Protective effects of safranal on kidney tissue in a rat model of distant ischemia-reperfusion injury with infrarenal aortic occlusion.

Background/aim: Ischemia-reperfusion (IR) injury to a part of the body can cause damage to distant organs such as the kidney and heart. This study investigated the protective effects of safranal against IR-induced renal injury. Materials and methods: Used in this study were 24 Wistar Albino male rats, which were divided into 3 equal and randomised groups. The sham group underwent laparotomy only. In the IR group, the infrarenal aorta was clamped for 1 h, and then reperfused for 2 h. In the IR-safranal group, safranal was administered 30 min before the procedure and IR injury was induced in the same way as in the IR group. After the procedure, blood and tissue samples were collected from the rats for biochemical and histopathological analyses. Antioxidant capacity and proinflammatory cytokine analyses were performed on the blood samples. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was performed to determine the number of cells undergoing apoptosis in the kidney tissue. Results: The estimated glomerular filtration rate, an indicator of renal function, was lower in the IR group (p1 = 0.024 vs. p3 = 0.041, respectively) compared to the other groups, while creatinine levels were higher in the IR group compared to the other groups (p1 = 0.032 vs. p2 = 0.044, respectively). The blood urea nitrogen level was higher in the IR group than in the other groups (p1 = 0.001vs p2 = 0.035, respectively). The total antioxidant and total oxidant status, indicating tissue oxidative stress, did not differ between groups (p = 0.914 vs. p = 0.184, respectively). Among the proinflammatory cytokines, the interleukin-1ß (IL-1ß) and IL-6 levels were significantly higher in the IR group (p = 0.034 vs. p = 0.001, respectively), but the tumour necrosis factor-α (p = 0.19), and interferon-γ (p = 0.311) levels did not differ between groups. Histopathological examination showed significantly less damage to glomerular and tubular cells in the IR-safranal group (p < 0.001). The number of TUNEL-positive cells was higher in the IR group compared to the other groups (p < 0.001). Conclusion: Safranal may have protective effects against kidney damage caused by distant ischemia-reperfusion injury.

Role of glutathione S-transferase P1 polymorphism in early transplant complications in patients undergoing allogeneic stem cell transplantation.

INTRODUCTION: Complications in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) cause serious morbidity and mortality. Predicting patients at risk in advance and changing the symptomatic care and/or preparation regimen according to this risk assessment have been emphasized recently. Several single-nucleotide polymorphisms have been studied, and some were found to be responsible for early complications. Glutathione S-transferase P1 (GSTP1) is an enzyme involved in the detoxification process that reduces oxidative stress by reducing the number of free oxygen radicals. AIM: This study aimed to investigate the relationship between GSTP1 polymorphism and early complications of allo-HSCT, iron parameters, overall survival (OS), and transplantation-related mortality (TRM). MATERIALS AND METHODS: A total of 50 patients diagnosed with acute myeloid leukemia (n = 23) or acute lymphoblastic leukemia (n = 27) who underwent allo-HSCT between May 2008 and February 2011 at Gazi University Faculty of Medicine, Stem Cell Transplantation Unit, were included. RESULTS: Of the 50 patients, 24 (48%) were women and 26 (52%) were men. The median age of the patients was 26 (16-74) years. GSTP1 polymorphism was detected in 23 (46%) patients, and 27 (54%) had no polymorphism (wild type). The two groups were compared in terms of early toxicity after transplantation, according to the preparation regimen. The group with GSTP1 polymorphism was found to have a high transferrin saturation index (P < 0.05). Patients with no GSTP1 polymorphism showed a high grade III-IV anemia ratio (P < 0.05). The presence of sinusoidal obstruction syndrome and graft-versus-host disease was similar in both groups (P > 0.05). OS and TRM were higher in the GSTP1 polymorphism group, but no statistical difference was found between the two groups (P > 0.05). CONCLUSIONS: TSI was higher in the GSTP1 polymorphism group. GSTP1 polymorphism had no effect on early transplantation complications. Although the OS and TRM ratios were higher in the GSTP1 polymorphism group, no statistically significant difference was found between the groups. Further studies with larger sample size are needed.

Long-term Results of Kidney Transplantation in Patients With Familial Mediterranean Fever and Amyloidosis.

INTRODUCTION: Amyloid A amyloidosis is most commonly caused by familial Mediterranean fever (FMF) in Turkey. Amyloidosis secondary to FMF is an important cause of end-stage renal failure, and kidney transplantation (KT) in these cases can be complicated, with long-term results oftentimes inferior compared with organ transplant in patients without FMF. The present study aims to show the long-term results of patients with secondary amyloidosis caused by FMF undergoing KT . METHODS: We enrolled 27 patients with a history of FMF amyloidosis undergoing KT and a control group of 614 patients undergoing KT between 2005 and 2018 at Ankara University Medical School. All data were recorded retrospectively from patients files. RESULTS: Twenty-two patients (81.5%) were treated with triple immunosuppressive therapy consisting of mycophenolate mofetil, tacrolimus, and a steroid; 5 patients (18.5%) were treated with tacrolimus, azathioprine, and prednisolone. Acute cellular rejection was seen in 3 patients (11.1%), and acute cellular- and antibody-mediated rejection occurred in 1 patient (3.7%). During the follow-up period, graft loss due to acute cellular rejection was observed in only 1 patient. One patient was lost to follow-up.

Outcomes of Canakinumab Treatment in Recipients of Kidney Transplant With Familial Mediterranean Fever: A Case Series.

Familial Mediterranean fever (FMF) is an important and preventable cause of chronic kidney disease due to secondary amyloidosis. Although colchicine is the first-line therapy in patients with FMF with 60% to 65% complete remission rates, 5% to 10% of patients are colchicine-resistant and 5% to 10% of them are intolerant to the therapy. Anti-interleukin-1 agents, such as anakinra and canakinumab, are safe and efficient therapeutic options in patients with colchicine resistance or intolerance. However, the data on management of these targeted agents is limited in recipients of kidney transplant (RKT). In this case series, we aim to share our experience on canakinumab therapy of 4 RKTs with FMF-related amyloidosis, who were followed up in our clinic between 2010 and 2017. All of the 4 patients with end-stage renal disease were colchicine- resistant and on other alternative therapies, which provided poor disease control. For efficient control of secondary amyloidosis, canakinumab therapy was initiated in 1 of the patients before the renal transplant, and for the remaining patients after renal transplant. Any serious adverse effect, development of proteinuria, or graft dysfunction has not been observed in any of the patients. Under the canakinumab treatment, complete clinical responses, prevent typical familial Mediterranean fever attacks with fever and arthritis and abdominal pain, normalized serum amyloid A and C-reactive protein levels were achieved in all patients. Canakinumab treatment is a safe and effective therapeutic option for RKTs with FMF who are resistant or intolerant to colchicine and anakinra.