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1.  Does HIV infection promote early kidney injury in women? 
Antiviral therapy  2013;19(1):79-87.
Background
In HIV-infected women, urine concentrations of novel tubulointerstitial injury markers, interleukin-18 (IL-18) and kidney injury marker-1 (KIM-1) are associated with kidney function decline and all-cause mortality. We hypothesized that HIV-infected individuals with preserved kidney filtration function would have more extensive kidney injury, as determined by urine injury markers, compared to the uninfected controls, and that risk factors for tubulointerstitial injury would differ from risk factors for albuminuria.
Methods
In this cross-sectional study, we compared urine concentrations of IL-18, KIM-1, and ACR in 908 HIV-infected and 289 HIV-uninfected women enrolled in the Women’s Interagency HIV Study, utilizing stored urine specimens from visits between 1999 and 2000.
Results
After multivariate-adjusted linear regression analysis, mean urine concentrations were higher in HIV-infected individuals by 38% for IL-18 (p<0.0001), 12% for KIM-1 (p=0.081), and 47% for ACR (p<0.0001). Higher HIV RNA level (15% per 10-fold increase, p<0.0001), lower CD4 count (8% per doubling, p=0.0025), HCV infection (30%, p=0.00018), and lower HDL (5% per 10 mg/dL, p=0.0024) were each associated with higher IL-18 concentrations. In contrast, hypertension (81%, p<0.0001) and diabetes (47%, p=0.018) were among the strongest predictors of higher ACR, though HIV RNA level (15% per 10-fold increase, p=0.0004) was also associated with higher ACR.
Conclusions
HIV-infected women had more extensive tubulointerstitial and glomerular injury than uninfected women, but the associated factors differed among the urine biomarkers. Combinations of urinary biomarkers should be investigated to further characterize early kidney injury in HIV-infected women.
doi:10.3851/IMP2677
PMCID: PMC3933452  PMID: 23970313
2.  Risk Factors for ESRD in HIV-Infected Individuals: Traditional and HIV-Related Factors 
Background
Despite improvements in survival with HIV infection, kidney disease remains an important complication. Few studies have evaluated risk factors associated with development of end-stage renal disease (ESRD) in HIV-infected individuals. We sought to identify traditional and HIV-related risk factors for ESRD in HIV-infected individuals, and to compare ESRD risk by eGFR and proteinuria levels.
Study design
Retrospective cohort study.
Setting and Participants
22,156 HIV-infected veterans without preexisting ESRD receiving healthcare in the Veterans’ Affairs medical system between 1996 and 2004.
Predictors
Hypertension, diabetes, cardiovascular disease, hypoalbuminemia (serum albumin<3.5mg/dL), CD4 lymphocyte count, HIV viral load, hepatitis C virus coinfection, proteinuria, and estimated glomerular filtration rate (eGFR) were identified using the Veterans’ Affairs electronic record system.
Outcomes
ESRD was ascertained by the United States Renal Data System.
Results
366 cases of ESRD occurred, corresponding to 3 cases per 1,000 person-years. Hypertension (HR, 1.9; 95% CI, 1.5–2.4), diabetes (HR, 1.7; 95% CI, 1.3–2.2), and cardiovascular disease (HR, 2.2; 95% CI, 1.7–2.7) were independently associated with ESRD risk in multivariate-adjusted models, as were CD4 lymphocyte count <200 cells/mm3 (HR, 1.5; 95% CI, 1.2–2.0), HIV viral load ≥30,000 copies/mL (HR, 2.0; 95% CI, 1.5–2.8), hepatitis C virus coinfection (HR, 1.9; 95% CI, 1.5–2.4), and hypoalbuminemia (HR, 2.1; 95% CI, 1.8–2.5). Compared to persons without chronic kidney disease (CKD), defined as eGFR>60mg/min/1.73m2 and no proteinuria, lower eGFR and higher proteinuria categories were jointly associated with exponentially higher ESRD rates, ranging from 6.6 per 1000 person-years for persons with proteinuria 30–100 mg/dL and eGFR>60ml/min/1.73m2, to 193 per 1000 person-years for persons with proteinuria ≥300mg/dL and eGFR<30ml/min/1.73m2.
Limitations
Results may not be generalizable to female and nonveteran populations.
Conclusions
In HIV-infected persons, ESRD risk appears attributable to a combination of traditional and HIV-related risk factors for kidney disease. Combining eGFR and proteinuria for CKD staging is most effective for stratifying risk for ESRD.
doi:10.1053/j.ajkd.2011.10.050
PMCID: PMC3324595  PMID: 22206742
End-stage renal disease; HIV; chronic kidney disease; risk factors
3.  Reduced Kidney Function and Preclinical Atherosclerosis in HIV-Infected Individuals: The Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM) 
American Journal of Nephrology  2011;33(5):453-460.
Background/Aims
Reduced kidney function and albuminuria are associated with higher risk for cardiovascular disease (CVD) and mortality in HIV-infected individuals. We investigated whether reduced estimated glomerular filtration rate (eGFR) and albuminuria are associated with subclinical vascular disease, as assessed by carotid intima-medial thickness (cIMT).
Methods
Cross-sectional analysis of 476 HIV-infected individuals without clinical evidence of CVD enrolled in the Fat Redistribution and Metabolic Change in HIV infection (FRAM) study, using multivariable linear regression. eGFRCys and eGFRCr were calculated from cystatin C and creatinine levels. Albuminuria was defined as a positive urine dipstick (≥1+) or urine albumin-to-creatinine ratio ≥30 mg/g. Common and internal cIMT were measured by high-resolution B-mode ultrasound.
Results
In unadjusted analyses, eGFRCys and eGFRCr were strongly associated with common and internal cIMT. Each 10 ml/min/1.73 m2 decrease in eGFRCys and eGFRCr was associated with a 0.008 mm higher common cIMT (p = 0.003, p = 0.01) and a 0.024 and 0.029 mm higher internal cIMT (p = 0.003), respectively. These associations were eliminated after adjustment for age, gender, and race. Albuminuria showed little association with common or internal cIMT in all models.
Conclusions
In HIV-infected individuals without prior CVD, reduced kidney function and albuminuria were not independently associated with subclinical vascular disease, as assessed by cIMT. These results suggest that research should focus on searching for novel mechanisms by which kidney disease confers cardiovascular risk in HIV-infected individuals.
doi:10.1159/000327606
PMCID: PMC3100378  PMID: 21508633
Cystatin C; Intima-medial thickness; HIV; Atherosclerosis; Cardiovascular disease; Kidney

Results 1-3 (3)