Linda Jennings Ph.D.

Asrani, S. K., L. W. Jennings, J. F. Trotter, J. Levitsky, M. K. Nadim, W. R. Kim, S. A. Gonzalez, B. Fischbach, R. Bahirwani, M. Emmett and G. Klintmalm (2018). “A model for Glomerular filtration Rate Assessment In Liver disease (GRAIL) in the presence of renal dysfunction.” Hepatology Oct 19. [Epub ahead of print].

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Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in presence of renal dysfunction. We developed a model for GFR Assessment In Liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction. Measured GFR (mGFR) by iothalamate clearance (n=12,122, 1985-2015) at protocol time points before/after LT was used as reference. GRAIL was compared to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD-4, MDRD-6) equations for mGFR<30ml/min/1.73m(2) . Prediction of development of chronic kidney disease (mGFR < 20ml/min/1.73m(2) , initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n=785) and external validation (n=68,217, 2001-2015). GRAIL had less bias, was more accurate and precise as compared to CKD-EPI, MDRD-4 and MDRD-6 at time points before/after LT for low GFR. For mGFR<30ml/min/1.73m(2) , the median difference (eGFR-mGFR) was GRAIL: 5.24 [9.65] ml/min/1.73m(2) as compared to CKD-EPI: 8.70 [18.24]ml/min/1.73m(2) , MDRD-4: 8.82 [17.38]ml/min/1.73m(2) , and MDRD-6: 6.53[14.42] ml/min/1.73m(2) . Prior to LT, GRAIL correctly classified 75% as having mGFR<30ml/min/1.73m(2) vs. 36.1% (CKD-EPI), 36.1%(MDRD-4), and 52.8%(MDRD-6).(p<0.01) An eGFR<30ml/min/1.73m(2) by GRAIL predicted development of CKD (26.9% vs. 4.6% CKD-EPI, 5.9% MDRD-4, and 10.5% MDRD-6) in center data and needing kidney after LT (48.3% vs. 22.0% CKD-EPI vs. 23.1% MDRD-4 vs. 48.3% MDRD-6, p<0.01) in national data within 5 years after LT. CONCLUSION: GRAIL may serve as an alternative model to estimate GFR amongst patients with liver disease before and after LT at low GFR.

O’Leary, J. G., C. Smith, J. Cai, B. Hart, L. W. Jennings, M. Everly, G. B. Klintmalm and A. J. Demetris (2017). “Chronic amr in liver transplant: Validation of the 1-year camr score’s ability to determine long-term outcome.” Transplantation 101(9): 2062-2070.

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BACKGROUND: A proposed chronic antibody-mediated rejection (AMR) score has recently predicted 50%10-year death-censored allograft loss in patients with donor-specific alloantibodies (DSA) mean florescence intensity (MFI) greater than 10 000 and requires confirmation in patients with lower MFI (1000-10 000). METHODS: All patients who underwent liver transplantation from January 2000 to April 2009, had DSA (MFI >/=1000) in serum 10 to 14 months postliver transplantation, and had a protocolized liver biopsy were evaluated (n = 230). The previously proposed chronic AMR (cAMR) score was used to risk-stratify putative chronic AMR in DSA+ patients with MFI from 1000 to 10 000. RESULTS: The MFI distribution of DSA+ recipients were as follows: 66% had MFI 1000 to 4999, 14% had MFI 5000 to 10 000, and 20% had MFI greater than 10 000. The cAMR score distribution on 1-year protocol liver biopsy found that 41% had a score less than 13; 27% a score of 13 to 27.5, and 32% a score greater than 27.5. MFI correlated with 1-year cAMR category (<13, 46% vs 21% and >27.5, 29% vs 42% when MFI was 1000-10 000 vs MFI >10 000; P = 0.047). In patients with a cAMR score less than 13, 10-year death-censored allograft survival was 96% to 100% regardless of MFI (P = NS). The risk of allograft loss increased in patients with a cAMR score greater than 13 (P = 0.004) in DSA+ patients with MFI 1000 to 10 000. DSA MFI greater than 10 000 versus MFI 1000 to 10 000 at 1 year was also more likely to persist at 5 years (95% vs 68%; P < 0.0001). CONCLUSIONS: Validation of the previously proposed cAMR score in a separate cohort predicts death-censored long-term allograft failure in DSA+ patients regardless of MFI, and higher MFI at 1 year predicts DSA persistence at 5 years.