Short- and long-term results with kidneys from non-heart-beating donors☆

Kidney transplantation is victim of its own success. Due to its excellent outcome, indications have expanded and more and more patients are registered in the waiting list. However, the number of available organs has not been able to rise at the same pace, and this has led to a dramatic increase of the mortality and dropout rate of patients while on the waiting list. This chapter will illustrate the strategies that are currently being devised and implemented in order to increase the supply of transplantable kidneys.

Confronting the organ donor shortage, many transplant centers around the world increasingly use donors after cardiac death (DCD). Over the past 20 years, follow-up studies in kidney recipients comparing DCD and donors after brain death (DBD) have shown comparable long-term graft function and survival. As a consequence, DCD programs should be continued and expanded, for these donors constitute a potential solution to the imbalance between the numbers of end-stage kidney disease patients on waiting lists versus available kidney grafts. DCD kidneys do not necessarily signify suboptimal grafts; they may merit to be allocated the same as DBD grafts.

Donors after cardiac death (DCD) could increase the organ pool. Data supports good long‐term renal graft survival. However, DCDs are <10% of deceased donors in the United States, due to delayed graft function, and primary nonfunction. These complications are minimized by extracorporeal support after cardiac death (ECS‐DCD). This study assesses immediate and acute renal function from different donor types. DCDs kidneys were recovered by conventional rapid recovery or by ECS, and transplanted into nephrectomized healthy swine. Warm ischemia of 10 and 30 min were evaluated. Swine living donors were controls (LVD). ECS‐DCDs were treated with 90 min of perfusion until organ recovery. After procurement, kidneys were cold storage 4–6 h. Renal vascular resistance (RVR), urine output (UO), urine protein concentration (UrPr) and creatinine clearance (CrCl), were collected during 4 h posttransplantation. All grafts functioned with adequate renal blood flow for 4 h. RVR at 4 h posttransplant returned to baseline only in the LVD group (0.36 mmHg/mL/min ± 0.03). RVR was higher in all DCDs (0.66 mmHg/mL/min ± 0.13), without differences between them. UO was >50 mL/h in all DCDs, except in DCD‐30 (6.8 mL/h ± 1.7). DCD‐30 had lower CrCl (0.9 mL/min ± 0.2) and higher UrPr >200 mg/dL, compared to other DCDs >10 mL/min and <160 mg/dL, respectively. Normothermic ECS can resuscitate kidneys to transplantable status after 30 min of cardiac arrest/WI.

To determine how long a period of having had no cardiopulmonary-resuscitation (CPR) (delay time) is considered to result in subsequent futile efforts at resuscitation.

In 2007 a survey was mailed to all 77 paediatric intensivists in Canada. Three scenarios of witnessed cardiac arrest were presented: out-of-hospital, in-hospital, and in-hospital with extracorporeal-CPR (E-CPR). Each scenario asked what delay time would make attempts at resuscitation futile for survival to hospital discharge, and for survival to hospital discharge in a better than vegetative state. Comparisons of median [inter-quartile range] used Wilcoxon-signed-rank or Friedman tests with Bonferroni corrections.

The response rate was 49/77 (64%). The delay time was significantly different between rhythms within all scenarios (p < .001); and was significantly shorter for survival than for better than vegetative survival (p < .006) except when E-CPR was to be used. The delay time was not significantly different between the in-hospital and out-of-hospital scenario with the same rhythms (p > .01). The delay time was significantly shorter in scenarios with asystole versus pulseless electrical activity with (p = .010) or without (p < .001) an arterial line with absent pulsation. In out-of-hospital arrest, the delay time for survival varied from 15 [10–20] min for asystole to 20 [15–20] min for pulseless electrical activity. In in-hospital scenarios, the delay time for survival varied from 10 [10–20] min for asystole, to 15 [10–20] min for most other rhythms.

A delay time of 15 [10–20] (range 5–30) min was considered futile for survival. This has implications for pronouncing death in donation after cardiac death.

La posibilidad de obtener órganos para Trasplante Renal, tras un período de parada cardio-circulatoria, exige un conocimiento previo del mecanismo de lesión por isquemia-reperfusión. Para poder estudiar el mecanismo de lesión celular por isquemia caliente en Trasplante Renal se ha diseñado un estudio experimental en cerdos, con tiempos variables (0-30-45 y 90’ de isquemia caliente) con la finalidad de conocer el mecanismo celular de dicha lesión isquémica.

La determinación de parámetros bioquímicos (creatinina y diuresis), carga energética (ATP, ADP, AMP y carga energética global) y estudio histológico, así como análisis de supervivencia del animal e injerto al 5º día.

- La supervivencia de los animales a los 5 días ha sido del 100% (en los grupos control y 30’ de isquemia caliente), 90% (enlos 45’) y 60% (en los 90’).- La viabilidad del injerto ha sido 100% (grupo control), 80% (isquemia 30’), 80% (isquemia 45’) y 60% (90’).- Los niveles de creatinina aumentan al 1er, 3er y 5º día sobre todo en los riñones no viables con diferencias estadísticamente significativas con respecto al grupo control.- Los niveles de ATP decrecen tras el período de isquemia caliente, aumentan los niveles de ADP y AMP y se recuperan en los riñones viables después de la reperfusión del injerto.

El autotrasplante renal laparoscópico experimental proporciona un buen modelo para aprendizaje de cirugía laparoscópica. Creemos que aporta recursos laparoscópicos adecuados para cirugía retroperitoneal y pélvica. No proponemos, en el momento actual, su aplicación a la cirugía laparoscópica en humanos.

Renal procurement after a period of heart stop demands a previous knowledge of ischemia-reperfusion injuries means. To study cell injury mechanisms an experimental study has been designed in pigs, with different rangres of warm ischemia (0-30-45 and 90 min). The main goal was to research on the basis of ischemic injury.

Biochemical parameters (creatinine, urine output), energetic loading (ATP, ADP, AMP and global energetic loading) and pathological studies as long as survival analysis by 5th day were completed.

Animal survival and graft viability range from 100% at 5th day in control and 30 min warm ischemia groups to 60% in 90 min warm ischemia group. Creatinine levels rises at 1st, 3rd and 5th day, especially in those non-viable organs. ATP levels decrease after warm ischemia period, increases ADP and AMP levels after reperfusion in those viable organs.

Prolonged periods of warm ischemia do not result necessarily in non-viable kidneys. Viable organs recover nucleotide levels early.Study of energetic cell loading levels is a good way to get on better in the knowledge of injury mechanisms after ischemiareperfusion.

Reluctance to accept non–heart-beating donors (NHBD) as a source of kidneys, is due to medical, ethical, and logistical reasons. Evidence suggest that the short-term graft survival is similar to that of kidneys obtained from heart-beating donors (HBD). However, few studies, with long-term follow-up are available. We conducted a single-center study of kidneys obtained from NHBD, in a 14-year period.

We studied 100 patients transplanted with kidneys between 1989 and 2004, using NHBD, supported by heart compression and mechanical ventilation (n = 24), intravascular in situ cooling (n = 59), or cardiorespiratory resuscitation plus manual abdominal counterpulsation without cooling (n = 17), the last technique being used from 1998. The median follow-up was 51 ± 51 months (range, 1 to 170). The outcomes of these procedures were compared to those of 1025 transplantations of kidneys from HBD performed during the same period.

The characteristics of the recipients did not differ significantly between the two groups. Kidneys from NHBD showed a significantly higher rate of delayed graft function (DGF; 84% vs 26%; (P < .001), furthermore, the primary nonfunction (PNF) incidence was significantly higher with NHBD vs HBD (16% vs 10%; P < .001). The incidence of acute rejection episodes (ARE) within 3 months and at 1 year did not differ between the groups of donors; however, more NHBD kidneys were lost from ARE. The short-term (3-month and 1 year) and long-term (5 and 10 years) renal function, determined by the serum creatinine levels, and patient and graft survival were not different for kidneys obtained from NHBD.

The incidences of PNF and DGF were significantly higher with NHBD, which produced poorer renal function at the time of hospital discharge. One-, 5-, and 10-year graft survivals and renal function did not differ between NHBD and HBD grafts. In our series, PNF was the main barrier to the use of NHBD.