Abstract This cross-sectional study investigated the association of SNPs rs670 (C>T) and rs693 (G>A) with parameters of lipid metabolism and endothelial activation in 167 subjects, including 86 COVID-19 outpatients and 81 healthy subjects (control group) matched for sex and age. Serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), non-high-density lipoprotein cholesterol (non-HDL-c), triglycerides (TG), apolipoproteins (Apo A-I and B), and vascular cell adhesion molecule-1 (VCAM-1) were determined. The SNPs were genotyped by quantitative polymerase chain reaction (qPCR). A p -value<0.05 was assumed. COVID-19 outpatients showed increases in TC (187.0±48.3 vs . 160.8±32.0 mg/dL), LDL-c (110.3±41.5 vs . 98.8±28.2 mg/dL), non-HDL-c (138.3±45.8 vs . 115.6±31.6 mg/dL), TG (139.7±80.3 vs . 84.9±35.1 mg/dL), and Apo A-I (149.5±40.0 vs . 133.3±20.9 mg/dL), along with a high frequency of hypercholesterolemia and hypertriglyceridemia. VCAM-1 levels were double those of the control (682.7±231.8 vs. 299.3±102.9 ng/mL) and a strong predictor of COVID-19 (AUC=0.946). Moreover, VCAM-1 correlated with TC (r = -0.223) and HDL-c (r = -0.225). The decrease in TG and VCAM-1 is predicted by the dominance of the T allele (rs670) and its codominance with the A (rs693) allele in COVID-19 outpatients. COVID-19 has been shown to be associated with dyslipidemias and endothelial activation, and apolipoprotein polymorphisms may influence this. crosssectional cross sectional rs rs67 C>T CT C (C>T rs69 G>A GA G (G>A 16 8 COVID19 COVID 19 COVID-1 group age TC, , (TC) highdensity density HDLc, HDLc HDL c (HDL-c) lowdensity low LDLc, LDLc LDL (LDL-c) nonhighdensity non nonHDLc, nonHDLc (non-HDL-c) TG, (TG) AI I B, B B) molecule1 molecule 1 molecule- VCAM1 VCAM (VCAM-1 determined qPCR. qPCR (qPCR) value<0.05 value005 value 0 05 -value<0.0 assumed 187.0±48.3 1870483 187 48 3 (187.0±48. 1608320 160 32 160.8±32. mg/dL, mgdL mg/dL mg dL mg/dL) 110.3±41.5 1103415 110 41 5 (110.3±41. 988282 98 28 2 98.8±28. 138.3±45.8 1383458 138 45 (138.3±45. 1156316 115 6 31 115.6±31. 139.7±80.3 1397803 139 7 80 (139.7±80. 849351 84 9 35 84.9±35. 149.5±40.0 1495400 149 40 (149.5±40. 1333209 133 20 133.3±20. hypertriglyceridemia VCAM- 682.7±231.8 68272318 682 231 (682.7±231. 29931029 299 102 299.3±102. ng/mL ngmL ng mL AUC=0.946. AUC0946 AUC AUC=0.946 946 (AUC=0.946) Moreover r 0.223 0223 223 -0.223 0.225. 0225 0.225 225 -0.225) (rs670 (rs693 this rs6 COVID1 COVID- (TC (HDL-c (LDL-c (non-HDL-c (TG (VCAM- (qPCR value<0.0 value00 -value<0. 187.0±48. 187048 18 4 (187.0±48 160832 160.8±32 110.3±41. 110341 11 (110.3±41 98828 98.8±28 138.3±45. 138345 13 (138.3±45 115631 115.6±31 139.7±80. 139780 (139.7±80 84935 84.9±35 149.5±40. 149540 14 (149.5±40 133320 133.3±20 682.7±231. 6827231 68 23 (682.7±231 2993102 29 10 299.3±102 AUC094 AUC=0.94 94 (AUC=0.946 0.22 022 22 -0.22 -0.225 (rs67 (rs69 (VCAM value<0. value0 -value<0 187.0±48 18704 (187.0±4 16083 160.8±3 110.3±41 11034 (110.3±4 9882 98.8±2 138.3±45 13834 (138.3±4 11563 115.6±3 139.7±80 13978 (139.7±8 8493 84.9±3 149.5±40 14954 (149.5±4 13332 133.3±2 682.7±231 682723 (682.7±23 299310 299.3±10 AUC09 AUC=0.9 (AUC=0.94 0.2 02 -0.2 (rs6 value<0 -value< 187.0±4 1870 (187.0± 1608 160.8± 110.3±4 1103 (110.3± 988 98.8± 138.3±4 1383 (138.3± 1156 115.6± 139.7±8 1397 (139.7± 849 84.9± 149.5±4 1495 (149.5± 1333 133.3± 682.7±23 68272 (682.7±2 29931 299.3±1 AUC0 AUC=0. (AUC=0.9 0. -0. (rs value< -value 187.0± (187.0 160.8 110.3± (110.3 98.8 138.3± (138.3 115.6 139.7± (139.7 84.9 149.5± (149.5 133.3 682.7±2 6827 (682.7± 2993 299.3± AUC=0 (AUC=0. -0 187.0 (187. 160. 110.3 (110. 98. 138.3 (138. 115. 139.7 (139. 84. 149.5 (149. 133. 682.7± (682.7 299.3 AUC= (AUC=0 - 187. (187 110. (110 138. (138 139. (139 149. (149 682.7 (682. 299. (AUC= (18 (11 (13 (14 682. (682 (AUC (1 (68 ( (6

Abstract Diabetes mellitus (DM) is a major cause of chronic kidney disease (CKD) and changes in lipoprotein. Literature data suggest that cholesterol associated with high-density lipoprotein (HDLc) plays a protective role against albuminuria and diabetic nephropathy. These factors are related with changes in serum apolipoproteins such Apo A-I. This work aims to evaluate the correlation of apolipoprotein A-I with renal function in diabetic outpatients. Samples were collected from 281 outpatients for analyses of glycated hemoglobin (HbA1c), serum creatinine (SCr), urea (BUN), cholesterol (TC), triglycerides (TG), HDL-cholesterol (HDLc) and estimation of glomerular filtration rate (eGFR). Urinary samples were obtained to assess urine albumin creatinine ratio (UACR). Triglyceride-glucose index (TyG) was calculated to estimate insulin resistance. The mean age was 61,5 ± 16,4 years. Most patients were female, Afro-Mestizo and over 50 years of age. Pearson's revealed negative correlation of creatinine with HDLc and Apo A-I. There was a correlation of eGFR with HbA1c, TG and HDLc. TyG presented a negative correlation with Apo A-I and HDLc. The highest quartiles of UACR presented the highest TyG and the lowest Apo A-I. In conclusion, Apo A-I indicated an association with insulin resistance and changes in renal function parameters, especially as a factor associated with the onset of albuminuria, with a better predictive potential than the HDLc. DM (DM CKD (CKD highdensity high density (HDLc nephropathy AI. AI A I. I 28 HbA1c HbAc , HbA c (HbA1c) SCr, SCr (SCr) BUN, BUN (BUN) TC, TC (TC) TG, (TG) HDLcholesterol HDL eGFR. . (eGFR) UACR. (UACR) Triglycerideglucose Triglyceride glucose (TyG 615 61 5 61, 164 16 4 16, female AfroMestizo Afro Mestizo Pearsons Pearson s conclusion parameters 2 (HbA1c (SCr (BUN (TC (TG (eGFR (UACR 6 1

ABSTRACT Introduction: Kidney transplantation is the most commonly performed type of transplant in Brazil. Tacrolimus is one of the primary drugs used in post-transplant immunosuppressive therapy, and one of its main adverse effects is nephrotoxicity. Laboratory tests to assess renal function are of great importance in monitoring post-kidney transplant patients, helping to diagnose events indicative of graft dysfunction. Objective: The present study aimed to evaluate the association between laboratory changes in renal function and blood levels of tacrolimus in post-kidney transplant patients. Methods: Observational, analytical and cross-sectional study. The results of blood levels of tacrolimus and measurements of urea, creatinine and estimated Glomerular Filtration Rate (eGFR) were analyzed, as well as the sociodemographic data of kidney transplant recipients followed at a university hospital who underwent laboratory tests between months from January 2021 to July 2022 in a period close to 1 year after the transplant. The variables analyzed in the research were collected from the patient's medical records and subsequently analyzed; the statistical analyses considered p < 0.05. The project was approved by the Ethics Committee of the Walter Cantídio University Hospital under opinion number 5,436,434 and CAAE number 57396622.1.0000.5045. Results: The sample was mainly composed of males, mixed race, with an average age of 51.5 years (SD ± 12.5) and from cities in the interior of Ceará. Regarding the percentage of patients with laboratory changes, 50.62% (n = 45) showed changes in tacrolimus blood levels. 56.79% (n = 46) had changes in serum creatinine levels, 49.38% (n = 40) had changes in serum urea levels, and 59.26% (n = 48) had altered eGFR. The correlation analyses suggested a low significance between variations of the variables studied. Conclusion: The results indicate no relationship between variations in tacrolimus blood concentrations and the appearance of changes in the results of classic renal biomarkers at the end of the first year post-transplant. However, it is necessary to carry out new studies to understand better the impact of changes in blood levels of tacrolimus on the renal function of renal allograft recipients. Introduction Brazil posttransplant post therapy nephrotoxicity postkidney dysfunction Objective Methods Observational crosssectional cross sectional eGFR (eGFR 202 patient s 005 0 05 0.05 5436434 5 436 434 5,436,43 57396622100005045 57396622 0000 5045 57396622.1.0000.5045 Results males race 515 51 51. SD 12.5 125 12 Ceará 5062 50 62 50.62 n 45 5679 56 79 56.79 46 4938 49 38 49.38 40 5926 59 26 59.26 48 studied Conclusion posttransplant. However 20 00 0.0 543643 43 5,436,4 5739662210000504 5739662 000 504 57396622.1.0000.504 12. 506 6 50.6 4 567 7 56.7 493 3 49.3 592 2 59.2 0. 54364 5,436, 573966221000050 573966 57396622.1.0000.50 50. 56. 49. 59. 5436 5,436 57396622100005 57396 57396622.1.0000.5 543 5,43 5739662210000 5739 57396622.1.0000. 54 5,4 573966221000 573 57396622.1.0000 5, 57396622100 57 57396622.1.000 5739662210 57396622.1.00 573966221 57396622.1.0 57396622.1. 57396622.1 57396622.

RESUMO Introdução: O transplante renal constitui o tipo de transplante mais realizado no Brasil. O tacrolimo é um dos principais fármacos utilizados na terapia imunossupressora pós-transplante e possui como um de seus principais efeitos adversos a nefrotoxicidade. Os exames laboratoriais de avaliação da função renal possuem grande importância no acompanhamento de pacientes pós-transplante renal, auxiliando no diagnóstico de eventos indicativos de disfunção do enxerto. Objetivo: O presente estudo objetivou avaliar a associação entre alterações laboratoriais de função renal e os níveis sanguíneos de tacrolimo em pacientes pós-transplante renal. Métodos: Estudo observacional, analítico e transversal. Foram analisados os resultados dos níveis sanguíneos de tacrolimo e das dosagens de ureia, creatinina e estimativa da Taxa de Filtração Glomerular (eTFG), bem como os dados sociodemográficos de receptores de transplante renal acompanhados em um hospital universitário, que realizaram exames laboratoriais entre os meses de janeiro de 2021 e julho de 2022 no período próximo a 1 ano após a realização do transplante. As variáveis analisadas na pesquisa foram colhidas a partir dos registros dos prontuários dos pacientes e posteriormente analisadas, as análises estatísticas consideraram p < 0,05. O projeto foi aprovado pelo Comitê de Ética do Hospital Universitário Walter Cantídio sob o parecer número 5.436.434 e CAAE número 57396622.1.0000.5045. Resultados: A amostra foi composta, majoritariamente, pelo sexo masculino, cor parda, idade média de 51,5 anos (DP ± 12,5) e de cidades do interior do Ceará. Quanto ao percentual de pacientes com alterações laboratoriais, 50,62% (n = 45) deles apresentaram alterações dos níveis sanguíneos de tacrolimo; ainda, 56,79% (n = 46) apresentaram alterações na dosagem de creatinina sérica, 49,38% (n = 40) apresentaram alterações na dosagem de ureia sérica e 59,26% (n = 48) apresentaram uma eTFG alterada. As análises de correlação realizadas sugeriram uma baixa significância entre variações das variáveis estudadas. Conclusão: Os resultados obtidos sugerem não existir relação entre variações das concentrações sanguíneas de tacrolimo e o surgimento de alterações nos resultados de biomarcadores renais clássicos ao final do primeiro ano pós-transplante. Entretanto, faz-se necessária a realização de novos estudos para uma maior compreensão do impacto causado por alterações dos níveis sanguíneos de tacrolimo na função renal de receptores de aloenxerto renal. Introdução Brasil póstransplante pós nefrotoxicidade enxerto Objetivo Métodos observacional transversal eTFG, , (eTFG) universitário 202 005 0 05 0,05 5436434 5 436 434 5.436.43 57396622100005045 57396622 0000 5045 57396622.1.0000.5045 Resultados composta majoritariamente masculino parda 515 51 51, DP 12,5 125 12 Ceará 5062 50 62 50,62 n 45 ainda 5679 56 79 56,79 46 4938 49 38 49,38 40 5926 59 26 59,26 48 alterada estudadas Conclusão póstransplante. Entretanto fazse faz se (eTFG 20 00 0,0 543643 43 5.436.4 5739662210000504 5739662 000 504 57396622.1.0000.504 12, 506 6 50,6 4 567 7 56,7 493 3 49,3 592 2 59,2 0, 54364 5.436. 573966221000050 573966 57396622.1.0000.50 50, 56, 49, 59, 5436 5.436 57396622100005 57396 57396622.1.0000.5 543 5.43 5739662210000 5739 57396622.1.0000. 54 5.4 573966221000 573 57396622.1.0000 5. 57396622100 57 57396622.1.000 5739662210 57396622.1.00 573966221 57396622.1.0 57396622.1. 57396622.1 57396622.

Abstract Changes in lipoprotein metabolism are among the main causes of hemodynamic impairment in renal function. COVID-19 is an multisystemic inflammatory disease, aggravating this situation. This cross-sectional study investigated the relationship of serum lipoprotein profile with inflammatory parameters and renal function in 95 COVID-19 outpatients in comparison with 173 with flu-like symptoms. Serum samples were collected for the determination of total cholesterol and fractions, apolipoproteins (Apo A-I and Apo B), urea (sUr) and creatinine (sCr). The glomerular filtration rate (eGFR) was calculated. Neutrophil/lymphocyte (NLR) and platelet/lymphocyte (PLR) ratios were calculated as inflammatory parameters derived from the blood tests. COVID-19 patients presented lower high-density lipoprotein cholesterol (HDL-c) (47.90 ± 1.543 vs. 51.40 ± 0.992) and higher PLR (190.9 ± 9.410 vs. 137.6 ± 5.534) and NLR (3.40 ± 0.22 vs. 2.80 ± 0.15). Both NLR and PLR correlated with each other (r = 0.639). Furthermore, the Apo B/Apo A-I ratio was correlated with PLR (r = 0.5818) and eGFR (r = -0.2630). COVID-19 patients classified as at high risk of developing acute myocardial infarction based on the Apo B/ Apo A-I ratio had higher values for sUr/sCr. Thus, serum apolipoproteins, PLR, and NLR could be related to renal dysfunction in COVID-19. COVID19 COVID 19 COVID-1 disease situation crosssectional cross sectional 9 17 flulike flu like symptoms fractions AI A I B, B , B) sUr (sUr sCr. sCr . (sCr) (eGFR Neutrophillymphocyte Neutrophil lymphocyte (NLR plateletlymphocyte platelet (PLR tests highdensity density HDLc HDL c (HDL-c 47.90 4790 47 90 (47.9 1543 1 543 1.54 vs 5140 51 40 51.4 0.992 0992 0 992 190.9 1909 190 (190. 9410 410 9.41 1376 137 6 137. 5.534 5534 5 534 3.40 340 3 (3.4 022 22 0.2 280 2 80 2.8 0.15. 015 0.15 15 0.15) r 0.639. 0639 0.639 639 0.639) Furthermore BApo 0.5818 05818 5818 0.2630. 02630 0.2630 2630 -0.2630) sUrsCr sUr/sCr Thus COVID19. 19. COVID1 COVID- (sCr 47.9 479 4 (47. 154 54 1.5 514 51. 0.99 099 99 190. (190 941 41 9.4 13 5.53 553 53 3.4 34 (3. 02 0. 28 8 2. 01 0.1 063 0.63 63 0.581 0581 581 0263 0.263 263 -0.2630 47. (47 1. 0.9 09 (19 94 9. 5.5 55 3. (3 06 0.6 0.58 058 58 026 0.26 26 -0.263 (4 (1 5. ( 0.5 05 -0.26 -0.2 -0. -0 -

Abstract Obesity and dyslipidemia are conditions often associated with cardiovascular risk, inflammation, oxidative stress, and death. Thus, a new approach has been highlighted to promote research and development of pharmacological tools derived from natural sources. Among the most widely studied groups of substances, polyphenols such as tyramine stand out. This study investigated hypolipidemic and anti-obesity properties of tyramine. Oral toxicity evaluation, models of dyslipidemia and obesity were used. To induce dyslipidemia, Poloxamer-407 (P-407) was administered intraperitoneally. In the hypercholesterolemic and obesity model, specific diet and oral tyramine were provided. After 24h of P-407 administration, tyramine 2 mg/kg (T2) decreased triglycerides (TG) (2057.0 ± 158.5 mg/dL vs. 2838 ± 168.3 mg/dL). After 48h, TG were decreased by T2 (453.0 ± 35.47 vs. 760.2 ± 41.86 mg/dL) and 4 mg/kg (T4) (605.8 ± 26.61 760.2 ± 41.86 mg/dL). T2 reduced total cholesterol (TC) after 24h (309.0 ± 11.17 mg/dL vs. 399.7 ± 15.7 mg/dL); After 48h, 1 mg/kg (T1) (220.5 ± 12.78 mg/dL), T2 (205.8 ± 7.1 mg/dL) and T4 (216.8 ± 12.79 mg/dL), compared to P-407 (275.5 ± 12.1 mg/dL). The treatment decreased thiobarbituric acid reactive substances and nitrite in liver, increased superoxide dismutase, reduced the diet-induced dyslipidemia, decreasing TC around 15%. Tyramine reduced body mass, glucose, and TC after hypercaloric feed. Treatment with 5 mg/L (0.46 ± 0.04 ng/dL) and 10 mg/L (0.44 ± 0.02 ng/dL) reduced plasma insulin (1.18 ± 0.23 ng/dL). Tyramine increased adiponectin at 5 mg/L (1.02 ± 0.02 vs. 0.83 ± 0.02 ng/mL) and 10mg/L (0.96 ± 0.04 ng/mL). In conclusion, tyramine has low toxicity in rodents, has antioxidant effect, reduces plasma triglycerides and cholesterol levels. However, further studies should be conducted in rodents and non-rodents to better understand the pharmacodynamic and pharmacokinetic properties of tyramine.

Abstract Ischemia-reperfusion (I/R) plays an important role in the process of acute kidney injury (AKI) due to the generation of reactive oxygen species (ROS). Substances of natural origin have been studied in the prevention of oxidative damage related to I/R. Quercetin is a flavonoid with antioxidant potential and modulate enzymes, such the inhibition of the Rennin-Angiotensin System (RAS). The aim of this study is to evaluate the nephroprotective effect of quercetin against the I/R and analyze the inhibition of RAS. Rhesus monkey Kidney Epithelial Cells (LLC-MK2 line) were submitted to an in vitro ischemia/reperfusion model. After the reperfusion cells were treated with quercetin, the cell viability was accessed by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Tubular cell damage was assessed by the Kidney Injury Molecule-1 (KIM-1) measurement. Oxidative stress was evaluated through Thiobarbituric Acid Reactive Substances (TBARS) and reduced glutathione (GSH). The evaluation of cell death and the mitochondrial depolarization were analyzed by flow cytometry. Quercetin prevents cell death reducing oxidative stress and preventing mitochondrial membrane depolarization. Molecular docking showed that quercetin prevents cell damage better than losartan and lisinopril, inhibitors of RAS. Quercetin has a potential to interact with type 1 angiotensin II receptor (AT1) with greater affinity through the formation of five hydrogen bonds of strong intensity.