International Journal of Organ Transplantation Medicine
Volume:8 Issue: 2, Spring 2017

As already proven in solid tumors, increased angiogenesis leads to increased number of blood vessels, resulting in unfavorable outcomes and resistance to chemotherapy. It was previously thought that angiogenesis plays no role in the pathogenesis of acute myeloid leukemia (AML), due to the fact that AML is a liquid tumor. However, many studies have suggested that increased angiogenesis has important roles in patients with AML, including increased numbers of vessels in bone marrow and pro-angiogenic factors, as well as decreased anti-angiogenic factors. Also a large number of studies demonstrated that a two-way communication is established between leukemic and endothelial cells, as a component of the vessel wall, in the bone marrow of patients with AML. These two cells support the survival and proliferation of each other through a paracrine pathway, resulting in resistance to chemotherapy. In addition, It is well established that increased angiogenesis is associated with unfavorable prognosis, lower survival rate, resistance to chemotherapy, and relapse. Furthermore, increased angiogenesis affects the response to treatment, hematopoietic stem cell transplantation (HSCT) outcome and graft versus host disease (GVHD) occurrence. In this regard, this review will address vascular endothelial growth factor (VEGF) and angiopoietin (Ang), two of the most important angiogenic factors, in patients with AML before and after HSCT. By increasing our understanding of the role of endothelial cells and angiogenic factors in patients with AML from diagnosis to post-HSCT, new therapeutic strategies can be developed to reduce angiogenesis, improve patients’ survival and reduce complications.

Immunosuppressive therapies are important parts of renal transplantation.
To assess the present literature on the effectiveness of early introduction of mTOR inhibitors with or without calcineurin inhibitors (CNI) in renal transplant recipients in terms of renal functioning and graft survival.
The current literature was reviewed following PROSPERO approval, assessing the role of immunosuppressive agent, mTOR inhibitors as an alternative to CNI within 6 months of renal transplantation by searching PubMed, EMBASE, Cochrane, Crossref, and Scopus.
6 articles of early withdrawal of CNI and introduction of mTOR inhibitors within 6 months of renal transplantation were sought. Glomerular filtration rate (GFR) and serum creatinine were better in mTOR inhibitor group at 12 months. Biopsy-proven acute rejection (BPAR) was significantly higher in mTOR inhibitor group, though survival was comparable.
On the basis of present literature, the early introduction of mTOR inhibitors causes substantial CNI minimization. The mTOR inhibitors are more favorable due to their complementary mechanism of action and favorable nephrotoxicity profile, better glomerular filtration, and lower serum creatinine with equivalent survival. However, the higher rejection rate may influence the use of these regimens in patients with moderate to high immunological risk.

Kidney transplantation is the most cost-effective therapy for end stage renal disease. Postoperative complications account for 15%–17% of all cases and are associated with significant morbidity. Currently 4.8% of post-transplantation patients have returned to dialysis. Our center’s main transplant origin is cadaveric donation.
To review surgical complications of kidney transplantation over the past 5 years.
This was an observational descriptive study that included all patients from 2011 to 2015.
A total of 55 cases were reviewed. Diabetic nephropathy was the etiology in 30.9% of cases. Postsurgical complications occurred in 12.7% of patients with a post-operative mortality of 4%. Graft survival at 1 year was 82.4% with a 91% 1-year patient survival.
Early identification and treatment of surgical complications are critical for patient and graft survival. Complications are low but significant.

Kidney transplantation is the optimal treatment for end-stage renal disease in children. However, long-term graft survival has not significantly improved among pediatric patients.
To investigate the determinants of long-term graft survival among Iranian pediatric recipients of kidney transplantation.
In a single-center cohort study, we studied 314 pediatric kidney transplantations performed from 1989 to 2013 at Dr. Shariati Hospital, Tehran, Iran. Different variables were collected for each patient and graft survival rates were calculated.
After a mean±SD follow-up period of 15.8±4.0 years, the mean±SD graft survival rate was 14.5±0.5 years; the 1-, 5-, 10-, and 20-year mean graft survival rates were 90%, 81%, 62%, and 62%, respectively. The corresponding patient survival rates were 100%, 99.4%, 97.8%, and 96.5%, respectively. Pre-emptive transplantation (p=0.006), and living graft donation (p=0.002) led to higher graft survival, while acute rejection (p=0.002), and primary disease of primary hyperoxaluria (p=0.001) led to lower graft survival. Chronic rejection was the most frequent cause of graft loss.
Short-term graft survival still outpaces the long-term outcome. Modifying the mentioned determinants, with more intense immunosuppression for greater prevention of acute and chronic rejection, and increased rate of pre-emptive transplantation and living donor transplantation, long term graft survival may significantly improve in future.

The shortage of cadaveric kidney donors has prompted transplant teams to expanding the donor selection criteria. The usage of pediatric cadaveric kidneys is one of those expanded criteria. But the main concern is the probability of hyperfiltration syndrome due to small renal mass of pediatric donors.
To compare the graft and patient survivals, post-transplantation complications, rate and severity of proteinuria secondary to hyperfiltration injury and the kidney growth of recipients who underwent transplantation from adult (group 1) and pediatric deceased donors (group 2).
In this historical cohort study, each group contains 36 patients. Outcome measures included patient and graft survivals, quality of graft function as assessed by serum creatinine (SCr) and estimated GFR (eGFR), surgical complications, proteinuria that was detected by routine urinalysis and then confirmed by a 24-h urine protein >150 mg, blood pressure, and kidney length and volume measured by early and follow-up ultrasonography.
The mean donor age in groups 1 and 2 was 36 and 6.5 years, respectively. 9 (25%) kidneys taken from pediatric donors (group 2) were offered en-bloc. The mean follow-up was 28 month. The two groups were not significantly different in terms of the incidence of DGF, rate of acute rejection, -year graft survival, SCr and eGFR levels, rates of surgical complications requiring surgical interventions, development of proteinuria, and rate of post-transplantation rise in blood pressure. The mean±SD kidney length within 24 hours of transplantation was significantly higher in group 1 compared to group 2 recipients (112±14 vs. 75±12 mm; p=0.001), but the rate of increase in kidney length in group 2 was significantly higher than that in group 1 recipients (43±4 vs. 10±2 mm; p=0.002) during the follow-up period. 80% of the increase in the kidney size was observed during the first 12 months of surgery; another 20% happened between 12 and 18 months.
We found that obligatory and compensatory growth of pediatric kidney donors can overcome the concern of hyperfiltration syndrome and that the outcome is the same as adult donors.

Natural history of HCV-infected renal transplant recipients is about to change with the invention of new drugs available for the treatment of HCV.
To analyze the evolution of renal transplant recipients infected with HCV in 30 years of activity of a Renal Transplantation Unit.
We studied 1334 patients who underwent renal transplantation between 1985 and 2015.
189 (14.2%) of these 1334 were found HCV seropositive. 60 were HCV RNA positive for >6 months. 5 died with a functioning graft; 19 lost their graft and resumed dialysis. Most of the rejections occurred within the first year of the transplantation and none resulted in immediate loss of the graft. In post-transplantation period, 14 patients developed clinical hepatic disease, 10 manifested new-onset diabetes after transplantation, and 4 had de novo neoplasia, none of them had hepatocellular carcinoma. The outcomes of the different variables analyzed were similar between patients with HCV infection and those with HCV and HBV co-infection. The median survival time was 13.4 (95% CI: 10.7 16.1) years; the median survival time of patients without HCV infection was 14.6 (95% CI: 13.8–15.4) years (p=0.23).
In the era before the availability of new anti-HCV drugs, our experience with HCV-infected renal transplant recipients revealed similar post-transplantation complications, graft and patient survival as those not infected with HCV.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease.
To evaluate the changes in serum soluble TNF-like weak inducer of apoptosis (sTWEAK) and fibroblast growth factor 23 (FGF-23) in hemodialysis (HD) patients and renal transplant recipients (RTR).
Serum samples were obtained from 30 patients on chronic HD, 30 RTRs, and 30 normal controls. Biochemical factors, sTWEAK, FGF-23, and interlukin-6 (IL-6) were measured by standard methods.
Serum levels of sTWEAK in RTRs were significantly higher than those in the HD patients (p=0.025); RTR and HD patients had significantly lower sTWEAK levels than the controls (p=0.001 and p= 0.038, respectively). Serum levels of FGF-23 in HD patients were significantly (p 0.001) higher than those in the RTR; the level was higher in both studied groups compared to that in the controls (p=0.001 for both groups). The mean serum level of IL-6 in HD was significantly higher than that in RTR patients (p=0.013). IL-6 levels in both groups were significantly higher than those in controls (p 0.001 and p= 0.012, respectively). In HD group a negative correlation was found between FGF-23 and sTWEAK (r= ‑0.375, p=0.041); there were also a significant correlation between FGF-23 and IL-6 (r= 0.480, p= 0.007) and between IL-6 and sTWEAK (r= ‑0.409, p=0.025).
We found that serum sTWEAK is decreased and FGF-23 is increased in HD and RTR groups comparing with the control group. However, further studies are needed to shed light over their direct role on atherosclerosis and cardiovascular outcomes.

Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESRD). Prediction of the transplant survival is of paramount importance. The objective of this study was to develop a model for predicting survival in kidney transplant recipients. In a cross-sectional study, 717 patients with ESRD admitted to Nemazee Hospital during 2008–2012 for renal transplantation were studied and the transplant survival was predicted for 5 years. The multilayer perceptron of artificial neural networks (MLP-ANN), logistic regression (LR), Support Vector Machine (SVM), and evaluation tools were used to verify the determinant models of the predictions and determine the independent predictors. The accuracy, area under curve (AUC), sensitivity, and specificity of SVM, MLP-ANN, and LR models were 90.4%, 86.5%, 98.2%, and 49.6%; 85.9%, 76.9%, 97.3%, and 26.1%; and 84.7%, 77.4%, 97.5%, and 17.4%, respectively. Meanwhile, the independent predictors were discharge time creatinine level, recipient age, donor age, donor blood group, cause of ESRD, recipient hypertension after transplantation, and duration of dialysis before transplantation. SVM and MLP-ANN models could efficiently be used for determining survival prediction in kidney transplant recipients.