Renal Dysfunction at 12 Months Is Not Associated with Everolimus Exposure in De Novo Renal Transplant Recipients.
1University of Utah, Salt Lake City, UT
2University of Southern California, Los Angeles, CA
3Barnabas Health, West Orange, NJ
4Novartis Pharmaceuticals Corporation, East Hanover, NJ
5California Pacific Medical Center, San Francisco, CA
6Vanderbilt University, Nashville, TN.
Meeting: 2016 American Transplant Congress
Abstract number: B135
Keywords: Glomerular filtration rate (GFR), Kidney transplantation, Renal dysfunction
Session Information
Session Name: Poster Session B: Drug Minimization
Session Type: Poster Session
Date: Sunday, June 12, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Renal dysfunction at 1 year post-transplantation is associated with poor graft outcome. Here, we assess post-transplant renal function associated with everolimus (EVR) and tacrolimus (TAC) exposure at 12 months in a Phase IIIb, multi-center, randomized, open-label non inferiority study (US92).
De novo renal transplant recipients (n=309) received EVR 0.75 mg b.i.d. as starting dose, adjusted to maintain a trough level of 3–8 ng/mL. Patients received TAC and prednisone per local guidelines, with TAC dosing adjusted to achieve trough levels of 4–7 ng/mL (0–2 Months [M]), 3–6 ng/mL (2–6 M) and 2–5 ng/mL (6–12 M). At 12 months, incidences of low estimated glomerular filtration rate (eGFR; <30 mL/min/1.73 m2), decreased eGFR (decrease in eGFR by 30% compared to month 1), and proteinuria (urinary protein:creatinine ratio of ≥500 mg/g) were assessed to evaluate the relationship between renal dysfunction and time-normalized EVR and TAC exposure.
Measures of low eGFR and decreased eGFR were more frequent in patients with higher concentrations of TAC, but were not associated with increasing EVR concentrations (Table 1, n=306). The incidence of proteinuria correlated independently with both increasing EVR and TAC concentrations.
These results demonstrate that rates of low eGFR and decreased eGFR were higher with increased TAC concentrations, but not with increased EVR concentrations, at 12 months in de novo renal transplant recipients. Proteinuria was more frequent with increasing TAC and EVR concentrations.
| Table 1: n/N, (%) | Low eGFR | Decreased eGFR | Proteinuria (≥500 mg/g) |
| Total incidence | 27/306 (8.8) | 55/306 (18.0) | 69/306 (22.5) |
| Everolimus (ng/ml) | |||
| <3 | 2/21 (9.5) | 3/21 (14.3) | 4/22 (18.2) |
| 3–<6 | 21/206 (10.2) | 44/204 (21.6) | 46/206 (22.3) |
| 6–<8 | 3/62 (4.8) | 6/62 (9.7) | 15/59 (25.4) |
| 8–<12 | 0/9 (0.0) | 2/12 (16.7) | 4/12 (33.3) |
| ≥12 | 1/1 (100.0) | 0 | 0 |
| Tacrolimus (ng/ml) | |||
| <2 | 0/2 (0.0) | 0/2 (0.0) | 0/2 (0.0) |
| 2–<5 | 5/98 (5.1) | 9/93 (9.7) | 11/96 (11.5) |
| 5–<8 | 19/178 (10.7) | 43/184 (23.4) | 52/178 (29.2) |
| ≥8 | 3/21 (14.3) | 3/20 (15.0) | 6/23 (26.1) |
CITATION INFORMATION: Shihab F, Qazi Y, Mulgaonkar S, McCague K, Patel D, Peddi V, Shaffer D. Renal Dysfunction at 12 Months Is Not Associated with Everolimus Exposure in De Novo Renal Transplant Recipients. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Shihab F, Qazi Y, Mulgaonkar S, McCague K, Patel D, Peddi V, Shaffer D. Renal Dysfunction at 12 Months Is Not Associated with Everolimus Exposure in De Novo Renal Transplant Recipients. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/renal-dysfunction-at-12-months-is-not-associated-with-everolimus-exposure-in-de-novo-renal-transplant-recipients/. Accessed May 31, 2025.« Back to 2016 American Transplant Congress