positive impact on the donor pool by minimizing disincentives to living donation. The results of our program were acceptable; this approach may be the procedure of choice in the future in our center.

Serum LDL levels are a major prognostic factor for arteriovenous fistula thrombosis (AVFT) in hemodialysis patients.

INTRODUCTION: Arteriovenous fistula thrombosis (AVFT) is still a common cause of morbidity in patients undergoing regular hemodialysis (HD). Many factors have been found to induce AVFT. Some of those factors are local and others are systemic ones. In this study, we evaluated some local and systemic factors simultaneously, to predict the most potent risk factor for AVFT in HD patients. PATIENTS AND METHODS: One hundred and eighteen patients aged 20-80 yrs with end-stage renal disease (ESRD) were evaluated prospectively for a period of 14 months. First, anticardiolipin antibodies (ACLA), TG, cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL) were analyzed by conventional methods. Other basic data were accessed from patients medical records. All fistulas were evaluated clinically as patent at the start of this study. Patients were followed-up for any evidence of AVFT within 14 months. Finally, all factors (diabetes, hypertension, presence of ACLA, ultrafiltration >or=3 L, age, gender, weight, hypotension during dialysis, fistula site, epoetin alpha usage, TG, HDL, LDL and total cholesterol) were analyzed in a stepwise regression analysis. RESULTS: Eighteen episodes of AVFT documented with Doppler sonography occurred in 17 patients (15.3%). Regression analysis showed only LDL values were the AVFT predictor in our patients (p=0.002, beta-coefficient=0.3). Kaplan-Meier analysis showed a significantly lower AVF patency time in patients with LDL >130 mg/dl than those with LDL <130 mg/dl (log rank=0.0014). DISCUSSION: LDL value is a major prognostic factor for AVFT in HD patients and lowering it to <130 mg/dl could improve fistula patency.

Are large nonfunctional kidneys risk factors for posttransplantation urinary tract infection in patients with end-stage renal disease due to autosomal dominant polycystic kidney disease?

OBJECTIVES: The objective of this study was to evaluate the effect of bilateral nephrectomy on posttransplantation urinary tract infection (UTI) among patients with end-stage renal disease (ESRD) due to autosomal dominant polycystic kidney disease (ADPKD). METHODS: In a retrospective case-control design, 62 patients with ESRD with ADPKD were divided into 2 groups: (A) 24 patients who underwent bilateral nephrectomies, and (B) 38 patients in whom bilateral nephrectomies had not been done. Pretransplantation and posttransplantation urine cultures were evaluated for UTI. RESULTS: Sixty-two patients with ESRD with ADPKD were enrolled in this study. The average age was 42 years (range, 6-60 years). Forty patients (64.5%) were male and 22 (35.5%) were female. The mean duration of hemodialysis was 24 months (range, 2-120 months), which was the same for both groups. Bilateral nephrectomies were done for 24 participants (38.7%). There were 38 patients (61.3%) in group B who did not have the operation. UTI occurred in 23 patients (37.1%): 6 patients (25%) in group A and 17 patients (44.7%) in group B. The incidence of UTI was not statistically different between the 2 groups (P>.05). Furthermore, no relationship was found between age, gender, blood group, and UTI in patients with ADPKD (P>.05). CONCLUSION: According to our study, the presence of large nonfunctional kidneys is not a risk factor for posttransplantation UTI in patients with ADPKD and ESRD.