Introduction of everolimus in kidney transplant recipients at a late posttransplant stage

Table 2 Summary of retrospective or nonrandomized studies for late everolimus conversion

Ref.	No. of subjects/follow-up	EVL treatment	Outcomes
Morales et al[20] (2007)/ retrospective	8/1-16 mo	Conversion to EVL with CNI elimination or reduction at mean of 5 yr	CrCl increased by 42% in recipients with CAN (grade 1 or 2) and CNI nephrotoxicity (P = 0.017)
Sanchez-Fructuoso et al[21] (2012)/ retrospective	220/1 yr	Conversion from CNI to EVL at mean of 69.4 mo	CrCl increased in recipients with baseline CrCl ≥ 40 mL/min and baseline proteinuria < 550 mg/d (P = 0.005) Median proteinuria increased from 304 mg/d to 458 mg/d (P < 0.001) EVL discontinuation rate was 24%
Chow et al[22] (2015)/ open-label, single arm	17/1 yr	Conversion to EVL with CNI minimization in recipients with CAN at mean of 4.2 yr	Mean slope of eGFR was - 4.31 mL/min/1.73 m2 per yr before conversion, as compared with 1.29 mL/min/1.73 m2 per yr at 12 mo after conversion (P = 0.036) Renal biopsy showed significant decrease of tubular atrophy (15.7% vs 7.1%, P = 0.005) and interstitial fibrosis (14.8% vs 7.2%, P = 0.013)
Miura et al[23] (2015)/ retrospective	13/1 yr	Conversion to EVL with Tac reduction in recipients with CNIA at mean of 43 mo	aah scores improved in 5 recipients (38%); No improvement was observed in recipients with aah3; No deterioration was observed. eGFR improved from 44.3 mL/min/1.73 m2 to 49.8 mL/min/1.73 m2 (P < 0.01).
Uchida et al[24] (2016)/ retrospective (our report)	26/1 yr	Conversion from antimetabolites (MMF or MZ) to EVL with CNI minimization at mean of 39.5 mo	eGFR significantly increased from 50.7 mL/min/1.73 m2 to 53.6 mL/min/1.73 m2 in the EVL continuation group EVL discontinuation rate was 42.3%
Nojima et al[25] (2017)/ retrospective	56/1 yr	Conversion to EVL with CNI reduction in recipients with CNI nephrotoxicity or IF/TA at mean of 7.4 yr	eGFR increased by 7% (P < 0.005) EVL discontinuation rate was 11%
Nanmoku et al[26] (2017)/ nonrandomized	86/ 1 yr	Conversion to EVL with Tac minimization, MMF reduction and steroid withdrawal in cases of complications such as diabetes, viral infection etc	Conventional group (n = 50); EVL group (n = 36) Biopsy-proven acute rejection rate exhibited no significant difference between these groups (12% vs 17%, P = 0.55) Serum creatinine significantly improved in the EVL group (P = 0.031) EVL discontinuation rate was 13.8%

CAN: Chronic allograft nephropathy; CNI: Calcineurin inhibitor; CNIA: Calcineurin inhibitor arteriolopathy; CrCl: Creatinine clearance; eGFR: Estimated glomerular filtration rate; EVL: Everolimus; IF/TA: Interstitial fibrosis/tubular atrophy; MMF: Mycophenolate mofetil; MZ: Mizoribine; No.: Number; Tac: Tacrolimus.