Search

This study aimed to investigate the association between novel biomarkers and renal injury in people with HIV (PWH). A cohort study was carried out with PWH under chronic use of antiretroviral therapy (ART), followed at a public outpatient service. Clinical and laboratory parameters of the patients were evaluated year by year, from 2015 [at baseline (year 1, Y1)] to 2019 [year 5 (Y5)]. At baseline, biomarkers of renal damage (e.g., neutrophil gelatinase-associated lipocalin-NGAL, monocyte chemoattractant protein-1-MCP-1, and kidney injury molecule-1-KIM-1) and endothelial activation or glycocalyx damage [e.g., intercellular adhesion molecule 1 (ICAM-1), E-selectin, and syndecan-1] were quantified using enzyme-linked immunosorbent assays and their levels were used to classify patients into different groups. However, only syndecan-1 showed a significant correlation with serum creatinine ( p  < .001) and glomerular filtration rate (GFR) ( p  = .003) over the years. Moreover, both serum creatinine and GFR in almost 5 years were significantly associated with serum levels of syndecan-1 at baseline. The multivariate linear regression with confounders showed a significant and independent association between GFR and levels of syndecan-1 and CD4 cell count in the beginning of the study, as well as age in Y5. The data reinforce the screening for kidney diseases with novel biomarkers, especially syndecan-1, as an important strategy for a timely diagnostic and therapeutic approach.

HIV-infected patients are at high risk for developing critical diseases, including opportunistic infections (OI), with consequent admission in intensive care units (ICU). Renal disfunctions are risk factors for death in HIV/AIDS patients, and survival rates in patients undergoing hemodialysis are smaller than the ones observed in the general population. In this context, this study aimed to investigate death-related factors in HIV/AIDS patients in an intensive care setting. This is a retrospective cross-sectional study performed through the analysis of medical records from 271 HIV/AIDS-diagnosed patients hospitalized in an intensive care unit of an infectious disease hospital, in Fortaleza, Ceara State, Brazil. Patients were divided into two groups: those who underwent dialysis during hospitalization and those who did not. Clinical and demographic parameters that could be associated with death were evaluated. Results indicated a prevalence of death of 19.1% (CI 95%: 14.8-24.3). The median age of patients was 47 years, with a male predominance (71.3%). The main causes of admission were pulmonary tuberculosis (16.9%), followed by neurotoxoplasmosis (14.9%). In the bivariate analysis, for those that did not undergo dialysis, age, fever, dyspnea, oliguria, disorientation, kidney injury, use of lamivudine and efavirenz, length of hospitalization, CD4 count, WBC count, platelet count, urea, sodium and LDH levels were the associated variables. In those who needed dialysis, the use of stavudine, abacavir and ritonavir, and the length of hospitalization were associated factors. Renal toxicity by the antiretroviral agents and length of hospitalization increased the risk of death among HIV patients under dialysis.

The wide variation found in the size of eukaryotic genomes is largely related to the accumulation of repetitive sequences. Studies show that these sequences can go through an evolutionary process (molecular co-optation) and acquire new genomic functions. Cytogenetic studies reveal a wide karyotypic variation between chelonians (order Testudines) (2n = 26-68), attributed mainly to the number of microchromosomes. The study of repetitive DNAs has the potential to provide data on the dynamics of these sequences, and how they influence the organization of the genome. Here, we reveal the first in situ mapping data of 45S rDNA, histone H3 genes, and telomeric sequences, for a species of the genus Rhinoclemmys, R. punctularia. The karyotype described here for R. punctularia is different from previous reports for the diploid complement of this species, with differences probably attributable to centric fissions and pericentric inversions or centromere repositioning. The 45S rDNA are on a single chromosome pair (like in other turtles), telomeric sequences are in terminal position on all the chromosomes, and histone H3 is dispersed in low copy number, with clusters in pericentromeric regions of three chromosome pairs. We report on the presence of a Gypsy retrotransposon insert located within H3 histone of R. punctularia, and the H3 region sequenced contained the open reading frame of the histone sequence. Comparative modeling revealed a functional pattern for the protein, thus suggesting that the Gypsy element might have been recruited for new functions in the genome of this species., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Eukaryotic genomes exhibit substantial accumulation of repetitive DNA sequences. These sequences can participate in chromosomal reorganization events and undergo molecular cooption to interfere with the function and evolution of genomes. In turtles, repetitive DNA sequences appear to be accumulated at probable break points and may participate in events such as non-homologous recombination and chromosomal rearrangements. In this study, repeated sequences of 5S rDNA, U2 snRNA and Tc1/Mariner transposons were amplified from the genomes of the turtles, Podocnemis expansa and Podocnemis unifilis , and mapped by fluorescence in situ hybridization. Our data confirm the 2n=28 chromosomes for these species (the second lowest 2n in the order Testudines). We observe high conservation of the co-located 5S rDNA and U2 snRNA genes on a small chromosome pair (pair 13), and surmise that this represents the ancestral condition. Our analysis reveals a wide distribution of the Tc1/Mariner transposons and we discuss how the mobility of these transposons can act on karyotypic reorganization events (contributing to the 2n decrease of those species). Our data add new information for the order Testudines and provide important insights into the dynamics and organization of these sequences in the chelonian genomes., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Objective: HIV-related mortality is still high, especially in developed countries. The aim of this study is to investigate factors associated to death in HIV-infected patients., Methods: This is a cross-sectional study with all HIV adult patients admitted to a tertiary infectious diseases hospital in Fortaleza, Northeast Brazil, from January 2013 to December 2014. Patients were divided into two groups: survivors and non-survivors. Demo-graphical, clinical and laboratory data were compared and a logistic regression was performed in order to investigate risk factors for death. P values ≤0.05 were considered statistically significant., Results: A total of 200 patients with mean age of 39 years were including in the study, 69.5% males. Fifteen patients (7.5%) died. Non-survivors presented a higher percentage of males (93.3 vs. 67.3%, p = 0.037). Non-survivors presented AKI (73.3 vs. 10.3%, p < 0.001), liver dysfunction (33.3 vs. 11.5, p = 0.031), dyspnea (73.3 vs. 33.0%, p = 0.002) and disorientation (33.3 vs. 12.4%, p = 0.025) more frequently. Non-survivors also had higher levels of urea (73.8 ± 52.7vs. 36.1 ± 29.1 mg/dL, p < 0.001), creatinine (1.98 ± 1.65 vs. 1.05 ± 1.07 mg/dL, p < 0.001), aspartate aminotransferase (130.8 vs. 84.8 U/L, p = 0.03), alanine aminotransferase (115.6 vs. 85.4 U/L, p = 0.045) and lactate dehydrogenase (LDH) (1208 vs. 608 U/L, p = 0.012), as well as lower levels of bicarbonate (18.0 ± 4.7 vs. 21.6 ± 4.6 mEq/L, p = 0.016) and PCO2 (27.8 ± 7.7 vs. 33.0 ± 9.3 mmHg, p = 0.05). In multivariate analysis, disorientation (p = 0.035, OR = 5.523, 95%CI = 1.130 - 26.998), dyspnoea (p = 0.046, OR = 4.064, 95%CI = 1.028 - 16.073), AKI (p < 0.001, OR = 18.045, 95%CI = 4.308 - 75.596) and disseminated histoplasmosis (p = 0.016, OR = 12.696, 95%CI = 1.618 - 99.646) and LDH > 1000 U/L (p = 0.038, OR = 4.854, 95%CI = 1.093 - 21.739) were risk factors for death.]CONCLUSION: AKI and disseminated histoplasmosis (DH) were the main risk factors for death in the studied population. Neurologic and respiratory impairment as well as higher levels of LDH also increased mortality in HIV-infected patients.

Cytogenetic studies show that there is great karyotypic diversity in order Testudines (2n = 26-68), and that this may be mainly attributed to the presence/absence of microchromosomes. Members of the Podocnemididae family have the smallest diploid numbers of this order (2n = 26-28), which may be a derived condition of the group. Diverse studies suggest that repetitive-DNA-rich sites generally act as hotspots for double-strand breaks and chromosomal reorganization. In this context, we used fluorescent in situ hybridization (FISH) to map telomeric sequences (TTAGGG)n, 45S rDNA, and the genes encoding histones H1 and H3 in two species of genus Podocnemis. We also observed conservation of the 45S rDNA and H1 histone sequences (probable case of conserved synteny), but multiple conserved and non-conserved clusters of H3 genes, which colocalized with the interstitial telomeric sequences in the Podocnemis genome. Our results suggest that fusions have occurred between macro and microchromosomes or between microchromosomes, leading to the observed reduction in diploid number in the family Podocnemididae., Competing Interests: The authors have declared that no competing interests exist.

Widespread use of combined antiretroviral therapy (cART) increased HIV patients' life expectancy, however, favored the development of kidney and cardiovascular diseases. The aim of this study was to investigate endothelial glycocalyx (eGC) damage and its association with renal function in HIV patients receiving cART. This is a cross-sectional study with HIV-infected patients with no renal and cardiovascular disease, recruited in public health centers in Brazil. Clinical and laboratory parameters of HIV patients were compared according to cART use and with a healthy control group. Blood ICAM-1 and syndecan-1 levels were quantified by ELISA kit. Estimated glomerular filtration rate (eGFR) was evaluated. A total of 69 HIV patients were included, with mean age of 33.4 ± 8.9 years, and 77.3% were male. Serum urea, creatinine, and eGFR were similar in all groups. No HIV patient had decreased GFR <60 ml/min. All HIV patients had higher systemic syndecan-1 compared with healthy controls (71.8 ± 25.4 ng/ml vs. 36.5 ± 14.3 ng/ml, p < .001). Syndecan-1 showed a significant positive correlation with serum creatinine (r = 0.437, p = .001), serum urea levels (r = 0.352, p = .006), and a negative correlation with eGFR (r = -0.315, p = .015) in HIV patients. Syndecan-1 remained independently associated with serum creatinine and reduced GFR even after we forced variables related with HIV infection status, tenofovir use, treatment time, dyslipidemia, and others in a multivariate analysis. HIV patients using cART with no clinical renal and cardiovascular disease presented eGC damage and it is associated with clinical markers of kidney dysfunction. Syndecan-1 may be a useful early biomarker to monitoring renal dysfunction in HIV patients in chronic use of cART. Further research is needed to evaluate this applicability.

Introduction: The Brazilian HIV/AIDS management and treatment guideline (PCDT), published in 2013, recommends and standardizes the use of highly active antiretroviral therapy (HAART) in all adult patients, in spite of LTCD4 count. This study aimed to analyze the first year of HAART use in patients from a reference center on HIV/AIDS management in Fortaleza, Ceará., Method: This descriptive study reviewed all prescription forms of antiretroviral regimens initiation and changes from January to July 2014. All antiretroviral regimen changes that occurred during the first year of therapy were evaluated. Data were analyzed with SPSS version 20. Mean, standard deviation and frequency, Student's t and Mann-Whitney tests calculations were used, with significance at p<0.05., Results: From 527 patients initiating HAART, 16.5% (n=87) had a regimen change in the first year. These patients were mostly male (59.8%; n=52), aged 20 to 39 years, with only one HAART change (72.4%; n=63). Efavirenz was the most often changed drug, followed by tenofovir, zidovudine and lopinavir/ritonavir. Mean time of HAART changes was 120 days, with adverse reactions as the most prevalent cause. HAART was effective in decreasing viral load since second month of treatment (p=0.003) and increasing LTCD4 lymphocytes since fifth month (p<0.001)., Conclusion: The main cause of initial HAART changes was adverse reaction and most patients had only one change in the HAART regimen. HAART prescription was in accordance to the PCDT from 2013.

Objective: To assess clinical and laboratory data, and acute kidney injury (AKI) in HIV-infected children using and not using highly active antiretroviral therapy (HAART) prior to admission., Methods: A retrospective study was conducted with HIV-infected pediatric patients (<16 years). Children who were using and not using HAART prior to admission were compared., Results: Sixty-three patients were included. Mean age was 5.3±4.27 years; 55.6% were females. AKI was observed in 33 (52.3%) children. Patients on HAART presented lower levels of potassium (3.9±0.8 vs. 4.5±0.7mEq/L, p=0.019) and bicarbonate (19.1±4.9 vs. 23.5±2.2mEq/L, p=0.013) and had a higher estimated glomerular filtration rate (102.2±36.7 vs. 77.0±32.8mL/min/1.73m 2 , p=0.011) than those not on HAART. In the multivariate analysis, the use of HAART prior to the admission was a protective factor for AKI (p=0.036; OR=0.30; 95% CI=0.097-0.926)., Conclusion: AKI is a common complication of pediatric HIV infection. Use of HAART prior to the admission preserved glomerular filtration and was a protective factor for AKI, but increased medication side effects, such as hypokalemia and renal metabolic acidosis., (Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Background: The aim of this study is to describe clinical characteristics, outcomes and risk factors for death among patients with HIV-related acute kidney injury (AKI) admitted to an intensive care unit (ICU)., Methods: A retrospective study was conducted with HIV-infected AKI patients admitted to the ICU of an infectious diseases hospital in Fortaleza, Brazil. All the patients with confirmed diagnosis of HIV and AKI admitted from January 2004 to December 2011 were included. A comparison between survivors and non-survivors was performed. Risk factors for death were investigated., Results: Among 256 AKI patients admitted to the ICU in the study period, 73 were identified as HIV-infected, with a predominance of male patients (83.6%), and the mean age was 41.2 ± 10.4 years. Non-survivor patients presented higher APACHE II scores (61.4 ± 19 vs. 38.6 ± 18, p = 0.004), used more vasoconstrictors (70.9 vs. 37.5%, p = 0.02) and needed more mechanical ventilation - MV (81.1 vs. 35.3%, p = 0.001). There were 55 deaths (75.3%), most of them (53.4%) due to septic shock. Independent risk factors for mortality were septic shock (OR = 14.2, 95% CI = 2.0-96.9, p = 0.007) and respiratory insufficiency with need of MV (OR = 27.6, 95% CI = 5.0-153.0, p < 0.001)., Conclusion: Non-survivor HIV-infected patients with AKI admitted to the ICU presented higher severity APACHE II scores, more respiratory damage and hemodynamic impairment than survivors. Septic shock and respiratory insufficiency were independently associated to death.