Evaluation of Glomerular Filtration Rate Trends in People Living With HIV Corrected by the Baseline Glomerular Filtration Rate.

BACKGROUND: Chronic kidney disease, for which estimated glomerular filtration rate (eGFR) trajectories are early markers, is frequent in people living with HIV. SETTING: Identify eGFR trajectory patterns according to kidney function and assess associated factors over a 13-year follow-up period. METHODS: We evaluated longitudinal changes and its associated factors in eGFR of 3366 participants according to kidney function with a 2-level, linear, mixed model. RESULTS: Participants with initial kidney dysfunction experienced a slight eGFR increase, whereas others showed a slight decrease. A weak relationship was observed between baseline eGFR and its variation over time. Baseline eGFR was affected by age, CD4 + count, viral load, hypertension, hyperlipidemia, AIDS-defining illness and tenofovir (TDF) with integrase inhibitor (INSTI) or efavirenz. Significant factors for eGFR change included the following: in kidney dysfunction, CD4 + cell count of >350 cells per cubic millimeter and undetectable viral load increased eGFR, whereas TDF + protease inhibitor decreased eGFR; in mildly decreased kidney function, CD4 + cell count of >350 cells per cubic millimeter, AIDS-defining illness, and TDF + efavirenz increased eGFR, whereas age, hypertension, hyperlipidemia, and TDF + INSTI decreased eGFR; in normal kidney function, age, CD4 + cell count of > 350 cells per cubic millimeter, undetectable viral load, hypertension, hyperlipidemia, and TDF + INSTI decreased eGFR, whereas TDF + efavirenz increased eGFR (all P value for interaction < 0.05). CONCLUSION: Our findings suggest that eGFR trajectories varied widely between individuals in people living with HIV. In the lower eGFR group, virus-related factors were more relevant, whereas traditional risk factors for renal dysfunction were more prominent in the highest eGFR group.

Acute kidney injury and renal replacement therapy: terminology standardization / Injúria renal aguda e métodos de suporte: padronização da nomenclatura

Abstract The Department of Acute Kidney Injury (IRA) of the Brazilian Society of Nephrology prepared this document for the purpose of standardizing AKI terminology and dialysis modalities in the Portuguese language for Brazil. Several terms with similar meanings have been used in AKI and its dialysis modalities, causing confusion and disparities among patients, nephrologists, health institutions, private care companies, insurance companies and government entities. These disparities can impact medical care, hospital organization and care, as well as the funding and reimbursement of AKI-related procedures. Thus, consensual nomenclature and definitions were developed, including the definitions of AKI, acute kidney disease (AKD) and chronic kidney disease (CKD). Additionally, we addressed all dialysis modalities and extracorporeal procedures related to AKI, currently approved and available in the country. The Brazilian Society of Nephrology hopes that this Consensus can standardize the terminology and provide technical support to all involved in AKI care in Brazil.

Resumo O Departamento de Injúria Renal Aguda (IRA) da Sociedade Brasileira de Nefrologia elaborou o presente documento para fins de padronização da terminologia em IRA e modalidades dialíticas na língua portuguesa para o Brasil. Diversos termos com significados semelhantes têm sido empregados em IRA e suas modalidades dialíticas, causando confusão e disparidades entre pacientes, nefrologistas, instituições de saúde, empresas privadas de assistência, seguradoras e entidades governamentais. Essas disparidades podem impactar a assistência médica, a organização e o atendimento hospitalares, assim como o financiamento e reembolso dos procedimentos relacionados com a IRA. Assim, nomenclatura e definições consensuais foram elaboradas, incluindo-se as definições de IRA, doença renal aguda (DRA) e doença renal crônica (DRC). Adicionalmente, todas as modalidades dialíticas e os procedimentos extracorpóreos relacionados a IRA, atualmente aprovados e disponíveis no país, foram abordados. A Sociedade Brasileira de Nefrologia espera que este Consenso possa padronizar a nomenclatura e prover suporte técnico para todos os atores envolvidos na assistência à IRA no Brasil.

Acute kidney injury and renal replacement therapy: terminology standardization.

The Department of Acute Kidney Injury (IRA) of the Brazilian Society of Nephrology prepared this document for the purpose of standardizing AKI terminology and dialysis modalities in the Portuguese language for Brazil. Several terms with similar meanings have been used in AKI and its dialysis modalities, causing confusion and disparities among patients, nephrologists, health institutions, private care companies, insurance companies and government entities. These disparities can impact medical care, hospital organization and care, as well as the funding and reimbursement of AKI-related procedures. Thus, consensual nomenclature and definitions were developed, including the definitions of AKI, acute kidney disease (AKD) and chronic kidney disease (CKD). Additionally, we addressed all dialysis modalities and extracorporeal procedures related to AKI, currently approved and available in the country. The Brazilian Society of Nephrology hopes that this Consensus can standardize the terminology and provide technical support to all involved in AKI care in Brazil.

Screening for decreased glomerular filtration rate and associated risk factors in a cohort of HIV-infected patients in a middle-income country.

With the introduction of combined active antiretroviral therapy and the improved survival of HIV-infected patients, degenerative diseases and drug toxicity have emerged as long-term concerns. We studied the prevalence of decreased glomerular filtration rate (GFR) and associated risk factors in a cohort of HIV-infected patients from a middle-income country. Our cross-sectional study included all adult patients who attended an urban outpatient clinic in 2008. GFR was estimated using the CKD-EPI equation. The prevalence ratio (PR) of decreased GFR (defined as <60 mL/min/1.73 m(2)) was estimated using generalizing linear models assuming a Poisson distribution. We analyzed data from 1,970 patients, of which 82.9% had been exposed to ART. A total of 249 patients (12.6%) had a GFR between 60 and 89 mL/min/1.73 m(2), 3.1% had a GFR between 30 and 59, 0.3% had a GFR between 15 and 29, and 0.4% had a GFR <15. Decreased GFR was found in only 74 patients (3.8%). In the multivariate regression model, the factors that were independently associated with a GFR below 60 mL/min/1.73 m(2) were as follows: age ≥ 50 years (PR = 3.4; 95% CI: 1.7-6.8), diabetes (PR = 2.0; 95% CI: 1.2-3.4), hypertension (PR = 2.0; 95% CI: 1.3-3.2), current CD4+ cell count <350 cells/mm3 (PR = 2.1; 95% CI: 1.3-3.3), past exposure to tenofovir (PR = 4.7; 95% CI: 2.3-9.4) and past exposure to indinavir (PR =1.7; 95% CI: 1.0-2.8). As in high-income countries, CKD was the predominant form of kidney involvement among HIV-infected individuals in our setting. The risk factors associated with decreased glomerular filtration were broad and included virus-related factors as well as degenerative and nephrotoxic factors. Despite the potential for nephrotoxicity associated with some antiretroviral drugs, in the short-term, advanced chronic renal disease remains very rare.

Pseudomonas aeruginosa toxin ExoU induces a PAF-dependent impairment of alveolar fibrin turnover secondary to enhanced activation of coagulation and increased expression of plasminogen activator inhibitor-1 in the course of mice pneumosepsis.

BACKGROUND: ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, was shown to induce vascular hyperpermeability and thrombus formation in a murine model of pneumosepsis. In this study, we investigated the toxin ability to induce alterations in pulmonary fibrinolysis and the contribution of the platelet activating factor (PAF) in the ExoU-induced overexpression of plasminogen activator inhibitor-1 (PAI-1). METHODS: Mice were intratracheally instilled with the ExoU producing PA103 P. aeruginosa or its mutant with deletion of the exoU gene. After 24 h, animal bronchoalveolar lavage fluids (BALF) were analyzed and lung sections were submitted to fibrin and PAI-1 immunohistochemical localization. Supernatants from A549 airway epithelial cells and THP-1 macrophage cultures infected with both bacterial strains were also analyzed at 24 h post-infection. RESULTS: In PA103-infected mice, but not in control animals or in mice infected with the bacterial mutant, extensive fibrin deposition was detected in lung parenchyma and microvasculature whereas mice BALF exhibited elevated tissue factor-dependent procoagulant activity and PAI-1 concentration. ExoU-triggered PAI-1 overexpression was confirmed by immunohistochemistry. In in vitro assays, PA103-infected A549 cells exhibited overexpression of PAI-1 mRNA. Increased concentration of PAI-1 protein was detected in both A549 and THP-1 culture supernatants. Mice treatment with a PAF antagonist prior to PA103 infection reduced significantly PAI-1 concentrations in mice BALF. Similarly, A549 cell treatment with an antibody against PAF receptor significantly reduced PAI-1 mRNA expression and PAI-1 concentrations in cell supernatants, respectively. CONCLUSION: ExoU was shown to induce disturbed fibrin turnover, secondary to enhanced procoagulant and antifibrinolytic activity during P. aeruginosa pneumosepsis, by a PAF-dependent mechanism. Besides its possible pathophysiological relevance, in vitro detection of exoU gene in bacterial clinical isolates warrants investigation as a predictor of outcome of patients with P. aeruginosa pneumonia/sepsis and as a marker to guide treatment strategies.

ExoU-induced vascular hyperpermeability and platelet activation in the course of experimental Pseudomonas aeruginosa pneumosepsis.

To address the question whether ExoU, a Pseudomonas aeruginosa cytotoxin with phospholipase A2 activity, can induce hemostatic abnormalities during the course of pneumosepsis, mice were instilled i.t. with the ExoU-producing PA103 P. aeruginosa or with a mutant obtained by deletion of the exoU gene. Control animals were instilled with sterile vehicle. To assess the role of ExoU in animal survival, mice were evaluated for 72 h. In all the other experiments, animals were studied at 24 h after infection. PA103-infected mice showed significantly higher mortality rate, lower blood leukocyte concentration, and higher platelet concentration and hematocrit than animals infected with the bacterial mutant, as well as evidences of increased vascular permeability and plasma leakage, which were confirmed by our finding of higher protein concentration in bronchoalveolar lavage fluids and by the Evans blue dye assay. Platelets from PA103-infected mice demonstrated features of activation, assessed by the flow cytometric detection of higher percentage of P-selectin expression and of platelet-derived microparticles as well as by the enzyme immunoassay detection of increased thromboxane A2 concentration in animal plasma. Histopathology of lung and kidney sections from PA103-infected mice exhibited evidences of thrombus formation that were not detected in sections of animals from the other groups. Our results demonstrate the ability of ExoU to induce vascular hyperpermeability, platelet activation, and thrombus formation during P. aeruginosa pneumosepsis, and we speculate that this ability may contribute to the reported poor outcome of patients with severe infection by ExoU-producing P. aeruginosa.