Effects of mTOR inhibitor–related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients. Issue 2 (21st July 2020)

• Record Type: Journal Article
• Authors: Asleh, Rabea; Alnsasra, Hilmi; Lerman, Amir; Briasoulis, Alexandros; Pereira, Naveen L.; Edwards, Brooks S.; Toya, Takumi; Stulak, John M.; Clavell, Alfredo L.; Daly, Richard C.; Kushwaha, Sudhir S.
• Is Part Of: American journal of transplantation. Volume 21:Issue 2(2021)
• Page Start: 626
• Page End: 635
• Publication Date: 2020-07-21
• Subjects: clinical research/practice -- coronary artery disease -- glomerular filtration rate (GFR) -- heart transplantation/cardiology -- immunosuppressant -- immunosuppression/immune modulation -- vasculopathy; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.16155
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR ( P = .005) but similar GFR during follow‐up. Delta PV ( P < .001) and Δ PI ( P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all‐cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV‐related events ( P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk. Abstract : Proteinuria after conversion to sirolimus as primary immunosuppressive maintenance therapy occurs in more than 25% of heart transplant recipients and is associated with less attenuation of cardiac allograft vasculopathy progression and increased risk of all‐cause mortality but similar rates of cardiac allograft vasculopathy‐related adverse events. See Eisen's editorial on page 449 .