Probability of developing CKD in the next five years in HIV-positive patients who take or do not take tenofovir.
Measured Factor Detail
Patients with HIV are at an increased risk of developing CKD, especially when they take Tenofovir. Other factors that increase CKD risk include advanced age, diabetes or uncontrolled blood glucose, hypertension, proteinuria, and medications that may cause renal damage. Renal function decreases with age. Diabetes (for which blood glucose is a measure) is the leading cause of CKD and end-stage renal disease (ESRD) as it causes hyperfiltration injury, advanced glycosylation end products, and reactive oxygen species. Hypertension (for which systolic BP is a surrogate marker) causes increased intraglomerular capillary pressure that leads to glomerulosclerosis and loss of kidney function. Proteinuria is a marker of CKD. Tenofovir is an antiretroviral drug that can cause proximal tubular damage and chronic tubular damage.
Infectious Disease Specialist
Measured Factor Low Impact
- Lower value means lower chance of patient getting CKD in the next five years. Thus, if the patient has lower chance, then he/she may be a good candidate for tenofovir antiretroviral drug regimen.
Measured Factor High Impact
- Higher than normal values means that patient has higher chance of developing CKD in the next five years, and therefore, may not be a good candidate for tenofovir antiretroviral drug regimen.
- Critical High: ≥ 9 points (21.4% rate of CKD within 5 years)
- Normal: 0 point (0.5% rate of CKD within 5 years)
- Normal Adult Male: 0 point (0.5% rate of CKD within 5 years)
- Normal Adult Female: 0 point (0.5% rate of CKD within 5 years)
- Normal Geriatric Male: 6 points (5.1% rate of CKD within 5 years)
- Normal Geriatric Female: 6 points (5.1% rate of CKD within 5 years)
This calculator was primarily designed for treatment naive patients who have not yet tried multiple antiretroviral regimens, which is not too easily generalizable to the general public. Additionally, factors such as intravenous drug use, hepatitis C coinfection, lower baseline eGFR, also influence CKD risk in HIV positive patients, but they are not included in this calculator.
Study Validation 1
Woolnough et al. conducted a retrospective cohort study from 2008 to 2016 in HIV positive patients with estimated glomerular filtration rate (eGFR) >60mL/min, excluding those with chronic kidney disease (CKD) prior to the study. The goal of their study was to test the validity and accuracy of two CKD risk scores for HIV positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) and the Scherzer risk scores. Progression to CKD was defined by Woolnough et al. as two consequent eGFR measurements of less than 60 ml/min within 90 days of each other, which is a diagnostic standard. 5% of the 748 patients enrolled progressed to CKD within a median of 4.7 years. Risk factors associated with the development of CKD in these patients included: older age, diabetes, proteinuria, higher baseline creatinine, lower eGFR, longer known duration of HIV infection, and lower nadir CD4+ cell count. Those with the strongest association with CKD development are older age (odds ratio (OR) 3.03, 95% confidence interval (CI): 1.20, 7.65; p= 0.02) and lower baseline eGFR (OR 0.39, 95% CI: 4.73, 22.83; p< 0.001). The authors concluded that those of advanced age and with lower eGFR have a higher risk of progressing to CKD. They concluded additionally, that tenofovir exposure alone was not associated with a higher risk of developing CKD but may influence patient progression with other factors. The D:A:D score performed better than the score developed by Scherzer et al (short D:A:D area under the receiver operator curve (AUROC) 0.85, Scherzer AUROC 0.78, P = 0.02). Woolnough et al. suggest that the Scherzer score may not be as robust as the D:A:D score, but is useful in treatment naive patients. The authors recommend both scores be used more often to help guide clinicians treating this at-risk patient population.
Study Additional 1
This study derived a scoring system to predict 5-year risk of developing chronic kidney disease (CKD) in HIV-infected individuals and estimated the risk associated with Tenofovir use. Scherzer R et al. analyzed data of 21,590 HIV-infected US male veterans initiating antiretroviral therapy from1997 to 2010 in order to compose their chronic kidney disease (CKD) risk score. Patients with preexisting renal dysfunction or baseline estimated glomerular filtration rate (eGFR) <60ml/min were excluded from the analysis. The primary outcome of their study was time to first eGFR <60ml/min which was calculated using using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula based on age, sex, race and serum creatinine. This is a clinically relevant as two eGFRs of less than 60ml/min within 3 months of each other defines CKD. The authors created their risk score calculator and found that tenofovir treatment increased CKD risk. The 5-year risk of developing CKD rate was 7.7% in Tenofovir users and 3.8% in Tenofovir nonusers (overall adjusted hazard ratio 2.0, 95% confidence interval (CI) 1.8-2.2). There was a progressive increase in 5-year CKD risk, ranging from less than 1% to 16% in Tenofovir nonusers, and from 1.4% to 21.4% inTenofovir users. Scherzer et al. conclude their risk score is a useful tool to facilitate clinical descion-making about Tenofovir use, although further analysis in different, more diverse patient populations is warranted.