The positive effects of preoperative chlorhexidine rinse to reduce postoperative pneumonia after kidney transplantation surgery.

BACKGROUND: Postoperative pneumonia is one of the most observed hospital-acquired infections and increases the postoperative mortality rate. Further, it drives the healthcare systems under a severe financial burden. Preventing postoperative pneumonia is an incredibly challenging issue for clinicians. Since immunosuppression therapy, the patients who had kidney transplants are more vulnerable to postoperative infections. There is no data in the scientific literature focusing on the effects of preoperative oral care with chlorhexidine antiseptic solutions on postoperative pneumonia in kidney transplantation surgery cases. In the present research, we studied this topic. METHODS: A prospective, randomized clinical trial was conducted at our institution between August 2020 and August 2022. Group A: Received 0.12 % chlorhexidine oral rinse preoperatively; Group B: Not received 0.12 % chlorhexidine oral rinse preoperatively. We analyzed the differences between the two trial groups using a chi-square or t-test. The Mann-Whitney U test was used for the categorical data. RESULTS: Nine patients (17.6 %) were diagnosed with postoperative pneumonia in Group A and fourteen (25.9 %) in Group B (p < 0.05). Hospitalization time of Group B was prolonged (p < 0.05). In multivariate analysis, significant risk factors associated with postoperative pneumonia were advanced age, diabetes mellitus, smoking, delayed graft function and not gargling with 0.12 % chlorhexidine (p < 0.05). CONCLUSIONS: To reduce postoperative pneumonia risk in patients undergoing kidney transplantation surgery, an oral health protocol including 0.12 % chlorhexidine mouth rinse seems beneficial.

Three-Dimensional Analysis of Binding Sites for Predicting Binding Affinities in Drug Design.

Understanding the interaction between drug molecules and proteins is one of the main challenges in drug design. Several tools have been developed recently to decrease the complexity of the process. Artificial intelligence and machine learning methods offer promising results in predicting the binding affinities. It becomes possible to do accurate predictions by using the known protein-ligand interactions. In this study, the electrostatic potential values extracted from 3-dimensional grid cubes of the drug-protein binding sites are used for predicting binding affinities of related complexes. A new algorithm with a dynamic feature selection method was implemented, which is derived from Compressed Images For Affinity Prediction (CIFAP) study, to predict binding affinities of Checkpoint Kinase 1 and Caspase 3 inhibitors.

Inhibitory effects of indole α-lipoic acid derivatives on nitric oxide production in LPS/IFNγ activated RAW 264.7 macrophages.

Alpha-lipoic acid (α-lipoic acid) is a potent antioxidant compound that has been shown to possess anti-inflammatory effects. RAW 264.7 macrophages produce various inflammatory mediators such as nitric oxide, IL-1ß, IL-6 and TNF-alpha upon activation with LPS (Lipopolysaccharide) and IFNγ (interferon gamma). In this study, the effect of 12 synthetic indole α-lipoic acid derivatives on nitric oxide production and iNOS (inducible nitric oxide synthase) protein expression in LPS/IFNγ activated RAW 264.7 macrophages was determined. Cell proliferation, nitric oxide levels and iNOS protein expression were examined with thiazolyl blue tetrazolium blue test, griess assay and western blot, respectively. Our results showed that all of the indole α-lipoic acid derivatives showed significant inhibitory effects on nitric oxide production and iNOS protein levels (p < 0.05). The most active compounds were identified as compound I-4b, I-4e and II-3b. In conclusion, these indole α-lipoic acid derivatives may have the potential for treatment of inflammatory conditions related with high nitric oxide production.

Compressed images for affinity prediction-2 (CIFAP-2): an improved machine learning methodology on protein-ligand interactions based on a study on caspase 3 inhibitors.

The aim of this study is to propose an improved computational methodology, which is called Compressed Images for Affinity Prediction-2 (CIFAP-2) to predict binding affinities of structurally related protein-ligand complexes. CIFAP-2 method is established based on a protein-ligand model from which computational affinity information is obtained by utilizing 2D electrostatic potential images determined for the binding site of protein-ligand complexes. The quality of the prediction of the CIFAP-2 algorithm was tested using partial least squares regression (PLSR) as well as support vector regression (SVR) and adaptive neuro-fuzzy inference system (ANFIS), which are highly promising prediction methods in drug design. CIFAP-2 was applied on a protein-ligand complex system involving Caspase 3 (CASP3) and its 35 inhibitors possessing a common isatin sulfonamide pharmacophore. As a result, PLSR affinity prediction for the CASP3-ligand complexes gave rise to the most consistent information with reported empirical binding affinities (pIC(50)) of the CASP3 inhibitors.

Synthesis and antiproliferative evaluation of novel 5-(4-methylpiperazin-1-yl)-2-phenyl- 1H-benzimidazole derivatives.

A series of novel 5-(4-methylpiperazin-1-yl)-2-phenyl-1H-benzimidazoles (5-14) were synthesized and evaluated for their in vitro antiproliferative activities against the human leukemia cell line HL-60. Compounds 5-7 and 10-12 exhibited potent antiproliferative activities against this cell line. The quantitative analysis of apoptosis by flow cytometry demonstrated that the percentages of apoptotic HL-60 cells treated with compounds 5 and 10-12 were significantly higher than in the control.

Nilotinib exhibits less toxicity than imatinib and influences the immune state by modulating iNOS, p-p38 and p-JNK in LPS/IFN gamma-activated macrophages.

In this study, we aimed to analyze the effects of first and second-generation Bcr-Abl tyrosine kinase inhibitors, imatinib and nilotinib on LPS/IFN gamma activated RAW 264.7 macrophages. Our data revealed that imatinib was less effective on nitrite levels and more toxic on macrophages compared to nilotinib. Therefore, we further analysed the effect of nilotinib on various inflammatory markers including iNOS, COX-2, NFkB, IL-6, p-ERK, p-p38 and p-JNK in LPS/IFN gamma activated RAW264.7 macrophages. Spectrophotometric viability test and Griess assay,western blot, RT-PCR and luciferase reporter assays were used to analyze the biological activity of nilotinib. Our findings revealed that nilotinib decreases nitrite levels, iNOS mRNA, iNOS and p-p38 protein expressions significantly whereas induces IL-6 mRNA and p-JNK protein expressions at particular doses. We did not find significant effect of nilotinib on COX-2, p-ERK and nuclear p65 proteins and NFkB transcriptional activity. In addition, the binding mode of nilotinib to iNOS protein was predicted by molecular docking. According to the docking analyses, nilotinib exhibited hydrophobic interactions between MET349, ALA191, VAL346, PHE363, TYR367, MET368, CYS194, TRP366 residues at the binding pocket and the molecule as well as van der Waals interactions at specific residues. In conclusion, our results reveal that, in addition to its anticancer activity, nilotinib can exhibit immune modulatory effects on macrophages through its effects on iNOS, IL-6, p-p38 and p-JNK.

Synthesis and biological evaluation of a series of dithiocarbamates as new cholinesterase inhibitors.

In the present paper, a novel series of dithiocarbamates was synthesized via the treatment of 4-(trifluoromethyl)benzyl chloride with appropriate sodium salts of N,N-disubstituted dithiocarbamic acids. The chemical structures of the compounds were elucidated by (1) H NMR, mass spectral data, and elemental analyses. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using a modification of Ellman's spectrophotometric method. The most potent AChE inhibitor was found as compound 2g (IC50 = 0.53 ± 0.001 µM) followed by compounds 2f (IC50 = 0.74 ± 0.001 µM) and 2j (IC50 = 0.89 ± 0.002 µM) when compared with donepezil (IC50 = 0.048 ± 0.001 µM). Compounds 2f and 2g were more effective than donepezil (IC50 = 7.88 ± 0.52 µM) on BuChE inhibition. Compounds 2f and 2g exhibited the inhibitory effect on BuChE with IC50 values of 1.39 ± 0.041 and 3.64 ± 0.072 µM, respectively.

Some 2-[4-(1H-benzimidazol-1-yl) phenyl]-1H-benzimidazole derivatives overcome imatinib resistance by induction of apoptosis and reduction of P-glycoprotein activity.

Imatinib (IMA) is a tyrosine kinase inhibitor (TKI) introduced for the chronic myeloid leukemia (CML) therapy. Emergence of IMA resistance leads to the relapse and failure in CML therapy. Benzimidazole is a heterocyclic organic compound which is widely investigated for the development of anticancer drugs. In this study, we aimed to explore the anticancer effects of some 2-[4-(1H-benzimidazol-1-yl) phenyl]-1H-benzimidazole derivatives on K562S (IMA-sensitive) and K562R (IMA-resistant) cells. To analyze the cytotoxic and apoptotic effects of the compounds, K562S, K562R, and L929 cells were exposed to increasing concentrations of the derivatives. Cytotoxic effects of compounds on cell viability were analyzed with MTT assay. Apoptosis induction, caspase3/7 activity were investigated with flow cytometry and BAX, BIM, and BAD genes expression levels were analyzed with qRT-PCR. Rhodamine123 (Rho-123) staining assays were carried out to evaluate the effect of compounds on P-glycoprotein (P-gp) activity. The hit compounds were screened using molecular docking, and the binding preference of each compounds to BCR-ABL protein was evaluated. Our results indicated that compounds triggered cytotoxicity, caspase3/7 activation in K562S and K562R cells. Rho-123 staining showed that compounds inhibited P-gp activity in K562R cells. Overall, our results reveal some benzimidazole derivatives as potential anticancer agents to overcome IMA resistance in CML.

Novel indole retinoid derivative induces apoptosis and cell cycle arrest and modulates AKT and ERK signaling in HL-60 cells.

Chemotherapy with targeted drugs is the first line therapy option for acute and chronic myeloid leukemia. However, hematopoietic stem cell transplantation may be used in high-risk patients or patients with failed responses to chemo drugs. Discovery and development of more effective new agents with lower side effects is the main aim of leukemia treatment. In this study, a novel retinoid compound with tetrahydronaphthalene ring was synthesized and evaluated for anticancer activity in human chronic and acute myeloid leukemia cell lines K562 and HL-60. Novel N-(1H-indol-1-yl)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carboxamide was synthesized based on molecular hybridization of the two different bioactive structures retinoid head and indole. The effects of the synthesized carboxamide compound, which was referred to as compound 5, were determined in K562 chronic myeloid leukemia and HL-60 acute myeloid leukemia cell lines and L929 fibroblast cell line, which served as a control. Colorimetric MTT and caspase3 activity tests, flow cytometry, western blot, and microscopic examinations were used to evaluate biological activity. Compound 5 more effectively induced cell death in HL60 cells in comparison to K562 cells and L929 fibroblast cells. Therefore, further mechanism of cell death was investigated in HL60 cell line. It was found that compound 5 induced remarkable cytotoxicity, caspase3 activation, and PARP fragmentation in HL60 cells. Flow cytometric staining showed that the percentage of cells arrested in G0/G1 was also increased with compound 5 treatment. Important modulator proteins of cell proliferation p-ERK, p-AKT, and p-m-TOR were also found to be inhibited with compound 5 treatment. Collectively, our results reveal compound 5, which is a novel indole retinoid compound as a potential active agent for the treatment of acute promyelocytic leukemia.

Diagnostically challenging rupture of pancreaticoduodenal artery aneurysm: A case report.

Splanchnic artery aneurysms are rare vascular lesions with a high risk of rupture regardless of their size. Symptoms may vary from simple abdominal pain or vomiting to morbid conditions like haemorrhagic shock; however, most aneurysms are asymptomatic and difficult to diagnose. In this study, it was aimed to present the case of a 56-year-old female with a ruptured pancreaticoduodenal artery aneurysm treated by coil embolization.

Global Effects of SARS-CoV-2 Era on Kidney Transplantation Activities: Analysis of WHO Data.

BACKGROUND: Uncertainty raises questions in kidney transplant during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic regarding the recipient, the donor, and health care professionals. The pandemic not only has disrupted kidney transplanted patients but also has influenced transplant systems, donation chains, and timely and safe transplant surgeries. In the present study, we aimed to explore the global effects of the SARS-CoV-2 pandemic on kidney transplant. METHODS: We collected transplantation statistics and SARS-CoV-2 pandemic data from the World Health Organization website on June 15, 2021. Spearman correlation analysis was applied to assess the strength of a monotonic relationship among quantitative variables. We also demonstrated the clinical characteristics of our kidney recipients with SARS-CoV-2 infection. RESULTS: Comparison of the mean of global kidney transplantation statistics between 2010 and 2019 with 2020 statistics showed a significant decrease in kidney transplant from living donors (P < .001). From the beginning of the pandemic to June 15, 2021, 1 of the 43 kidney transplant patients we treated in our clinic died of SARS-CoV-2 infection after discharge. Two of the patients we transplanted and saw in follow-up before the pandemic died of SARS-CoV-2 infection. CONCLUSION: While the overall kidney transplant numbers have increased in the year to date, kidney transplants decreased drastically at the onset of the pandemic.

Description and Outcomes of Three Different End-to-Side Microsurgical Techniques for the Anastomosis of Accessory Renal Artery With the Dominant Renal Artery in Kidney Transplantation.

BACKGROUND: In this study, we compared the outcomes of three different surgical microscope-assisted end-to-side anastomosis techniques between the dominant and accessory renal arteries during living donor kidney transplant. METHODS: The demographics, serum creatinine levels, warm and cold ischemia times, rate of complications, and incidence of delayed graft function of 135 kidney recipients were analyzed according to the type of arterial anastomosis. Group A (n = 98) had one dominant renal artery (DRA) with one end-to-side anastomosis to the external iliac artery (EIA) using a surgical microscope. Group B (n = 17) had one DRA plus one accessory renal artery (ARA) with two separate end-to-side anastomoses to the EIA using a surgical microscope. Group C (n = 20) had one DRA with end-to-side anastomosis to the EIA and one ARA with an ex vivo on-bench end-to-side anastomosis to the DRA using a surgical microscope. RESULTS: Compared with groups A and B, the cold ischemia time and the rate of delayed graft function were significantly higher in group C (P ≤ .001). At 6 months after transplant, group B demonstrated a higher creatinine value (2.40 ± 3.41 mg/dL) than group A and group B (P = .032). Also, the decrease in creatinine at postoperative month 6 was limited in group B as compared with groups A and C. CONCLUSIONS: An end-to-side anastomosis between ARA (group B) and DRA (group A) of the kidney graft using a surgical microscope on the bench ex vivo results in superior outcomes. Single arterial anastomosis techniques are associated with a better function in a 6-month follow-up than two separate arterial anastomoses.

A Comparative Analysis of Once-daily and Twice-daily Formulation of Tacrolimus in De Novo Kidney Transplant Recipients.

OBJECTIVES: We aimed to compare the once-daily and twice-daily formulation of tacrolimus concerning the efficiency and effects on graft function in de novo kidney transplant patients. METHODS: Twenty once-daily (TAC-OD) and twenty twice-daily (TAC-BID) tacrolimus administrated de novo kidney recipients who had received initial immunosuppressive therapy according to protocols at our institution (0.2 mg/kg of tacrolimus combined with 1000 milligrams of steroid taper plus 720 mg of mycophenolate and with 2.5mg/kg anti-thymocyte globulin) assessed concerning demographics, drug doses and blood concentration, and graft function. RESULTS: The mean tacrolimus blood concentration measurements were higher in the TAC-OD group in the first sixty days after transplantation, and the TAC-OD group showed more blood concentration overshoots/fluctuations in the first 30 days of the treatment. The initial drug dose was significantly higher in the TAC-OD group than the TAC-BID group (p=0.04). There was no meaningful difference among groups according to graft function (creatinine measurements) (p>0.05). CONCLUSION: Between de novo kidney recipients, the new TAC-OD formulation presents a similar short-term efficacy profile as TAC-BID. However, a higher daily dosage of TAC-OD is needed to achieve similar blood concentrations in the early postoperative period.

Reduced exposure to calcineurin inhibitors in renal transplantation.

BACKGROUND: Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens. METHODS: We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus. The primary end point was the estimated glomerular filtration rate (GFR), as calculated by the Cockcroft-Gault formula, 12 months after transplantation. Secondary end points included acute rejection and allograft survival. RESULTS: The mean calculated GFR was higher in patients receiving low-dose tacrolimus (65.4 ml per minute) than in the other three groups (range, 56.7 to 59.4 ml per minute). The rate of biopsy-proven acute rejection was lower in patients receiving low-dose tacrolimus (12.3%) than in those receiving standard-dose cyclosporine (25.8%), low-dose cyclosporine (24.0%), or low-dose sirolimus (37.2%). Allograft survival differed significantly among the four groups (P=0.02) and was highest in the low-dose tacrolimus group (94.2%), followed by the low-dose cyclosporine group (93.1%), the standard-dose cyclosporine group (89.3%), and the low-dose sirolimus group (89.3%). Serious adverse events were more common in the low-dose sirolimus group than in the other groups (53.2% vs. a range of 43.4 to 44.3%), although a similar proportion of patients in each group had at least one adverse event during treatment (86.3 to 90.5%). CONCLUSIONS: A regimen of daclizumab, mycophenolate mofetil, and corticosteroids in combination with low-dose tacrolimus may be advantageous for renal function, allograft survival, and acute rejection rates, as compared with regimens containing daclizumab induction plus either low-dose cyclosporine or low-dose sirolimus or with standard-dose cyclosporine without induction. (ClinicalTrials.gov number, NCT00231764 [ClinicalTrials.gov].).

Approach of the Clinicians Practicing in Intensive Care Units to Brain Death Diagnosis and Training Expectations in Turkey: A Web-Based Survey.

BACKGROUND: For health professionals, recognizing and diagnosing brain death is vital for the development of organ transplantation. However, cadaveric organ donation rates remain insufficient, and this problem has become one of the most serious obstacles in the treatment of end-organ failure. OBJECTIVES: This study examines the attitude and knowledge level of clinicians who practice in intensive care units (ICUs) concerning the determination of brain death and describes the hindrances in diagnosing brain death. MATERIALS AND METHODS: A survey study was designed with 26 questions, including questions regarding the determination of characteristics of respondents' trainings, practicing preferences, and their knowledge and approach toward brain death diagnosis. Clinicians practicing in ICUs in Turkey were invited to the survey. RESULTS: A total of 244 surveys were fully completed. Physicians working at the university hospitals or university-affiliated hospitals answered the basic knowledge questions about brain death more accurately (P < .001). Also, physicians employed in university or university-affiliated hospitals feel more capable in diagnosing brain death (P = .002) and are more willing to receive education on the brain death issue (P < .001). CONCLUSION: There is a gap separating the practices suggested in guidelines and the daily practice of ICU clinicians working in state hospitals or private institutions. Academic organizations producing and leading the education curricula may assist in informing ICU clinicians who should be trained.

Effect of Visceral, Subcutaneous and Retroperitoneal Adipose Tissue on Renal Function After Living Donor Nephrectomy: A Retrospective Analysis of 69 Cases.

PURPOSE: Recent studies reported that the presence of metabolic syndrome is closely correlated with impaired kidney function after living donor nephrectomy. Since the measurement of body mass index cannot differentiate the amount of body adipose tissue from total body weight, body mass index is not a reliable parameter for determining metabolic syndrome. In the present study, we investigated the correlation between body adipose tissue and kidney function recovery following living donor nephrectomy. MATERIALS AND METHODS: The patients who underwent living kidney donor nephrectomy consequently from July 2016 through December 2017 were enrolled in the study. We preoperatively measured the visceral (VAdT), retroperitoneal (RPAdT), and subcutaneous (SCAdT) adipose tissue volume by a computed tomography scan. Body mass index, adipose tissue measurements, and postoperative estimated glomerular filtration rate (eGFR) were evaluated. RESULTS: The decrease between preoperative eGFR, and the first day, the first month and the sixth month eGFR after surgery were statistically significant (P = .001; P = .001; P = .001, respectively). The negative correlation between VAdT/SCAdT measurements and changes in eGFR at the first and the sixth postoperative month compared to preoperative eGFR were statistically significant (P = .049; P = .041, respectively). Additionally, RPAdT measurements and changes in eGFR at the first and the sixth postoperative month compared to preoperative eGFR (decreasing as RPAdT value increased) were statistically significant (P = .035; P = .026, respectively). CONCLUSION: According to a preoperative computed tomography scan, VAdT, RPAdT, and VAdT-to-SAdT ratio can predict impaired kidney function recovery. Furthermore, RPAdT measurement is a new variable to predict the impaired kidney function after living donor nephrectomy.

Synthesis of Some Benzimidazole-derived Molecules and their Effects on PARP-1 Activity and MDA-MB-231, MDA-MB-436, MDA-MB-468 Breast Cancer Cell Viability.

BACKGROUND: Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibitors are compounds that are used to treat cancers, which are defective in DNA-repair and DNA Damage-Response (DDR) pathways. OBJECTIVE: In this study, a series of potential PARP-1 inhibitor substituted (piperazine-1-carbonyl)phenyl)-1Hbenzo[ d]imidazole-4-carboxamide compounds were synthesised and tested for their PARP-1 inhibitory and anticancer activities. METHODS: Compounds were tested by cell-free colorimetric PARP-1 activity and MTT assay in MDA-MB-231, MDA-MB-436, MDA-MB-468 breast cancer, and L929 fibroblast cell lines. RESULTS: Our results showed that compound 6a inhibited viability in MDA-MB-231 and MDA-MB-468 cells whereas 8a inhibited viability in MDA-MB-468 cells. Compound 6b significantly inhibited cell viability in tested cancer cells. However, 6b exhibited toxicity in L929 cells, whereas 6a and 8a were found to be non-toxic for L929 cells. Compounds 6a, 6b and 8a exhibited significant inhibition of PARP-1 activity. CONCLUSION: These three compounds exhibited PARP-1 inhibitory activities and anticancer effects on breast cancer cells, and further research will enlighten the underlying mechanisms of their effects.

The Effect of Infrared Drying on Color, Projected Area, Drying Time, and Total Phenolic Content of Rose (Rose electron) Petals.

The effects of different drying temperatures (50, 60, 70 °C) on the quality of rose (Rose electron) petals were evaluated in this study. Drying time decreased from 1680 s to 600 s with increased infrared temperature. The temperature and time were increased from 50 °C to 70 °C and 30 min to 60 min, respectively, and a decrease in the fruit color quality was observed. The projected area (PA) of rose petals was affected significantly from temperature. After the drying process, the largest PA was observed as 33.35 cm2 (50 °C, 30 min), while the smallest achieved at 70 °C, 60 min (27.96 cm2). Depending on the temperature values (50, 60, 70 °C), the average projection area of dry samples of the rose petals decreased 2.17 times compared to the projection area of fresh samples. The dried samples demonstrated an increase in the total phenolic (TP) content compared to the fresh samples. The maximum TP (44.49 mg GAE/g) was achieved at 45 min and 70 °C rose petals sample. The results concluded that infrared drying for 45 min at 70 °C could be recommended for drying rose (rosa electron) petals.

Treatment of hepatitis C in hemodialysis patients using pegylated interferon alpha-2a in Turkey.

PURPOSE: Hepatitis C virus (HCV) is prevalent in renal insufficient patients. The aim of the present study was to evaluate the efficacy and tolerability of pegylated interferon alpha-2a (peg-IFN-alpha-2a) among these patients. METHODS: Among 437 patients within total hemodialysis population in hemodialysis units, in total 83 patients (19.0%) were anti-HCV positive and of these 83 patients, 33 (39.7%) were HCV-RNA positive. Treatment was initiated in 33 patients who had chronic HCV infection. All patients were found to be HCV-RNA positive. During treatment, peg-IFN-alpha-2a (40 kDa), 135 microg/week was used on these 33 patients. RESULTS: Twenty-six (78.8%) of the 33 patients enrolled in the study completed the treatment. Two patients (6.0%) did not complete treatment because they had serious adverse events such as anemia and thrombocytopenia. At the onset of treatment, while all of 26 patients were HCV RNA positive, HCV RNA turned to negative in all 26 patients 3 months after treatment. CONCLUSIONS: At the end of the study, peg-IFN-alpha-2a treatment of patients with chronic hepatitis C on maintenance hemodialysis may improve prognosis and their quality of life.

Low toxicity regimens in renal transplantation: a country subset analysis of the Symphony study.

Regional transplant practices may affect clinical outcomes within multinational studies. This study evaluated whether the overall results from the Symphony study can be generalized to the participating countries. De novo adult renal transplant recipients (n = 1645) were randomized to receive standard-dose cyclosporine, or daclizumab induction plus low-dose cyclosporine, low-dose tacrolimus,or low-dose sirolimus, all in addition to mycophenolate mofetil and steroids. Data for the highest patient-recruiting countries, Spain (n = 275),Germany (n = 316) and Turkey (n = 258), were compared. Patient transplant characteristics were different among the country subsets; only deceased donors in Spain, more expanded criteria donors in Germany, and mainly living donors in Turkey. Efficacy results for the three countries were consistent with that of the overall study - renal function and biopsy-proven acute rejection (BPAR)rates were superior with low-dose tacrolimus. Turkey had higher mean calculated glomerular filtration rate across all treatment groups (60.6-72.2 ml/min)compared with that of Spain (51.1-57.5 ml/min) and Germany (51.3-62.9 ml/min). Spain and Turkey had lower BPAR rates across the four treatment groups compared with the overall study; Germany had much higher rates(21.0-54.2%). These findings confirm the general applicability of the Symphony study results and highlight the importance of inclusion of patients from different geographic origins in randomized clinical trials.