Inadequate dosing is common among CKD patients and it has been associated with treatment inefficacy, viral resistance and organ toxicity . HIV . Nowadays, life expectancy of highly educated PLWH treated chronically with combined ART has reached that of the uninfected counterpart . The aging PLWH are therefore at risk for several age-related diseases including chronic kidney disease (CKD) . Besides aging, several risk factors such as viral infection itself, ART, HIV-related comorbidities (e.g., diabetes mellitus, cardiovascular disease), coinfection (Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), tuberculosis) and polypharmacy impact significantly on the development of kidney disease in this vulnerable population. CKD is a relentlessly progressive disease that may evolve toward end-stage renal disease (ESRD). It contributes to poor quality of life and increases mortality of all affected subjects because it is associated with increased risk of cardiovascular disease, dyslipidemia, cognitive decline and bone disorderscomorbidities commonly found in PLWH, irrespective of their renal function . Hence, superimposition of renal impairment on a complex disease Tyk2-IN-8 such as HIV infection tends to increase the burden of comorbidities and, theoretically, predicts a worse outcome in this population. The best strategy to counteract the risk of CKD is based on prevention and early recognition of renal dysfunction as well as early initiation of ART in order to prevent long-lasting viral replication, which in turn is Tyk2-IN-8 responsible for potential kidney damage . The aim of this review is to provide a descriptive overview of the current understanding of CKD in the setting of HIV infection, focusing on prevalence, presentation, pathogenesis and treatment. Description of collateral issues such as comorbidities, coinfection and polypharmacy in PLWH who experienced CKD is out of the scope of this review. 2. Epidemiology of CKD in the Setting of HIV Infection The measure of incidence and prevalence of CKD in the setting of HIV infection varies across geographic areas with large differences also within the same continent. Variability depends on a series of multiple factors such as methods to evaluate renal function, CKD definition, genetic heterogeneity, prevention program, access to health care system and initiation of combined ART. The first obstacle to overcome is the correct assessment of renal function since none of the methods used to estimated glomerular filtration rate (eGFR) have been validated in PLWH. The most widely used serum creatinine-based GFR estimating equations tend to be inaccurate in PLWH . The major pitfall is the measurement of serum creatinine since it does not reflect true renal function in individuals with loss of lean body mass and malnutrition. Even cystatin C, an alternative marker of kidney function not-related to lean muscle mass, needs further studies before to be used in this population because it Rabbit Polyclonal to ALDH1A2 is influenced by HIV replication . In addition, as in noninfected patients, it is unclear whether age-related decline in GFR reflects or not a physiologic process in this subset of population. Nuclear medicine method using 99mTc DTPA plasma clearance is the gold standard for GFR assessment, but it is impractical in resource-limited countries. In these settings, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) or Cockcroft?Gault (CG) based eGFRs result in the most practical and economical methods to asses renal function. The estimated prevalence of CKD in HIV populationmeasured using CKD-EPI equation ranges from 2.5 % in Europe to 7.4% in North America . If we consider that 36.9 million of people are currently living with HIV worldwide , CKD represents a challenging problem with enormous implications for the national health care systems, probably not destined to be managed effectively in the next years given that the prevalence of CKD is expected to increase in this population . PLWH have a slightly higher risk of developing CKD than HIV-uninfected subjects, but once CKD has commenced, the likelihood of developing ESRD is 2- to 20-fold greater compared to the uninfected counterpart [11,12]. The increased susceptibility is given by the combination of both traditional and HIV-specific risk factors for kidney disease. The first ones, Tyk2-IN-8 commonly encountered in general population, include age, hypertension and diabetes . The second are HIV replication, AIDS status, hepatitis B and C coinfection, low CD4 nadir, lipodystrophy and ART [10,14,15,16]. In a recent paper, Althoff et al. Tyk2-IN-8  elegantly estimated the population attributable fractions of preventable or modifiable HIV-related (CD4+ T-cell count and viral load) and traditional risk factors for several conditions including ESRD. The findings of this study showed that a substantial proportion of cases of ESRD could be prevented.