Chronic dialysis in patients with end‐stage renal disease: Relevance to kidney xenotransplantation

Abstract

Renal allotransplantation clearly offers better survival and quality of life for end‐stage renal disease (ESRD) patients than chronic dialysis. The median waiting time for a deceased donor kidney in a suitable ESRD patient is 3.9 years. The initial candidates for pig kidney xenotransplantation will be those with ESRD unlikely to receive an allograft within a reasonable period of time. It is thus reasonable to ascertain whether clinical trials of xenotransplantation might likewise offer superior outcomes. Chronic dialysis in patients with ESRD is associated with poor quality of life, significant morbidity, and relatively high mortality, with only 56% surviving 3 years and 42% at 5 years. However, a significant number of these patients, because of comorbidities, frailty, etc, would not be considered for renal allotransplantation and likely not for xenotransplantation. As genetically engineered pig kidneys have satisfactorily supported life in immunosuppressed nonhuman primates for many months or even more than a year, consideration in carefully selected patients could be given to pig kidney xenotransplantation. We suggest that, in order to give a patient the best possible outcome, the pig kidney could be transplanted pre‐emptively (before dialysis is initiated). If it fails at any stage, the patient would then begin chronic dialysis and continue to await an allograft. The present (limited) evidence is that failure of a pig graft would not be detrimental to a subsequent allograft.

Pig kidney xenotransplantation: Progress toward clinical trials

“…The pathobiological response to a pig xenograft is complex, involving antibody, complement, coagulation, inflammatory, and cellular responses. 7 The transplantation of an untreated wildtype (ie, genetically-unmodified) pig kidney into a non-immunosuppressed NHP or human results in the almost immediate F I G U R E 1 Percentage survival of patients with end-stage renal disease by treatment modality (modified from Jagdale et al 2018, 1 and based on data from two sources (i) USRDS annual data, 2017, 4 and (ii) Orandi 3. Avoids the detrimental effects of brain death on the organs.…”

“…Hemodialysis is life‐sustaining for thousands of patients with end‐stage renal disease, but chronic dialysis is a suboptimal form of therapy for many and their quality of life remains poor 1,2 . Renal transplantation often offers a better quality of life and improved survival, but there is a continuing shortage of deceased human donor kidneys.…”

“…Percentage survival of patients with end‐stage renal disease by treatment modality (modified from Jagdale et al 2018, 1 and based on data from two sources (i) USRDS annual data, 2017, 4 and (ii) Orandi et al, 2016 3 )…”

Clinical Pig Kidney Xenotransplantation: How Close Are We?

“…Patients with various conditions have been discussed (Table 4). 1,50 An important point is that, because xenotransplantation will be offered to patients who are unable to receive a timely allograft, the results of the initial pig kidney xenotransplants should be compared with those for comparable patients maintained on chronic dialysis, but not with those for patients receiving kidney allografts. A second major point is that the patient's general physical state should make him or her an acceptable candidate for allotransplantation.…”

“…There is a continuing shortage of deceased human donor kidneys for transplantation in patients with ESKD. [1][2][3] The overall survival of patients on chronic hemodialysis is 78% at 1 year, 57% at 3 years, and only 42% at 5 years (Figure 1). 4 Forty percent of waitlisted patients are likely to die within 5 years.…”