Current HIV treatment guidelines recommend using the Cockcroft–Gault equation for drug dosing adjustments. The use of newer glomerular filtration rate (GFR) estimating equations for drug dosing and the appropriateness of physician antiretroviral dosing based on estimated kidney function have not been studied in an HIV-positive population.
Methods
We evaluated concordance between measured and estimated GFR for the assignment of kidney function categories designated by the US Food and Drug Administration (FDA) Guidance for industry for pharmacokinetic studies, and appropriateness of physician antiretroviral drug dosing for level of kidney function in 200 HIV-positive patients on stable antiretroviral therapy. Estimated kidney function was determined using the Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study and Cockcroft–Gault equations.
Results
For assignment of FDA-designated kidney function categories, concordance rates between measured and estimated GFR using the CKD-EPI, MDRD Study and Cockcroft–Gault equations were 79%, 71% and 77%, respectively. This pattern was consistent across most subgroups. When actual prescribed dosages were compared with recommended dosages based on the level of estimated kidney function, 3–19% of study participants were prescribed higher than recommended dosages. The largest discordance between prescribed and recommended dosages was observed for the Cockcroft–Gault equation.
Conclusions
The CKD-EPI equation has the highest concordance with measured GFR for the assignment of FDA-designated kidney function categories. Its use may lead to lower dosing-related errors in HIV-infected US adults on stable antiretroviral therapy. More education is required with respect to dose adjustment for level of kidney function.
References
1.
FlandreP., PuglieseP., CuzinL.Risk factors of chronic kidney disease in HIV-infected patients. Clin J Am Soc Nephrol2011; 6: 1700–1707.
2.
NaftalinC., NathanB., HamzahL., PostF.A.HIV-associated kidney disease in the context of an aging population. Sex Health2011; 8: 485–492.
3.
EstrellaM.M., ParekhR.S., AstorB.C.Chronic kidney disease and estimates of kidney function in HIV infection: a cross-sectional study in the multicenter AIDS cohort study. J Acquir Immune Defic Syndr2011; 57: 380–386.
4.
FernandoS.K., FinkelsteinF.O., MooreB.A., WeissmanS.Prevalence of chronic kidney disease in an urban HIV infected population. Am J Med Sci2008; 335: 89–94.
5.
LeveyA.S., StevensL.A., SchmidC.H.A new equation to estimate glomerular filtration rate. Ann Intern Med2009; 150: 604–612.
6.
Panel on Antiretroviral Guidelines for Adults and Adolescents.Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.Department of Health and Human Services. (Updated 14 October 2011. Accessed 25 March 2012.) Available from http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
7.
GuptaS.K., EustaceJ.A., WinstonJ.A.Guidelines for the management of chronic kidney disease in HIV-infected patients: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis2005; 40: 1559–1585.
8.
AbergJ.A., KaplanJ.E., LibmanH.Primary care guidelines for the management of persons infected with human immunodeficiency virus: 2009 update by the HIV medicine Association of the Infectious Diseases Society of America. Clin Infect Dis2009; 49: 651–681.
9.
LeveyA.S., CoreshJ., GreeneT.Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med2006; 145: 247–254.
10.
CockcroftD.W., GaultM.H.Prediction of creatinine clearance from serum creatinine. Nephron1976; 16: 31–41.
EarleyA., MiskulinD., LambE.J., LeveyA.S., UhligK.Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann Intern Med2012; 156: 785–795.
13.
StevensL.A., LeveyA.S.Use of the MDRD study equation to estimate kidney function for drug dosing. Clin Pharmacol Ther2009; 86: 465–467.
14.
MatzkeG.R., AronoffG.R., AtkinsonA.J.Jr.Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int2011; 80: 1122–1137.
15.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group.KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl2013; 3: 1–150.
16.
StevensL.A., NolinT.D., RichardsonM.M.Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations. Am J Kidney Dis2009; 54: 33–42.
17.
StöhrW., WalkerA.S., MunderiP.Estimating glomerular filtration rate in HIV-infected adults in Africa: comparison of Cockcroft-Gault and Modification of Diet in Renal Disease formulae. Antivir Ther2008; 13: 761–770.
18.
BarracloughK., ErL., NgF.A comparison of the predictive performance of different methods of kidney function estimation in a well-characterized HIV-infected population. Nephron Clin Pract2009; 111: c39–c48.
19.
BeringerP.M., OwensH., NguyenA.Estimation of glomerular filtration rate by using serum cystatin C and serum creatinine concentrations in patients with human immunodeficiency virus. Pharmacotherapy2010; 30: 1004–1010.
20.
BonjochA., BayesB., RibaJ.Validation of estimated renal function measurements compared with the isotopic glomerular filtration rate in an HIV-infected cohort. Antiviral Res2010; 88: 347–354.
21.
VrouenraetsS.M., FuxC.A., WitF.W.A comparison of measured and estimated glomerular filtration rate in successfully treated HIV-patients with preserved renal function. Clin Nephrol2012; 77: 311–320.
22.
PraditpornsilpaK., AvihingsanonA., ChaiwatanaratT.Comparisons between validated estimated glomerular filtration rate equations and isotopic glomerular filtration rate in HIV patients. AIDS2012; 26: 1781–1788.
23.
InkerL.A., WyattC., CreamerR.Performance of creatinine and cystatin C GFR estimating equations in an HIV-positive population on antiretrovirals. J Acquir Immune Defic Syndr2012; 61: 302–309.
24.
SchwartzG.J., FurthS., ColeS.R., WaradyB., MunozA.Glomerular filtration rate via plasma iohexol disappearance: pilot study for chronic kidney disease in children. Kidney Int2006; 69: 2070–2077.
25.
StevensL.A., LeveyA.S.Measured GFR as a confirmatory test for estimated GFR. J Am Soc Nephrol2009; 20: 2305–2313.
26.
Bröchner-MortensenJ.A simple method for the determination of glomerular filtration rate. Scand J Clin Lab Invest1972; 30: 271–274.
StevensL.A., CoreshJ., FeldmanH.I.Evaluation of the modification of diet in renal disease study equation in a large diverse population. J Am Soc Nephrol2007; 18: 2749–2757.
30.
CoreshJ., StevensL.A.Kidney function estimating equations: where do we stand?Curr Opin Nephrol Hypertens2006; 15: 276–284.
31.
GolikM.V., LawrenceK.R.Comparison of dosing recommendations for antimicrobial drugs based on two methods for assessing kidney function: Cockcroft-Gault and modification of diet in renal disease. Pharmacotherapy2008; 28: 1125–1132.
32.
HealyM.F., SperoniK.G., EugenioK.R., MurphyP.M.Adjusting eptifibatide doses for renal impairment: a model of dosing agreement among various methods of estimating creatinine clearance. Ann Pharmacother2012; 46: 477–483.
33.
McFarlandM.S., MarkleyB.M., ZhangP., HudsonJ.Q.Evaluation of Modification of Diet in Renal Disease study and Cockcroft-Gault equations for sitagliptin dosing. J Nephrol2012; 25: 515–522.
34.
HermsenE.D., MaiefskiM., FlorescuM.C., QiuF., RuppM.E.Comparison of the Modification of Diet in Renal Disease and Cockcroft-Gault equations for dosing antimicrobials. Pharmacotherapy2009; 29: 649–655.
35.
de LemosM.L., HsiehT., HamataL.Evaluation of predictive formulae for glomerular filtration rate for carboplatin dosing in gynecological malignancies. Gynecol Oncol2006; 103: 1063–1069.
36.
BookstaverP.B., JohnsonJ.W., McCoyT.P., StewartD., WilliamsonJ.C.Modification of Diet in Renal Disease and modified Cockcroft-Gault formulas in predicting aminoglycoside elimination. Ann Pharmacother2008; 42: 1758–1765.
37.
WargoK.A., EilandE.H.III, HammW., EnglishT.M., PhillippeH.M.Comparison of the modification of diet in renal disease and Cockcroft-Gault equations for antimicrobial dosage adjustments. Ann Pharmacother2006; 40: 1248–1253.
38.
GillJ., MalyukR., DjurdjevO., LevinA.Use of GFR equations to adjust drug doses in an elderly multi-ethnic group–a cautionary tale. Nephrol Dial Transplant2007; 22: 2894–2899.
39.
MelloniC., PetersonE.D., ChenA.Y.Cockcroft-Gault versus modification of diet in renal disease: importance of glomerular filtration rate formula for classification of chronic kidney disease in patients with non-ST-segment elevation acute coronary syndromes. J Am Coll Cardiol2008; 51: 991–996.
40.
MoranvilleM.P., JenningsH.R.Implications of using modification of diet in renal disease versus Cockcroft-Gault equations for renal dosing adjustments. Am J Health Syst Pharm2009; 66: 154–161.
StevensL.A., SchmidC.H., GreeneT.Comparative performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study equations for estimating GFR levels above 60 mL/min/1.73 m2. Am J Kidney Dis2010; 56: 486–495.
43.
InkerL.A., SchmidC.H., TighiouartH.Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C. N Engl J Med2012; 367: 20–29.
