scholarly journals Association of Urinary Biomarkers of Kidney Injury with Estimated GFR Decline in HIV-Infected Individuals following Tenofovir Disoproxil Fumarate Initiation

2018 ◽  
Vol 13 (9) ◽  
pp. 1321-1329 ◽  
Author(s):  
Simon B. Ascher ◽  
Rebecca Scherzer ◽  
Michelle M. Estrella ◽  
William R. Zhang ◽  
Anthony N. Muiru ◽  
...  

Background and objectivesTenofovir disoproxil fumarate (tenofovir) is associated with elevated concentrations of biomarkers of kidney damage and dysfunction in individuals with HIV. The relationship of these kidney biomarkers with longitudinal kidney function decline is unknown.Design, setting, participants, & measurementsWe evaluated associations of 14 urinary biomarkers of kidney injury with changes in eGFR among 198 men and women with HIV who initiated tenofovir between 2009 and 2015 in the Multicenter AIDS Cohort Study and Women’s Interagency HIV Study. Urinary biomarkers included albumin-to-creatinine ratio, α-1-microglobulin, β-2-microglobulin, cystatin C, kidney injury molecule-1 (KIM-1), IL-18, neutrophil gelatinase–associated lipocalin (NGAL), clusterin, osteopontin, uromodulin, monocyte chemoattractant protein-1, EGF, trefoil factor 3, and chitinase 3-like protein 1. We used multivariable linear mixed-effect models controlling for demographics, traditional kidney disease risk factors, and HIV-related risk factors to evaluate associations of baseline biomarkers with first-year changes in eGFR, and associations of year 1 and first-year change in biomarkers with changes in eGFR from year 1 to year 3. We used the least absolute shrinkage and selection operator method to identify a parsimonious set of biomarkers jointly associated with changes in eGFR.ResultsMedian eGFR before tenofovir initiation was 103 (interquartile range, 88–116) ml/min per 1.73 m2. During the first year of tenofovir use, eGFR decreased on average by 9.2 (95% confidence interval, 6.5 to 11.9) ml/min per 1.73 m2 and was stable afterward (decrease of 0.62; 95% confidence interval, −0.85 to 2.1 ml/min per 1.73 m2 per year). After multivariable adjustment, higher baseline β-2-microglobulin, KIM-1, and clusterin were associated with larger first-year eGFR declines, whereas higher baseline uromodulin was associated with a smaller eGFR decline. First-year increase in urinary cystatin C and higher year 1 IL-18 were associated with larger annual eGFR declines from year 1 to year 3. The parsimonious models identified higher pre-tenofovir clusterin and KIM-1, lower pre-tenofovir uromodulin, and higher year 1 IL-18 as jointly associated with larger eGFR declines.ConclusionsUrinary biomarkers of kidney injury measured before and after tenofovir initiation are associated with subsequent changes in eGFR in individuals with HIV.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_08_28_CJASNPodcast_18_9_S.mp3

Author(s):  
Stephen Duff ◽  
Ruairi Irwin ◽  
Jean Maxime Cote ◽  
Lynn Redahan ◽  
Blaithin A McMahon ◽  
...  

Abstract Background Acute Kidney Injury (AKI) is common in hospitalized patients and is associated with high morbidity and mortality. The Dublin Acute Biomarker Group Evaluation (DAMAGE) Study is a prospective cohort study of critically ill patients (n = 717). We hypothesised that novel urinary biomarkers would predict progression of AKI and associated outcomes. Methods The primary (diagnostic) analysis assessed the ability of biomarkers levels at the time of early Stage 1 or2 AKI to predict progression to higher AKI Stage, RRT or Death within 7 days of ICU admission. In the secondary (prognostic) analysis, we investigated the association between biomarker levels and RRT or Death within 30 days. Results In total, 186 patients had an AKI within 7 days of admission. In the primary (diagnostic) analysis, eight of the 14 biomarkers were independently associated with progression. The best predictors were Cystatin C (aOR 5.2; 95% CI, 1.3-23.6), IL-18 (aOR 5.1; 95% CI, 1.8-15.7), Albumin (aOR 4.9; 95% CI, 1.5-18.3) and NGAL (aOR 4.6; 95% CI, 1.4-17.9). ROC and Net Reclassification Index analyses similarly demonstrated improved prediction by these biomarkers. In the secondary (prognostic) analysis of Stage 1-3 AKI cases, IL-18, NGAL, Albumin, and MCP-1 were also independently associated with RRT or Death within 30 days. Conclusions Among 14 novel urinary biomarkers assessed, Cystatin C, IL-18, Albumin and NGAL were the best predictors of Stage 1-2 AKI progression. These biomarkers, after further validation, may have utility to inform diagnostic and prognostic assessment and guide management of AKI in critically ill patients.


2019 ◽  
Vol 50 (5) ◽  
pp. 401-410 ◽  
Author(s):  
Simon B. Ascher ◽  
Rebecca Scherzer ◽  
Michelle M. Estrella ◽  
Michael G. Shlipak ◽  
Derek K. Ng ◽  
...  

Background: HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV–) men. Methods: In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV– men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR. Results: Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m2/year in HIV+ men and 1.22 mL/min/1.73 m2/year in HIV– men. Among HIV+ men, the highest vs. lowest tertiles of albumin (–1.78 mL/min/1.73 m2/year, 95% CI –3.47 to –0.09) and α1m (–2.43 mL/min/1.73 m2/year, 95% CI –4.14 to –0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV– men, the highest vs. lowest tertile of α1m (–2.49 mL/min/1.73 m2/year, 95% CI –4.48 to –0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus. Conclusions: Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR.


2019 ◽  
Vol 13 (1) ◽  
pp. 46-54
Author(s):  
Julia Arnold ◽  
Don Sims ◽  
Paramjit Gill ◽  
Paul Cockwell ◽  
Charles Ferro

AbstractBackgroundAcute kidney injury (AKI) diagnosis requires ascertainment of change from a known baseline. Although pre-admission serum creatinine (SCr) is recommended, to date, all studies of AKI in acute stroke have used the first SCr on admission.MethodsAll patients admitted with an acute stroke to an emergency hospital were recruited. We compared use of pre-admission SCr with admission SCr to diagnose AKI. Regression analyses were used to identify risk factors for 30-day and 1-year mortality, respectively.ResultsA total of 1354 patients were recruited from December 2012 to September 2015. Incidence of AKI was 18.7 and 19.9% using pre-admission SCr and admission SCr, respectively. Diagnosis of AKI was associated with significantly increased 30-day and 1-year mortality. Diagnosis of AKI using pre-admission SCr had a stronger relationship with both 30-day and 1-year mortality. In 443 patients with a pre-admission SCr and at least two SCr during admission, AKI diagnosed using pre-admission SCr had a stronger relationship than AKI diagnosed using admission SCr with 30-day mortality [odds ratio (OR) = 2.64; 95% confidence interval (CI) 1.36–5.12; P = 0.004 versus OR = 2.10; 95% CI 1.09–4.03; P = 0.026] and 1-year mortality [hazard ratio (HR) = 1.90, 95% CI 1.32–2.76; P = 0.001 versus HR = 1.47; 95% CI 1.01–2.15; P = 0.046] in fully adjusted models.ConclusionsAKI after stroke is common and is associated with increased 30-day and 1-year mortality. Using first SCr on admission gives a comparable AKI incidence to pre-admission SCr, but underestimates 30-day and 1-year mortality risk.


QJM ◽  
2020 ◽  
Vol 113 (12) ◽  
pp. 876-882 ◽  
Author(s):  
J Li ◽  
T Guo ◽  
D Dong ◽  
X Zhang ◽  
X Chen ◽  
...  

Summary Background Cardiovascular disease (CVD) was in common in coronavirus disease 2019 (COVID-19) patients and associated with unfavorable outcomes. We aimed to compare the clinical observations and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients with or without CVD. Methods Patients with laboratory-confirmed SARS-CoV-2 infection were clinically evaluated at Wuhan Seventh People’s Hospital, Wuhan, China, from 23 January to 14 March 2020. Demographic data, laboratory findings, comorbidities, treatments and outcomes were collected and analyzed in COVID-19 patients with and without CVD. Results Among 596 patients with COVID-19, 215 (36.1%) of them with CVD. Compared with patients without CVD, these patients were significantly older (66 vs. 52 years) and had higher proportion of men (52.5% vs. 43.8%). Complications in the course of disease were more common in patients with CVD, included acute respiratory distress syndrome (22.8% vs. 8.1%), malignant arrhythmias (3.7% vs. 1.0%) including ventricular tachycardia/ventricular fibrillation, acute coagulopathy(7.9% vs. 1.8%) and acute kidney injury (11.6% vs. 3.4%). The rate of glucocorticoid therapy (36.7% vs. 25.5%), Vitamin C (23.3% vs. 11.8%), mechanical ventilation (21.9% vs. 7.6%), intensive care unit admission (12.6% vs. 3.7%) and mortality (16.7% vs. 4.7%) were higher in patients with CVD (both P < 0.05). The multivariable Cox regression models showed that older age (≥65 years old) (HR 3.165, 95% CI 1.722–5.817) and patients with CVD (HR 2.166, 95% CI 1.189–3.948) were independent risk factors for death. Conclusions CVD are independent risk factors for COVID-19 patients. COVID-19 patients with CVD were more severe and had higher mortality rate, early intervention and vigilance should be taken.


2017 ◽  
Vol 34 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Henock Woldu ◽  
B. Joseph Guglielmo

Background: Particularly with the current increased vancomycin dosing trends, the true risk of the agent’s nephrotoxicity is not well characterized and remains of concern. Objective: To determine the incidence of vancomycin nephrotoxicity in acutely ill hospitalized children and to secondarily characterize the risk factors for this complication. Methods: A single-center retrospective cohort study conducted at UCSF Benioff Children’s Hospital from June 2012 to June 2015. Inpatients 3 months to <19 years who received intravenous vancomycin for ≥48 hours were included. The primary outcome was incidence of nephrotoxicity, defined as an increase in serum creatinine by ≥50% from baseline. Univariate and multivariate analyses were conducted to identify risk factors for vancomycin nephrotoxicity. Results: A total of 291 patients (272 nonnephrotoxic and 19 nephrotoxic) were included in the analysis. Of the 19 patients, 12 (4.1%) were found to have moderate to severe toxicity. The median duration of therapy was 3 (3-5) and 4 (3-6) days for the group with “no nephrotoxicity” and “nephrotoxicity,” respectively. The mean time for the serum creatinine to return to normal in patients with nephrotoxicity was 5.1 days. In the multivariate analysis, only final trough concentration ≥15mg/dL (odds ratio = 3.49, 95% confidence interval = 1.2-10.1; P = .021) and receipt of piperacillin/tazobactam (odds ratio = 3.14, 95% confidence interval = 1.02-9.6; P = .046) were significantly associated with nephrotoxicity. Conclusion: The rate of moderate to severe vancomycin-associated nephrotoxicity in acutely ill children is relatively uncommon and reversible. Kidney injury is associated with increased vancomycin trough concentrations and concomitant receipt of nephrotoxins, particularly piperacillin/tazobactam.


2021 ◽  
Vol 15 (9) ◽  
pp. e0009679
Author(s):  
Gwenyth O. Lee ◽  
Luis Vasco ◽  
Sully Márquez ◽  
Julio C. Zuniga-Moya ◽  
Amanda Van Engen ◽  
...  

Dengue is recognized as a major health issue in large urban tropical cities but is also observed in rural areas. In these environments, physical characteristics of the landscape and sociodemographic factors may influence vector populations at small geographic scales, while prior immunity to the four dengue virus serotypes affects incidence. In 2019, a rural northwestern Ecuadorian community, only accessible by river, experienced a dengue outbreak. The village is 2–3 hours by boat away from the nearest population center and comprises both Afro-Ecuadorian and Indigenous Chachi households. We used multiple data streams to examine spatial risk factors associated with this outbreak, combining maps collected with an unmanned aerial vehicle (UAV), an entomological survey, a community census, and active surveillance of febrile cases. We mapped visible water containers seen in UAV images and calculated both the green-red vegetation index (GRVI) and household proximity to public spaces like schools and meeting areas. To identify risk factors for symptomatic dengue infection, we used mixed-effect logistic regression models to account for the clustering of symptomatic cases within households. We identified 55 dengue cases (9.5% of the population) from 37 households. Cases peaked in June and continued through October. Rural spatial organization helped to explain disease risk. Afro-Ecuadorian (versus Indigenous) households experience more symptomatic dengue (OR = 3.0, 95%CI: 1.3, 6.9). This association was explained by differences in vegetation (measured by GRVI) near the household (OR: 11.3 95% 0.38, 38.0) and proximity to the football field (OR: 13.9, 95% 4.0, 48.4). The integration of UAV mapping with other data streams adds to our understanding of these dynamics.


Lupus ◽  
2018 ◽  
Vol 27 (11) ◽  
pp. 1778-1789 ◽  
Author(s):  
Y Ding ◽  
L-M Nie ◽  
Y Pang ◽  
W-J Wu ◽  
Y Tan ◽  
...  

Objective This study aimed to evaluate the clinical value of urinary biomarkers including kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein-1 (MCP-1) in lupus nephritis. Methods A total of 109 biopsy-proven lupus nephritis patients were included and 50 healthy individuals were used as normal controls. Urinary KIM-1, NGAL, and MCP-1 levels were measured by ELISA and their correlations with clinical and histological features were assessed. Receiver operating characteristic curves were performed and the Cox regression model was applied to identify prognostic factors associated with renal outcomes. Results Active lupus nephritis patients exhibited elevated urinary levels of KIM-1, NGAL, and MCP-1 compared with lupus nephritis patients in remission ( P < 0.001) and normal controls ( P < 0.001). The urinary KIM-1 level was correlated with pathological tubular atrophy ( r = 0.208, P < 0.05) and increased significantly in the presence of interstitial inflammatory lesions ( P = 0.031). Urinary KIM-1, NGAL, and MCP-1 levels were higher in patients with active tubulointerstitial lesions than in those with only chronic lesions ( P = 0.015, P = 0.230, and P = 0.086, respectively). A combination of KIM-1, NGAL, and MCP-1 was a good indicator for diagnosing active tubulointerstitial lesions (area under the curve: 0.796). The combination of KIM-1 and NGAL was identified as an independent risk factor for renal outcomes (hazard ratio = 7.491, P < 0.05). Conclusion Urinary KIM-1, NGAL, and MCP-1 levels were associated with kidney injury indices in lupus nephritis. The combination of the three biomarkers showed increased power in predicting tubulointerstitial lesions and renal outcomes.


PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251036
Author(s):  
Arzu Velioglu ◽  
Gokhan Guneri ◽  
Hakki Arikan ◽  
Ebru Asicioglu ◽  
Elif Tukenmez Tigen ◽  
...  

Background The most common infections among renal transplant patients are urinary tract infections (UTI). Our main objective in this study is to determine the incidence of UTIs in patients who have undergone renal transplantation in our hospital, to identify the causative microbiological agents, risk factors and determine the effects of UTI on short-term graft survival. Methods Urinary tract infections, which developed within the first year of renal transplantation, were investigated. Patients were compared regarding demographic, clinical, laboratory characteristics and graft survival. Results 102 patients were included in our study. Fifty-three patients (53%) were male and 49 (48%) were female. Sixty-seven urinary tract infection attacks in 21 patients (20.5%) were recorded. Age (p = 0.004; 95% Confidence Interval [CI]: 1.032–1.184), longer indwelling urinary catheter stay time (p = 0.039; 95% Confidence Interval [CI]: 1.013–1.661) and urologic complications (p = 0.006; 95% Confidence Interval [CI]: 0.001–0.320) were found as risk factors for UTI development in the first year of transplantation. Escherichia coli and Klebsiella pneumoniae were the most frequently isolated microorganisms. Of these bacteria, 63.2% were found to be extended spectrum beta lactamase (ESBL) positive. Multidrug resistant microorganisms (MDROs) were more frequent in male patients (32 episodes in males vs. 14 episodes in females, p = <0.001). UTI had no negative impact on short-term graft survival. Conclusion Our study results represent the high incidence of UTI with MDROs in KT recipients. Infection control methods should be applied even more vigorously especially in male transplant patients since a higher incidence of UTI caused by resistant microorganisms was reported in male patients.


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