Relationship of Urothelial Gene Expressions in Urine-Deprived Bladders of Renal Recipients With Posttransplant Urinary Infections.

OBJECTIVE: In this study, we analyzed gene expression levels of apoptotic (Fas, FasL, Bcl-2, Bax) and survival (CXCR1, CXCR2, IL-8) signal pathways of the urine-deprived bladder tissues and the relation of urinary tract infections with these pathways. MATERIAL AND METHODS: We included 37 patients admitted for renal transplantation between December 2009 and December 2012. Bladder mucosal samples were obtained at the time of transplantation and 6-8 weeks posttransplantation, at the time of ureteral catheter removal. RNA extraction and cDNA synthesis were done using guanidium-thiocyanate and colon filter methods. Expression analysis was studied with quantitative real-time polymerase chain reaction optimized with ROX dye and internal control ß-actin. RESULTS: According to our findings Fas, FasL, Bcl-2, and Bax expression was higher in urine-deprived bladder samples than those in the posttransplant samples (P < .05). Although Fas, FasL, Bcl-2, and Bax expression levels increased in pretransplant samples, there was an increase in posttransplant bladder samples; however, this increase was not as marked as those of pretransplant samples. IL-8, CXCR1, and CXCR2 expression was decreased at the pretransplant samples and increased in posttransplant bladder samples. CONCLUSIONS: We have found an upregulated apoptotic process and decreased survival signals at the urine-deprived bladder tissue. After transplantation, bladder tissue survival parameters were increased, demonstrating the importance of urinary flow for bladder tissue.

Effects of Urethral Stricture on Allografts in Kidney Transplantation.

BACKGROUND: Iatrogenic urethral stricture after renal transplantation is mostly seen after urethral manipulations. Early diagnosis and treatment are crucial for the safe continuity of the graft functions. In this study, the effect of urethral strictures on graft functions during the post-transplantation period was investigated. METHODS: A total of 477 kidney transplantations were carried out from both live and cadaveric donors in our center from 2004 to 2014. Thirty-two patients who had insufficient data were excluded from the study. All the patients' urine cultures were negative before the surgery, and antibiotic prophylaxis were applied to all. Urethral catheters were taken out 4-7 days after transplantation. Double-J catheters were removed 6 weeks later. Internal urethrotomy and open urethroplasty surgeries were done for the patients who had urethral stricture. The results of creatinine, post-micturitional residual urine (PMR), International Prostate Symptom Score (IPSS), and uroflow examinations were evaluated. RESULTS: Average preoperative creatinine and postoperative creatinine values were, respectively, 1.74 ± 0.65 mg/dL (range, 0.83-3.03) and 1.24 ± 0.57 mg/dL (range, 0.9-2.24). A meaningful improvement was observed in terms of preoperative and postoperative IPSS values. A significant difference was seen between preoperative and 6th-month postoperative PMR values: 192.6 ± 57.2 mL and 36.7 ± 17.4 mL, respectively. CONCLUSIONS: Urethral strictures in transplant patients may arise due to many factors, such as repetitive urethral catheterization and inflammation. Early diagnosis helps to have better results for the treatment of the kidney functions.

Cancer Screening of Renal Transplant Patients Undergoing Long-Term Immunosuppressive Therapy.

OBJECTIVE: With this study we aimed to research the effects of immunosuppressive drugs, their cumulative doses, and viral infections on development of malign tumors in patients who have undergone treatment for 5 years. METHODS: We examined 100 patients who underwent renal transplantation from 2004 to 2009. Patients had mycophenolate mofetil and steroid in addition to cyclosporine, sirolimus, or tacrolimus as immunosuppressive treatment. For malignancy screening, physical examination, radiologic and endoscopic screening were done, and immunosuppressive drugs and their cumulative doses, age, sex, body mass index (BMI), dialysis history, and viral infection history were investigated. RESULTS: The mean age of patients was 42.03 ± 11.30 years. There were 1 colon cancer patient, 1 retroperitoneal liposarcoma, 1 renal oncocytoma, 3 Kaposi sarcoma patients treated with cyclosporine; in those treated with Tac there were 1 basal cell carcinoma, 1 Kaposi sarcoma, 2 thyroid carcinoma, 1 breast carcinoma, 1 bladder carcinoma, 1 renal cell carcinoma, and 1 colon carcinoma patients. The mean age of patients having carcinoma was statistically significant compared with those without cancer (P < .01). The prednisolone cumulative dose was significantly higher in carcinoma patients than in patients without carcinoma (P < .01). RESULTS: The use of long-term chronic immunosuppressive therapy may increase the development of cancer. The risk of carcinoma increases with increasing drug dose and time period of the immunosuppressive drug. There was not a negative effect on cancer prevalence in patients with cyclosporine or tacrolimus. But the cumulative dose of steroids significantly increased malignancy occurence.

Tacrolimus-Induced Diabetic Ketoacidosis and Effect of Switching to Everolimus: A Case Report.

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a common metabolic complication. Most conventional immunosuppressive medications, especially steroids and tacrolimus, are responsible for its development. NODAT may rarely be associated with severe, life-threating complications in kidney transplantation recipients. CASE REPORT: A 44-year-old man was admitted to our polyclinic for a routine post kidney transplantation visit. He reported polyuria, polydipsia, and general weakness. The patient had undergone preemptive, living-related kidney transplantation 5 weeks previously. Immunosuppressive treatment comprised tacrolimus, prednisolone, and mycophenolate mofetil. Physical examination revealed no abnormalities except signs of mild dehydration. Although he had no history of diabetes before kidney transplantation and his serum fasting glucose levels were within the reference range at the follow-up visits, his laboratory tests revealed high serum glucose and creatinine levels, ketosis, and metabolic acidosis. Our diagnosis was NODAT with diabetic ketoacidosis and prerenal azotemia. Initial treatment comprised intravenous saline and insulin infusion and subsequently involved intensive subcutaneous insulin administration. Despite the intensive insulin therapy and reduction of the tacrolimus dose, sufficient glucose regulation was not achieved. Tacrolimus was switched to everolimus on day 6 of hospitalization. The patient's insulin requirement gradually decreased to one-half of the primary dose over the following several days, and he was discharged on day 10 with successful serum glucose regulation. Although the diabetogenic potential of sirolimus is similar to that of tacrolimus, the impact of everolimus on glucose metabolism remains unclear. CONCLUSIONS: We have reported a life-threating metabolic complication associated with tacrolimus and successful treatment of NODAT by switching from tacrolimus to everolimus.

Monitoring of CD3(+) T-cell count in patients receiving antithymocyte globulin induction after cadaveric renal transplantation.

AIM: Although antithymocyte globulin (ATG) has been used for years, its ideal dose and administration period is obscure. Herein, we sought to use the CD3(+) cell count to detect the optimal ATG dosage. MATERIAL AND METHODS: Twenty-one patients who underwent cadaveric donor renal transplantation from January 2009 to January 2012 received a 1 mg/kg ATG initial dose at the time of the operation. Patients were randomized into 2 cohorts. Group 1 (n = 11) received ATG according to the clinical and total lymphocyte count and group 2 (n = 10), the dose was tailored according to the CD3(+) cell count. We compared the total and daily ATG dosages, ATG administration period, side effects of ATG, the number of days to a serum creatinine level <2 mg/dL, graft function at 3 months, acute rejection episodes, infection rates, costs of CD3(+) analysis, and ATG amounts. RESULTS: Both groups showed similar gender, age, and human leukocyte antigen matching data. There was no difference in presensitizing events or panel-reactive antibody class 1 and 2 levels. The number of days to a serum creatinine level of <2 mg/dL was 11 ± 1.5 for group 1 versus 10.4 ± 0.8 for group 2 (P = .45). Between groups 1 and 2, there was a significant difference between the mean total (P = .031) and mean daily ATG dosages (P = .006). We used a total dose of 3800 mg ATG for group 1 and 2200 mg for group 2 and for the group 2 who underwent 43 CD3(+) cell counts. The expenditure per patient was 20% higher among group 1 than group 2. CONCLUSION: Determination of appropriate ATG dosages by CD3(+) cell counts was useful, reliable, and cost effective.