EFFECTS OF ALLO-HEMODIALYSIS ON DONOR (“BUDDY”) KIDNEY FUNCTION IN A PORCINE AKI MODEL

Each year, millions of kidney patients—particularly in low- and lower-middle-income countries—die prematurely from kidney failure due to the lack of affordable kidney replacement therapies. To address this urgent global need, we developed a novel, low-cost dialysis modality termed allo-hemodialysis (alloHD), in which blood from a patient with kidney failure flows counter-current to that of a healthy “buddy” through a dialyzer. Uremic solutes and excess fluid are transferred to the buddy and subsequently cleared by their healthy kidneys. We previously demonstrated the adequacy of alloHD through mathematical modeling and ex vivo testing and confirmed its technical feasibility in porcine models of acute kidney injury (AKI) induced by renal artery ligation and embolization. Here we further evaluated the effects of alloHD on buddy pig kidney function using an embolization-induced AKI porcine model.

The study was approved by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), New Delhi, India. Two female Yorkshire pigs (weighing 80–90 kg) received a central venous catheter for vascular access. AKI was induced by transcatheter embolization of both renal arteries using Contour™ polyvinyl alcohol particles (Boston Scientific, Marlborough, MA, USA). The AKI pig and the buddy pig were connected to the dialysate and blood compartments of a Nipro Cellentia 17H dialyzer, respectively. AlloHD was conducted for four hours. Both pigs received systemic heparin anticoagulation (5,000 IU/h) during alloHD. The buddy pig received 1-2% isoflurane anesthesia. Plasma samples were collected before, during, and after alloHD. Hourly urine samples from the buddy pig were collected during alloHD via an indwelling urinary catheter. Plasma and urine samples were analyzed for urea and creatinine concentrations, and urea and creatinine clearances were calculated. 

Nine alternate-day alloHD sessions were conducted with the same pair of pigs. During these sessions, plasma urea and creatinine levels declined in the AKI pig, while levels in the buddy pig transiently rose above baseline before returning toward baseline post-dialysis (Figure 1A & B). Building on these findings, we extended the investigation to assess the impact of alloHD on buddy kidney function. During alloHD, urine output of the buddy pig increased sharply after alloHD initiation and then gradually decreased over the first three hours and returned to normal during the final hour of alloHD (Figure 1C). In parallel, the buddy kidneys exhibited an initial increase in uremic solute clearance of urea and creatinine followed by a gradual return toward baseline (Figure 1D & E).

We showed that during alloHD in a porcine AKI model, the kidneys of a healthy buddy pig can accommodate the acute fluid and solute load imposed by the AKI pig. We found no indication that the buddy kidney function was adversely affected. Histological analysis of the buddy kidneys is pending. Long term studies are warranted to assess the sustained effects of alloHD on buddy kidney structure and function over an extended period.