Dolores Prats

Victims of Cardiac Arrest Occurring Outside the Hospital: A Source of Transplantable Kidneys

Context Waiting lists for kidney transplants are long. Contribution This study from Madrid, Spain, compared transplantation outcomes of 584 recipients of kidneys from heart-beating donors and 320 recipients of kidneys from nonheart-beating donors who died of cardiac arrest that occurred outside the hospital. One-year (about 90%) and 5-year (about 85%) graft survival rates were similar for transplantations from nonheart-beating donors and those from heart-beating donors who were younger than 60 years of age. Cautions This retrospective study is from a center with a well-developed nonheart-beating donor transplantation program. Implications People who die of cardiac arrest that occurs outside the hospital can be a viable source for kidney transplantations. The Editors The waiting list and waiting time for transplantations will inevitably become longer as the demand for kidneys continues to exceed the supply. The kidney waiting list of the United Network for Organ Sharing currently increases at a rate of 20% per year, and the list will be 100000 to 150000 patients long by the year 2010 (1). The overall annual mortality rate for wait-listed patients for kidney transplants is estimated to be 6.3% (2). While obtaining more organs from brain-dead donors with heartbeats is necessary, additional sources of organs are also needed, which has prompted the use of the nonheart-beating donor. Nonheart-beating donors are categorized into 5 types (Appendix Table) (3). Type I and type II are considered uncontrolled donors because cardiac arrest events in these patients occur outside the hospital and, thus, the transplant team is unaware of them. In type III and type IV nonheart-beating donors, cardiac arrest is managed, or controlled, in the hospital, and the transplant team can prepare for the procurement process. In type V nonheart-beating donors, this aspect can vary. Several reports have discussed the use of nonheart-beating donors (424), and the incidence of this type of donation is increasing. However, most patients described in these studies have in-hospital cardiac arrest, and few references have been made to donors whose deaths occur outside the hospital. Appendix Table. Description of the NonHeart-Beating Donor Types (Maastricht System) In 1989, our institution (Hospital Clnico San Carlos, Madrid, Spain) began a nonheart-beating donor procurement and transplant program. Our hospital is currently the largest procurement center for this type of transplantation in Spain, supplying 46% of the nonheart-beating donor kidneys transplanted in Spain in 1997 (3, 25). Most of our donors are adults who die suddenly outside the hospital and are transferred to the hospital for the sole purpose of donation (Maastricht type I donors) (26). We aimed to compare the graft survival of kidneys from uncontrolled nonheart-beating donors (Maastricht donors type I and II) and kidneys from heart-beating donors. Methods Donor Program In 1989, our hospital started a program to obtain organs from nonheart-beating donors (3). In 1996, we signed a formal agreement with the Madrid emergency facilities (SAMUR, 061, SERCAM) and established a standard protocol for obtaining organs from persons who die suddenly outside the hospital of irreversible cardiac arrest (type I Maastricht donor category) and are transported to our center for organ donation. Before 1996, most of these persons were directly transported to the morgue, but after 1996, patients were transferred to our hospital after unsuccessful cardiovascular pulmonary resuscitation (CPR). This protocol does not affect any CPR maneuver. All measures and times specified in the established CPR procedures are undertaken, and we evaluate the patient as a potential donor only when the cardiac arrest is considered irreversible (when an effective heartbeat cannot be recovered after a stipulated period [usually 30 minutes] or when the lesions provoking the cardiac arrest are incompatible with life). The following conditions should also be met when considering a potential donor: known cause of death, ruling out violence; known time of cardiac arrest; no bleeding injuries to the thorax or abdomen to avoid blood leaks in subsequent cardiopulmonary bypass during procurement; external cardiac massage and mechanical ventilation performed within 15 minutes of the cardiac arrest; no external signs of possible intravenous drug abuse suggesting a risk for HIV, hepatitis C, or hepatitis B infection; and donor age less than 60 years. When an individual has been classified as a potential donor, the emergency team continues with cardiac massage, mechanical ventilation, and intravenous fluid perfusion to maintain adequate hemodynamic conditions during transport to our hospital. Upon arrival, the transplant coordination team checks for the conventional prerequisites for donation (for example, no infections; negative results on serologic tests for HIV and hepatitis B and C; and no tumors) and then transfers the cadaver to the operating room. In type I and type II nonheart-beating donors, the femoral vein and artery are cannulated via an incision in the right side of the groin and are connected to a cardiopulmonary bypass machine with external oxygenation and hypothermia. The maximum time of warm ischemia (from the start of cardiac arrest until bypass) should not exceed 120 minutes. Maximum pump cold perfusion time is 240 minutes. While the organ is being perfused, the transplant coordination team fulfills the legal requirements for donation. The first step is to locate the family of the deceased person and obtain consent for organ extraction. Organ retrieval is performed according to the Maastricht protocol, which requires a diagnosis of death by physicians independent of those of the procurement team and a procurement protocol approved by the local medical ethics committee according to the current organ procurement legislation. Since 1999, Spain has had a law (Real Decreto 2070/1999) that allows organ donation after cardiac arrest. Under this law, the donor can undergo cardiopulmonary bypass until the necessary consent is obtained for organ extraction. In the past year, only 7% of families declined consent for organ extraction. Study Design and Sample From January 1989 to December 2004, our center transplanted 342 kidneys from nonheart-beating donors. According to the modified Maastricht donor classification scheme (3), these graft donors are classified as follows: 273 (79.8%) type I donors (dead on arrival), 47 (13.7%) type II donors (unsuccessful resuscitation in the emergency department), 6 (1.8%) type III donors (cardiac arrest in intensive care), 4 (1.2%) type IV donors (cardiac arrest during or after a diagnosis of brain death), and 12 (3.5%) type V donors (unexpected cardiac arrest in intensive care). In our retrospective study of procedures at our center, we compared data from 320 recipients of kidneys from uncontrolled, nonheart-beating donors (type I or type II Maastricht donor category) with those from 584 recipients of kidneys from adult cadaveric heart-beating donors between January 1989 and December 2004. We divided the heart-beating donor transplants into 2 groups according to donor age: younger than 60 years of age (n= 458) and 60 years of age or older (n= 126). Figure 1 shows data on the transplantations performed per year. We excluded transplantations from types III, IV, and V nonheart-beating donors and those from heart-beating donors other than adult cadaveric donors (en bloc pediatric renal transplantations or double renal transplantations from older donors). Figure 1. Kidney transplantations at the Hospital Clnico San Carlos, Madrid, Spain, January 1989December 2004. Other transplantations are those involving other than single adult cadaveric heart-beating donors (en bloc pediatric renal transplantations or double renal transplantations from donors 60 years of age) and those involving types III, IV, and V nonheart-beating donors. Treatment and Outcome Measures We treated transplant recipients with quadruple sequential therapy (antithymocyte globulin for 7 days, azathioprine, prednisone from the time of transplantation, and cyclosporine from day 5) from January 1989 to July 1996. From July 1996 to March 2001, the immunosuppression regimen used was triple therapy with cyclosporine or tacrolimus (plus prednisone and mycophenolate). After March 2001, recipients of kidneys from nonheart-beating donors and from heart-beating donors 60 years of age or older received daclizumab and a half-dosage of tacrolimus (0.1 mg/kg of body weight per day to achieve trough levels between 5 ng/mL and 8 ng/mL) during the first 2 weeks to avoid delayed graft function, whereas recipients of kidneys from heart-beating donors younger than 60 years of age did not receive daclizumab and were treated with full-dosage tacrolimus (0.2 mg/kg per day to achieve trough levels between 8 ng/mL and 12 ng/mL). The dosages of mycophenolate and steroids were similar for the 3 groups. Hyperimmunized patients (preformed reactive antibodies 50%) were treated with the monoclonal antibody muromonab-CD3 or antithymocyte globulin. We defined delayed graft function as the need for dialysis during the immediate post-transplantation period. Patients who showed delayed graft function underwent a biopsy every 7 days until renal function started to improve. We graded acute rejection according to the Banff 97 classification (27). We treated grade I rejection (interstitial infiltration and tubulitis) with high doses of pulse steroids. We treated grade II (intimal arteritis) or grade III (transmural arteritis) rejection with either muromonab-CD3 or antithymocyte globulin. Our policy is to discharge patients when graft function starts to improve. Subsequent ambulatory patient management does not vary according to donor type. The end point of the study was graft loss, defined as nephrectomy, retransplantation, or permanent return to dialysis. We followed pa

Increasing the donor pool using en bloc pediatric kidneys for transplant.

Objectives. En bloc pediatric kidney transplants (EBPKT) are still a subject of controversy. The aim of this study was to determine whether acceptable long-term graft survival and function can be achieved in EBPKT compared with the transplant of single, cadaveric, adult donor kidneys. Methods. A retrospective review was conducted of 66 recipients of en bloc kidneys from cadaveric pediatric donors and 434 patients who underwent transplantation with a single kidney from an adult donor between January 1990 and May 2002 at the authors’ hospital. The recipients were well-matched demographically. Both transplant groups were analyzed for short- and long-term performance in terms of transplant outcome and quality of graft function. Results. Overall death-censored actuarial graft survival rates at 1 and 5 years were 89.2% and 84.6% in the adult kidney transplants (AKT) and 83.3% and 81.1% in EBPKT, respectively (P =0.56). In the EBPKT group, graft function was improved over that observed in AKT. Vascular thrombosis was the most common cause of graft loss in EBPKT. Acute rejection occurred more frequently in AKT and Cox’s regression analysis indicated that undergoing an AKT was a predictive factor for acute vascular rejection (adjusted risk ratio, 3.8; 95% confidence interval, 1.4–10.2; P =0.001). Conclusions. Overall graft survival was similar in both groups, vascular complications were the main cause of graft loss in EBPKT, and the EBPKT showed excellent long-term graft function and a low incidence of acute rejection.

Does renal mass exert an independent effect on the determinants of antigen-dependent injury?

The aim of this retrospective study was to determine whether nephron mass may exert a direct, independent effect on immunological tolerance. To this end, data corresponding to patients transplanted with en block pediatric kidneys (EBPK) (n=48) were compared with those of renal transplants with a low risk of hyperfiltration (LRH) comprised of recipients of a kidney from young donors (age 5–40 years) (n=173), and transplants with a high risk of hyperfiltration (HRH) comprised of patients who had received a graft from an elderly donor (older than 55 years) (n=91). All the patients had been subjected to the same immunosuppressive treatment. The median follow-up period was 54 months (6–127 months). The EBPK group showed lowest serum creatinine and highest creatinine clearance levels at each follow-up time. The rate of proteinuria >500 mg/day was 5.7% in EBPK, 7.4% in LRH, and 27.3% in HRH (P =0.000). The incidence of acute corticoresistant rejection was minor in EBPK (7.0% in EBPK, 21.3% in LRH, and 23.3% in HRH;P =0.04). Logistic regression analysis showed that the type of transplant was predictive of acute corticoresistant rejection [RR 5.33 (95% confidence interval (CI) 1.15–24.62) for HRH and RR 4.75 (95%CI 1.06–21.27) for LRH, P =0.03]. Multivariate analyses for graft failure due to chronic rejection and for graft failure due to acute rejection according to Cox’s regression analysis demonstrated that HRH transplant was a significant predictive variable of both types of failure [4.08 (95%CI 1.27–13.04) for graft loss due to chronic rejection and 8.69 (95%CI 1.69–44.67) for graft loss due to acute rejection]. The present stratification of data according to nephronal mass would appear to indicate that the greater the mass, the lower the incidence of both acute and chronic rejection. This finding lends support to the hypothesis that a large mass of transplanted tissue relative to recipient mass may dampen the immune response.

Functional glomerular reserve in recipients of en bloc pediatric transplant kidneys

BACKGROUND The transplantation of an adequate renal mass is increasingly recognized to be of importance. The improved graft survival is probably due to a lesser risk of developing hyperfiltration-associated lesions. METHODS We have reviewed the glomerular reserve in our recipients of en bloc pediatric transplant kidneys after an intravenous amino acid overload and compared them to single adult kidney transplant recipients. RESULTS En bloc transplants evidenced increased glomerular filtration rate as compared with baseline as from the second hour of amino acid infusion (from 71+/-14 to 84.9+/-17 ml/min, 1.73 m2, P<0.05) and increased renal plasma flow as from the third hour (from 335+/-116 to 402+/-155 ml/min, 1.73 m2, P<0.05). In the single adult kidney recipient group, no change was seen either in the glomerular filtration rate (from 62.5+/-13 to 58.1+/-13 ml/min, 1.73 m2, P=NS) nor in renal plasma flow (from 354+/-125 to 304+/-98 ml/min, 1.73 m2, P=NS). CONCLUSIONS These results show that patients receiving en bloc pediatric kidney transplantations have a greater renal functional reserve and show a lesser risk of hyperfiltration.

Incidence of renal artery stenosis in pediatric en bloc and adult single kidney transplants.

Background. The incidence, time of onset, and outcome of transplant renal artery stenosis (TRAS) in pediatric en bloc (PT) and adult single-kidney (AT) transplants were reviewed. Methods. Forty-three cases (7 PT and 36 AT) of suspected TRAS were selected out of 367 functioning grafts (35 of them PT). Diagnosis was performed by digital subtraction arteriography. Percutaneous transluminal angioplasty (PTA) was performed when needed. Results. Seven (20%) PT and 24 (7.1%) AT presented TRAS. Time of onset was 7±1 months in PT and 18±17 months in AT (P <0.05). PTA was performed in all cases of TRAS in PT and in 19 AT. One PT and 7 AT had re-stenosis. There was no significant difference in renal function after treatment. Control of blood pressure improved in both groups. Conclusions. Recipients of PT grafts showed a higher incidence and earlier onset of TRAS. Re-stenosis was more frequent in AT.

A 2 year evaluation of diabetic patients on continuous ambulatory peritoneal dialysis

Nineteen diabetic patients with end-stage renal disease on CAPD were evaluated over a 2 year period. All but one patient was insulin-dependent, with a mean age of 47.7 years. Average time on CAPD was 16.1 months (range, 2-28 months). Thirteen patients were followed for more than 12 months, and nine for more than 18 months. The mean training period was 22.9 days. Good blood glucose control was obtained with intraperitoneal (IP) insulin in all of the patients. Mean blood glucose levels of 125 +/- 23.08 mg/dl were achieved with 103 +/- 38.5 U/day of regular IP insulin. Glycosalated hemoglobin decreased from a mean of 12.7 +/- 2.35% before CAPD to 10.08 +/- 0.97% during CAPD. Peritoneal creatinine clearance remained stable during the study period, with a concommitant decrease (P less than 0.001) in the mean residual renal creatinine clearance. The incidence of peritonitis was one episode per 7.8 patient-months. Average length of hospitalization was 33.24 days/year. Visual acuity remained stable after 1 year in 73% of the 26 eyes evaluated. No amputations were required in more than 2 years of follow-up. Actuarial survival was 100% at 1 year and 86% at 2 years, and the technique survival of CAPD was 91 and 79%, respectively. These results demonstrate that CAPD is a good dialysis procedure for treating diabetic patients with chronic renal failure, and it offers the advantage of controlling glycemia better than other dialysis methods.