A Randomized, Pilot Trial to Evaluate Glomerular Filtration Rate by Creatinine or Cystatin C in Naive HIV-Infected Patients After Tenofovir/Emtricitabine in Combination With Atazanavir/Ritonavir or Efavirenz

BackgroundGlomerular filtration rate (GFR) estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on creatinine or cystatine C may be more accurate methods especially in patients without chronic kidney disease. There is lack of data on GFR estimated by these methods in patients on highly active antiretroviral therapy. MethodsAntiretroviral-naive HIV-infected patients were randomized to tenofovir/emtricitabine in association with atazanavir/ritonavir (ATV/r) or efavirenz (EFV) Patients had to have an actual creatinine clearance >50 mL/minute (24-hour urine collection) and were followed for 48 weeks. ResultsNinety-one patients (48 ATV/r, 43 EFV) were recruited. Using the CKD-EPI creatinine formula, there was a significant decrease in GFR up to week 48 in patients receiving ATV/r (4.9 mL/minute/m2, P = 0.02) compared with a not statistically significant increment in patients prescribed EFV. Using the cystatin C–based equation, we found greater decrease in GFR in both arms, although, in the EFV arm, the decrease was not statistically significant (5.8 mL/minute/m2, P = 0.92). At multivariable analysis, ATV/r was a significant predictor of greater decrease in estimated glomerular filtration rate (eGFR) (P = 0.0046) only with CKD-EPI creatinine. ConclusionsATV/r plus tenofovir caused greater GFR decreases compared with EFV. The evaluation of eGFR by cystatin C confirmed this result, but this method seemed to be more stringent, probably precluding the possibility to detect a significant difference in the pattern of eGFR evolution between the two arms over time. More studies are needed to understand the clinical relevance of these alterations and whether cystatin C is a more appropriate method for monitoring GFR in clinical practice.

[1]  M. Moroni,et al.  Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons. Update 2011. , 2011, The new microbiologica.

[2]  J. George,et al.  A comparison of cystatin C- and creatinine-based prediction equations for the estimation of glomerular filtration rate in black South Africans. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[3]  D. Katzenstein,et al.  Atazanavir Plus Ritonavir or Efavirenz as Part of a 3-Drug Regimen for Initial Treatment of HIV-1 , 2011, Annals of Internal Medicine.

[4]  M. Moroni,et al.  Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons. , 2011, The new microbiologica.

[5]  Christopher H Schmid,et al.  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. , 2010, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[6]  V. Soriano,et al.  Renal toxicity associated with tenofovir use , 2010, Expert opinion on drug safety.

[7]  D. Jacobs,et al.  Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. , 2010, The Journal of infectious diseases.

[8]  B. Astor,et al.  Risk implications of the new CKD Epidemiology Collaboration (CKD-EPI) equation compared with the MDRD Study equation for estimated GFR: the Atherosclerosis Risk in Communities (ARIC) Study. , 2010, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[9]  Amalio Telenti,et al.  Antiretroviral Treatment of Adult HIV Infection2010 Recommendations of the International AIDS Society–USA Panel , 2010 .

[10]  D. Fine,et al.  Screening for chronic kidney disease in HIV-infected patients. , 2010, Advances in chronic kidney disease.

[11]  Richard D Moore,et al.  Renal function with use of a tenofovir-containing initial antiretroviral regimen , 2009, AIDS.

[12]  V. Soriano,et al.  Predictors of kidney tubular dysfunction in HIV-infected patients treated with tenofovir: a pharmacogenetic study. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[13]  C. Schmid,et al.  A new equation to estimate glomerular filtration rate. , 2009, Annals of internal medicine.

[14]  Christopher H Schmid,et al.  Factors other than glomerular filtration rate affect serum cystatin C levels. , 2009, Kidney international.

[15]  A. Levin,et al.  A Comparison of the Predictive Performance of Different Methods of Kidney Function Estimation in a Well-Characterized HIV-Infected Population , 2008, Nephron Clinical Practice.

[16]  M. Shlipak,et al.  Association of kidney function with inflammatory and procoagulant markers in a diverse cohort: A cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA) , 2008, BMC nephrology.

[17]  C. Schmid,et al.  Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. , 2008, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[18]  C. Aquilante,et al.  The Effect of Lopinavir/Ritonavir on the Renal Clearance of Tenofovir in HIV‐infected Patients , 2008, Clinical pharmacology and therapeutics.

[19]  R. Haubrich,et al.  Greater tenofovir-associated renal function decline with protease inhibitor-based versus nonnucleoside reverse-transcriptase inhibitor-based therapy. , 2008, The Journal of infectious diseases.

[20]  S. Sidney,et al.  Cystatin C level as a marker of kidney function in human immunodeficiency virus infection: the FRAM study. , 2007, Archives of internal medicine.

[21]  H. Furrer,et al.  Tenofovir Use is associated with a Reduction in Calculated Glomerular Filtration Rates in the Swiss HIV Cohort Study , 2007, Antiviral therapy.

[22]  Tom Greene,et al.  Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. , 2007, Clinical chemistry.

[23]  P. Sax,et al.  Renal safety of tenofovir disoproxil fumarate. , 2007, The AIDS reader.

[24]  R. Ebrahimi,et al.  Pharmacokinetics and Safety of Tenofovir Disoproxil Fumarate on Coadministration With Lopinavir/Ritonavir , 2006, Journal of acquired immune deficiency syndromes.

[25]  L. Stevens,et al.  Serum cystatin C as a marker of glomerular filtration rate , 2006, Current opinion in nephrology and hypertension.

[26]  Tom Greene,et al.  Using Standardized Serum Creatinine Values in the Modification of Diet in Renal Disease Study Equation for Estimating Glomerular Filtration Rate , 2006, Annals of Internal Medicine.

[27]  Tom Greene,et al.  Assessing kidney function--measured and estimated glomerular filtration rate. , 2006, The New England journal of medicine.

[28]  Mark R Wallace,et al.  Comparisons of Causes of Death and Mortality Rates Among HIV-Infected Persons: Analysis of the Pre-, Early, and Late HAART (Highly Active Antiretroviral Therapy) Eras , 2006, Journal of acquired immune deficiency syndromes.

[29]  Joel E Gallant,et al.  Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. , 2006, The New England journal of medicine.

[30]  B. Stilwell,et al.  Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. 2006 revision. , 2006 .

[31]  P. Hauptman,et al.  The natural history of renal function following orthotopic heart transplant , 2005, Clinical transplantation.

[32]  L. Stevens,et al.  Measurement of kidney function. , 2005, The Medical clinics of North America.

[33]  E. Daugas,et al.  HAART-related nephropathies in HIV-infected patients. , 2005, Kidney international.

[34]  K. Yaffe,et al.  Chronic kidney disease and cognitive impairment in menopausal women. , 2005, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[35]  G. Filler,et al.  Cystatin C as a marker of GFR--history, indications, and future research. , 2005, Clinical biochemistry.

[36]  T. Larson,et al.  Using Serum Creatinine To Estimate Glomerular Filtration Rate: Accuracy in Good Health and in Chronic Kidney Disease , 2004, Annals of Internal Medicine.

[37]  Joel E Gallant,et al.  Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial. , 2004, JAMA.

[38]  Davis Massey.  Commentary: Clinical diagnostic use of cystatin C , 2004, Journal of clinical laboratory analysis.

[39]  V. Dharnidharka,et al.  Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[40]  Kdoqi Disclaimer.  K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[41]  V. D’Agati,et al.  Renal epithelium is a previously unrecognized site of HIV-1 infection. , 2000, Journal of the American Society of Nephrology : JASN.

[42]  D. Kotler.  Nutritional Alterations Associated With HIV Infection , 2000, Journal of acquired immune deficiency syndromes.

[43]  D. Cocchetto,et al.  Decreased rate of creatinine production in patients with hepatic disease: implications for estimation of creatinine clearance. , 1983, Therapeutic drug monitoring.

[44]  M. H. Gault,et al.  Prediction of creatinine clearance from serum creatinine. , 1975, Nephron.

[45]  D. DuBois,et al.  A formula to estimate the approximate surface area if height and weight be known , 1989 .

[46]  D. D. Bois,et al.  CLINICAL CALORIMETRY: TENTH PAPER A FORMULA TO ESTIMATE THE APPROXIMATE SURFACE AREA IF HEIGHT AND WEIGHT BE KNOWN , 1916 .