TY - JOUR
T1 - Predictors of atrasentan-associated fluid retention and change in albuminuria in patients with diabetic nephropathy
AU - Kohan, Donald E.
AU - Heerspink, Hiddo J Lambers
AU - Coll, Blai
AU - Andress, Dennis
AU - Brennan, John J.
AU - Kitzman, Dalane W.
AU - Correa-Rotter, Ricardo
AU - Makino, Hirofumi
AU - Perkovic, Vlado
AU - Hou, Fan Fan
AU - Remuzzi, Giuseppe
AU - Tobe, Sheldon W.
AU - Toto, Robert
AU - Parving, Hans Henrik
AU - De Zeeuw, Dick
N1 - Publisher Copyright:
© 2015 by the American Society of Nephrology.
PY - 2015/9/4
Y1 - 2015/9/4
N2 - Background and objectives Endothelin A receptor antagonists (ERAs) decrease residual albuminuria in patients with diabetic kidney disease; however, their clinical utility may be limited by fluid retention. Consequently, the primary objective of this study was to identify predictors for ERA-induced fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs. Design, setting, participants, &measurements A post hoc analysis was conducted of the phase IIb atrasentan trials assessing albuminuria reduction in 211 patientswith type 2 diabetes, urine albumin/creatinine ratios of 300–3500 mg/g, and eGFRs of 30–75 ml/min per 1.73 m2 who were randomly assigned to receive placebo (n=50) or atrasentan 0.75 mg/d (n=78) or 1.25 mg/d (n=83) for 12 weeks. Changes in body weight and hemoglobin (Hb) after 2 weeks of treatment were used as surrogate markers of fluid retention. Results Baseline predictors of weight gain after 2 weeks of atrasentan treatment were higher atrasentan dose, lower eGFR, higher glycated hemoglobin, higher systolic BP, and lower homeostatic metabolic assessment product. Higher atrasentan dose and lower eGFR also predicted decreases inHb. There were no changes in B-type natriuretic peptide. There was no correlation between reduction in albuminuria after 2 weeks of atrasentan treatment and changes in body weight or Hb. Conclusions In the Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan/JAPAN trials, atrasentan-associated fluid retention was more likely in patients with diabetes and nephropathy who had lower eGFR or received a higher dose of atrasentan. Finding that albuminuria reduction was not associated with changes in body weight and Hb suggests that the albuminuria-reducing efficacy of atrasentan is not impaired by fluid retention.
AB - Background and objectives Endothelin A receptor antagonists (ERAs) decrease residual albuminuria in patients with diabetic kidney disease; however, their clinical utility may be limited by fluid retention. Consequently, the primary objective of this study was to identify predictors for ERA-induced fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs. Design, setting, participants, &measurements A post hoc analysis was conducted of the phase IIb atrasentan trials assessing albuminuria reduction in 211 patientswith type 2 diabetes, urine albumin/creatinine ratios of 300–3500 mg/g, and eGFRs of 30–75 ml/min per 1.73 m2 who were randomly assigned to receive placebo (n=50) or atrasentan 0.75 mg/d (n=78) or 1.25 mg/d (n=83) for 12 weeks. Changes in body weight and hemoglobin (Hb) after 2 weeks of treatment were used as surrogate markers of fluid retention. Results Baseline predictors of weight gain after 2 weeks of atrasentan treatment were higher atrasentan dose, lower eGFR, higher glycated hemoglobin, higher systolic BP, and lower homeostatic metabolic assessment product. Higher atrasentan dose and lower eGFR also predicted decreases inHb. There were no changes in B-type natriuretic peptide. There was no correlation between reduction in albuminuria after 2 weeks of atrasentan treatment and changes in body weight or Hb. Conclusions In the Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan/JAPAN trials, atrasentan-associated fluid retention was more likely in patients with diabetes and nephropathy who had lower eGFR or received a higher dose of atrasentan. Finding that albuminuria reduction was not associated with changes in body weight and Hb suggests that the albuminuria-reducing efficacy of atrasentan is not impaired by fluid retention.
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U2 - 10.2215/CJN.00570115
DO - 10.2215/CJN.00570115
M3 - Article
C2 - 26153128
AN - SCOPUS:84941205359
SN - 1555-9041
VL - 10
SP - 1568
EP - 1574
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 9
ER -