Abstract: TH-PO1131
Effect of Ledipasvir and Sofosbuvir (LDV/SOF) on Kidney Function and Urinary Biomarkers in Patients (Pts) with Proteinuric CKD
Session Information
- CKD: Clinical, Outcomes, Trials - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials
Authors
- Sise, Meghan E., Massachusetts General Hospital, Boston, Massachusetts, United States
- Chute, Donald F., Massachusetts General Hospital, Boston, Massachusetts, United States
- Gustafson, Jenna L., Massachusetts General Hospital, Boston, Massachusetts, United States
- Waikar, Sushrut S., Harvard Medical School, Boston, Massachusetts, United States
- Chung, Raymond T., Massachusetts General Hospital, Boston, Massachusetts, United States
Background
HCV infection is associated with CKD incidence and progression. HCV may lead to immune-complex mediated glomerulonephritis, however HCV also promotes atherosclerosis, insulin resistance and chronic inflammation. We sought to determine whether HCV treatment improves kidney function, as assessed by biomarkers of kidney disease.
Methods
NCT02503735 was an investigator-initiated pilot trial that used SOF/LDV to treat pts with HCV genotype 1 or 4 and proteinuria (>300mg proteinuria/g Cr). Baseline proteinuria, cystatin-c, and creatinine were compared to on treatment values and post-therapy values. Insulin resistance (IR) was calculated by HOMA-IR. Urine biomarkers were measured by Luminex. The primary outcome was change in natural log proteinuria-to-creatinine (UPC) ratio from baseline to 12-weeks post SOF/LDV compared by paired t-test.
Results
10 pts began 12-weeks of LDV/SOF mean age 64 (SD 10), 70% male, 60% White, 30% Black, 10% Native American. 4/10 had cirrhosis. 8/10 were cured of HCV, 2 relapsed. Baseline eGFR was 63.2 mL/min/1.73m2 (SD 26.2), baseline proteinuria was 1.05g/g (SD 0.95). Baseline to post-treatment values are in Table 1. Non-diabetic pts cured of HCV (pts 1-4) all had improvement in proteinuria: 1.8g/g, (SD 1.6) to 0.69g/g (SD 0.7g/g) (p=0.01). Diabetic pts and pts with HCV relapse had worsening proteinuria 0.77g/g, (SD 0.3) to 2.2g/g (SD 1.4) (p=0.05). Complement and cryoglobulins normalized in the majority, IR decreased slightly.
Conclusion
Non-diabetic pts with HCV-associated CKD had substantial improvement in proteinuria when HCV was eradicated with SOF/LDV.
| Pt | Viral Outcome | Diabetes | Baseline | Follow-Up 12 Weeks After SOF/LDV | ||||||||||||
| Creatinine | Cystatin C | Proteinuria UPC Ratio | Cryocrit | Low C4 | CRP | Homa-IR | Creatinine | Cystatin C | Proteinuria UPC Ratio | Cryocrit | Low C4 | CRP | Homa-IR | |||
| 1 | Cured | No | 1.00 | 1.43 | 3.56 | 4% | Yes | 1.7 | 4.3 | 0.93 | 1.37 | 1.78 | None | No | 11.8 | 3.7 |
| 2 | Cured | No | 1.35 | 2.14 | 0.50 | 1% | Yes | 16 | 4.7 | 1.45 | 2.11 | 0.12 | 2% | Yes | 9.2 | 2.5 |
| 3 | Cured | No | 0.78 | 0.80 | 1.44 | 3% | Yes | 0.9 | 1.7 | 0.79 | 0.76 | 0.76 | 1% | No | 5.0 | 1.9 |
| 4 | Cured | No | 1.30 | 1.02 | 0.39 | None | No | 0.1 | 3.6 | 1.66 | 1.03 | 0.11 | None | No | 0.6 | 5.4 |
| 5 | Cured | Yes | 1.22 | 1.09 | 0.84 | None | No | 0.3 | 6.7 | 1.23 | 0.87 | 2.18 | None | No | 0.5 | 9.3 |
| 6 | Cured | Yes | 1.03 | 0.64 | 1.13 | 3% | Yes | 1.5 | 19.8 | 0.70 | 0.56 | 1.00 | None | No | 1.9 | 17.2 |
| 7 | Cured | Yes | 1.53 | 2.42 | 1.15 | 1% | No | 0.5 | 5.5 | 1.91 | 2.75 | 2.01 | None | No | 4.1 | 3.7 |
| 8 | Cured | Yes | 1.68 | 2.00 | 0.68 | 2% | No | 0.2 | 2.2 | 2.02 | 2.14 | 4.36 | None | No | 0.1 | 1.2 |
| 9 | Relapsed | No | 1.42 | 1.84 | 0.31 | 2% | No | 3 | 2.8 | 1.48 | 1.63 | 0.35 | ND | No | 9.1 | 2.4 |
| 10 | Relapsed | No | 0.77 | 0.67 | 0.53 | None | No | 0.3 | 4.8 | 0.69 | 0.71 | 2.18 | None | No | 0.4 | 6.7 |
Abbreviations: Pt = patient, UPC = urine protein to creatinine, CRP = c-reactive protein, HOMA-IR = homeostatic model assessment of insulin resistance
Funding
- Commercial Support – Gilead Sciences