J. H. van Bockel

Carotid Recurrent Stenosis and Risk of Ipsilateral Stroke A Systematic Review of the Literature

BACKGROUNDnThe main goal of follow-up after carotid endarterectomy is to prevent new strokes caused by recurrent stenosis. To determine the most cost-effective follow-up schedule, it is necessary to know the incidence of recurrent stenosis and the risk of stroke it carries.nnnMETHODSnA systematic review of the literature was performed using standard meta-analytical techniques.nnnRESULTSnIncidence of recurrent stenosis: The data were very heterogeneous. The risk of recurrent stenosis was 10% in the first year, 3% in the second, and 2% in the third. Long-term risk of recurrent stenosis is about 1% per year. Risk of stroke: The reported relative risks of stroke in patients with recurrent stenosis compared with patients without recurrent stenosis showed extreme heterogeneity and ranged from 10 to 0.10. The random effects summary estimator of relative risk was 1.88.nnnCONCLUSIONSnThe data were very heterogeneous, and much better data are needed to arrive at truly reliable estimates of these important parameters of follow-up. It is clear, though, that the risk of recurrent stenosis is highest in the first few years after carotid endarterectomy and very low in later years. By use of general decision-analytic arguments, it can be argued that, given the test characteristics of carotid ultrasound, a small number of tests can be done in the first few years and that testing for restenosis should not be done after 4 years.

The clinical significance of allospecific antibodies against endothelial cells detected with an antibody-dependent cellular cytotoxicity assay for vascular rejection and graft loss after renal transplantation.

Serum samples of 64 consecutive patients who underwent renal transplantation in our institution were examined for the presence of antibody-dependent cellular cytotoxicity (ADCC) activity against endothelial cells (EC). From each patient serum samples were obtained immediately before transplantation and 1 week, 1 month and 1 year thereafter. The results were evaluated in the context of tests to measure donor-specific humoral immunity against lymphocytes and monocytes, and related to parameters of presensitization, graft survival, and histology. Sera from 10 patients were positive for ADCC on a panel of HLA-typed endothelial cells. In 8 patients sera were already positive before transplantation and remained positive thereafter. In 4 patients a positive crossmatch with donor T and B cells and monocytes could be observed after transplantation. In only one patient were these crossmatches positive before transplantation. A significant correlation was found between ADCC positivity and vascular rejection (P=0.015); in addition graft survival was significantly better in the ADCC negative group vs. the positive group (P=0.0004). These data demonstrate the significance of allospecific anti EC antibodies for the occurrence of vascular rejection and graft loss after renal transplantation.

Donor-specific lysis of human kidney proximal tubular epithelial cells by renal allograft-infiltrating lymphocytes.

In the present study methods are described to obtain both graft infiltrating cells (GIC) of host origin and proximal tubular epithelial cells (PTEC) of donor origin simultaneously from biopsy material of renal allografts undergoing rejection. The identity of PTEC cultures was established using monoclonal antibodies. GIC were shown to exhibit T cell functional activity. These GIC were shown to lyse trypsinized PTEC as well as PTEC monolayers grown from the corresponding biopsy, and not PTEC isolated from biopsies obtained from other patients. Therefore the lytic activity appeared to be donor-specific. Major histocompatibility complex class I antigens were involved since donor PHA-blasts, a target population well known to express class I molecules, were lysed by GIC, and the anti-class I MoAb W6/32 blocked cytolytic activity of GIC against donor PHA-blasts and against donor PTEC. We thus established that donor-specific lysis of a defined population of kidney epithelial cells, namely PTEC, may occur. This model system, in which GIC and PTEC can be propagated from one biopsy specimen may be useful for further study of cell-cell interactions involved in allograft rejection.

Long-term graft survival after liver transplantation in the UW era: late effects of cold ischemia and primary dysfunction

Abstract The use of University of Wisconsin (UW) solution in liver transplantation (LTX) has significantly prolonged preservation times and facilitated semielective transplant procedures. Despite this advantage potential risk factors related to the donor, recipient, or cold storage method will persist in the UW era and detrimental effects will be reflected by primary dysfunction (PDF) after LTX. Concern has been voiced about the maximum period of UW preservation in LTX and various cold ischemia times (CIT) are mentioned. To evaluate the effect of UW solution in LTX, a prospective European multicenter study was initiated in 1988 and short‐term results have been reported previously. This report focuses on the long‐term effects and survival of prolonged preservation with UW solution and primary function after LTX. Three hundred and fifteen LTXs were performed in 288 patients in participating European centers. Complete follow up of at least 6 years was available for 296 grafts in 277 patients. Effects of donor, preservation, and recipient risk factors on PDF including primary non‐function (PNF) and initial poor function (IPF) were evaluated. Next, the effect of risk factors on graft survival (GS) was analyzed including the long‐term impact of PNF and IPF using multivariate analyses and the Kaplan‐Meyer method. PDF occurred in 15.2% (45/296) with PNF in 7.8% and IPF in 7.4%. Patients with IPF had a 34% lower GS at 3 months those with immediate function (IF; 58% vs 91 %; P < 0.001). This difference persisted up to 6 years for patients with IPF with a 39 % GS vs 72 % after IF (P < 0.001). Median CIT was significantly longer in grafts with PNF compared to IPF or IF (P= 0.03). Long‐term GS, however, was significantly influenced at a lower CIT threshold with a 6‐year GS for CIT ≤ 16 h of 67%, compared to a CIT > 16 h of 51% (P= 0.02). Other independent risk factors for the 6‐year survival rate were re‐LTX, ABO incompatibility, and recipient diagnosis of acute hepatic failure. In conclusion, liver patients with PNF, but not with IPF, have a significantly lower CIT. IPF is associated with a significantly lower 3 month GS compared to IF, but this difference of 34% does not further increase during a 6‐year follow up. Although a short term follow up (3 months) shows that with UW solution CIT up to 18 h has no adverse effect on GS, the 6‐year data clearyl suggest that CIT should be kept to less than < 16 h to avoid tetrimental effects on lang‐term GS after LTX.

Long-term cardiovascular morbidity and mortality in autosomal dominant polycystic kidney disease patients after renal transplantation.

Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased incidence of hypertension and cardiovascular abnormalities. In this long-term follow-up study (5.88 years on average), we evaluated cardiovascular disease and patient and graft survival in 101 ADPKD patients and 692 nondiabetic control patients receiving cadaveric renal transplants between March 1967 and April 1991 at the Leiden University Hospital. Graft and patient survival was not different between patient groups, using the same immunosuppressive therapy. However, death with functioning graft, mainly due to cardiovascular disease, was significantly more frequent in the ADPKD patients than in controls using AZA (P < 0.01). Multivariate analysis of pretransplant data showed that ADPKD patients on AZA therapy demonstrated an elevated age-adjusted relative risk of 2.07 (95% confidence interval [95% CI]: 1.12-3.80) for cardiovascular events and 2.88 (95% CI: 1.41-5.90) for cardiovascular mortality alone. After adjustment for age, gender, and other cardiovascular risk factors, a relative risk of 2.39 (95% CI: 1.06-5.40) was found. This was 2.87 (95% CI: 1.04-7.93) when cardiovascular mortality was the dependent variable. With posttransplant data, the age-adjusted relative risk for cardiovascular morbidity and mortality in ADPKD patients using AZA was 2.16 (95% CI: 1.12-4.15) and 2.97 (95% CI: 1.40-6.27), with only cardiovascular mortality as the dependent variable. After adjustment for age, gender, and other cardiovascular risk factors, this was 1.59 (95% CI: 0.64-3.91) and 2.28 (95% CI: 0.79-6.53), respectively. With CsA treatment, an elevated risk for cardiovascular morbidity and mortality in ADPKD patients was present, but the corresponding 95% CI were wide and include unity, due to the shorter period of follow-up (CsA: 3.81 +/- 2.50 years vs. AZA: 7.28 +/- 6.74 years). Survival of ADPKD patients using AZA was less in those patients without pretransplant nephrectomy as compared with control patients, but the morbidity and mortality of pretransplant nephrectomies should be taken into account. We conclude that ADPKD patients show a similar graft and patient survival after renal transplantation as control patients, but they are especially at risk for cardiovascular disease after renal transplantation.

Ischemic and hemorrhagic stroke in patients on oral anticoagulants after reconstruction for chronic lower limb ischemia.

Background and Purpose Information on the long-term fate of patients with chronic lower limb ischemia is limited. We investigated the long-term risk of the first ischemic and hemorrhagic cerebral stroke in patients on long-term anticoagulant therapy after reconstruction for chronic limb ischemia. Methods In a retrospective study, 376 consecutive patients were seen at regular intervals according to a standard protocol. Only 3 (0.7%) were lost during follow-up (mean duration, 5.9 years). Anticoagulation was with coumarin derivatives followed by prothrombin times periodically. Primary end points were ischemic and hemorrhagic cerebral stroke events, which were confirmed by CT scan, autopsy, or operation in 85% of the cases. Major vascular events were analyzed as a composite secondary end point. The influence of several clinical variables on these outcome events was evaluated in univariate and multivariate analyses. Results Thirty-nine patients (10%) had 41 stroke events (23 ischemic, 18 hemorrhagic); 22 of these patients (56%) died from stroke. The cumulative ischemic stroke risk was 5% at 5 years and 12% at 15 years. Prior myocardial infarction was the only independent predictor (relative risk [RR], 3.1; P<05). The cumulative hemorrhagic stroke risk was 3% at 5 years and 17% at 15 years. Systolic hypertension (RR, 4.8; P<.01) and insulin-dependent diabetes mellitus (RR, 5.4; P<.01) were significant and independent predictors. The risk for a major vascular event was 29% at 5 years and increased to 56% at 15 years. Independent predictors were advanced age (RR, 1.4; P<.005), insulin-dependent diabetes (RR, 2.2; P<.005), and prior myocardial infarction (RR, 1.8; P<.01). Conclusions Patients with chronic lower limb ischemia, notably those with prior myocardial infarction, are at high risk for ischemic stroke. Those with systolic hypertension or insulin-dependent diabetes mellitus are at high risk for hemorrhagic stroke. (Stroke. 1993;24:1655-1663.)