Non-heart-beating Donors Kidneys Research Articles

Survival and Evolution of Renal Function in Kidney Transplant Recipients From Type II Asystolic Donations: A Single-center Experience

BackgroundIn recent years, stagnation in the number of kidneys from after brain-dead donors (DBD) has stimulated the use of non–heart beating donors (NHBDs). Herein we present our 5-year experience with type II Maastricht NHBDs in renal transplantation. MethodsAll patients (n = 50) in this study received type II Maastricht NHBD kidneys (March 2012 to February 2017), with a median follow-up of 33 months. ResultsMean donor age was 39 ± 12 years, mean creatinine 1.24 ± 0.2 mg/dL, and the most frequently observed blood group (donors and recipients) was type A (64%). Recipients were slightly younger (51 ± 11 years old), with mean time on dialysis of 30 ± 24 months. Almost all were primary transplants. Pre-transplant panel-reactive antibodies (PRA) were <25%; initial immunosuppression was thymoglobulin, corticosteroids, mycophenolate mofetil, and delayed introduction of tacrolimus. Six percent were nonfunctioning kidneys; 79.6% presented with delayed renal function (mean duration 14 ± 9 days). Acute rejection was seen in 6% of patients. Mean creatinine at month 3 was 1.7 ± 0.8 mg/dL, and 1.5 ± 0.8 mg/dL in the first year. The last available mean creatinine was 1.54 ± 0.7 mg/dL. Proteinuria in the third month, first year, and third year was 0.70, 0.41, and 0.26 g/d, respectively. Recipient survival at the first, third, and fifth year was 100%, 100%, and 86%, and when graft-censored for death was 94%, 91%, and 91%, respectively. The incidence of acute rejection during first year was 6%, and 2% in the second year. Exitus incidence was 4% and cytomegalovirus infection was 21.3%. BK viremia between 1000 and 10,000 copies/mL was seen in 4.3%, and reached >10,000 copies/mL in 2.1%. ConclusionsType II NHBD has shown limited frequency of nonfunctioning kidney and high functional delay. The results in survival and renal function are very acceptable, comparable with levels seen in donation after brain death.

Non–Heart-Beating Donor Kidney Transplantation Survival Is Similar to Donation After Brain Death: Comparative Study With Controls in a Regional Program

Non–heart-beating donors (NHBD) are an increasing source of organs for kidney transplantation (KT) compared with donation after brain death (DBD), but the results in each regional transplantation program require local analysis. We compared 164 KT from NHBD (83 Maastrich type II A-B [T2] and 81 type III [T3]) with 328 DBD controls. NHBD kidneys were implanted with less cold ischemia, mean time on renal replacement therapy for NHBD recipients before transplantation was less too, and a higher proportion of thymoglobulin was also used. Besides NHBD-T2 more frequently showing the A group and patients being younger (48.9 ± 11 vs DBD 55.2 ± 15 years old; P < .001), there was a lower proportion of retransplant recipients and HLA sensitization; HLA-DR compatibility was slightly worse. Proportion of nonfunctioning allograft and necessity of dialysis after transplantation for NHBD were 4.9 and 68.3% versus DBD 4.3 and 26.9% (P < .001); renal function after a year was significantly less in NHBD (serum creatinine 1.79 ± 0.9 mg/dL vs 1.46 ± 0.5 in DBD; P < .001). NHBD recipient survival rates were 96% and 96% for the 1st and 3rd years, respectively, versus 96% and 94% for DBD, respectively (not significant [NS]). Graft survival rates censored by death were 91% and 89% (1st and 3rd years, respectively) versus 95% and 94% for DBD, respectively (NS). We did not find significant differences about survival between NHBD-T2 and T3. In the multivariable survival study (Cox, covariables with statistical significance demonstrated previously in our region), NHBD is not a prognosis factor for recipient or graft survival. Regarding current criteria for choosing donors and the graft allocation applied in Andalusia, short-term survival for NHBD transplantation is similar to DBD. Renal function in the short term is slightly worse, which is why it is important to monitor results over a long term, especially those from NHBD-T2.

A Prospective Randomised Paired Trial of Sirolimus versus Tacrolimus as Primary Immunosuppression following Non-Heart Beating Donor Kidney Transplantation

Introduction: With calcineurin inhibitors potentiating damage from ischaemia-reperfusion injury in kidneys from donors after cardiac death we wanted to investigate the role of substituting sirolimus for tacrolimus in the delayed introduction of calcineurin inhibitor regime used in our centre. Method: A prospective randomised paired open-label study was performed taking pairs of kidneys from each donor and randomising one to a tacrolimus-based regime and the other to a similar regime based on sirolimus. Graft function at one year was the primary endpoint. Results: Total 31 pairs of kidneys were randomised to each group, with 19 pairs of recipients available for analysis after post-randomisation study exclusions. Despite a higher incidence of biopsy proven acute rejection in the sirolimus group, renal allograft function was similar in both groups at three-monthly intervals up to one year post-transplant. All episodes of acute rejection in the sirolimus group occurred in the first three months. Graft and patient survival at one year was 100% in the tacrolimus group, with one death with functioning graft in the sirolimus group (95% survival). Unfortunately, 10 of the 19 patients in the sirolimus arm required switch of medication to tacrolimus due to acute rejection or intolerable drug side effects. Conclusions: Graft survival and function were very similar in the two groups despite the higher rate of acute rejection in the sirolimus arm, raising the possibility that the damage done by acute rejection was adequately offset by the nephron-sparing effect of sirolimus compared to tacrolimus. Sirolimus may have a role as a longer-term maintenance immunosuppressant after initial treatment with a different agent such as tacrolimus or belatacept.

Obstacles of Non–heart-beating Donor Kidney Transplantation in Japan to Date and Future Perspectives

In Japan, multiple organ retrieval from brain-dead heart-beating donors has been gradually increasing since the law was adopted in 1997 and amended in 2009. However, almost more than 90% of total deceased donor kidney transplantation (DDKT) in Japan are still obtained from non–heart-beating donors (NHBD). The majority of NHBD are Maastricht categories IV and III. In category IV, we usually place a double balloon arterial and a venous drainage catheter via the femoral vessels after the diagnosis of clinical brain death and acquisition of informed consent from the family. After controlled cardiac arrest, the double balloons are inflated and in situ cold perfusion started as soon as possible to minimize warm ischemic time (WIT), seeking to achieve a zero to within a few minutes WIT in most cases. In category III, it is impossible to place the device prior to cardiac arrest. In these cases, after declaration of cardiac death, cardiopulmonary compression is accompanied by systemic heparinization, immediate laparotomy, and insertion of a cold perfusion catheter at the aortic and caval bifurcations to minimize WIT. NHBD kidney retrieval is critical; extirpation must be performed as rapidly as possible. The results of NHBD kidney transplantation in Japan are excellent, according to the advancement and utilization of in situ cannulation, organ perfusion, and sophisticated retrieval techniques. The patient and graft survival rates of DDKT at 1, 3, and 5 years in most recent 2001 to 2007 era were 95.4%, 92.2%, 89.1% (n = 945) and 89.2%, 83.7%, 77.8% (n = 919), respectively.

Non-Heart Beating Donor Kidney Transplantation Is not Associated with An Increased Risk of Post-Transplant Infection

Objectives: The use of kidneys from non-heart beating donors (NHBD) has increased notably over the last years. The impact of such strategy on the risk of post-transplant infection remains unclear. Methods: We performed a prospective cohort study including 225 patients (143 males; mean age: 54.4 ± 14.1 years) who underwent kidney transplant (KT) at our institution from November 2008 to August 2010. We compared the incidence and clinical and microbiological characteristics of post-transplant infection between recipients of brain-dead donor (BDD) and NHBD grafts (154 and 71 patients, respectively). NHBD belonged mostly to categories I and II of the Maastricht classification (uncontrolled donnors). All patients in the NHBD group received induction therapy with antithymocyte globulin (ATG) and antiviral prophylaxis (mainly valganciclovir) during the first 3 months. Multivariate adjusted odds ratios (ORs) for infection were calculated using those covariates found to be significant at P < 0.10 by univariate analysis. Results: As compared to patients in the BDD group, those in the NHBD group were younger (P < 0.001), had fewer years on pre-transplant dialysis (P = 0.004), shorter cold-ischemia times (P < 0.001), and higher number of HLA mismatches (P = 0.052). Delayed graft function (requirement for dialysis within the first week after transplantation) was more frequent in the NHBD group (84.5% vs. 52.6%; P < 0.001), as well as donor/recipient cytomegalovirus (CMV) mismatch (12.7% vs. 5,8%; P = 0.079). Incidence rates of overall infection in the NHBD and BDD groups were 1.94 and 3.25 episodes per 1,000 transplant-days, respectively (P < 0.0001). Incidence rate of early infection (during the first month) was also lower in the NHBD group than in the BDD group (8.4 vs. 14.12 episodes per 1,000 transplant-days, respectively; P = 0.006). Patients in the NHBD group exhibited lower cumulative incidences of bacterial infection (P = 0.044), acute graft pyelonephritis (P = 0.081), CMV infection (P = 0.016), and non-CMV viral infection (P = 0.028). We found no differences in the incidence of other types of infection. On the regression model, and after adjusting for age, induction therapy, and cold-ischemia time, among other variables, the receipt of a NHBD graft did not remain as an independent risk factor for post-transplant infection (OR 0.63; 95% CI 0.35-1.15; P = 0.191). Conclusion: In our experience, and despite the higher occurrence of delayed graft function and CMV mismatch and the universal use of ATG induction, KT from uncontrolled NHBD does not entail an increased risk of post-transplant infection.

Non-Heart Beating Donor Kidney Transplantation Is not Associated with An Increased Risk of Post-Transplant Infection

Objectives: The use of kidneys from non-heart beating donors (NHBD) has increased notably over the last years. The impact of such strategy on the risk of post-transplant infection remains unclear. Methods: We performed a prospective cohort study including 225 patients (143 males; mean age: 54.4 ± 14.1 years) who underwent kidney transplant (KT) at our institution from November 2008 to August 2010. We compared the incidence and clinical and microbiological characteristics of post-transplant infection between recipients of brain-dead donor (BDD) and NHBD grafts (154 and 71 patients, respectively). NHBD belonged mostly to categories I and II of the Maastricht classification (uncontrolled donnors). All patients in the NHBD group received induction therapy with antithymocyte globulin (ATG) and antiviral prophylaxis (mainly valganciclovir) during the first 3 months. Multivariate adjusted odds ratios (ORs) for infection were calculated using those covariates found to be significant at P < 0.10 by univariate analysis. Results: As compared to patients in the BDD group, those in the NHBD group were younger (P < 0.001), had fewer years on pre-transplant dialysis (P = 0.004), shorter cold-ischemia times (P < 0.001), and higher number of HLA mismatches (P = 0.052). Delayed graft function (requirement for dialysis within the first week after transplantation) was more frequent in the NHBD group (84.5% vs. 52.6%; P < 0.001), as well as donor/recipient cytomegalovirus (CMV) mismatch (12.7% vs. 5,8%; P = 0.079). Incidence rates of overall infection in the NHBD and BDD groups were 1.94 and 3.25 episodes per 1,000 transplant-days, respectively (P < 0.0001). Incidence rate of early infection (during the first month) was also lower in the NHBD group than in the BDD group (8.4 vs. 14.12 episodes per 1,000 transplant-days, respectively; P = 0.006). Patients in the NHBD group exhibited lower cumulative incidences of bacterial infection (P = 0.044), acute graft pyelonephritis (P = 0.081), CMV infection (P = 0.016), and non-CMV viral infection (P = 0.028). We found no differences in the incidence of other types of infection. On the regression model, and after adjusting for age, induction therapy, and cold-ischemia time, among other variables, the receipt of a NHBD graft did not remain as an independent risk factor for post-transplant infection (OR 0.63; 95% CI 0.35-1.15; P = 0.191). Conclusion: In our experience, and despite the higher occurrence of delayed graft function and CMV mismatch and the universal use of ATG induction, KT from uncontrolled NHBD does not entail an increased risk of post-transplant infection.

Hydrogen sulphide ameliorates ischaemia–reperfusion injury in an experimental model of non-heart-beating donor kidney transplantation

: Therapies to alleviate ischaemia-reperfusion (IR) injury have an important role in kidney transplantation. This study used a porcine model of non-heart-beating (NHB) donor kidneys to investigate the effects of hydrogen sulphide on IR injury. : Porcine kidneys were subjected to 25 min of warm ischaemia and 18 h of cold storage. They were reperfused ex vivo with autologous oxygenated blood to assess renal function. A group treated with hydrogen sulphide (0.5 mmol/l) infused 10 min before and after reperfusion (n = 6) was compared with an untreated control group (n = 7). : Hydrogen sulphide significantly improved renal blood flow compared with control values (mean(s.d.) area under the curve (AUC) 614.9(165.5) versus 270.3(86.7) ml per min per 100 g.h; P = 0.001) and renal function (AUC creatinine: 1640(248) versus 2328(154) micromol/l.h; P = 0.001; AUC creatinine clearance: 6.94(5.03) versus 0.96(0.32) ml per min per 100 g.h; P = 0.004). Oxidative damage was also reduced by hydrogen sulphide (urinary 8-isoprostane at 1 h of reperfusion: 478.9(237.1) versus 1605.6(632.7) pg/ml per mmol/l creatinine; P = 0.032). : Hydrogen sulphide ameliorated the renal dysfunction associated with ischaemic damage, and has potential as a therapy against IR injury in NHB donor kidney transplantation.

Dual Transplantation of Marginal Kidneys From Nonheart Beating Donors Selected Using Machine Perfusion Viability Criteria

Viability testing can be used to avoid the transplantation of nonheart beating donor organs that are likely to have primary nonfunction. Such testing also identifies a second group of kidneys which, although unsuitable for solitary transplantation, may be considered for dual transplantation. In kidneys in this group solitary transplants would be unlikely to produce a sufficient glomerular filtration rate to support the recipient. However, if used together as a dual transplant, they have the potential to produce sufficient renal function in 1 patient. The group at our unit has performed 23 dual nonheart beating donor renal transplants from 2003 to date. Using 3 and 12-month post-transplantation recipient glomerular filtration rates as primary end points we compared our dual transplant group with our series of 115 single nonheart beating donor transplants from 1998 to 2006. At 3 and 12 months mean glomerular filtration rates in the dual group were 46.2 and 45.5 ml per minute per 1.73 m(2), respectively. These values were not significantly different from the mean glomerular filtration rates of 40.7 and 43.0 ml per minute per 1.73 m(2), respectively, in the single transplant group. We have observed that a subset of nonheart beating donor kidneys that do not satisfy the viability criteria for single organ transplantation may become successful dual organ grafts, thus, avoiding unnecessary organ nonuse and maximizing organ resources.

Carbon Monoxide Protects Against Ischemia-Reperfusion Injury in an Experimental Model of Controlled Nonheartbeating Donor Kidney

CO-releasing molecule-3 (CORM-3) is a transitional metal carbonyl that liberates carbon monoxide under appropriate conditions. Carbon monoxide exerts effects on intracellular apoptotic and inflammatory pathways, which suggest a role in reducing the effects of renal ischemia/reperfusion (I/R) injury. This study investigated the effects of CORM-3 administered at the time of reperfusion in a model of controlled nonheartbeating donor kidneys. Porcine kidneys (n=4) were subjected to 10 min warm ischemia and 18 hr cold storage (CS) and then treated as follows: CORM-3 (50, 100, 200, and 400 microM doses), iCORM-3 (inactive carbon monoxide-releasing molecule, 50 microM), and control (no further intervention). Renal hemodynamics and function were then measured during 3-hr reperfusion with autologous blood using an isolated organ-perfusion system. CORM-3 at a concentration of 50 microM improved renal blood flow (RBF) compared with the iCORM and control groups (area under the curve 774+/-19 vs. 448+/-88 vs. 325+/-70, respectively, P=0.002). CO-releasing molecule-3 at a concentration of 50 microM also improved renal function during reperfusion with a greater area under the curve for creatinine clearance (CORM-3: 14+/-6 vs. iCORM: 3.3+/-0.1 vs. control: 2.2+/-2 mL/min, P=0.006) and higher urine output (CORM-3: 793+/-212 vs. iCORM: 368+/-72 vs. control: 302+/-211 mL, P=0.01). CO-releasing molecule-3 at a concentration of 100 microM exerted similar effects. Treatment with CORM-3 at higher doses (200 and 400 microM) led to poor renal hemodynamics and function after reperfusion. Low-dose CORM-3 significantly ameliorates the effects of ischemia/reperfusion in a porcine model of controlled nonheartbeating donor kidney transplantation.

Effects of erythropoietin on ischaemia/reperfusion injury in a controlled nonheart beating donor kidney model

Erythropoietin (EPO) has been shown to have an anti-apoptotic action and has the potential to protect against ischaemia/reperfusion injury. This study investigated the effect of high dose EPO (5000 U), administered as a bolus at the onset of reperfusion and at the onset of cold storage in a model of controlled nonheart beating donors kidneys. Porcine kidneys(n = 6) were subjected to 10min warm ischaemia and preserved as follows: Group 1:16 h Cold storage +2 h Normothermic perfusion (16 h CS + 2 h NP) Group 2:16 h CS + 2 h NP + EPO given at the onset of reperfusion Group 3:18 h CS (static hypothermic storage) Group 4:18 h CS + EPO given at the onset of cold storage Haemodynamic and functional parameters were assessed during 3-h reperfusion using autologous blood. Renal blood flow improved in Groups 1 and 2 vs. Groups 3 and 4 though no difference was noted between Groups 3 and 4 (563 +/- 119 vs. 491 +/- 95 vs. 325 +/- 70 vs. 418 +/- 112, respectively; P = 0.012). Total urine output showed no difference between Groups (271 +/- 172 vs. 359 +/- 184 vs. 302 +/- 21 vs. 421 +/- 88; P = 0.576). Percentage serum creatinine fall at 3 h was significantly better in Groups 1 and 2 vs. Group 3 (64 +/- 17 vs. 60 +/- 11 vs. 44 +/- 13 vs. 52 +/- 8; P = 0.04). Fractional-excretion of sodium was significantly lower for Groups 1 and 2 vs. Group 3 and 4 (17 +/- 14 vs. 18 +/- 9 vs. 49 +/- 21 vs. 45 +/- 16 respectively; P = 0.002). There was significant improvement in oxygen consumption in Groups 2 vs. Groups 3 and 4 (P = 0.037) (39 +/- 10 vs. 46 +/- 10 vs. 24 +/- 12 vs. 24 +/- 7 respectively). EPO added at the time of reperfusion improved oxygen consumption when added to NP in comparison to static hypothermic storage but did not exert any other major benefits.

The Relative Effects of Warm and Cold Ischemic Injury in an Experimental Model of Nonheartbeating Donor Kidneys

Ischemia reperfusion injury (I/R) leads to delayed graft function and remains an important problem in renal transplantation. The aim of this experimental study was to assess the effects of warm (WI) and cold ischemia (CI) in models of heartbeating (HBD) and controlled/uncontrolled nonheartbeating donor (NHBD) kidneys. A reperfusion model utilizing cardiopulmonary bypass technology was used to perfuse isolated porcine kidneys with autologous blood after the following conditions: 0 min WI+2 h cold storage (CS); 0 min WI+18 h CS; 10 min WI+2 h CS; 10 min WI+18 h CS; 25 min WI+2 h CS; 25 min WI+18 h CS. Renal function was measured over a period of 3 hr. Renal functional parameters were not significantly different between 0, 10, 25 WI with 2 h CS [AUC creatinine (Cr) decrease of 1057+/-177, 1102+/-260, and 1245+/-143 micromol/L h, P=0.338; AUC creatinine clearance (CrCl) of 37.7+/-15.8, 36.2+/-21.7, 19.8+/-9.1 ml/min/100 g h, P=0.099]. After 18 h CS, renal function was severely impaired in the 10 and 25 WI groups compared to 0 min WI [AUC Cr of 2156+/-401, 2287+/-148, 1563+/-395 micromol/L h, P=0.037; AUC CrCl of 2.2+/-1.7, 1.5+/-1.5, 21.7+/-13.4 ml/min/100 g h, P=0.007). Warm ischemia of up to 25 min was only detrimental to renal function when kidneys were subsequently preserved in cold storage for 18 hr. This data suggests that limiting the cold storage period is of paramount importance when transplanting kidneys subjected from nonheartbeating donors.

心停止下腎臓提供における臓器提供意思表示カード所持確認と臓器提供オプション提示の意義 : 脳神経外科医師に期待される腎臓移植医療への貢献

われわれは28献腎該当例の家族にドナーカード所持確認とオプション提示を行った.その結果カード所持2例を含む19例で承諾が得られた.19例の承諾は,6例では本人の積極的意思に基づき,残る13例では家族の積極的意思に基づいた.他方提供拒否9例では家族が臓器提供に基本的に反対であった.2006年では国民の8%がカードを所持して41.6%が臓器提供に理解を示している.しかし脳神経外科医師によるカード所持確認やオプション提示は稀で,提供のほとんどは家族の自発的カード提出に依存する.そこで提供可能な腎臓が年間1万個以上破棄されている.臓器移植医療への脳神経外科医師の貢献が期待される.

Kidney transplantation from non–heart-beating donors: a Spanish view

All over the world, the waiting list and waiting time for transplant will inevitably become longer as the demand for kidneys continues to exceed the supply. Although there is a need to extend the use of brain-dead donors with heartbeats, there is still room for additional sources of organs, and this has prompted the use of the non–heart-beating donor (NHBD). The viability of the kidney from the NHBD, which is invariably subjected to a period of warm ischemia, is the most crucial factor for transplant outcome. However, in our experience, by applying a strict warm ischemia protocol and carefully managing the donor, the percentage of non-functioning grafts is low. The results presented in terms of graft survival and mid-term renal function with NHBD are encouraging and comparable to those related to the use of kidneys from young heart-beating donors. Based on these data, NHBDs should not be considered suboptimal, since other marginal donors such as elderly donors, for instance, have resulted in worse outcomes. In our experience, the NHBD kidney is an extremely useful contribution to the donor pool, and its use has allowed us to increase the total number of kidney transplants performed and, as consequence, to decrease the waiting list.

Sequential Quadruple Immunosuppression Including Sirolimus in Extended Criteria and Nonheartbeating Donor Kidney Transplantation

The aim was to evaluate feasibility and safety of calcineurin inhibitor-free immunosuppression in high-risk donor kidney transplantation with sequential sirolimus introduction. Kidney transplant patients (n=76) with a donor aged >60 years, donor with acute renal failure, or a nonheartbeating donor were included. Immunosuppression consisted of antithymocyte globulin or basiliximab, mycophenolate mofetil, prednisone, and sequential introduction of sirolimus. One-year patient survival was 96.2% and 95.8%; graft survival was 94.2% and 91.7%; acute rejection rates were 21.2% and 12.4%; delayed graft function was 21.2% and 66.7%; and creatinine clearance was 58+/-20 mL/min and 56+/-21 mL/min for the brain-dead donor group and the nonheartbeating donor group, respectively. Most adverse events were infections, but also three lymphoceles, three urinary fistulas, three wound seromas. Sequential sirolimus introduction in high-risk donor kidney transplantation was found to lead to good patient and graft survival and incidence of acute rejection and delayed graft function.

Recipient Hemodynamics During Non-Heart-Beating Donor Kidney Transplantation Are Major Predictors of Primary Nonfunction

Non-heart-beating donor (NHBD) kidneys may substantially expand the donor pool, but many transplant centers are reluctant to use these kidneys because of the relatively high incidence of primary nonfunction (PNF). In heart-beating donor kidneys, intravascular fluid depletion during transplant surgery is associated with delayed graft function (DGF). Therefore, we studied the effect of the recipients' hemodynamic status on the outcome of 177 NHBD kidney transplantations. Independent statistically significant predictors of PNF were average central venous pressure (CVP) below 6 cmH(2)O (adjusted odds ratio (AOR) 3.1 (95% CI: 1.4-7.1), p=0.007), average systolic blood pressure below 110 mmHg (AOR 2.6 (95% CI: 1.1-5.9), p=0.03) and pre-operative diastolic blood pressure below 80 mmHg (AOR 2.4 (95% CI: 1.0-5.9), p=0.05). Donor characteristics were not independently associated with PNF (p>0.10). In a subgroup analysis of 56 paired kidneys, 29% of the recipients with the lower CVP of the pair experienced PNF compared with 11% of their counterparts with higher CVP (p=0.09). Our study indicates that recipient hemodynamics during transplant surgery are major predictors of PNF. Therefore, improving recipient hemodynamics by expansion of the intravascular volume is expected to enhance the results of NHBD kidney transplantations and may enlarge the donor pool by increasing the acceptance of NHBD kidneys.

Comparison of HTK and Hypertonic Citrate to Intraarterial Cooling in Human Non–Heart-Beating Kidney Donors

Intraarterial cooling (IAC) of non–heart-beating donors (NHBD) for renal donation requires a cheap, low-viscosity solution. HTK contains a high hydrogen ion buffer level that theoretically should reduce the observable acidosis associated with ongoing anaerobic metabolism. A retrospective comparison of all retrieved NHBD kidneys as well as of viability on the Organ Recovery Systems Lifeporter machine perfusion circuit was performed with respect to the preservation solution HTK or Marshall’s HOC. Forty-two NHBD kidneys (19 HTK and 23 HOC) were machine perfused between February 2004 and May 2005. Most of the HTK kidneys were obtained from uncontrolled donors (12 vs 5; Fisher exact test, P = .01). As a consequence, the glutathione- s-transferase viability assay (411 vs 292 IU/L, P = .12) and the lactate concentrations (2.33 vs 1.94 mmol/L, P = .13) were higher among the HTK cohort. There was evidence of greater buffering capacity in HTK, since the lactate:hydrogen ion ratios were consistently lower during the first 2 perfusion hours (1 hour P = .03, 2 hour P = .02). A linear regression analysis confirmed that this was related to the IAC solution (ANCOVA, P < .001). All controlled donor kidneys passed viability testing and were transplanted. In contrast, 83% (10/12) of the uncontrolled donor kidneys preserved with HTK passed the viability test and were transplanted, compared with only 20% (1/5) of the HOC-treated comparators (Fisher exact test, P = .03). It may be concluded that the postulated advantages of improved pH buffering with HTK appear to have clinical relevance.

Non-heartbeating donation of kidneys for transplantation

There is a persistent shortage of kidneys available for transplantation. In the early 1980s, therefore, we published the concept of non-heartbeating (NHB) donation; that is, procurement of kidneys from donors whose death has been accompanied by irreversible circulatory arrest. NHB donors are generally categorized using four definitions; category III (awaiting cardiac arrest) and category IV (cardiac arrest while braindead)--or 'controlled'--donors are the most suitable for initiating NHB donation programs. Delayed graft function is associated with use of kidneys from such donors, but has no effect on graft survival in the short or long term. Use of kidneys from category I (dead upon arrival at hospital) and category II (unsuccessfully resuscitated), or 'uncontrolled', donors is likewise associated with delayed graft function, but also with an increased risk of primary nonfunction. Viability testing of donated organs from these sources is a prerequisite for transplantation. Machine preservation parameters and enzyme release measurements help to distinguish viable from nonviable kidneys. The proportion of NHB donor kidneys in the total pool of postmortem kidneys differs considerably between countries. In The Netherlands, the proportion is nearly 50%. This figure is markedly higher than that in the US and Canada, where national programs have now been initiated to increase rates of NHB donation. In the future, warm preservation techniques might facilitate better viability testing, thereby increasing NHB donation from category I and II donors and further reducing the shortage of kidneys available for transplantation.

Non-Heart-Beating Kidney Transplantation: 6-Year Outcomes

Non-heart-beating donor kidneys (NHBD) are being used to increase the donor pool due to the scarcity of cadaveric heart beating donors (HBD). We evaluated the long-term outcomes of renal transplantation using NHBD kidneys, comparing the first 100 NHBD kidneys transplanted at our facility to the next consecutive cadaveric HBD kidneys for graft survival, recipient survival, and quality of graft function. Recipient survival ( P = .22) and graft survival ( P = .19) at 6 years did not differ between recipients of NHBD (83%, 80%) and HBD (89%, 87%) kidneys. Quality of graft function using the mean glomular filtration rates were significantly lower in the NHBD group up to 3 months following discharge (41 ± 2 vs 47 ± 2, P = .007) but were then comparable up to 6 years following transplantation (43 ± 5 vs 46 ± 4, P = .55).

Redox-Active Iron Released During Machine Perfusion Predicts Viability of Ischemically Injured Deceased Donor Kidneys

Redox-active iron, catalyzing the generation of reactive oxygen species, has been implicated in experimental renal ischemia-reperfusion injury. However, in clinical transplantation, it is unknown whether redox-active iron is involved in the pathophysiology of ischemic injury of non-heart-beating (NHB) donor kidneys. We measured redox-active iron concentrations in perfusate samples of 231 deceased donor kidneys that were preserved by machine pulsatile perfusion at our institution between May 1998 and November 2002 using the bleomycin detectable iron assay. During machine pulsatile perfusion, redox-active iron was released into the preservation solution. Ischemically injured NHB donor kidneys had significantly higher perfusate redox-active iron concentrations than heart-beating (HB) donor kidneys that were not subjected to warm ischemia (3.9 +/- 1.1 vs. 2.8 +/- 1.0 micromol/L, p = 0.001). Moreover, redox-active iron concentration was an independent predictor of post-transplant graft viability (odds ratio 1.68, p = 0.01) and added predictive value to currently available donor and graft characteristics. This was particularly evident in uncontrolled NHB donor kidneys for which there is the greatest uncertainty about transplant outcomes. Therefore, perfusate redox-active iron concentration shows promise as a novel viability marker of NHB donor kidneys.

Dual Renal Transplantation for Kidneys From Marginal Non-Heart-Beating Donors

Kidneys transplanted from non-heart-beating donors (NHBD) are generally regarded as marginal or extended criteria grafts due to the associated period of warm ischemia. The most prolonged periods occurring in the category II (uncontrolled) donor. This potential for injury can adversely affect the glomular filtration rate (GFR), which in severe cases results in primary nonfunction. Viability testing can identify a group of kidneys that, although unsuitable for solitary transplantation, may be considered for dual transplant. This retrospective study examined a series of 11 dual renal transplants, comparing 3- and 12-month GFR outcome data with 81 single NHBD transplants. The mean GFR at 3 months in the dual group was 47.6 and at 12 months was 48.6. In the single group the GFR at 3 months was 40.6 and at 12 months was 41.9. Thus using viability testing to identify NHBD kidneys suitable for dual transplant appears reliable and predictable.