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1.  Incidence and Risk Factors for Acute Kidney Injury in HIV Infection 
American Journal of Nephrology  2012;35(4):327-334.
Background/Aims
Although HIV-infected persons are at higher risk for acute kidney injury (AKI) during hospitalization compared with their uninfected counterparts, risk factors for AKI are not well-defined. We aimed to describe the evolving incidence of AKI among HIV-infected individuals and to identify important AKI risk factors.
Methods
We conducted a prospective cohort study of 56,823 HIV-infected persons in the Department of Veterans Affairs Clinical Case Registry. Outcomes were: AKI (acute in-hospital serum creatinine increase of ≥0.3 mg/dl, or a relative increase by 50% or greater), and dialysis-requiring AKI. We used proportional hazards regressions to identify risk factors.
Results
From its peak in 1995 at 62 per 1,000 person-years, the incidence of AKI declined after the introduction of highly active antiretroviral therapy (HAART) in 1996 to a low point of 25 per 1,000 person-years in 2006. Incidence of dialysis-requiring AKI declined in the early 1990s, but doubled between 2000 and 2006. Using multivariate proportional hazard regression, we identified the following strong risk factors for AKI: chronic kidney disease (eGFR <60 ml/min/1.73 m2) (5.38, 95% CI: 5.11–5.67), proteinuria (1.78, 1.70–1.87), low serum albumin (<3.7 mg/dl) (5.24, 4.82–5.71), low body mass index (<18.5 kg/m2) (1.69, 1.54–1.86), cardiovascular disease (1.77, 1.66–1.89), low CD4 count (<200 cells/mm3) (2.54, 2.33–2.77), and high viral load (≥100,000 copies/ml) (2.51, 2.28–2.75). In addition, there was substantial heterogeneity in the strengths of risk factors for dialysis-requiring AKI before and after the introduction of HAART.
Conclusions
Although AKI incidence has decreased during the HAART era, it remains common in HIV-infected persons and appears attributable to both kidney- and HIV-related factors.
doi:10.1159/000337151
PMCID: PMC3362304  PMID: 22456100
Acute kidney injury; HIV; Chronic kidney disease; Proteinuria; Hypoalbuminemia
2.  The Association of African Ancestry and Elevated Creatinine in the Coronary Artery Risk Development in Young Adults (CARDIA) Study 
American Journal of Nephrology  2009;31(3):202-208.
Whether genetic factors account for differences in early kidney disease among blacks in a young healthy population is not well known. We evaluated the association of self-reported race and genetic African ancestry with elevated creatinine (≥1.3 mg/dl for men, ≥1.1 mg/dl for women) among 3,113 black and white participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study, ages 38–50 years. We estimated individual African ancestry using 42 ancestry informative markers. Blacks were more likely to have elevated creatinine than whites, and this effect was more pronounced in men: adjusted odds ratio (AOR) for black versus white men = 7.03, 4.15–11.91; AOR for women = 2.40, 1.15–5.02. Higher African ancestry was independently associated with elevated creatinine among black men (AOR = 1.53,1.08–2.16 per SD increase in African ancestry), but not women. A graded increase in odds of elevated creatinine by African Ancestry was observed among black men compared with white men: AOR = 4.27 (2.26–10.06) for black men with 40–70% African ancestry; AOR = 8.09 (4.19–15.61) for black men with 70–80% African ancestry; AOR = 9.05 (4.81–17.02) for black men with >80% African ancestry. Genetic factors common to African ancestry may be associated with increased risk of early kidney dysfunction in a young, healthy population, particularly among black men.
doi:10.1159/000268955
PMCID: PMC3487144  PMID: 20029176
Ancestry; Creatinine; Race; Kidney
3.  Rate of Kidney Function Decline in Older Adults: A Comparison Using Creatinine and Cystatin C 
American Journal of Nephrology  2009;30(3):171-178.
Background/Aims
The aim of this study was to determine the decline in the estimated glomerular filtration rate (eGFR) in elderly persons and to compare estimates based on creatinine and cystatin C.
Methods
In the Cardiovascular Health Study, GFR changes in an elderly cohort were estimated from serum creatinine and cystatin C measured at baseline, year 3 and year 7 in 4,380 participants (age 72 ± 5 years at entry). Outcomes were mean eGFR decline, incident chronic kidney disease (CKD) and rapid decline in eGFR (annual loss >3 ml/min/1.73 m2).
Results
Mean annual eGFR loss as estimated from creatinine was 0.4 ± 3.6 ml/min/1.73 m2, with 16% of the participants experiencing a rapid decline. Mean eGFR loss as estimated from cystatin C was 1.8 ± 2.6, with 25% of the participants experiencing a rapid decline (p < 0.001 for both). Among participants without baseline CKD, incident CKD was detected at year 7 in 10% (n = 263) using creatinine and 19% (n = 544) using cystatin C (p < 0.001). Increasing age was the strongest predictor of rapid decline; adjusted odds ratios were 1.38 (1.16–1.65), 1.62 (1.31–1.99) and 2.96 (2.28–3.84) for participants aged 70–74, 75–79 and 80+ at baseline, compared with those aged 65–69.
Conclusion
In elderly persons, cystatin C estimated substantially larger declines in kidney function than creatinine did. Defining the optimal measurement of kidney function in elderly persons should be a high priority for future research.
doi:10.1159/000212381
PMCID: PMC2820322  PMID: 19349699
Glomerular filtration rate; Creatinine; Cystatin C; Chronic kidney disease
4.  Risk Factors for Chronic Kidney Disease among American Indians and Alaska Natives – Findings from the Kidney Early Evaluation Program 
American Journal of Nephrology  2008;29(5):440-446.
Background
American Indians and Alaska Natives (AIAN) have a high incidence of end-stage renal disease. Less is known about chronic kidney disease (CKD) among AIAN and whether risk factors differ for low estimated glomerular filtration rate (eGFR) versus albuminuria with a normal eGFR.
Methods
Cross-sectional study examining the associations of age, sex, smoking, obesity, diabetes, hypertension, family history, and geographic region with CKD among a screened population of AIAN participants in the Kidney Early Evaluation Program from 2000 to 2006. CKD was defined by the presence of either a low eGFR, <60 ml/min/1.73 m2, or albuminuria, a urine albumin/creatinine ratio ≥30 mg/g.
Results
The prevalence of any CKD was 29%, of low eGFR was 17%, and of albuminuria with a normal eGFR was 12%. Older age was the strongest predictor of low eGFR (61+ years OR 8.42, 95% CI 5.92–11.98), followed by hypertension (OR 2.38, 95% CI 1.74–3.26). In contrast, diabetes (OR 2.04, 95% CI 1.57–2.64) and hypertension (OR 2.63, 95% CI 1.93–3.59) were the only predictors of albuminuria among persons with a normal eGFR.
Conclusion
The burden of CKD was high among this screened population of AIAN, and different risk factor patterns were associated with low eGFR and albuminuria. Innovative programs and longitudinal research are needed to address CKD among AIAN.
doi:10.1159/000174857
PMCID: PMC2821946  PMID: 19011277
Chronic kidney disease; Risk factors; American Indians; Alaska Natives
5.  Change in Cardiovascular Risk Factors with Progression of Kidney Disease 
American Journal of Nephrology  2008;29(4):334-341.
Background
Prior studies evaluating the relationship of kidney disease with cardiovascular risk factors have been limited by their cross-sectional design. We evaluated the change in lipids, inflammatory and procoagulant biomarkers with decline in kidney function in a nested case-cohort study in the Cardiovascular Health Study, a community-based study of adults aged >65 years.
Methods
Individuals with an increase in serum creatinine ≥0.3 mg/dl (baseline to 3 years later, n = 207) were matched to controls of similar age, race, gender, diabetes and baseline serum creatinine, but whose change in creatinine was <0.3 mg/dl. Baseline and change in risk factors were analyzed with conditional logistic regression.
Results
Changes in C-reactive protein were similar. In contrast, cases had larger increases in fibrinogen (OR 1.38 per standard deviation, 95% confidence interval 1.08–1.76) and factor VIII [1.38 (1.10–1.72)] and larger decreases in HDL [OR 0.80 (0.64, 1.00)]. Change in interleukin-6 was greater in cases than controls, but this did not persist after multivariate adjustment. However, in linear regression, change in interleukin-6 was correlated with change in creatinine.
Conclusion
Cardiovascular risk factors and kidney function may change concurrently. This could lead to an increased risk of cardiovascular disease as kidney function worsens.
doi:10.1159/000166598
PMCID: PMC2786019  PMID: 18948687
Cardiovascular risk factors; Chronic kidney disease; Disease progression; Inflammation; Lipids

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