The relationship between uric acid levels and graft function in renal transplant patients who discontinued steroid therapy / Relación entre niveles de ácido úrico y función del injerto en pacientes de trasplante renal que interrumpieron la terapia con esteroides

ABSTRACT Introduction: High uric acid levels are commonly encountered in kidney transplant recipients, and can be associated with allograft dysfunction. Our study aims to examine the relationship between UA levels and graft function in patients discontinuing steroids. Methods: In this single-center-retrospective study, 56 patients discontinued steroid therapy from among 678 RT patients transplanted from living donors between 1999-2020 were included. The mean age of the study group was 45.8±8.8 years. Causes of steroid discontinuation, creatinine levels concurrent with uric acid levels before and after steroid discontinuation (mean 3.9 ± 2.1 years), acute rejection numbers, demographics, durations of dialysis and transplantation, medications, laboratory data, human leukocyte antigen (HLA) mismatch numbers, blood-pressure (BP), body mass index, delayed acute rejection (DAR) numbers (3 months post-transplantation) were all recorded. Results: Creatinine and uric acid levels were seen to have increased after steroid discontinuation, there was a significant relationship between them (p<0.001). Statistically significant correlation was found between increased creatinine levels after steroid discontinuation and graft survival with higher HLA mismatch; 39 (69.6%) patients with mismatch ≥2, and 17 patients with mismatch <2 (30.4%) (p=0.049) . No significant relationship was found between DAR numbers before and after steroid discontinuation, and creatinine levels after steroid discontinuation. Conclusion: Per model obtained as a result of multivariate linear analysis, hyperuricemia and HLA mismatch numbers (p= 0.048 and p= 0.044, respectively) are independent predictive factors for graft dysfunction in patients discontinuing steroids. Accordingly, negative effects of modeling should be kept in mind for long-term graft survival in patients who plan to continue with steroid-sparing regimens.

RESUMEN Introducción: Con frecuencia se registran niveles elevados de ácido úrico en receptores de trasplantes renales que pueden estar asociados a disfunción de aloinjerto. El presente estudio tiene por objeto examinar la relación entre los niveles de AU y la función del injerto en pacientes que interrumpieron la terapia con esteroides. Métodos: En este estudio retrospectivo en un solo centro participaron 56 pacientes con interrupción de la terapia con esteroides de un total de 678 pacientes con TR receptores de trasplante de donantes vivos en el período 1999-2020. La edad promedio de la población de estudio fue de 45,8 ± 8,8 años. En el estudio se registraron causas de la interrupción de la terapia con esteroides, niveles de creatinina concurrentes con niveles de ácido úrico antes y después de la interrupción de la terapia con esteroides (promedio de 3,9 ± 2,1 años), números de rechazo agudo, datos demográficos, duraciones del período de diálisis y trasplante, medicación (uso de inmunosupresores, antihipertensivos), datos de laboratorio, números de desajuste del antígeno leucocitario humano (HLA), presión arterial (PA), índice de masa corporal, números de rechazo agudo retardado (DAR) (3 meses después del trasplante). Resultados: Se observó que los niveles de creatinina y ácido úrico aumentaron tras interrumpir la administración de esteroides, con una relación significativa entre ambos (p<0,001). Se identificó una correlación estadísticamente significativa entre el aumento en los niveles de creatinina tras la interrupción de la terapia de esteroides y la supervivencia del injerto con un mayor desajuste de HLA: 39 pacientes (el 69,6%) con desajuste ≥2 y 17 (el 30,4%) pacientes con desajuste <2 (p=0,049). No se encontró una relación significativa entre el número de DAR antes y después de la interrupción del tratamiento con esteroides, así como en los niveles de creatinina tras la interrupción de la terapia con esteroides. Conclusión: De acuerdo con el modelo obtenido como resultado del análisis lineal multivariable, la hiperuricemia y los números de desajuste de HLA (p=0,048 y p=0,044, respectivamente) constituyen factores predictivos independientes para la disfunción del injerto en pacientes que interrumpen la terapia con esteroides. En consecuencia, se deben tener en cuenta los efectos negativos del modelado para la supervivencia del injerto a largo plazo en pacientes que planean proseguir con regímenes con reducción de la administración esteroides.

A two-year analysis of therapeutic apheresis practices in a tertiary center: are we chasing the new indications?

BACKGROUND: Therapeutic apheresis (TA) as primary or adjunctive therapy proved itself in a broad spectrum of diseases. This study aims to present TA practices in a tertiary center with an emphasis on the rate of the utility of TA on the new American Society for Apheresis (ASFA) indications. METHODS: We conducted a retrospective analysis of data regarding TA applications through our electronic medical database from June 2016 to July 2018. The data included demographics, clinical indications, and procedural characteristics. We also searched for the rate of the utility of TA procedures on new ASFA indications by entering both the diagnostic and TA modality codes for these indications on the electronic database during the study interval. RESULTS: A total of 720 TA procedures were performed on 96 patients (54 males, 42 females, with a mean age of 48.15 ± 26.71 years). The procedures were 68.8 % therapeutic plasma exchange (TPE), 16.4 % leukocytapheresis, 11.5 % immunoadsorption (IA), 3.1 % double filtration plasmapheresis (DFPP), and 0.13 % erythrocyte exchange. The categorical indications included 60.41 % category I and category II, 28.12 % category III, and 1.04 % category IV. The most common indication was thrombotic thrombocytopenic purpura (TTP) (26.04 %). The procedure failure rate was 2.08 %. Patient-related adverse events were reported in 7.5 % of procedures. The case mortality rate was 16.66 %. TA utility rate was 0.98 % for the new indications in the ASFA 2016 guideline. CONCLUSION: Therapeutic apheresis is a progressively developing, safe, and effective treatment modality with add-on indications.  Physicians should keep track of new developments on this modality to implement the appropriate indications into clinical practice. HIPPOKRATIA 2018, 22(4): 167-172.

Relationship of Interleukin-10 and Transforming Growth Factor-ß Levels With Short-Term Graft Function After Kidney Transplantation.

INTRODUCTION: We evaluated the relationship of interleukin-10 (IL-10) and transforming growth factor-ß (TGF-ß) levels with graft function in kidney transplantation patients receiving tacrolimus-based immunosuppression during the early post-transplantation period. MATERIAL AND METHODS: There were 112 patients who underwent kidney transplantation from live donors between May 2011 and May 2013. Eight patients had at least 1 of the exclusion criteria, and the remaining 104 patients were included in the study. The recipients underwent evaluation for biochemical markers, complete blood count, and creatinine and cytokine (IL-10, TGF-ß) levels during the pretransplantation and post-transplantation 6 months. RESULTS: The creatinine level was negatively correlated with IL-10 and positively correlated with TGF-ß levels in both the pretransplantation and early post-transplantation period. CONCLUSION: Low serum TGF-ß and high IL-10 levels at post-transplantation month 6 might have a positive effect on graft survival in living donor kidney recipients on tacrolimus-based immunosuppressive treatment.

Synthesis and antimicrobial activity of N-[(alpha-methyl)benzylidene]-(3-substituted-1,2,4-triazol-5-yl-thio) acetohydrazides.

In this study 18 new hydrazones have been synthesized by reacting ortho- or para-substituted acetophenones with (3-substituted-1,2,4-triazol-5-yl-thio)acetohydrazide in ethanol. The prepared compounds were tested for antimicrobial activity. The prepared compounds exhibited only poor activity against Gram (+) and Gram (-) bacteria with the minimal inhibitory concentration (MIC) > or = 400 micrograms/ml. Moderate activity was observed against Candida species with MIC in the range 100-400 micrograms/ml.

Synthesis and antimicrobial activities of 2-[(alpha-methylbenzylidene)-hydrazino]benzoxazoles.

New 2-[(alpha-methylbenzylidene)hydrazino]benzoxazole derivatives have been synthesized by reacting ortho or para substituted acetophenones with 2-hydrazinobenzoxazole in ethanol. The structures of the synthesized compounds were confirmed by microanalysis, IR and NMR spectral data. Antimicrobial activities of the compounds were investigated by the microdilution susceptibility test in Mueller-Hinton broth and Sabouraud liquid medium. Test organisms: Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as Gram (+) bacteria, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa, ATCC 27853 as Gram (-) bacteria, and Candida albicans, Candida stellatoidea, Candida parapsilosis and Candida pseudotropicalis as yeasts. Among the compounds tested 2-[(alpha-methyl-4-chlorobenzylidene)hydrazino]benzoxazole (compounds 4) and 2-[(alpha-methyl-4-nitrobenzylidene)hydrazino]benzoxazole (compound 8) showed the most favorable activity.

Studies on analgesic and anti-inflammatory activities of 1-dialkylaminomethyl-2-(p-substituted phenyl)-5-substituted benzimidazole derivatives.

In this study the analgesic and anti-inflammatory activity of 1,2,5-trisubstituted benzimidazole derivatives have been examined. Analgesic activities of these compounds were investigated by using the modified Koster test. Among the compounds synthesized especially compound 1g (1-diethylaminomethyl)-2-(p-chlorophenyl)-5-nitro benzimidazole hydrochloride) has shown higher activity than acetylsalicylic acid (ASA) and indometacin. Compound 1e (1-(diethylaminomethyl)-2-(p-methoxyphenyl)-5-nitro benzimidazole hydrochloride, 1f (1-(diethylaminomethyl)-2-(p-tolyl)-5-nitro benzimidazole hydrochloride and 1i (1-(pipenridinomethyl)-2-(p-methoxyphenyl)-5-nitro benzimidazole hydrochloride) proved as potent as the standard ASA. Therefore the compounds 1e, 1f, 1g and 1i were screened for their anti-inflammatory activities using the carrageenan-induced hind paw edema test. Except 1g all compounds were almost inactive against this model of inflammation compared to indometacin.

Synthesis and antimicrobial activity of beta-[(2-benzimidazolyl)thio]-beta-benzoyl styrene derivatives.

In this study some new beta-[(2-benzimidazolyl)thio]-beta-benzoyl styrene derivatives have been synthesized by reacting 2-(phenacetylthio)benzimidazole and substituted benzaldehydes in piperidine/dry benzene. Structures were verified by microanalysis, IR and NMR spectral analysis. Antimicrobial activities of the compounds were investigated by the microdilution susceptibility test; Muller-Hinton Broth and Sabouraud Dextrose Broth were used for the determination of antibacterial and antifungal activity. Test organisms: Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as Gram (+) bacteria, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATTC 27853 as Gram (-) bacteria, and Candida albicans, Candida pseudotropicalis, Candida parapsilosis and Candida stellatoidea as yeast-like fungi. All the compounds showed good antimicrobial effect, especially against gram (+) bacteria. Among the compounds tested beta-[(2-benzimidazolyl)thio]-beta-benzoyl-4-chloro styrene (compound 9), beta-[(2-benzimidazolyl)thio]-beta-benzoyl-4-nitro styrene (compound 10) and beta-[(2-benzimidazolyl)thio]-beta-benzoyl-4-acetylamino styrene (compound 11) showed the most favorable activity.

Synthesis and antimicrobial activity of 1-dialkylaminomethyl- 2-(p-substituted phenyl)-5-substituted benzimidazole derivatives.

1-(Dialkylaminomethyl)-2-(p-substituted phenyl)-5-substituted benzimidazole derivatives 1 have been synthesized by reacting 2-phenylbenzimidazole derivatives with formaldehyde and a secondary amine. The derivatives of 2-phenylbenzimidazole were obtained by reacting the bisulfide addition product of substituted benzaldehydes with 4-substituted-o-phenylenediamines. Their structures were confirmed by microanalysis, IR and NMR spectral analysis. Antimicrobial activity of the compounds was investigated by the microdilution susceptibility test in Mueller-Hinton Broth and Sabouraud Dextrose Broth was used for the determination of antibacterial and antifungal activities. Test organisms: Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as Gram-positive bacteria, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 as Gram-negative bacteria, and Candida albicans, C. parapsilosis, C. stellatoidea as yeast-like fungi. Compounds 1a, 1b, 1c, 1e and 1i showed slight to moderate activity against all microorganisms. Compound 1g showed the highest activity. It was found more potent than streptomycin against Enterococcus faecalis and Pseudomonas aeruginosa.