Update on the results of non-heart-beating donor kidney transplants.
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Biomedical subjects
Publications and source records attributed to G Kootstra.
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Given the shortage of donor kidneys for transplantation, we have focused on the use of non heart-beating (NHB) donor kidneys since 1982. The major drawback for the use of NHB donor kidneys is the inherent possibility of severe ischaemic damage leading to primary non function. Thus viability assessment of ischaemically damaged kidneys is crucial, and, therefore, a machine perfusion programme was reinstituted in 1993. Machine perfusion (MP) enables viability assessment through analysis of perfusion characteristics and measurement of enzyme release into the perfusate. Of the last 100 consecutive MP NHB donor kidneys, 71 kidneys were transplanted and 29 kidneys were discarded. Nine kidneys started functioning immediately, 51 kidneys showed delayed function and 11 kidneys never functioned. When analysing in retrospect different parameters for viability assessment, only alpha-GST, an enzyme specific for damage of proximal tubular cells within the kidney, could discriminate between functioning and non-functioning kidneys. With this promising viability assessment, the large NHB donor potential and the good transplant results, we recommend the use of these donors.
One of the ways to fight the growing organ shortage in transplantation is by procuring organs from non-heart-beating (NHB) donors. In order to determine the NHB kidney donor pool and evaluate its significance for renal transplantation, the potential is estimated in this study by retrospective death chart review. All 200 in-hospital deaths aged 3-65 yr reported at the University Hospital Maastricht in 1994, including 25 deaths at the Emergency Department (ED), were analyzed. After exclusion of deaths by computerized ICD-9-CM codes, 109 charts were abstracted and reviewed by experts. As a result a potential of eight brain dead, heart-beating (HB) donors and 56 NHB donors were identified. Medical suitability and logistic availability were scored in an attempt to quantify the likelihood of the donation to proceed towards successful organ procurement. These scores resulted in a range of potential NHB donors from 4.5 to 9.2 per 100 in-hospital deaths. Including rates of refusal to consent, as well as rates of technical failures, 24.0-49.6 kidneys were calculated to be realistically available annually, 2-4.5 times the projected number of kidneys from HB donors. With this increase of available grafts, at least growth of the renal waiting list would be prevented. This estimate shows that the potential of NHB kidney donors is large, and its impact on organ shortage would be considerable. Since 68% of potential NHB kidney donors, and also 70% of the medically most suitable donors, were found in ED, ICU, and CCU, focusing on these hospital units for implementation of routine procurement of kidneys from NHB donors is probably most effective. We therefore plead for the introduction of NHB kidney procurement protocols in EDs, ICUs, and CCUs.
BACKGROUND: Shouldice repair for primary inguinal hernia is reported to have better results than classic Bassini-type repairs. The indirect inguinal hernia with a firm posterior wall is often assumed to be adequately treated by high ligation and ring narrowing. STUDY DESIGN: This double randomized controlled trial compared high ligation and ring narrowing with Bassini-Stetten repair for the indirect inguinal hernia with a firm posterior wall, and Shouldice with Bassini-Stetten repair for the inguinal hernia with a weakened posterior wall, direct or indirect. This report focuses on longterm (12-15 years) recurrence rates. RESULTS: From July 1980 to May 1983, 102 indirect primary inguinal hernias with a firm posterior wall (group I) and 263 primary inguinal hernias with a weakened posterior wall (group II) were included. By 1995, 89 patients with 100 hernia repairs had died, and for 30 repairs the patients could not be located. In 41 hernia repairs, a recurrence had been established previously. Of the remaining 194 hernia repairs, followup was updated by physical examination in 179 (92%) and by telephone interview in 15 (8%). A total of 83 recurrences were recorded, 42% of which were asymptomatic at the time of diagnosis. Seventy-three percent of the recurrences happened > 2 years after the operation. The life-table method showed the following longterm (12-15 years) recurrence rates: group I, Bassini-Stetten 33% versus ring narrowing 34%; group II, Bassini-Stetten 32% versus Shouldice 15% (p = 0.033). CONCLUSIONS: The Shouldice is the best type of hernia repair, although the 15% recurrence rate is high. Bassini-Stetten and high ligation with ring narrowing are inadequate repairs, regardless of the type of hernia.
The aim of combined pancreas-kidney transplantation (PKT) in type I diabetic patients with end-stage nephropathy is to restore both functions. Quality of life (QoL) is supposed to improve as a result of this combined transplantation. The objectives of this study are to evaluate QoL before and after PKT and to compare the results with patients in whom the pancreas graft failed soon after the transplantation (PKT-P). The trial is a prospective controlled multicenter study. The control group consists of patients before transplantation and patients who received a PKT in whom the pancreas rejected or thrombosed soon after the transplantation. (PKT-P). A standardized home-based interview is done during dialysis, and repeated 5, 12, and 18 months after transplantation in both groups by the same interviewer. The interview consisted of disease-specific questions (RSCL), general questionnaires (NHP I and II, ABS), the Visual Analogue Scale, a specific questionnaire (Anxiety), and evaluative questions about social support and transplantation. Patients in whom the PKT is successful (n=17) improve significantly or show a strong tendency toward improvement on many aspects of quality of life. Patients in whom the pancreas failed (n=5) still demonstrate improvement, although this is not statistically significant in most cases. Intergroup comparison shows that PKT patients are less anxious, suffer of less itching, have better average daily living conditions, have no diet restrictions, and have a better [correction of have and] global quality of life.
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The purpose of this study was to investigate whether treatment with TCV-309, a PAF antagonist, improves life-sustaining function of renal grafts that have suffered warm ischemia (WI) prior to cold storage (CS) and whether TCV-309 influences leukocyte sequestration in tissues. Syngeneic kidneys with 20 min of WI and 24 hr of CS were transplanted into bilateral nephrectomized rats. In the treated group, TCV-309 was administered (i.v. 1 mg/kg) 5 min before reperfusion. Rats in the control group received saline. On day 14, 80% rats survived in the treated group, which was higher than the controls (0%). At 24 hr of reperfusion, myeloperoxidase (MPO) activity, a marker enzyme for PMNs, in the treated kidney was significantly lower than the controls, but did not differ from the normal values. The MPO activity in the controls was higher than the normal values. In conclusion, the PAF antagonist improves posttransplant function of rat kidneys subjected to a period of WI and CS. PMNs are involved in postischemic renal injury, which is, at least partially, mediated by PAF. The effectiveness of PAF antagonist in treatment of recipients may lead to its clinical application in transplantation of ischemically injured kidneys.
In this study, the short-term outcome of renal transplants from non-heart-beating donors (NHBD) preserved by machine perfusion (MP) is evaluated and compared to preservation by cold storage (CS). Twenty-two NHBD kidneys were procured during 1993 and 1994 after in situ perfusion with histidine-tryptophan ketoglutarate and preserved by continuous perfusion using University of Wisconsin organ preservation solution for MP as a perfusate. Between 1980 and 1992, 57 NHBD kidneys were procured and preserved by CS. Donors in the MP group sustained increased first warm ischemia times (WIT1) (P < 0.1) and recipients in the MP group suffered longer anastomosis time, worse HLA-DR mismatch, and more initial use of cyclosporin as immunosuppressant; all these factors are known to be deleterious to short-term outcome. Despite these unfavorable conditions, delayed function (DF) rate was decreased in the MP group, although not significantly. However, when considering only kidneys with WIT1 > or = 45 min, short-term outcome was significantly better in the MP group (P < 0.05). We conclude that MP is superior for the preservation of NHBD kidneys, especially after prolonged warm ischemia.
Retrograde oxygen persufflation (ROP) has been reported to be beneficial to kidney preservation. The purpose of this study was to investigate whether use of ROP during cold storage (CS) with Universita of Wisconsin (UW) solution could ameliorate energy metabolism and functional recovery of ischemically injured rat kidneys and, moreover, to study the particular role of adenosine (ADO) in CS with ROP. Kidneys subjected to 30 min of warm ischemia (WI) were preserved for 24 h in 4 degrees C UW solution with or without ROP and with or without ADO. Measurements of tissue high-energy phosphate levels showed that reduced total adenine nucleotides (TAN) after 30 min of WI further declined during the subsequent CS. In ROP kidneys, however, TAN were less reduced, suggesting that even during CS, TAN can still be regenerated in the injured kidneys when ROP is combined with UW solution. When UW did not contain ADO, regeneration of TAN by ROP was slightly less than in the case of UW with ADO. This indicates that the supply of molecular oxygen is a significant factor in TAN resynthesis during CS. There was no statistically significant difference in survival rate between the ROP and CS groups, indicating that an improved energy status is not the sole determinant of functional recovery. We conclude that the gaseous oxygen supply provided by ROP during CS in UW solution ameliorates the energy state of ischemically injured rat kidneys and that exogenous ADO from the UW solution contributes to the improvement of energy metabolism to a limited extent.
Percutaneous dilatational tracheotomy (PDT) is a new technique for the introduction of a tracheal cannula. It has been performed successfully in adults; however, in children, the open conventional technique is preferred because of the technical limitations of PDT, with fear of tracheal stenosis and adverse effects on tracheal growth. The authors studied the applicability of PDT in a growing animal. Two groups of goat kids (aged 10 days) underwent PDT or conventional open tracheotomy. They were cannulated for 7 days. Three months after decannulation, the tracheas were analyzed macroscopically and microscopically. The coronal (lateral) diameter and the cross-sectional area at the level of the stoma were 4.7 mm (SEM, 0.23 mm) and 41 mm2 (SEM, 3.0 mm2) after open tracheotomy, versus 8.1 mm (SEM, 0.13 mm) and 58 mm2 (SEM, 4.6 mm2) after PDT (P < .001 and P = .023, respectively). The quotient of the stomal cross-sectional area and the normal cross-sectional area was significantly smaller after open tracheotomy than after PDT (P < .001), with a cross-sectional area reduction of 24% to 40% in the open group. The authors conclude that PDT can be performed in growing animals without an increased risk of tracheal stenosis and adverse effects on tracheal growth. They recommended that PDT be investigated in children in a clinical setting.
Several pathophysiological mechanisms have been purported to be involved in the development of acute ischemic renal failure, such as impairment of tubular function and/or of the renal microcirculation. However, it has not been elucidated as yet which of these mechanisms relates to the extent of kidney damage. Besides, little is known about the time course relationship between tubular and microcirculatory disturbances during the development of ischemia-reperfusion injury. We therefore performed intravital videomicroscopy of the proximal tubules as well as the peritubular microcirculation of the rat renal cortex during the first 24 hr of reperfusion after varying lengths of warm ischemia (30 min, 30 WI group; 60 min, 60 WI group; 90 min, 90 WI group). In a separate group of animals subjected to the same protocol, the survival rate (SR) was determined. The SR in these groups were 100%, 20% and 0%, respectively. Initially, the tubular and microcirculatory changes (i.e., increased tubular diameter and reduced capillary blood flow) relate well to the length of warm ischemia as well as the SR. At a later stage of reperfusion, however, we observed that peritubular capillary blood flow and tubular diameter recovered more quickly in the 90 WI group than in the 30 WI and 60 WI groups. As a result, these parameters as obtained at 24 hr of reperfusion did not relate anymore to the survival rate. Besides, at this stage a severe loss of integrity of the tubular wall was noted in the 60 WI and 90 WI groups. These findings suggest that kidney viability is not determined by the extent of recovery of microcirculatory blood flow and/or tubular diameter during early reperfusion, but by the integrity of the tubular wall.
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OBJECTIVE: The outcome of renal transplantation with an arterial anastomosis to a vascular prosthesis in the aortofemoral tract is evaluated. PATIENTS AND METHODS: All 7 Dutch transplant centers were invited to review their experience. Among a total of 5791 cadaveric renal transplantations performed between 1978 and 1994, 13 cases (0.2%) in 3 different centres were identified. In 6 cases the vascular reconstruction and transplant operation were performed simultaneously, and in 7 cases separately, with a mean interval of 3.5 yr. The indications for vascular reconstruction were aneurysmal disease in 4 and obstructive disease in 9 cases. RESULTS: The early vascular complications of these procedures were hemorrhage in 4 and renal vein thrombosis in 1 and led to graft loss in 3 cases. The perioperative mortality was 2/13 (15%). The graft and patient survival were 68 and 83% respectively after 1 yr and 17 and 37% after 5 yr. Late mortality was mainly due to cardiovascular disease. CONCLUSIONS: Renal transplantation with an arterial anastomosis to a vascular prosthesis in the aortofemoral tract is a hazardous procedure with relatively poor short- and long-term results. These observations should be considered in the choice of renal replacement therapy in this special patient population.