Achieving Adequate Renal Xenograft Perfusion and Function in an LVAD Recipient with Strict Systolic and Pulse Pressure Parameters

I. Aljabban¹, J. I. Kim¹, A. Mattoo¹, V. Tatapudi¹, E. Y. Skolnik², I. S. Jaffe¹, K. Khalil¹, E. Weldon¹, D. Ayares³, B. S. Kadosh⁴, R. I. Goldberg⁴, T. Saraon⁴, A. Reyentovich⁵, D. E. Smith⁵, J. M. Stern¹, A. Griesemer¹, R. A. Montgomery¹, N. Moazami^5
1NYU Langone Transplant Institute, New York, New York ²Department of Medicine, NYU Langone, New York, New York ³Revivicor, Inc., Blacksburg, Virginia ⁴Department of Cardiology, NYU Langone, New York, New York ⁵NYU Langone Health, New York, New York

Purpose: Individuals with end-stage renal disease and contraindication to transplant are not considered for a left ventricular assist device (LVAD) as destination therapy due to high mortality rates. We report the course of the first 30 days of porcine renal xenograft perfusion and function in a human recipient with an LVAD.

Methods: The patient underwent a re-operative sternotomy with HeartMate III LVAD implantation. A week later after being maintained on CRRT, an alpha-gal knock-out porcine thymokidney was transplanted into the left iliac fossa. Hourly hemodynamic data and LVAD parameters were recorded. A complete metabolic panel was collected every 4 hours. Renal ultrasounds with color flow doppler and spectral analysis were performed weekly. Approval for this procedure was obtained from the FDA under a single patient expanded access Investigational New Drug application and the New York University Grossman School of Medicine Institutional Review Board.

Results: Renal xenograft dopplers demonstrated patent vasculature without stenosis or thrombosis throughout the duration of the study. Following transplant, main renal artery peak systolic velocity (MRA-PSV) was 53.4cm/s (normal: 60-100cm/s) with a resistive index (RI) of 0.7 (normal: 0.5-0.8). Spectral doppler showed a monophasic waveform with continuous antegrade flow. On post-operative day (POD) 2 creatinine clearance (CrCl) declined to 12mL/min from 75.8mL/min secondary to low effective circulating volume in setting of hypotension. Serum creatinine (Cr) peaked to 1.55mg/dL on POD4. Hemodynamic goals were broadened to prioritize a pulsatile flow with systolic blood pressure (SBP) of greater than 100mmHg per standard renal allotransplant protocols by a combination of inotropic and vasopressor support. When a SBP of >100mmHg and pulse pressure (PP) of >25mmHg was achieved, serum Cr and CrCl returned to baseline. Serum Cr reached a nadir of 0.48 mg/dL and CrCl increased to 72.9 mL/min on POD7. MRA-PSV and RI were normal at 88.4cm/s and 0.8, respectively. Renal artery doppler confirmed improved pulsatility with a sharp systolic upstroke. Between POD7 and POD30, serum Cr ranged from 0.49-1.11 mg/dL, and CrCl ranged from 35.9-72.9 mL/min. MRA-PSV and RI remained in reference range. LVAD flows were stable at 3.7L/min (range 3.1-4.4L/min).

Conclusion: Adequate xenograft perfusion was achieved in an LVAD recipient demonstrated by normal MRA-PSV and RI. Renal function normalized following an ischemic injury by maintaining a SBP of >100mmHg and PP of >25mmHg. Long-term impact of continuous flow on a transplanted kidney remains unclear, maintaining pulsatile flow seems beneficial.

Identify the source of the funding for this research project: United Therapeutics Corporation