{'fraction_non_alphanumeric': 0.04255819421584764, 'fraction_numerical': 0.014577944980014107, 'mean_word_length': 5.129682997118156, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 2, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 3, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Chronic Kidney Disease in the Aging Human Immunodeficiency Virus-Infected Population.

In this issue of The Journal of Infectious Diseases, Kooji and colleagues report on the prevalence of chronic kidney disease (CKD) in a prospective, longitudinal cohort of 598 human immunodeficiency virus–infected (HIV+) individuals, with a median age of 45 years [1]. This carefully performed study has deepened our understanding of kidney disease among middle-aged HIV+ subjects with longterm exposure to antiviral therapy, having a median duration of therapy of 10 years. The principal renal findings in the HIV+ cohort, compared to an age-matched human immunodeficiency virus–uninfected (HIV–) cohort, were increased rates of tubular dysfunction (odds ratio [OR], 7); albuminuria, defined as urine albumin/creatinine ratio >3 mg/mmol (equivalent to 27 mg/g) (OR, 6); and reduced estimated glomerular filtration rate (eGFR)–creatinine (OR, 2). The study had 3 principal renal outcomes: CKD, albuminuria, and proximal tubular dysfunction. CKD was defined as eGFR <60 mL/minute/1.73 m2, based on serum creatinine. Serum creatinine is chiefly influenced by muscle mass and by glomerular filtration rate; to the extent that some HIV+ individuals may have reduced muscle mass, this would tend to underestimate the prevalence of CKD. In multivariable analysis, variables significantly associated with baseline CKD included only age. Associations with baseline albuminuria were adjusted for diabetes, hypertension, dyslipidemia, and smoking; variables that remained significant included age, current smoking, use of hypertensive drugs, systolic blood pressure, diabetes, nadir body weight, and soluble CD14 (a lipopolysaccharide receptor expressed mainly on macrophages that is a marker for macrophage activation). The authors point out that chronic inflammation, present even when HIV replication is suppressed, is present and is a likely driver of CKD in this population. Nevertheless, at baseline, markers of inflammation were not different between those who had reduced eGFR and those who had normal eGFR. Associations with baseline proximal tubular dysfunction (defined as increased urine retinol binding protein and increased fractional excretion of phosphate) included age, smoking, cardiovascular disease, nadir body weight, protease inhibitor use, and, most strongly of all, cumulative tenofovir disoproxil fumarate (TDF) use. The study offers a longitudinal perspective regarding the effects of HIV infection on the aging kidney. Over a median of 4 years of follow-up, the HIV+ group (n = 377) manifested faster GFR decline (a difference of –0.56 mL/minute/year) and worsening albuminuria compared to the HIV– group (n = 479). Rapid GFR decline, defined as >5 mL/ minute/1.73 m2/year, was more common among HIV+ individuals (5.8%) vs controls (2.3%). Interestingly, baseline albuminuria predicted faster eGFR decline in the controls, but not the HIV+ group. One hypothesis might be that albuminuria in HIV disease involves glomerular disease in some subjects and tubular disease in others (as well as metabolic syndrome in still others, as discussed below), and it is glomerular disease that is most likely to progress, resulting in falling eGFR. Current atazanavir use (but not TDF use) and duration of prolonged T-cell lymphopenia also correlated with GFR decline. The study has several important strengths. The cohorts were of sufficient size (596 HIV+ and 544 HIV– subjects) to provide reasonable power. The longitudinal design provides insight into progression of CKD. The study also has certain limitations. Although the disease and control cohorts were generally well matched, there was an excess of individuals of African descent (14% vs 6%), current smokers (32% vs 25%), and hypertensive subjects (50% vs 37%) in the HIV+ group. All 3 factors are associated with an increased risk for CKD. By contrast, the rate of diabetes mellitus was similar (7% vs 5%) between the groups. The authors do not present data on the fraction of each subgroup that had albuminuria and/or reduced GFR at the end of the study. Studies from several large cohorts have documented increased rates of CKD in the setting of HIV infection; E D I T O R I A L C O M M E N T A R Y