Predictors of resolution and persistence of renal laboratory abnormalities in pediatric HIV infection.
Ontology highlight
ABSTRACT:
SUBMITTER: Mitchell CD
PROVIDER: S-EPMC4301405 | biostudies-literature | 2015 Jan
REPOSITORIES: biostudies-literature
Publications
Predictors of resolution and persistence of renal laboratory abnormalities in pediatric HIV infection.
Mitchell Charles D CD Chernoff Miriam C MC Seage George R GR Purswani Murli U MU Spiegel Hans M L HM Zilleruelo Gaston G Abitbol Carolyn C Heckman Barbara B Ponce Christopher B CB Oleske James M JM
Pediatric nephrology (Berlin, Germany) 20140824 1
<h4>Background</h4>Among human immunodeficiency virus (HIV)-infected youth, the role of renal disease (RD) and its management has become increasingly important as these children/adolescents mature into young adults. The identification of predictors of abnormal renal laboratory events (RLE) may be helpful in the management of their HIV infection and its associated renal complications.<h4>Methods</h4>Data collected from HIV-infected youth followed for ≥ 48 months were analyzed to identify predicto ...[more]
Similar Datasets
Project description:BackgroundReported complications of pediatric septic arthritis range from minor growth abnormalities to potentially life-threatening conditions and death; some children require multiple surgeries for eradication of infection. The purpose of this study is: (1) to determine the failure rate of a single surgical incision and drainage (I&D) in pediatric septic arthritis, (2) to identify risk factors for failure which are detectable at the time of initial presentation, and (3) to trend post-operative C-reactive protein (CRP) values to see if there is a difference between children who fail a single I&D and those who do not.MethodsThe medical records for 105 children who underwent operative management of septic arthritis were retrospectively reviewed. Single and multivariate analyses were performed.ResultsEighty-four children required one surgical intervention [mean age 5.18 years (±4.01); 38 females (45 %), 46 males (55 %)], 21 children required revision surgery [mean age 8.16 years (±4.54); 4 females (19 %), 17 males (81 %)], and the overall rate of revision surgery was 20 %. Delayed diagnosis (p = 0.015), elevated CRP at presentation (p = 0.000), positive blood culture (p = 0.000), and age (p = 0.009) were all associated with revision surgery in bivariate analysis. In multivariate analysis, CRP at presentation and positive blood culture were significant risk factors for revision surgery (p = 0.005 and p = 0.025, respectively). Additionally, markedly elevated CRP levels on post-operative days (POD) 1-4 were each independently significant risk factors for requiring multiple surgeries (all p < 0.000). Fever, elevated erythrocyte sedimentation rate, and leukocyte count were not risk factors for multiple surgeries.ConclusionsIn this study, a positive blood culture or marked elevation in CRP at presentation or on POD 1-4 were associated with revision surgery. These findings may help improve surgical planning for both the initial surgery in order to avoid revisions, as well as revision surgery, should it be indicated.Level of evidenceIII.
| S-EPMC4909651 | biostudies-literature
Project description:ObjectivesTo determine the bivariable associations between abnormalities of 28 common laboratory tests and hospital mortality and determine how mortality risks changes when the ranges are evaluated in the context of commonly used laboratory test panels.DesignA 2009-2016 cohort from the Health Facts (Cerner Corporation, Kansas City, MO) database.SettingHospitals caring for children in ICUs.PatientsChildren cared for in ICUs with laboratory data.InterventionsNone.Measurements and main resultsThere were 2,987,515 laboratory measurements in 71,563 children. The distribution of laboratory test values in 10 groups defined by population percentiles demonstrated the midrange of tests was within the normal range except for those measured predominantly when significant abnormalities are suspected. Logistic regression analysis at the patient level combined the population-based groups into ranges with nonoverlapping mortality odds ratios. The most deviant test ranges associated with increased mortality risk (mortality odds ratios > 5.0) included variables associated with acidosis, coagulation abnormalities and blood loss, immune function, liver function, nutritional status, and the basic metabolic profile. The test ranges most associated with survival included normal values for chloride, pH, and bicarbonate/total Co2. When the significant test ranges from bivariable analyses were combined in commonly used test panels, they generally remained significant but were reduced as risk was distributed among the tests.ConclusionsThe relative importance of laboratory test ranges vary widely, with some ranges strongly associated with mortality and others strongly associated with survival. When evaluated in the context of test panels rather than isolated tests, the mortality odds ratios for the test ranges decreased but generally remained significant as risk was distributed among the components of the test panels. These data are useful to develop critical values for children in ICUs, to identify risk factors previously underappreciated, for education and training, and for future risk score development.
| S-EPMC7855885 | biostudies-literature
Project description:Approximately 50% of late-stage HIV patients develop CXCR4-tropic (X4) virus in addition to CCR5-tropic (R5) virus. X4 emergence occurs with a sharp decline in CD4+ T cell counts and accelerated time to AIDS. Why this phenotypic switch to X4 occurs is not well understood. Previously, we used numerical simulations of a mathematical model to show that across much of parameter space a promising new class of antiretroviral treatments, CCR5 inhibitors, can accelerate X4 emergence and immunodeficiency. Here, we show that mathematical model to be a minimal activation-based HIV model that produces a spontaneous switch to X4 virus at a clinically-representative time point, while also matching in vivo data showing X4 and R5 coexisting and competing to infect memory CD4+ T cells. Our analysis shows that X4 avoids competitive exclusion from an initially fitter R5 virus due to X4v unique ability to productively infect nave CD4+ T cells. We further justify the generalized conditions under which this minimal model holds, implying that a phenotypic switch can even occur when the fraction of activated nave CD4+ T cells increases at a slower rate than the fraction of activated memory CD4+ T cells. We find that it is the ratio of the fractions of activated nave and memory CD4+ T cells that must increase above a threshold to produce a switch. This occurs as the concentration of CD4+ T cells drops beneath a threshold. Thus, highly active antiretroviral therapy (HAART), which increases CD4+ T cell counts and decreases cellular activation levels, inhibits X4 viral growth. However, we show here that even in the simplest dual-strain framework, competition between R5 and X4 viruses often results in accelerated X4 emergence in response to CCR5 inhibition, further highlighting the potential danger of anti-CCR5 monotherapy in multi-strain HIV infection.
| S-EPMC3118547 | biostudies-other
Project description:Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (TFH) cells and non-TFH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity. Fluorescence-activated cell sorting (FACS) was used to sort subsets of CD4 T cells from blood (peripheral blood mononuclear cells; PBMC) and lymph node from a cohort of HIV-infected people with natural control of the virus (termed HIV controllers). Subsets of CD4 T cells that were sorted are as follows: from blood, (1) naïve (N), (2) central memory (CM), (3) transitional memory (TM), and (4) effector memory (EM); from lymph node, (1) naïve (N), (2) non-germinal center T-follicular helpers (nGC), (3) germinal center T-follicular helpers (Tfh), (4) effector memory (EM), and (5) other central memory-like subsets (CMPD1lo57lo, CMPD1lo57hi, and/or CMPD1lo). Total RNA and total DNA were extracted from these sorted subsets in separate fractions using RNAzol RT and DNAzol. Total cellular DNA was used for HIV quantification and sequence analysis as describe in the publication. Total RNA used for mRNA library construction by oligo-dT purification (Dynabeads), random fragmentation by heating in the presence of Magnesium (in form of 5x first-strand buffer, LifeTech), reverse transcription (SuperScript III), and then second-strand synthesis, end repair, a-tailing, and adaptor ligation using NEBNext enzyme master mixes and oligonucleotides. Libraries were sequenced on an Illumina HiSeq2000. Please note that each 'source name' value represent individual who havs HIV infection with natural control of the virus.
2016-07-01 | E-GEOD-83482 | biostudies-arrayexpress
Project description:Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (TFH) cells and non-TFH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity.
2016-07-01 | GSE83482 | GEO
Project description:BACKGROUND:Higher levels of small low-density lipoprotein (LDL) and lower levels of high-density lipoprotein (HDL) subclasses have been associated with increased risk of cardiovascular disease. The extent to which HIV infection and HIV/hepatitis C virus (HCV) coinfection are associated with abnormalities of lipoprotein subclasses is unknown. METHODS:Lipoprotein subclasses were measured by nuclear magnetic resonance (NMR) spectroscopy in plasma samples from 569 HIV-infected and 5948 control participants in the Fat Redistribution and Metabolic Change in HIV Infection (FRAM), Coronary Artery Risk Development in Young Adults (CARDIA), and Multi-Ethnic Study of Atherosclerosis (MESA) studies. Multivariable regression was used to estimate the association of HIV and HIV/HCV coinfection with lipoprotein measures with adjustment for demographics, lifestyle factors, and waist-to-hip ratio. RESULTS:Relative to controls, small LDL levels were higher in HIV-monoinfected persons (+381?nmol/l, P?<0.0001), with no increase seen in HIV/HCV coinfection (-16.6?nmol/l). Levels of large LDL levels were lower (-196?nmol/l, P?<0.0001) and small HDL were higher (+8.2??mol/l, P?<?0.0001) in HIV monoinfection with intermediate values seen in HIV/HCV coinfection. Large HDL levels were higher in HIV/HCV-coinfected persons relative to controls (+1.70??mol/l, P?<0.0001), whereas little difference was seen in HIV-monoinfected persons (+0.33, P?=?0.075). Within HIV-infected participants, HCV was associated independently with lower levels of small LDL (-329?nmol/l, P?<0.0001) and small HDL (-4.6??mol/l, P?<0.0001), even after adjusting for demographic and traditional cardiovascular risk factors. CONCLUSION:HIV-monoinfected participants had worse levels of atherogenic LDL lipoprotein subclasses compared with controls. HIV/HCV coinfection attenuates these changes, perhaps by altering hepatic factors affecting lipoprotein production and/or metabolism. The effect of HIV/HCV coinfection on atherosclerosis and the clinical consequences of low small subclasses remain to be determined.
| S-EPMC4267724 | biostudies-literature
Project description:Studies of hematologic abnormalities in HIV-infected patients are confounded by a multitude of factors. A retrospective data analysis of simian immunodeficieny virus (SIV)-infected rhesus macaques (RM) of Indian origin was performed to determine the prevalence of hematologic abnormalities free of these confounds.Hematologic data from RM inoculated with SIV and without antiviral therapy were examined pre-inoculation, and throughout infection and the development of AIDS.Anemia, thrombocytopenia, lymphopenia, eosinophilia, and neutropenia all increased in prevalence with SIV infection. Significant increases in prevalence for both neutropenia and neutrophilia were also detected in SIV-infected macaques. SIV-infected macaques also had lower lymphocyte counts and increased prevalence of lymphopenia compared with non-infected subjects. The prevalence of eosinophilia was significantly increased during SIV infection.Concordance of hematologic abnormalities during SIV infection of macaques with similar changes in HIV infection of humans suggests that, like in HIV infection, hematologic abnormalities are major complications of SIV infection.
| S-EPMC3367385 | biostudies-literature
Project description:Targeted HIV cure strategies require definition of the mechanisms that maintain the virus. Here, we tracked HIV replication and the persistence of infected CD4 T cells in individuals with natural virologic control by sequencing viruses, T cell receptor genes, HIV integration sites, and cellular transcriptomes. Our results revealed three mechanisms of HIV persistence operating within distinct anatomic and functional compartments. In lymph node, we detected viruses with genetic and transcriptional attributes of active replication in both T follicular helper (TFH) cells and non-TFH memory cells. In blood, we detected inducible proviruses of archival origin among highly differentiated, clonally expanded cells. Linking the lymph node and blood was a small population of circulating cells harboring inducible proviruses of recent origin. Thus, HIV replication in lymphoid tissue, clonal expansion of infected cells, and recirculation of recently infected cells act together to maintain the virus in HIV controllers despite effective antiviral immunity.
| S-EPMC4983216 | biostudies-literature
Project description:ObjectiveThe predictors of Fanconi syndrome (FS) accompanied by renal function decline with use of the antiretroviral tenofovir disoproxil fumarate (TDF) have not been assessed. In addition, the natural history of renal recovery from FS after TDF discontinuation is not well-described.DesignWe prospectively enrolled HIV-infected patients receiving TDF with newly identified FS (defined as at least two markers of proximal tubulopathy and either a >25% decline in creatinine clearance (CrCl) from pre-TDF values or a CrCl <60 mL/min in those without a known pre-TDF CrCl) in a multicenter observational study. These case participants were matched 1:2 to controls; characteristics between the two groups were compared. Case participants with known pre-TDF CrCl values were then followed over 48 weeks to assess renal recovery.ResultsNineteen cases and 37 controls were enrolled. In multivariable analysis, previous or concurrent use of lopinavir/ritonavir [OR 16.37, 95% CI (2.28, 117.68); P = 0.006] and reduced creatinine clearance prior to initiation of TDF [OR 1.44 for every 5 mL/min reduction, 95% CI (1.09, 1.92); P = 0.012; OR 19.77 for pre-TDF CrCl lower than 83 mL/min, 95% CI (2.24, 174.67); P = 0.007] were significantly associated with FS. Of the 14 cases followed for resolution, 7 (50%) achieved at least partial resolution (defined as recovering CrCl >70% of pre-TDF values) although most participants had full normalization of proximal tubulopathy markers within two months of TDF discontinuation.ConclusionsFS, defined by specific CrCl decreases and markers of tubulopathy, is more likely in those who have received or are currently receiving concomitant lopinavir/ritonavir or who had lower CrCl prior to TDF initiation. Half of those with protocol-defined FS had CrCl recover to near pre-TDF values during the first year after TDF discontinuation.
| S-EPMC3961428 | biostudies-literature
Project description:BackgroundData on the prevalence of renal and urine abnormalities among HIV-infected children in Sub-Saharan Africa are limited. We set out to determine the prevalence of proteinuria; low estimated glomerular filtration rate (eGFR), urinary tract infection and associated factors among HIV-infected antiretroviral therapy (ART) naive children, aged 2-12 years, attending the paediatric HIV clinic at a tertiary hospital in Harare.MethodsConsecutive ART naive children attending the clinic between June and October 2009 were recruited. Detailed medical history was obtained and a complete physical examination was performed. Children were screened for urinary tract infection and for significant persistent proteinuria. Serum creatinine was used to estimate GFR using the modified Counahan-Barratt formula. The Student's t-test was used to analyse continuous variables and the chi-square or Fisher's exact test was used to analyse categorical data. Logistic regression was performed to assess the relationship between study factors and urine abnormalities, persistent proteinuria and the eGFR.ResultsTwo hundred and twenty children were enrolled into the study. The median age was 90 months (Q1=65.5; Q3=116.5). The prevalence of urinary tract infection was 9.5%. Escherichia coli was the predominant organism. There was uniform resistance to cotrimoxazole. Persistent proteinuria (urine protein to creatinine ratio greater than 0.2, a week apart) was found in 5% of the children. Seventy-five children (34.6%) had mild to moderate renal impairment shown by a low eGFR (30 to <90 ml/min/1.73 m2). Persistent proteinuria was more likely to be found in children who were wasted, weight-for-height (WHZ) z-score <-2 (p=0.0005). Children with WHO clinical stage 4 were more likely to have a low eGFR than children with less advanced stages (OR 2.68; CI 1.24-5.80). Urine abnormalities were more likely to be observed in children with WHO clinical stages 3 and 4 (OR 2.20; CI 1.06-4.60).ConclusionThere is significant renal impairment among HIV-infected, ART naive children aged 2-12 years attending the outpatient paediatric HIV clinic at Harare Central Hospital. The abnormalities are more likely to occur in children with advanced HIV/AIDS. Screening for renal impairment and urinary tract infections in HIV-infected children before initiation of ART and regularly thereafter would be helpful in their management.KeywordsHIV, renal disease, persistent proteinuria, glomerular filtration rate, urinary tract infection.
| S-EPMC3654941 | biostudies-literature