title: A comparison of iothalamate-GFR and serum creatinine-based outcomes: acceleration in the rate of GFR decline in the African American Study of Kidney Disease and Hypertension.
abstract: In renal clinical trials, both slope-based and time-to-event renal outcomes have been used. These outcomes are typically based on estimates of GFR obtained using creatinine or iothalamate GFR (iGFR). The African American Study of Kidney Disease and Hypertension (AASK) was a trial in 1094 African Americans with hypertensive nephrosclerosis, which examined the effects of two levels of BP control and three antihypertensive regimens. This study compared the effects of the AASK interventions on outcomes based on serum creatinine with corresponding outcomes based on iGFR using 9742 matched pairs of iGFR and serum creatinine measurements. The iGFR-based outcomes included (1) a time-to-event composite outcome including a 50% GFR decline, ESRD, or death; (2) a composite outcome including a 50% GFR decline or ESRD; (3) mean decline in GFR in the first 3 mo after randomization (acute slope); (4) mean decline in GFR starting 3 mo after randomization (chronic slope); and (5) mean decline in GFR from baseline (total slope). The corresponding creatinine-based outcomes were (1) a composite of doubling of serum creatinine, ESRD, or death and (2) a composite of doubling of serum creatinine or ESRD and acute, chronic, and total slopes defined by the mean change in estimated GFR (eGFR), where eGFR was estimated from a regression equation for GFR depending primarily on serum creatinine and developed in AASK enrollees. Mean changes in iGFR and eGFR were also compared under extended models that allowed for the possibility that the rate of GFR decline may change over time during the chronic phase. an apparent acceleration in rate of decline of renal function over time was found. Subtle differences were observed between effects of the interventions on some of the creatinine and iGFR slope-based outcomes, but the main conclusions of the trial were similar for the serum creatinine and iothalamate-based measurements. This has important implications for the design of clinical trials with renal outcomes.
authors.affiliation: Nephrology Clinical Trials Center, Vanderbilt University Medical Center, 1211 21st Avenue South, 215 Medical Arts Building, Nashville, TN 37232-1371, USA. julia.lewis@vanderbilt.edu
authors.forename: Julia
authors.initials: J
authors.lastname: Lewis
authors.forename: Tom
authors.initials: T
authors.lastname: Greene
authors.forename: Lawrence
authors.initials: L
authors.lastname: Appel
authors.forename: Gabriel
authors.initials: G
authors.lastname: Contreras
authors.forename: Janice
authors.initials: J
authors.lastname: Douglas
authors.forename: Jim
authors.initials: J
authors.lastname: Lash
authors.forename: Robert
authors.initials: R
authors.lastname: Toto
authors.forename: Fredrick
authors.initials: F
authors.lastname: Van Lente
authors.forename: Xuelei
authors.initials: X
authors.lastname: Wang
authors.forename: Jackson T
authors.initials: JT
authors.lastname: Wright
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data*; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use; D003287:Contrast Media / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006977:Hypertension, Renal / Q000175:diagnosis* / Q000188:drug therapy / Q000208:ethnology; D007457:Iodine Radioisotopes; D007483:Iothalamic Acid / Q000008:administration & dosage; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000208:ethnology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics
chemical_list: D000959:Antihypertensive Agents; D003287:Contrast Media; D007457:Iodine Radioisotopes; D007483:Iothalamic Acid; D003404:Creatinine