Impact of Subclinical Rejection on Kidney Graft Function.

BACKGROUND: In kidney transplant recipients with borderline infiltration, protocol biopsy results demonstrated the relationship with chronic injury. The purpose of this study was to evaluate the effect of subclinical rejection (SCR) on 6-month protocol biopsy results in long-term renal function in renal transplant recipients with stable graft function. MATERIAL AND METHODS: Transplant protocol biopsies performed in 45 patients with stable renal function were included in this study at 6 months. Biopsy specimens were evaluated for SCR. Study groups were divided into patients with and without SCR. Renal functions were compared with pathologic evaluation. The effect of immunosuppressive regimens on renal function were evaluated in patients with SCR RESULT: The median age of patients was 32 years (range, 18-64 years). The median follow-up was 56 months (range, 24-84 months). According to the 6-month protocol biopsy results, 20 of 45 patients (44.4%) met SCR criteria based on Banff 07 parameters. There was not a statistically significant difference in renal function with SCR. CONCLUSION: The presence of SCR on the 6-month protocol biopsy results in renal transplant recipients with a stable graft function does not cause deterioration in the long-term graft function.

Assessment and outcome of pediatric intestinal pseudo-obstruction: A tertiary-care-center experience from Turkey.

BACKGROUND/AIMS: Pediatric intestinal pseudo-obstruction (PIPO) is a severe disorder of gut motility. In this rare and difficult-to-manage disease, complex treatment method, such as intestinal transplantation, is sometimes needed. This study evaluated the management and follow-up results of patients with PIPO who received treatment at our center. MATERIALS AND METHODS: The cases of 13 patients with PIPO were reviewed retrospectively. Demographic data, clinical features, etiologies, pharmacological and surgical treatments, nutritional support, anthropometric findings, small bowel transplantation (SBT), and survival rates were assessed. RESULTS: Two of the patients were diagnosed at 1 and 5 years of age, while other patients were diagnosed during neonatal period. The etiological cause could not be identified for 5 patients. Pharmacological treatment response was observed in 38.4% of patients. Post-pyloric feeding was applied in 4 patients, but no response was observed. Gastrostomy decreased the clinical symptoms in 3 patients during the abdominal distension period. Total oral nutrition was achieved in 38.4% of the total-parenteral-nutrition (TPN)-dependent patients. It was observed that anthropometric findings improved in patients with total oral nutrition. Liver cirrhosis developed in 1 patient. Venous thrombosis developed in 4 patients. The SBT was performed on 3 patients. One of these patients has been followed up for the last 4 years. CONCLUSION: Pediatric intestinal pseudo-obstruction is a rare disease that can present with a wide range of clinical symptoms. While some patients require intestinal transplantation, supportive care may be sufficient in others. For this reason, patients with PIPO should be managed individually.

Pediatric small bowel transplantation: A single-center experience from Turkey.

BACKGROUND/AIMS: Small bowel transplantation (SBTx) is a treatment option for patients with serious parenteral nutrition-related problems in intestinal failure. Izmir Tepecik Training Research Hospital Organ Transplantation Center is still the only pediatric intestinal transplant center in Turkey. MATERIAL AND METHODS: This study was approved by the local ethics committee. Patients' data were analyzed from the medical charts and the hospital digital database. Seven isolated SBTxs were performed in six children between 2010 and 2016. RESULTS: One jejunal segment and six partial jejuno-ileal segments were used for seven transplants. All grafts were retrieved from deceased donors (one child and six adult donors). The six recipients had a mean age of 8.8±6.9 years (9 months to 17 years; M: 4, F: 2). The mean follow-up period of patients was 727±848 (34 to 1950) days. Acute cellular rejection (ACR) rates were 57% (n: 4) in the first 2 months. Graft loss due to severe ACR was seen in one patient. Central line-associated fungal (n: 3, 42%) and bacterial infections (n: 3, 42%) were seen in the first 2 months. Two Epstein-Barr virus (EBV) infections were recorded between 3 and 8 months in two patients. Our 1-year patient and graft survival rates were 71% and 71%, respectively. CONCLUSION: SBTx has become a treatment modality for patients with intestinal failures. Management of ACR and infections are still challenging problems in SBTx. Appropriate-sized cadaveric donors are very limited in Turkey for pediatric intestinal transplantation candidates. Although the number of SBTxs performed was small, this study shows promising results.

Delayed Graft Function in Kidney Transplantation: Risk Factors and Impact on Early Graft Function.

CONTEXT: Although kidney transplantations are routinely performed at many centers in Turkey, the incidence and risk factors associated with delayed graft function (DGF) here have not yet been well defined. OBJECTIVE: The aim of this study is to evaluate the incidence and risk factors of DGF and its impact on early graft function. DESIGN: The medical charts of 154 adult patients who underwent deceased donor kidney transplantation between 2000 and 2014 in a single center were reviewed retrospectively. SETTING: Delayed graft function-related risk factors for donors, recipients, and the transplant surgery itself were analyzed, and their relation with graft function was evaluated. MAIN OUTCOMES MEASURES: The median recipient age was 39 years. The median cold ischemia time (CIT) was 840 minutes (14 hours). The incidence of DGF and acute rejection were 57.8% and 8.4%, respectively. Higher serum creatinine levels at 3, 6, and 12 months were observed in patients with DGF compared to other patients without DGF (P < .05). Patients with DGF had poor graft function (glomerular filtration rate ≤ 50) at 3 and 6 months (P < .05), but these correlations were not seen at 12 months (P = not significant). RESULTS: This study showed that DGF was a common and serious problem associated with poor graft functions at 3, 6, and 12 months after transplantation. Extra effort to shorten CIT as an independent risk factor for DGF could have protective effect on graft functions.

Primary squamous cell carcinoma of the urethral diverticulum mimicking prostate cancer: Case report and review of the literature.

Primary urethral carcinomas are uncommon, with urothelial carcinoma as the most common subtype. Urethral diverticulum is also rarely seen in men. A 44-year-old male presented with voiding symptoms. Abdominoperineal resection, prostatectomy, bladder neck excision, and proximal urethral excision were performed. A pathological examination revealed a well-differentiated squamous cell carcinoma (SCC) located inside an urethral diverticulum. We report this unusual case because primary SCC of the male urethral diverticulum is extremely rare. To our knowledge, our patient is only the second reported case.

Renal tubular acidosis in renal transplant patients: the effect of immunosuppressive drugs.

BACKGROUND: Renal tubular acidosis (RTA) is a non-anion gap metabolic acidosis and is generally mild and asymptomatic in kidney recipients. Calcineurine inhibitors (CNIs) increase the frequency of RTA but the frequency of RTA development in kidney transplant recipients receiving mammalian target of rapamycin inhibitors (mTORi) treatment remains unclear. In this study, we aimed to investigate the frequency of RTA in kidney transplant recipients on mTORi and CNI treatment and to compare both groups. MATERIAL AND METHODS: We enrolled 137 adult renal transplant patients - 82 patients on mTORi and 55 patients on CNI who had similar age, sex, posttransplant follow-up period, and graft functions. We recorded the parameters of venous blood gas analysis, including serum pH value, serum bicarbonate (HCO3) concentration, presence of metabolic acidosis defined as low HCO3 (<22 mEq/L), and serum pH value (<7.35), as well as base excess and urine pH at last follow-up. RTA was defined to be metabolic acidosis with normal serum anion gap and positive urine anion gap. RESULTS: The mean age of our study population was 41.2±11.3 years. RTA frequency was 35% in the mTORi group and 41% in the CNI group. mTORi and CNI groups did not differ significantly in terms of the development of metabolic and renal tubular acidosis. Type I RTA was common in both groups. RTA was affected by duration of time since transplantation and graft functions in both groups. CONCLUSIONS: The rates of RTA development in patients on long-term CNI and mTORi treatment were similar.

The relation between serum testosterone levels and cardiovascular risk factors in patients with kidney transplantation and chronic kidney disease.

The objective of the study is to evaluate the relationship between serum testosterone levels and cardiovascular risk factors (CVRF) in patients after kidney transplantation and with chronic kidney disease (CKD). Seventy-five male patients, aged between 18 and 68 years, who had kidney transplantation at least six months earlier, were enrolled into the study. Only renal transplant recipients and CKD patients with a creatinine level of <2.5 mg/dL were included in this study. Patients were divided into three groups as patients receiving calcineurine inhibitors (CNIs) and Mammalian target of rapamycin inhibitors (m-TORi) and CKD. Serum ceatinine, testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, high-sensitivity C-reactive protein (hs-CRP), total cholesterol (TC), triglyceride (TG) as well as left ventricle mass (LVM), left ventricle mass index (LVMI), left atrium (LA), inferior vena cava (IVC) inspiratory and expiratory diameters and collapse index (CI) and blood pressure (BP) were evaluated. Serum testosterone levels were significantly higher in the m-TORi and CNIs groups when compared with the CKD cases (P <0.05). When kidney recipients (both groups) were compared with CKD patients, we observed positive outcomes in serum testosterone levels and CVRF at significant levels. There was no significant difference in terms of age, serum creatinine, serum testosterone, FSH, LH, prolactin, hs-CRP, LVMI, TC and TG and between the CNIs and mTORi groups (P >0.05). Serum testosterone levels were independent risk factors affecting IVC collapse index, systolic BP and LA. m-TORi and CNIs drugs might have no negative effect on serum testosterone levels, and improvement of the serum testosterone levels after transplantation might have a positive contribution on cardiac risk factors.

The effect of cold ischemia time on delayed graft function and acute rejection in kidney transplantation.

The objective of this study is to evaluate the impact of cold ischemia time (CIT) on delayed graft function (DGF) and acute rejection (AR) among deceased donor kidney transplant recipients. The medical records of 111 patients who underwent kidney transplantation from deceased donors between November 1994 and July 2009 were retrospectively analyzed. DGF was observed in 54% of the patients and the prevalence of AR in the first year after transplantation was 9.9%. The incidence of DGF was higher among patients with longer CIT. There was no correlation between CIT and AR episodes. Higher body weight of recipients and donors, history of prior blood transfusion and advanced donor age were related with DGF. Patients with DGF had higher serum creatinine levels at the first, third and fifth years. There was a negative correlation between recipient body weight and creatinine clearance at the first year. CIT has an important role in the development of DGF as a modifiable risk factor. Moreover, donors with advanced age and higher body weight as well as recipients with higher body weight and history of blood transfusions are at risk for the development of DGF. Prevention of DGF may help to improve graft function at the first, third and fifth years and shorten the hospital stay.

Mesenchymal stem cell therapy in patients with small bowel transplantation: single center experience.

AIM: To study the effects of mesenchymal stem cell (MSC) therapy on the prevention of acute rejection and graft vs host disease following small bowel transplantation. METHODS: In our transplantation center, 6 isolated intestinal transplants have been performed with MSC therapy since 2009. The primary reasons for transplants were short gut syndrome caused by surgical intestine resection for superior mesenteric artery thrombosis (n = 4), Crohn's disease (n = 1) and intestinal aganglionosis (n = 1). Two of the patients were children. At the time of reperfusion, the first dose of MSCs cultured from the patient's bone marrow was passed into the transplanted intestinal artery at a dose of 1000000 cells/kg. The second and third doses of MSCs were given directly into the mesenteric artery through the arterial anastomosis using an angiography catheter on day 15 and 30 post-transplant. RESULTS: The median follow-up for these patients was 10.6 mo (min: 2 mo-max: 30 mo). Three of the patients developed severe acute rejection. One of these patients did not respond to bolus steroid therapy. Although the other two patients did respond to anti-rejection treatment, they developed severe fungal and bacterial infections. All of these patients died in the 2(nd) and 3(rd) months post-transplant due to sepsis. The remaining patients who did not have acute rejection had good quality of life with no complications observed during the follow-up period. In addition, their intestinal grafts were functioning properly in the 13(th), 25(th) and 30(th) month post-transplant. The patients who survived did not encounter any problems related to MSC transplantation. CONCLUSION: Although this is a small case series and not a randomized study, it is our opinion that small bowel transplantation is an effective treatment for intestinal failure, and MSC therapy may help to prevent acute rejection and graft vs host disease following intestinal transplantation.

The effects of preoperative immunosuppressive therapy on ischemia and reperfusion (I/R) injury in healthy rats.

PURPOSE: Warm-ischemia-induced injuries might be encountered during renal transplants from cadavers and healthy donors. Toll-like receptors (TLR) in ischemia-reperfusion (I/R) injury are one of the indicators of intracellular injury pathways. The intensity of ischemic injury is directly proportionate to high TLR levels. To minimize the I/R injury, we investigated TLR2 and TLR4 levels on rats, which were pretreated with tacrolimus (FK506) before I/R. METHODS: Eight Wistar albino rats in the study group were administered .01 mg/kg intramuscular tacrolimus. Administration to the study group was performed 24 and 1 h before warm ischemia. Eight rats in the control group were injected with 0.1 c.c. of distilled water. Blood samples were collected from the tail veins of all the rats on the first, second and third days. Expression levels of TLR2 and TLR4 genes were analyzed using the polymerase chain reaction method, to determine any significant difference between the control and study groups on the days when blood was taken. RESULTS: TLR2 (p = 0.045) and TLR4 (p = 0.022) levels in the study group were found to be statistically, and significantly, lower than those in the control group, on the second day following warm-ischemia- and reperfusion-induced injury. CONCLUSIONS: Administration of immunosuppressive drugs to healthy donor rats led to a statistically significant reduction in the expression levels of TLR2 and TLR4 in the early period. In light of the data obtained by this study, we hypothesize that a preoperative therapy on donors might have a role in preventing I/R injury.

A retrospective analysis of long-term graft survival in 61 pediatric renal transplant recipients: a single-center experience.

BACKGROUND: Although short-term renal allograft survival in children has improved over the years, long-term graft outcomes remain unclear. In this study we report the characteristics and other variables that impact long-term kidney graft survival in children. MATERIAL AND METHODS: Records of 61 pediatric kidney transplant recipients (mean age: 14±3 years) performed at our institution between 1995 and 2011 were evaluated. Patients were divided into 2 groups (functional and non-functional grafts) to investigate the factors that impact graft survival. The groups were compared in terms of recipient characteristics, underlying disease, HLA status, immunosuppressive therapy, donor characteristics, acute rejection, and delayed graft function (DGF). Statistical significance was detected with the t and chi-squared tests (Pearson and Fisher's exact tests). Kaplan-Meier analysis was performed for graft survival. RESULTS: Overall graft survival at 1, 5, 10, and 15 years were 93%, 66%, 46%, and 41%, respectively. The median graft survival was 128.4 months (range: 3-188 months). Donor age, acute rejection, and DGF strongly predicted the chance of graft survival (p<0.05). CONCLUSIONS: It appears that several modifiable risk factors can partially account for poorer graft survival in pediatric kidney transplant recipients.

Effective weight control and normalization of metabolic parameters after laparoscopic sleeve gastrectomy: a single center experience.

BACKGROUND/AIMS: Obesity is one of the most serious public health problems. Laparoscopic sleeve gastrectomy (LSG), a type of bariatric surgery, is emerging as the new promising therapy for the treatment of morbid obesity. METHODOLOGY: In the present study we aimed to assess the effects of LSG on body weight and other obesity related pathological conditions. RESULTS: A total of 19 obese subjects underwent LSG surgery. All patients underwent complete evaluation including anthropometric/clinical parameters and laboratory tests. Hypertension (HT), diabetes mellitus (DM), body mass index (BMI), and hyperlipidemia were significantly reduced after LSG. CONCLUSIONS: Results of this study demonstrate that LSG induces stable weight loss and resolution of obesity-associated comorbidities.

Disseminated candidiasis developing during prophylaxis with fluconazole in a small-intestine transplant recipient.

A 31-year-old man underwent immunosuppressive treatment and was treated with 150 mg per day of prophylactic oral fluconazole after receiving a small-intestine transplant. The patient had acute rejection by the end of the first week after the transplant. Endoscopic examination showed white plaques. In blood and urine cultures, growth of Candida albicans was detected. Biopsy specimens showed high levels of conidia and hyphae in all regions. Intravenous treatment with caspofungin was started for the patient. Candidal findings had regressed on follow-up endoscopy. However, the patient died 3 months after transplant because of the effects of immunosuppression on his bone marrow and the development of disseminated intravascular coagulation. Candida species are the most common cause of invasive fungal infections that develop after solid-organ transplant. Following transplant, candidemia may develop during systemic antifungal treatment with a high level of mortality.

En-bloc pediatric kidney transplantation together with a partial bladder segment: a case report.

There is a continuing debate about the techniques of kidney transplantation from small donors because of the high vascular thromboses and ureteric leak rates. Transplantation of en-bloc pediatric kidneys with a partial bladder segment has potential benefits over established techniques. We transplanted cadaveric en-bloc kidneys together with a partial bladder segment from a 1.5-year-old donor to a 12-year-old boy with end-stage renal disease due to vesicoureteral reflux (VUR) of a solitary kidney. En-bloc kidneys were transplanted together with both ureters and a partial bladder segment. Using donor bladder segment augmented the recipient bladder. Thereby, potential complications of bilateral ureteroneocystostomies of small ureters were avoided. During the following 12 months, the clinical course was normal and there was no evidence of VUR. In conclusion, the technique of using en-bloc pediatric kidneys together with a partial bladder segment is feasible and safe as well as an efficient procedure to preserve the natural anti-reflux mechanism in childhood.

Non-heart-beating donors: is it worthwhile?

OBJECTIVE: Due to organ shortage in renal transplantation, many transplant centers attempt to increase the donor pool. Non-heart-beating donors seem to be a promising alternative. PATIENTS AND METHODS: We performed 14 renal transplantations from 8 non-heart-beating donors. 2, 1, 3 and 2 donors were from groups 1, 2, 3 and 4, respectively, according to Maastricht classification. RESULTS: In 6 of the patients' warm ischemia time was over 30 minutes. Three of them had primary non-function. In 6 patients delayed graft function was seen. The remaining 5 kidneys functioned immediately. Two patients whose kidney functioned returned to hemodialysis in the I I and 13th months after their transplantations. One of the patients with primary non-function died. 9 kidneys function well in their follow-up period between 5-111 months. 1 and 5-year graft survival rates were 69.8 and 61.1 percent, respectively. The mean graft survival time is 69.9 +/- 14.5 months. CONCLUSION: Despite the high primary non-function rate, we think that non-heart-beating donors especially in Maastricht classification 3 and 4 should be used due to dramatic shortage of organs.

Multiple renal arteries in laparoscopic donor nephrectomy.

BACKGROUND: Laparoscopic donor nephrectomy has gained popularity throughout the world recently. The more centers became experienced the more this technique began to be used, even in extreme cases. Kidneys with multiple renal arteries are one of the difficult cases for laparoscopic donor nephrectomy. PATIENTS AND METHOD: Thirty living laparoscopic donor nephrectomies have been performed between January 2001 and December 2002. Twenty-three of them had single and seven kidneys had multiple renal arteries. Single (SA) and multiple (MA) artery groups were statistically similar in terms of donor age, rate of received right kidneys and serum creatinine clearance of the donors. RESULTS: The mean duration of the donor surgery was 225 min and 240 min in SA and MA groups. In the SA and MA groups, the mean warm and cold ischemia times were statistically similar. Laparoscopic nephrectomy was converted to open procedure in five and one donors, in the SA and MA artery groups, respectively. Intraoperative bleeding (single artery: 4, multiple arteries: 1) was the most common cause for conversion. Postoperative urinary complications were seen in four and one patients, in the SA and MA groups, respectively. Lengths of hospital stay of the donors were similar in both groups. Serum creatinine levels of the patients on seventh, 30th, 90th days, and 1 year were found to be statistically similar in both groups. CONCLUSION: Laparoscopic donor nephrectomy was found to be a safe procedure in the donors with multiple renal arteries by the experienced surgical teams, as much as in donors with single arteries.

Marginal donors in kidney transplantation.

BACKGROUND: Due to organ shortage, it is not easy to find an ideal donor in renal transplantation. To enhance donor pool, marginal donors can be acceptable even in living renal transplantations. We compared optimal and marginal donor transplantations in terms of graft and patient survival. METHODS: We performed 32 living related renal transplantations, 11 of which were from marginal donors, from January 1999 to December 2000. Recipients from optimal and marginal donors were compared in terms of renal function, acute tubular necrosis (ATN) and acute rejection (AR) rates. RESULTS: Although mean serum creatinine level in the seventh day was found to be higher in the recipients from marginal donors (1,88 mg/dl vs. 2,51 mg/dl); it did not reach to a statistical difference (p = 0.1). Serum creatinine levels after thirtieth day, ATN and AR rates were statistically similar in both groups, as well. In optimal and marginal groups, 3-year graft survival rates were found to be 85 and 72 percent respectively (p = 0.72). 3-year patient survival rates were also found to be similar in both groups (90% vs. 91%) (p = 0.91). CONCLUSION: Functional and survival results in the transplantations from marginal donors were as good as from optimal donors. So, we thought that marginal donors could be used safely with a good preoperative evaluation to increase donor pool.

The toxicity rates of two different regimens of irinotecan.

The role of chemotherapy in the management of advanced colorectal cancer has been well established. Although fluorouracil has been the main cytotoxic agent used for colorectal cancer, newer drugs have been developed with promising results. In this study, we compared two different doses of irinotecan combined with 5-fluorouracil/leucoverin (5-FU/LV) in terms of progression-free and overall survival time and toxicity in the patients with recurrent or metastatic colorectal cancer. Patients were divided into groups. The first group received 350 mg/m2 irinotecan every three weeks. The second group was treated by 150 mg/m2 once a week for consecutive four weeks followed by a two-week drug-free interval. All the patients received 500 mg/m2 5-fluorouracil and 20 mg/m2 leucoverin every time they were treated with irinotecan. Median progression-free survival time was found to be 7 +/- 1 and 6 +/- 1 months in the first and seconds groups, respectively. Median overall survival time was found to be 19 +/- 4 and 12 +/- 4 months in the first and second groups, respectively. Alopecia grade 3-4 reaction rates were found to be significantly higher in the first group, while hematological grade 3-4 toxicity rates were higher in the second group. Although overall and progression-free survival curves were found to be similar in each group, hematological complications were less and response rates were higher in the 3-week course group. The 3-week course seemed to have a more comfortable administration schedule as well. So, we suggest the 350 mg/m2 once every 3 weeks regimen.