Chronic kidney disease (CKD) is common among the elderly. However, little is known about how the clinical implications of CKD vary with age. We examined the age-specific incidence of death, treated end-stage renal disease (ESRD), and change in estimated glomerular filtration rate (eGFR) among 209,622 US veterans with CKD stages 3 to 5 followed for a mean of 3.2 years. Patients aged 75 years or older at baseline comprised 47% of the overall cohort and accounted for 28% of the 9227 cases of ESRD that occurred during follow-up. Among patients of all ages, rates of both death and ESRD were inversely related to eGFR at baseline. However, among those with comparable levels of eGFR, older patients had higher rates of death and lower rates of ESRD than younger patients. Consequently, the level of eGFR below which the risk of ESRD exceeded the risk of death varied by age, ranging from 45 ml/min per 1.73 m 2 for 18 to 44 year old patients to 15 ml/min per 1.73 m 2 for 65 to 84 year old patients. Among those 85 years or older, the risk of death always exceeded the risk of ESRD in this cohort. Among patients with eGFR levels Ͻ45 ml/min per 1.73 m 2 at baseline, older patients were less likely than their younger counterparts to experience an annual decline in eGFR of Ͼ3 ml/min per 1.73 m 2 . In conclusion, age is a major effect modifier among patients with an eGFR of Ͻ60 ml/min per 1.73 m 2 , challenging us to move beyond a uniform stage-based approach to managing CKD. 18: 275818: -276518: , 200718: . doi: 10.1681 Chronic kidney disease (CKD) is common in the elderly, 1,2 leading some professional organizations to recommend routine age-based screening for CKD in the primary care setting 3 ; however, relatively little is known about the clinical course of CKD in older individuals. Most previous studies of CKD and current recommendations for its management have not distinguished between patients of different ages, and efforts to identify risk factors for progression of CKD have generally focused on patient characteristics other than age. 4 -17 We hypothesized that the frequency of clinically significant outcomes among patients who meet National Kidney Foundation criteria for stages 3 to 5 CKD would differ substantially across age groups. We tested this hypothesis among a national cohort J Am Soc Nephrol

Objective Despite widespread highly active antiretroviral therapy use, HIV disease remains associated with increased risk of kidney disease. Whether tenofovir use is associated with higher risk of kidney disease is controversial. Design We evaluated the association of cumulative and ever exposure to tenofovir on kidney outcomes in 10,841 HIV-infected patients from the Veterans Health Administration who initiated antiretroviral therapy from 1997-2007. Methods Cox proportional hazards and marginal structural models evaluated associations between tenofovir and time to first occurrence of 1) proteinuria (two consecutive urine dipstick measurements ≥30mg/dL), 2) rapid decline in kidney function (≥3ml/min/1.73m2 annual decline), and 3) CKD (estimated glomerular filtration rate <60ml/min/1.73m2). Results Median follow-up ranged from 3.9 years (proteinuria) to 5.5 years (CKD), during which 3400 proteinuria, 3078 rapid decline, and 533 CKD events occurred. After multivariable adjustment, each year of exposure to tenofovir was associated with 34% increased risk of proteinuria (95%CI 25-45%, p<0.0001), 11% increased risk of rapid decline (3-18%, p=0.0033), and 33% increased risk of CKD (18-51%; p<0.0001). Pre-existing renal risk factors did not appear to worsen the effects of tenofovir. Other ARVs showed weaker or inconsistent associations with kidney disease events. Among those who discontinued tenofovir use, risk of kidney disease events did not appear to decrease during follow-up. Conclusions Tenofovir exposure was independently associated with increased risk for three types of kidney disease events, and did not appear to be reversible. Because subtle kidney function decline affects long-term morbidity and mortality, the balance between efficacy and probable adverse effects requires further study.

Objective To determine the association of inflammatory markers, fibrinogen and C-reactive protein (CRP), with 5-year mortality risk. Methods Vital status was ascertained in 922 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. Multivariable logistic regression estimated odds ratios (OR) after adjustment for demographic, cardiovascular and HIV-related factors. Results Over a 5-year period, HIV-infected participants with fibrinogen levels in the highest tertile(>406mg/dL) had 2.6-fold higher adjusted odds of death than those with fibrinogen in the lowest tertile(<319mg/dL). Those with high CRP(>3mg/L) had 2.7-fold higher adjusted odds of death than those with CRP<1mg/L. When stratified by CD4 count category, fibrinogen (as a linear variable) remained independently associated [OR(95% confidence intervals) per 100mg/dL increase in fibrinogen: 1.93(1.57,2.37);1.43(1.14,1.79);1.43(1.14,1.81);and 1.30(1.04,1.63) for CD4 <200,200–350,>350–500, and >500cells/μL, respectively. Higher CRP also remained associated with higher odds of death overall and within each CD4 subgroup. Conclusion Fibrinogen and CRP are strong and independent predictors of mortality in HIV-infected adults. Our findings suggest that even in those with relatively preserved CD4 counts >500cells/μL, inflammation remains an important risk factor for mortality. Further investigation should determine whether interventions to reduce inflammation might decrease mortality risk in HIV-infected individuals.