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PubMed1995

Ischemic heart disease--major cause of death and graft loss after renal transplantation in Scandinavia.

Causes of graft loss and death were studied in 1347 recipients of primary renal transplants followed for 5 years after transplantation irrespective of graft function. Immunosuppression consisted of high or medium dose CsA and prednisolone or low dose CsA and prednisolone and azathioprine. In recipients of cadaver grafts, death with a functioning transplant was more common than graft rejection after the first posttransplant year, accounting for 49% and 41% of the graft losses, respectively. Of deaths with a functioning graft, 53% were due to ischemic heart disease (IHD) and 10% were due to other vascular disease. In the 55- to 64-year-old age group, the risk of death from IHD was 6.4 times higher in the transplanted nondiabetic patients, 8.6 times higher in the dialysis patients (European Dialysis and Transplant Association figures), and 20.8 times higher in the transplanted diabetic patients than in the general population (national figures). A multivariate Cox regression analysis showed that old age, diabetes mellitus, occurrence of acute rejection, pretransplant transfusions, delayed onset of graft function, and male gender were significant for death in IHD. We conclude that, in comparison to reports from other regions, Scandinavian renal transplant recipients are at high risk of dying of IHD. Future advances in long-term renal graft survival will depend largely on the success of preventing myocardial infarction and death in this patient population.

Adult↗
PubMed2002

Lipopolysaccharide-binding protein as a new and reliable infection marker after kidney transplantation.

The early and reliable differentiation of rejections, viral infections and bacterial infections is one of the main problems after organ transplantation. One promising solution to this problem is the lipopolysaccharide-binding protein (LBP), which is regulated upwards in gram-negative sepsis and related conditions. Therefore, the aim of our study was to explore the diagnostic potential of LBP serum levels in well-defined, non-infectious and infectious events after kidney transplantation (KTx). In a retrospective study the LBP serum levels were measured in a total of 686 serum samples from 52 kidney graft recipients. In all pre-KTx sera tested, the mean LBP level was 8.8+/-3.5 microg/ml (reference range: 2.0-15.2 microg/ml). In 7 of 52 recipients without intraoperative T-cell depletion, the mean LBP level was significantly ( P<0.01) increased (13.0+/-1.5 microg/ml) at post-KTx day 1, but was within the reference range. In contrast, the intraoperative T-cell depletion by antilymphocyte antibodies resulted in a significant ( P<0.01) increase to 25.8+/-11.4 microg/ml (range: 13.3-47.2 microg/ml). In recipients with immediate ( n=14) or delayed ( n=9) graft function without any other complications, all post-KTx values (except the post-KTx peak) were within the reference range. In 10 recipients with steroid-sensitive rejections and in 11 recipients with steroid-resistant rejections, no rejection-associated changes of the LBP levels could be shown. In six recipients with cytomegalovirus infection, the detection of an antigenemia (pp65) also was not associated with alterations of the LBP levels. In addition, there was no correlation between LBP levels and the number of pp65-positive leukocytes in peripheral blood. In contrast, a strong elevation of LBP levels was seen in five recipients with gram-positive bacteremia as well as in other severe bacterial infections (e.g., purulent extravasate, heavily infected grafts, bacterial pneumonia and contaminated hematoma). In two recipients with superinfected (bacterial and mycotic or viral) Pneumocystis carinii pneumonias requiring assisted ventilation, LBP levels were elevated, too. Thus, in our study only systemic non-viral infections and massive lymphocytolysis were associated with elevated LBP serum levels.

Acute-Phase Proteins↗
PubMed2000

Transplantation of both kidneys from 408 donors; comparison of results.

The outcome of 816 paired kidney transplantations from 408 cadaveric donors was evaluated. The transplantations were divided according to order of transplant surgery into group 1 [mean cold ischemia time (CIT) 22 h] and group 2 (mean CIT 28 h). In group 1 the frequency of delayed onset of graft function (DGF) was 22% versus 35% in group 2 (P < 0.005). The 1-year patient survival and graft survival (GS) in group 1 was 98% and 93% versus 94% (P < 0.005) and 90% in group 2. Hemodialysis patients in group 2 had significantly greater DGF (43%) and poorer GS (88%) than peritoneal dialysis patients and the success of transplantation was particularly poor in recipients over 50 years of age.

Adolescent↗
PubMed2004

Two decades of experience with cyclosporine in renal transplantation in Helsinki.

We present our experience on cyclosporine (CsA) triple immunosuppression in 2445 cadaveric kidney transplantations performed from 1984 to 2002 in Helsinki. Overall, delayed onset of graft function occurred in 30.2% and acute rejection in 25.6% of the transplantations. The 1-, 5-, and 10-year patient survival was 95.1%, 84.5%, and 69.1%; the graft survival rates were 90.0%, 74.9%, and 56.7%; and the death-censored graft survival, 93.3%, 83.5%, and 72.4%. During the study period, the 5-year patient survival improved from 70.8% to 90.6% and the graft survival from 58.2% to 88.0% with the graft half-life estimate of 1-year survivors improving from 7.6 to 21.8 years. Acute rejection episodes decreased from 33.0% to 19.9% and the calculated creatinine clearance at 1 year improved from 50.3 mL/min to 74.3 mL/min. Mean CsA dose diminished significantly, both at 3 weeks (from 8.2 mg/kg to 4.9 mg/kg) and at 1 year posttransplant (from 3.7 mg/kg to 2.8 mg/kg). In 16.7% of transplantations where azathioprine had to be discontinued early, significantly more rejections occurred (38.0% vs 23.2%) with inferior 1-year graft survival (80.2% vs 94.8%) compared to the transplantations continuing on triple therapy. Among 1-year survivors, the 6-month serum creatinine level was strongly associated with death-censored long-term graft survival. In this material, the CsA dosage at 1 year did not predict long-term graft survival.

Creatinine↗
PubMed2005

Ethical and legal issues in non-heart-beating organ donation.

Procurement of kidneys and livers from non-heart-beating donors (NHBDs) raises ethical and legal issues that need to be considered carefully before wider use of these donors. Although NHBDs were used in kidney transplantation as early as the 1960s, retrieval of these organs is by no means universally accepted today. From a medical point of view, these organs have long been considered "marginal" because the majority show delayed or impaired graft function. Legal problems include determination of death by cardiopulmonary criteria, the issue of proper consent, and the use of organ preservation measures. Among ethical issues raised are the observance of the Dead-donor Rule, the decision-making surrounding resuscitation, the withdrawal of life-support, the respect for a dying patient and the dead body, as well as proper information to and guidance for the family. In the Netherlands NHB donation was pioneered in the Maastricht Medical Center in 1980s. Today, all seven transplant centers retrieve and transplant organs from these donors, and NHBDs have become an important source of transplantable kidneys and livers. Recent legislation in the Netherlands also supports the use of NHBDs by making possible the use of organ preservation measures after circulatory arrest, even in the absence of family consent. As a result, one of every three kidneys transplanted in the Netherlands in 2004 was obtained from a NHBD. In this study, Dutch NHBD protocols, practice, and results are analyzed and compared with international practices.

Family↗
PubMedDate not supplied

Predictive value of Banff score of early kidney allograft biopsies for 1-year graft survival.

The aim of this study was to evaluate the Banff score of early kidney allograft biopsies, taken during the first month after transplantation, seeking an association between early rejection and acute tubular necrosis. We analyzed data from 71 patients transplanted between 2000 and 2004 who had renal allograft biopsies performed within the first posttransplant month (23 women, 48 men), ages 18 to 67 years. All biopsies performed in cases of delayed or deteriorated graft function were graded according to the Banff' 97 classification. Twelve months after transplantation, 19 patients exhibited excellent renal function (group 1, serum creatinine concentration [Scr] < or = 1.5 mg/dL); 25 patients demonstrated preserved renal function (group II, Scr 1.51-1.99 mg/dL); and 19 patients showed deteriorated renal function (group III, Scr > or = 2.0 mg/dL). Eight recipients lost their grafts within 1 year after transplantation (group IV). The Banff index was defined as a sum of all components (value of glomerulitis ["g"] + interstitial inflammation ["i"] + tubulitis ["t"] + arteriolar hyaline thickening ["ah"] + intimal arteritis ["v"]). The deterioration of renal function was associated with a higher Banff index; patients who lost their grafts showed the highest values of this index. Scores of "v," "ah," and Banff index were positively correlated with serum creatinine concentrations at 28, 90, 180, and 360 days (P < .05). Glomerulitis ("g") was correlated with creatinine concentrations at 90 and 360 days (P < .05). Tubulitis ("t") and interstitial inflammation ("i") displayed no association with renal function at any time.

Adolescent↗
PubMed2004

Gene therapy for liver transplantation using adenoviral vectors: CD40-CD154 blockade by gene transfer of CD40Ig protects rat livers from cold ischemia and reperfusion injury.

Liver injury induced by ischemia/reperfusion (I/R) is the prime factor in delayed or loss graft function following transplantation. CD4+ T lymphocytes are key cellular mediators of antigen-independent inflammatory response triggered by I/R. We attempted to modulate rat liver I/R injury by targeted gene therapy with CD40Ig, which blocks the CD40-CD154 costimulation pathway. One hundred percent of Ad-CD40Ig-pretreated orthotopic liver transplants (OLTs) subjected to 24 h of cold (4 degrees C) ischemia survived > 14 days (vs 50% in untreated/Ad-beta-gal groups). Ad-CD40Ig treatment decreased sGOT levels and depressed neutrophil infiltration, compared with controls. These functional data correlated with histological Suzuki's grading of hepatic injury, which in untreated/Ad-beta-gal groups showed severe necrosis (> 60%) and moderate to severe sinusoidal congestion; the Ad-CD40Ig-pretreated group revealed minimal sinusoidal congestion/necrosis. Unlike in controls, OLT expression of mRNA coding for IL-2/IFN-gamma remained depressed, whereas that of IL-4/IL-13 reciprocally increased in the Ad-CD40Ig group. Ad-CD40Ig reduced frequency of TUNEL+ cells and pro-apoptotic Caspase-3, but enhanced antioxidant HO-1 and anti-apoptotic Bcl-2/Bcl-xl expression. Thus, prolonged blockade of CD40-CD154 by CD40Ig exerts potent cytoprotection against hepatic I/R injury. These results provide the rationale for a novel gene therapy approach to maximize the organ donor pool through the safer use of liver transplants exposed to prolonged cold ischemia.

Adenoviridae↗
PubMed2000

Clinical determinants of multiple acute rejection episodes in kidney transplant recipients.

BACKGROUND: Recipients with multiple (more than one) acute rejection (AR) episodes have significantly lower graft survival rates than those with no AR or only one treated episode. However, fewer than 50% of recipients treated for one AR episode will have another episode. METHODS: We studied recipients with at least one AR episode to determine whether any clinical features could identify risk factors for multiple AR. RESULTS: Between January 1, 1984, and June 30, 1997, a total of 1793 recipients underwent a kidney transplant at our institution. Of these, 354 were treated for one AR episode, 307 for more than one. By multivariate analysis, recipients at highest risk for multiple AR episodes were those with initial delayed or slow graft function (relative risk=1.5, P=0.05), those with initially severe AR (as judged by vascular involvement or steroid resistance), and those with an initial early AR episode (<6 months posttransplant). The remaining variables tested were not significant. Graft survival in recipients with more than one AR episode was significantly lower than in those with only one AR episode. Graft survival at 5 years posttransplant was 52.5% in recipients with more than one AR episode and 85.1% in recipients with one AR episode (P=0.0001). Chronic rejection as a cause of graft loss was significantly more common in recipients with more than one vs. only one AR episode (34.8% vs. 8.9%, P=0.001). CONCLUSION: Clinical features may be used to identify recipients at higher risk for multiple AR episodes. These recipients can then be targeted with more aggressive or novel immunosuppressive regimens in an attempt to reduce the likelihood of another AR episode.

Acute Disease↗
PubMed2001

Pharmacological preconditioning with low-dose cyclosporine or FK506 reduces subsequent ischemia/reperfusion injury in rat kidney.

BACKGROUND: Ischemia/reperfusion (I/R) injury in the early posttransplant period is closely associated with delayed recovery of graft function, increased acute rejection, and late allograft dysfunction. Pharmacological preconditioning with low-dose cyclosporine (CsA) or FK506 was performed to induce ischemic tolerance in rat kidney with I/R injury. METHODS: Low-dose CsA (3 mg/kg, administered i.v.) or FK506 (0.3 mg/kg i.v.) were used to induce ischemic tolerance in Sprague-Dawley rats, and the induction of heat shock protein (hsp) 70 by CsA or FK506 was evaluated overtime. Rats were pretreated with CsA or FK506 6 hr before I/R injury when hsp70 was maximally expressed, and were killed 24 hr later. The effect of pharmacological preconditioning on subsequent I/R injury was evaluated in terms of renal function, histopathology score, assays for apoptosis (DNA fragmentation analysis, TUNEL staining, expressions of pro-apoptotic genes, and caspase activity), and the expression of inflammatory cytokine genes (interleukin-1 and tumor necrosis factor-alpha). RESULTS: Preconditioning with low-dose CsA or FK506 significantly improved renal function and renal histology, compared to rats with I/R injury. Apoptotic cell death (typical DNA laddering and increased TUNEL-positive cells) in rat kidneys with I/R injury, was decreased by pretreatment with low-dose CsA or FK506. Increased expression of pro-apoptotic genes (Fas, Fas-ligand, caspase 1 and 3) and activated caspases in ischemic rat kidneys were decreased after CsA or FK506 pretreatment. CONCLUSIONS: Pretreatment with low-dose CsA or FK506 prevents subsequent I/R injury, and this effect may be related to the induction of hsp70. Pretreatment of renal donors with low-dose CsA or FK506 may result in an improvement in immediate posttransplant function.

Animals↗
PubMed2005

Benefits of erythropoietin in renal transplantation.

Anemia is a common complication in patients with chronic kidney diseases (CKD), including transplanted patients. Recent studies have found a prevalence of anemia of about 30%, whereas less than 10% of these patients received recombinant human erythropoietin. Factors explaining this high incidence of anemia in renal transplant recipients include delayed and impaired graft function and use of drugs inhibiting the action of angiotensin II and preventing rejection. Like in CKD patients, chronic anemia may impact on the cardiovascular system and finally on the high mortality of these patients. Recent data suggest also that anemia may be a factor of progression of renal dysfunction in kidney transplant recipients. A French randomized multicenter study was designed to answer this question.

Anemia↗
PubMed2006

Reversal of diabetes by pancreatic islet transplantation into a subcutaneous, neovascularized device.

BACKGROUND: Transplantation of pancreatic islets for the treatment of type 1 diabetes allows for physiologic glycemic control and insulin-independence when sufficient islets are implanted via the portal vein into the liver. Intrahepatic islet implantation requires specific infrastructure and expertise, and risks inherent to the procedure include bleeding, thrombosis, and elevation of portal pressure. Additionally, the relatively higher drug metabolite concentrations in the liver may contribute to the delayed loss of graft function of recent clinical trials. Identification of alternative implantation sites using biocompatible devices may be of assistance improving graft outcome. A desirable bioartificial pancreas should be easy to implant, biopsy, and retrieve, while allowing for sustained graft function. The subcutaneous (SC) site may require a minimally invasive procedure performed under local anesthesia, but its use has been hampered so far by lack of early vascularization, induction of local inflammation, and mechanical stress on the graft. METHODS: Chemically diabetic rats received syngeneic islets into the liver or SC into a novel biocompatible device consisting of a cylindrical stainless-steel mesh. The device was implanted 40 days prior to islet transplantation to allow embedding by connective tissue and neovascularization. Reversal of diabetes and glycemic control was monitored after islet transplantation. RESULTS: Syngeneic islets transplanted into a SC, neovascularized device restored euglycemia and sustained function long-term. Removal of graft-bearing devices resulted in hyperglycemia. Explanted grafts showed preserved islets and intense vascular networks. CONCLUSIONS: Ease of implantation, biocompatibility, and ability to maintain long-term graft function support the potential of our implantable device for cellular-based reparative therapies.

Animals↗
PubMed1997

[Percutaneous transluminal angioplasty of the renal artery in transplanted kidneys].

UNLABELLED: The objective of the work was to evaluate the contribution of percutaneous transluminal angioplasty (PTA) to treatment of hypertension and the graft function of a transplanted kidney. Angioplasty of the graft artery was performed in 39 patients. Technical success rate: 85%. COMPLICATIONS: 13%--in particular during the first years after introduction of the method. Twenty seven patients were followed up on a long-term basis. Changes of the median arterial pressure (MAP) were evaluated as well as glomerular filtration (GF) assessed by creatinine clearance. Mean values: [table: see text] A statistically significant (p < 0.01) reduction of the median arterial pressure (drop by > 10 mm Hg) along with reduction of the number of antihypertensive drugs was recorded in 70% of the patients during the first year and in 80% kidney recipients in investigations extending beyond one year. A significant increase of glomerular filtration (by > 20%) was found in 40% of the patients, on average the rise was insignificant. During the follow up period 13 kidney recipients were transferred to a dialyzation programme due to failure of the grafts as a result of rejection. CONCLUSION: Percutaneous transluminal angioplasty of a stenosis of the graft artery is the method of first choice in the treatment of hypertension. It is of fundamental importance also in rare cases in order to preserve or improve graft function and thus delay dialyzation treatment.

Adult↗
PubMed1999

Venous function and delayed leg swelling following saphenectomy in coronary artery bypass grafting.

Some patients are troubled by leg swelling following saphenectomy long after CABG. Postsaphenectomy venous function in the leg has not, however, been well clarified. To determine whether venous dysfunction caused postsaphenectomy swelling, we measured the maximum venous outflow and time constant (tau) in the leg by venous occlusion strain-gauge plethysmography in 45 patients; a venous Doppler test was also conducted in 33 of the 45 at a mean 57.6 +/- 21.3 months after CABG. The saphenous vein was harvested unilaterally from the lower leg or from both the thigh and lower leg in all patients. Edema was seen in 4 patients (8.9%) and 8 reported leg swelling after saphenous vein harvest (17.8%). Legs were classified into three groups: group 1 consisted of 12 with edema or reports of swelling ipsilateral to the saphenous vein harvest site, group 2 consisted of 33 ipsilateral to the saphenous vein harvest without edema, and group 3 consisted of the 45 nonoperated-on, contralateral legs of the same patients as controls. No significant differences were seen in maximum venous outflow, tau, or the incidence of deep vein reflux among groups. No significant relationship was found between venous function and leg swelling occurring delayed after saphenectomy.

Aged↗
PubMed1999

Auto- and alloimmune reactivity to human islet allografts transplanted into type 1 diabetic patients.

Allogeneic islet transplantation can restore an insulin-independent state in C-peptide-negative type 1 diabetic patients. We recently reported three cases of surviving islet allografts that were implanted in type 1 diabetic patients under maintenance immune suppression for a previous kidney graft. The present study compares islet graft-specific cellular auto- and alloreactivity in peripheral blood from those three recipients and from four patients with failing islet allografts measured over a period of 6 months after portal islet implantation. The three cases that remained C-peptide-positive for >1 year exhibited no signs of alloreactivity, and their autoreactivity to islet autoantigens was only marginally increased. In contrast, rapid failure (<3 weeks) in three other cases was accompanied by increases in precursor frequencies of graft-specific alloreactive T-cells; in one of them, the alloreactivity was preceded by a sharply increased autoreactivity to several islet autoantigens. One recipient had a delayed loss of islet graft function (33 weeks); he did not exhibit signs of graft-specific alloimmunity, but developed a delayed increase in autoreactivity. The parallel between metabolic outcome of human beta-cell allografts and cellular auto- and alloreactivity in peripheral blood suggests a causal relationship. The present study therefore demonstrates that T-cell reactivities in peripheral blood can be used to monitor immune mechanisms, which influence survival of beta-cell allografts in diabetic patients.

Adult↗
PubMed1998

Short atrioventricular delay dual-chamber pacing early after coronary artery bypass grafting in patients with poor left ventricular function.

OBJECTIVE: To investigate the effect of short atrioventricular (AV) delay dual-chamber pacing on mean arterial pressure (MAP) and stroke volume index (SVI) in patients with poor left ventricular (LV) function after cardiac surgery. DESIGN: A prospective study. SETTING: A university hospital, single-center study. PARTICIPANTS: The study group consisted of 20 patients aged 63 +/- 9 years with a left ventricular ejection fraction (LVEF) less than 30%. The control group consisted of 20 patients aged 61 +/- 10 years, with an LVEF greater than 50%. INTERVENTIONS: Immediately after routine coronary artery bypass grafting (CABG) the AV delay was shortened from 160 to 40 milliseconds in atrial-paced (DDD) mode and from 100 to 40 milliseconds in atrial-sensed ventricular stimulation (VDD) mode. MAP was on-line monitored and SVI was calculated by thermodilution. In one patient with an LVEF of 18% (case study), transmitral flow velocity and LV isovolumetric relaxation time were assessed using Doppler echocardiography during VDD pacing at 40-, 80-, and 120-millisecond AV delay. RESULTS: Short-AV delay DDD pacing decreased MAP in the control group (84.3 +/- 9 v 75.7 +/- 9 mmHg; p < 0.05) and SVI in both groups (study group, 35.9 +/- 7 v 31.7 +/- 7 mL/m2; control group, 35.3 +/- 6 v 31.0 +/- 6 mL/m2; p < 0.05). Shortening the AV delay had no influence on MAP and SVI during VDD pacing. During the echocardiographic case study, AV delay shortening distinctly modified ventricular filling patterns. Optimal LV filling and transmitral flow were achieved with an intermediate AV delay of 80 milliseconds. CONCLUSION: Dual-chamber pacing with nonphysiologic short AV delay failed to improve acute hemodynamics in patients with poor LV function after CABG. Short AV delay VDD pacing was superior to DDD pacing in both normal and impaired LV function. The use of Doppler echocardiography enabled optimization of the AV delay on the basis of LV filling patterns.

Blood Flow Velocity↗
PubMed1988

Early arteriolopathy following "high-dose" cyclosporine in kidney transplantation.

Thirty-seven consecutive kidney graft biopsies from 37 patients immunosuppressed with "high-dose" cyclosporine (CsA) were mixed with 37 random biopsies obtained from 37 patients given azathioprine and prednisone (Aza/P) and reexamined by light microscopy, without knowledge of the therapy, for occurrence of early arteriolopathy. All biopsies were taken within 35 days after transplantation. Arteriolopathy was demonstrated in 12 biopsies from 37 patients given CsA but in none of those from 37 patients on Aza/P. The specific alteration found in those 12 biopsies was glycogen storage in the muscular layer of the arterioles. The average donor was significantly older in those grafts in which arteriolopathy was shown than in those without arteriolopathy but also given CsA (p less than 0.001). All kidneys from donors more than 53 yr old had arteriolopathy. The occurrence of arteriolopathy was independent of the average CsA level from transplantation to biopsy, but the CsA level had never been below 380 ng/ml in those patients with arteriolopathy. The clinical course in grafts with arteriolopathy was characterized by poorer graft function as judged from the renograms, delayed onset of function and a high proportion of "never-functioning" grafts (50%). We concluded that patients receiving a cadaver graft from a donor older than 50 yr should not be treated with "high-dose" CsA. If the arteriolopathy is demonstrated in kidney graft biopsies within the first 5 weeks after transplantation in patients treated with CsA, one should consider a change or modification of the treatment strategy.

Age Factors↗
PubMed1989

The initiation of erythropoiesis following renal transplantation.

Erythropoiesis has been examined in relation to kidney function in 38 patients during the 3-month period following successful renal transplantation, using serial determinations of erythropoietin, haemoglobin, and creatinine. Two peaks of serum erythropoietin were observed: an early peak that occurred within 2 days of transplantation and was observed in ten patients, and a late one between 8 and 30 days, observed in 28 patients. The early peak did not produce an increase in haemoglobin and occurred only in the presence of delayed onset of graft excretory function when serum creatinine was greater than 1000 mumols/l. The ineffectiveness of the early peak may be due to the uraemic environment, which is probably a sequel of the tubular damage associated with postoperative acute tubular necrosis. The late peak followed a decrease in serum creatinine to less than 200 mumols/l and was associated with an increase in haemoglobin of 3-4 g/dl during the next 2-6 weeks.

Adolescent↗