Publications

BACKGROUND

Compared with controls, human immunodeficiency virus (HIV)-infected persons have a greater prevalence of kidney disease, assessed according to high cystatin C level and albuminuria, but not according to creatinine level. However, the clinical importance of increased cystatin C level and albuminuria in the HIV-infected population has not been studied.

STUDY DESIGN

We conducted an observational cohort study to determine the association of kidney disease (measured according to albuminuria, cystatin C, and serum creatinine) with mortality.

SETTING & PARTICIPANTS

922 HIV-infected persons enrolled in the FRAM (Fat Redistribution and Metabolic Change in HIV Infection) Study.

PREDICTOR

Serum cystatin C and serum creatinine levels were used to estimate glomerular filtration rates (eGFR(SCysC) and eGFR(SCr), respectively). Albuminuria was defined as a positive urine dipstick result (≥ 1+) or urine albumin-creatinine ratio >30 mg/g.

OUTCOME

5-Year mortality.

RESULTS

At baseline, decreased kidney function (eGFR(SCysC) <60 mL/min/1.73 m(2)) or albuminuria was present in 28% of participants. After 5 years of follow-up, mortality was 48% in those with both eGFR(SCysC) < 60 mL/min/1.73 m(2) and albuminuria, 23% in those with eGFR(SCysC) < 60 mL/min/1.73 m(2) alone, 20% in those with albuminuria alone, and 9% in those with neither condition. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, and inflammatory marker levels, eGFR(SCysC) < 60 mL/min/1.73 m(2) and albuminuria were associated with a nearly 2-fold increase in mortality, whereas eGFR(SCr) < 60 mL/min/1.73 m(2) did not appear to have a substantial association with mortality. Together, eGFR(SCysC) <60 mL/min/1.73 m(2) and albuminuria accounted for 17% of the population-level attributable risk of mortality.

LIMITATIONS

Vital status was unknown in 261 participants from the original cohort.

CONCLUSIONS

Kidney disease marked by albuminuria or increased cystatin C level appears to be an important risk factor for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on serum creatinine to estimate kidney function in clinical practice.

Based on in vitro rat and human hepatocyte uptake studies showing inhibition of warfarin uptake in the presence of the nonspecific organic anion-transporting polypeptide (OATP) inhibitor rifampin, a clinical study was conducted in 10 healthy volunteers to examine the in vivo relevance of OATP hepatic uptake on the pharmacokinetics of warfarin. In a randomized, single-dose, two-period, crossover design, subjects received a 7.5-mg dose of warfarin, either alone or immediately following a 600-mg intravenous dose of rifampin. Rifampin did not significantly alter the R- or S-warfarin area under the concentration-time curves (AUCs) from 0 to 12 h (period of hepatic OATP inhibition by rifampin) or the maximum plasma concentration (C(max)) value. AUC(0-∞) was decreased on days rifampin was administered, for both R-warfarin (25% reduction; P < 0.001) and S-warfarin (15% reduction; P < 0.05). No differences were seen in the area under the international normalized ratio (INR)-time curve. Our study suggests that hepatic uptake via OATPs may not be clinically important in the pharmacokinetics of warfarin.

Curative endoscopic resection is now a viable option for a range of neoplastic lesions of the gastrointestinal tract (GIT) with low invasive potential. Risk of lymph node metastasis is the most important prognostic factor in selecting appropriate lesions for endoscopic therapy, and assessment of invasion depth is vital in this respect. To determine appropriate treatment, detailed endoscopic diagnosis and estimation of depth using magnifying chromoendoscopy is the gold standard in Japan. En bloc resection is the most desirable endoscopic therapy as risk of local recurrence is low and accurate histological diagnosis of invasion depth is possible. Endoscopic mucosal resection is established worldwide for the ablation of early neoplasms, but en bloc removal using this technique is limited to small lesions. Evidence suggests that a piecemeal resection technique has a higher local recurrence risk, therefore necessitating repeated surveillance endoscopy and further therapy. More advanced endoscopic techniques developed in Japan allow effective en bloc removal of early GIT neoplasms, regardless of size. This review discusses assessment of GIT lesions and options for endoscopic therapy with special reference to the introduction of endoscopic submucosal dissection into Western countries.