Abstract: SA-PO039
Novel Predictors of Hepatorenal Syndrome Response to Terlipressin: Biomarker Analysis from the CONFIRM Trial
Session Information
- AKI: Clinical, Outcomes, and Trials - Management
October 26, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Allegretti, Andrew S., Massachusetts General Hospital, Boston, Massachusetts, United States
- Levitsky, Josh, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Sharma, Pratima, University of Michigan, Ann Arbor, Michigan, United States
- Ouyang, Tianqi, Massachusetts General Hospital, Boston, Massachusetts, United States
- Silvey, Scott, Virginia Commonwealth University, Richmond, Virginia, United States
- Bajaj, Jasmohan S., Virginia Commonwealth University, Richmond, Virginia, United States
Background
Terlipressin is the only FDA approved vasoconstrictor for hepatorenal syndrome (HRS). The CONFIRM study is the largest trial of terlipressin vs. placebo (HRS response as primary outcome). Novel predictors of HRS response are required to enrich patient selection and optimize outcomes.
Methods
Samples at initiation were tested using (a) LC-MS of 1594 plasma/1420 urine metabolites (Metabolon Inc), (b) aptamer-based array of 7289 plasma proteins (SomaScan), and (c) 14 serum/urine ELISA assays. The CONFIRM trial’s original definition of HRS response was used (2 creatinine [SCr] <1.5 mg/dL).
Results
116 patients (79 terlipressin-treated [TT] and 36 placebo-treated [PT]) provided samples. Baseline characteristics, outcomes, and 2:1 TT:PT allocation were preserved from the original 300 patient trial. 36/116 (31.0%) patients achieved HRS reversal. Demographics were similar by HRS response (Table). In metabolite analysis, PT had the most significant differences in HRS responders (n=26 plasma, n=50 urine), with fewer in TT (n=1 plasma, n=2 urine), and in all patients (n=3 plasma, n=7 urine). There were no significant aptamers associated with HRS response after false-discovery correction. HRS responders had lower SCr (p = 0.001), cystatin C (p = 0.005), angiopoietin-2 (p = 0.04), and B2 microglobulin (p = 0.006), while osteopontin, VEGF, and NGAL were similar.
Conclusion
SCr, Cystatin C, angiopoietin-2, and B2 microglobulin, were associated with HRS response. Further study of predictors of HRS response may enrich for better candidates for terlipressin.
Demographics and Analytes by HRS Response
| HRS Response (n = 36) | No Response (n = 79) | P value | |
| Age (mean (SD)) | 53.91 (12.95) | 53.94 (11.67) | 0.99 |
| Male Sex (%) | 25 (69.4) | 42 (53.2) | 0.15 |
| Alcohol-related cirrhosis (%) | 28 (77.8) | 50 (63.3) | 0.19 |
| Creatinine at enrollment (median [IQR]) | 2.75 [2.50, 3.30] | 3.50 [2.65, 4.10] | 0.001 |
| Mean arterial pressure at enrollment (mmHg) | 78.67 [72.08, 84.25] | 76.67 [68.67, 86.00] | 0.477 |
| MELD score at enrollment | 31.00 [25.00, 39.25] | 33.00 [26.00, 39.00] | 0.499 |
| Serum albumin at enrollment (g/dL) | 3.60 [3.10, 4.05] | 3.70 [3.50, 4.20] | 0.083 |
| Serum Cystatin C (g/dL) | 3.39 [3.05, 4.21] | 4.02 [3.50, 4.88] | 0.005 |
| Serum TIMP-1 (ng/mL) | 370.1 [294.3, 489.9] | 450.3 [323.9, 831.7] | 0.082 |
| Serum Angiopoietin-2 (ng/mL) | 12.13 [9.52, 19.77] | 17.10 [11.59, 25.48] | 0.042 |
| Serum Osteopontin (ng/mL) | 95.02 [60.38, 143.00] | 109.50 [61.49, 232.69] | 0.201 |
| Serum B2 microglobulin (mg/L) | 6.47 [4.43, 8.60] | 8.70 [5.89, 11.26] | 0.006 |
| Serum NGAL (ng/mL) | 384.67 [273.99, 468.90] | 464.89 [335.84, 665.34] | 0.083 |
| Urine NGAL (ng/mL) n = 89 | 64.53 [6.08, 149.07] | 92.00 [31.22, 283.21] | 0.089 |
Funding
- Commercial Support – This work was supported by an investigator-initiated research grant from Mallinckrodt Pharmaceuticals.