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PubMed1995

Thromboxane synthase expression in renal transplant patients with rejection.

Thromboxane synthase (TS) catalyzes the formation of thromboxane (TxA2) in monocytes/macrophages, platelets, and various tissues. TxA2 is likely to play a role in graft dysfunction due to its vasoconstrictive and platelet aggregatory properties. We studied the expression of TS in 7 normal native kidneys, 29 consecutive renal allograft biopsies (performed for rising serum creatinine, n = 23, and delayed graft function, n = 6), and one transplant nephrectomy specimen with severe acute rejection. TS expression was determined by immunocytochemistry using a monoclonal antibody against human TS, Kon-7. Histologic grading of the transplant biopsy specimens was based on the Banff classification. The degree of TS staining was graded in the glomeruli, interstitium, tubules and vessels from 0 to 3+. Of 29 biopsies, 13 had chronic nephropathy (CN), 6 had acute rejection (AR) with chronic nephropathy (AR/CN), 4 had acute rejection (AR), and 6 had acute tubular necrosis (ATN). TS staining of native kidneys showed sporadic interstitial cells. The biopsy and transplant nephrectomy specimens showed significant staining, predominantly in the glomeruli and interstitium. Positively staining cells appeared to be of macrophage/monocyte lineage by morphology. The mean glomerular staining grade was significantly increased in specimens with AR (2.3 +/- 0.9) and the mean interstitial staining was increased in specimens with AR/CN (2.2 +/- 0.9). Follow-up renal function 6 months post-biopsy showed that patients with higher TS staining grades had a faster decline in graft function. In conclusion, TS expression is increased in patients with acute rejection with or without chronic nephropathy and is associated with more rapid deterioration in function.

Adult↗
PubMed1994

Calcium channel blockers in kidney transplantation.

PURPOSE: To review the question as to whether treatment with a calcium channel blocker (CCB) influences the course and outcome of cadaveric renal transplantation in recipients treated with cyclosporin A. METHODS: Computer-assisted search (Medline) and manual search of the literature. Odds ratio, Mantel-Haenszel test, Fischer's test and Chi 2 test. RESULTS: Two Randomised, placebo-controlled studies, 12 randomised, open studies, 3 retrospective studies, 1 study using a historic control group and 3 studies only reported in abstract form were identified. In the randomised, open studies treatment with CCB reduced the rate of delayed graft function but had no effect on the rate of rejection and graft survival. The effect on graft function was equivocal. In the blind, placebo-controlled studies no beneficial effects of treatment with CCB were found. Treatment with CCB reduced the dose of CyA needed to reach target whole blood level of CyA in nearly all studies. CONCLUSION: Results are conflicting. Further studies are needed.

Cadaver↗
PubMed1994

Outcome statistics of renal transplants with an emphasis on long-term survival.

Remarkable increases in cadaveric renal transplant survival rates have been seen following improvements in areas such as immunosuppression, organ preservation, HLA typing and cross-matching, and blood transfusion protocols. However, while these improvements have influenced survival in the early post-transplant period up to 6 months, the cumulative rate of graft loss beyond the 1st year has remained constant at about 9% a year over the past 25 years. Several factors that affect long-term survival have been identified through univariate and multivariate analyses. Chief among these is the detrimental effect of HLA-A and HLA-B antigen mismatching. Also important are the recipient's race, sex, and age, and presence of diabetes, as well as the donor's age, sex, and cause of death, and long cold ischemia times. Likewise, post-transplant events, including delayed graft function, early rejection episodes, and discharge serum creatinine levels strongly affect long-term graft survival. Chronic rejection should also be recognized as a major contributor to the long-term failure rate, but there is currently no reliable way to identify or classify it in the UNOS Scientific Renal Transplant Registry database. Characteristics that define chronic rejection must be identified to allow transplant centers to accurately report its incidence and to enable investigators to analyze and monitor its impact on transplant outcome.

Adult↗
PubMed1995

Tissue antigens in tubulointerstitial and vascular rejection.

We propose that tissue-specific alloantigens are of importance in interstitial and vascular rejection. To study this hypothesis we took the following approaches: multivariate analysis on our database (N = 482) was performed, the specificity of T cells cultured from kidneys with rejection was analyzed, and non-anti-HLA antibodies reactive with endothelium were studied. First we observed that in a cohort study of 482 patients receiving a cadaveric renal allograft 76 (15.8%) patients developed vascular rejection and 115 (23.9%) developed interstitial rejection. The incidence of vascular rejection was increased in patients with delayed graft function, HLA-DR mismatches, a prolonged cold ischemia period, and previous transplantations. Next we examined 40 graft infiltrating cell (GIC) lines cultured from renal biopsies taken during rejection episodes. Thirteen GIC lines reacted in a donor-specific fashion to proximal tubular cells (PTEC) but not to donor splenocytes. These GIC recognize polymorphic tissue-specific peptides in the context of allo-MHC Class I. Finally, we studied if non-conventional allo-antigen systems on endothelial cells could be the target of the humoral immune response during vascular rejection. We found the endothelial monocyte (EM) system, and another system that is present on endothelial cells and platelets, which can be tested in an antibody-dependent cellular cytotoxicity assay (ADCC).

Graft Rejection↗
PubMed1996

Primary renal graft thrombosis.

BACKGROUND: Renal allograft thrombosis is a serious complication of kidney transplantation that ultimately leads to graft loss. Its association with acute and hyperacute rejection is well documented; however, in a large proportion of patients the precise cause remains obscure. The exact incidence and the associated risk factors for those episodes of graft thrombosis lacking evidence of rejection have not yet been clearly established. METHODS: All reported episodes of graft thrombosis in 558 consecutive cadaveric kidney transplants performed in a single centre were examined to identify those without histopathological evidence of rejection, i.e. primary renal graft thrombosis. Univariate and multivariate types of analysis were applied to study the possibly related risk factors and any associated morbid event(s) of those episodes. Recipients without reported episodes of primary renal graft thrombosis (n = 493) represented the control group for the 34 identified cases. RESULTS: The calculated incidence of primary renal graft thrombosis was 6% (1.9% arterial, 3.4% venous and 0.7% both), comprising 45% of early (90 days) and 37% of 1-year graft losses in our centre. The multivariate analysis identified five independent risk factors for primary renal graft thrombosis: donor's right kidney P < 0.007, past history of venous thrombosis (renal or extrarenal) P = 0.000, and diabetic nephropathy P = 0.000 of the recipient, technical surgical problems P = 0.000, and recipient's haemodynamic status peri and early postoperatively P < 0.001. Primary renal graft thrombosis was related to the presentation with delayed graft function (DGF) P < 0.0005 and was significantly associated with extrarenal thromboembolic manifestations P < 0.0005. There was no association between primary renal graft thrombosis and recipient's age, sex, number of previous transplants, type of dialysis, pretransplant treatment with erythropoietin, antiplatelet agents, or oral anticoagulants, donor's age, sex, number or graft vessels, warm and cold ischaemia times, site of transplant (R/L iliac fossa) and type of immunosuppressive agent used for induction whether cyclosporin A (CsA) or OKT3. CONCLUSIONS: Primary renal graft thrombosis is an important cause of graft loss that may be accompanied by thrombosis of extrarenal sites and effective, safe prophylactic regimens are needed, especially for those at high risk.

Acute Disease↗
PubMed1996

Outcome of pediatric cadaveric renal transplantation: a 10 year study.

This report deals with 120 cadaveric renal transplants performed in 101 pediatric recipients in this Centre in two five-year periods, 1984 to 1988 (N = 65) and 1989 to 1993 (N = 55). In the first group transplants were allocated on the basis of best size (small donors for small recipients); in the second group priority was given to beneficial HLA matching. Initial immunosuppression was either cyclosporine (CsA) monotherapy (15 mg/kg/day), or triple therapy (CsA 5 mg/kg/day, prednisolone 1 mg/kg/day and azathioprine 1 mg/kg/day) if there was delayed graft function. Patient survival at one year and five years (97.5% and 92.3%, respectively) did not differ between the two groups, although there was an improvement in graft survival at one and five years in the second period relative to the first: 69.2% and 53.8% versus 78.6% and 65.6%. This did not achieve statistical significance. One year graft survival in recipients under five years did not differ significantly from older children (72%). There was a trend to improvement in one year graft survival in the < five years of age pediatric patients in Group 2, with beneficially matched kidneys and improved immunosuppressive management. Graft losses due to acute rejection were similar in both groups. Donor age < 4 years significantly reduced one year graft survival (63% vs. 85%, P = 0.01), while recipient age had no effect. Small donor kidneys were associated with a higher incidence of graft thrombosis. Transplantation resulted in the normalization or acceleration of growth velocity in (84%) of the pre-pubertal children who completed follow up. In conclusion, we have shown that excellent patient and graft survival can be achieved in children transplanted under the age of five years. Kidneys from donors under the age of four years are associated with an unacceptable rate of graft loss. Small children do not readily accept cyclosporine monotherapy. Successful early renal transplantation offers the best chance of normal growth and development.

Adolescent↗
PubMed1995

The UNOS scientific renal transplant registry. United Network for Organ Sharing.

Overall one-, 5-, and projected 10-year graft survival rates were 81%, 58% and 39%, respectively for 51,442 cadaveric kidney transplants performed at 251 U.S. transplant centers from October 1987-December 1994. The comparable results for recipients of living donor kidneys were significantly higher, 91%, 75%, and 60% (p<0.001). One-year first cadaver graft survival rates improved from 77% for transplants performed in 1987-1988 to 84% for transplants performed in 1991-1992 (p<0.001). Recipients of second cadaveric transplants in 1987-1988 had a 69% one-year graft survival rate compared with 81% for those transplanted after 1990 (p<0.001). Graft survival rates have been stable since 1991. The percentage of broadly sensitized first transplant recipients decreased from 13% before 1991 to 7% after, and the one-year graft survival rates increased by 4-6% for both sensitized and nonsensitized recipients between the 2 periods (p<0.001). Among retransplanted patients, the percent of broadly sensitized recipients fell from 40-33% over the same periods (p<0.01). One-year graft survival rates increased by 7-8% for sensitized and nonsensitized patients (p<0.001). One-year graft survival rates improved from 74-83% for Blacks (p<0.001) and from 78-85% for non-Blacks (p<0.001) transplanted for the first time when comparing transplants performed in 1987-88 with those performed in 1993-94. The cause of donor death had a significant effect on graft survival. The 5-year graft survival rate was 61% for 28,923 recipients of trauma donor kidneys compared with 54% for 16,956 transplants from CVA donors (p<0.001). Kidneys from CVA donors increased from 28% of all cadaveric kidneys in 1988 to 38% in 1994. The donor's age was a more important determinant of long-term survival, however, and correlated strongly with the cause of donor death. Only 16% of CVA donors were reportedly age 30 or less, compared with 75% of trauma donors. First cadaver graft survival decreased by approximately 2% for each 12 hours of cold ischemia time. Although there was a significant increase in the incidence of delayed graft function from 19% when the CIT was less than 12 hours to 35% when the CIT was more than 36 hours, there was no significant long-term effect of cold ischemia time. The recent change in UNOS policy to share zero-HLA mismatched kidneys resulted in a 2-fold increase (from 8%-16%) in the number of HLA-matched transplants performed during the first 6 months following the change. The percentage of Blacks who have received matched kidneys following this change has increased from less than 2% to more than 5%, a 3-fold increase. The 163 Blacks who received an HLA-matched kidney prior to 1995 had a 65% 4-year graft survival rate compared with 53% for mismatched Blacks (p<0.001). The incidence of early rejections was also reduced by 25% among matched recipients and the graft half-life was 8 years compared with 5 years for mismatched Blacks. About 25% of HLA-matched kidneys were transplanted to ABO compatible but not identical recipients. Although the effect of the policy allowing compatible transplants did not result in a large number of type O kidneys transplanted to non-O recipients when only 8% of kidneys were shared, the recent change in allocation policy may be detrimental to type O waiting patients.

Adolescent↗
PubMed1995

Primary disease effects and associations in patients without early posttransplant events.

Many patients receiving primary cadaver renal transplants have complications in their early post-transplant courses which can affect and possibly confound long-term outcome analyses. Forty-four percent of primary cadaver recipients in the present study were excluded because of early events: delayed graft function (DGF) and early rejection episodes (ERE). Even with these exclusions, similar conclusions to the previous study (1) were noted: that is, the patients with systemic diseases (NS, HTN and IDDM) had the lowest 5-year graft survivals (57-62%) compared to those with diseases that were primarily renal (ALP, IGA and PC) which had better 5-year graft survival results (76-81%). Long-term half-life calculations also demonstrated improved graft survival prognoses in patients with primarily renal diseases (15-18 years in ALP, IGA and PC vs 6-8 years in IDDM, HTN and NS). Again, with the exclusions of patients with early events, Black recipients with HTN did not fare as well as non-Blacks (5-year graft survival of only 52% vs 69%). Many long-term graft losses were due to deaths, oftentimes from cardiovascular diseases. This was especially prominent in disease states with the greatest potential for arteriosclerosis (IDDM, HTN and NS). When patients with early events were excluded, the percent of graft losses attributable to patient death ranged from 21-58%, but were the highest with HTN, PC (age related) and IDDM: 41%, 45% and 58%. A similar analysis in IDDM patients receiving either a LD, SPK or KAT-type transplant revealed that although there was a 10% reduction in 5-year graft survival for KAT patients, most of these graft losses were owing to patient death. Outcomes in SPK and LD in IDDM patients were similar, suggesting selection bias and center effects with the latter two types of transplants going to healthier IDDM patients. It is too soon to conclude whether FK506 has a particularly beneficial role in one primary disease or another as compared to CsA. Combined kidney transplantation with a liver or heart transplant appears to be a reasonable risk. When graft losses due to patient deaths are accounted for, kidney graft survival was approximately that of kidney alone transplantation, suggesting again that graft loss due to patient death must be accounted for when analyzing transplant graft survival.

Graft Survival↗
PubMedDate not supplied

[Surgical aspects of renal transplantation].

Expansion of donor criteria and more efficient use of the donor pool are needed to address the current organ shortage. Results of renal transplantation in older patients support broader recipient selection. To improve intraoperative donor and recipient management, and decrease the rate of delayed graft function, and refine surgical techniques to address more complicated patients are also attempts to expand donor pool. Use of hepatitis-C-positive donors is not safe in hepatitis-C-positive recipients for non-life-saving organs.

Adenosine↗
PubMed1997

Risk factors for prolonged hospitalization after kidney transplants.

A major variable in the cost of kidney transplants is the length of initial hospitalization. Using multivariate analysis, we studied risk factors for hospital stay > 10 d post-transplant. Between 1 January 1985 and 31 August 1995 a total of 1588 patients underwent first or second kidney transplants at the University of Minnesota. Antibody was used for 1 wk in cadaver donor recipients and for 2 wk in pediatric recipients (resulting in a long stay for all pediatric recipients). Adult living related donor recipients were immunosuppressed with triple therapy. Donor risk factors studied were age (< 15, 15-50, > 50 yr) and,- for cadaver recipients, preservation time (< 12, 12-18, 18-24, 24-30, > 30 h) and cause of death (trauma, cerebrovascular accident, or cardiac). Recipient risk factors studied were age (< 18, 18-55, > 55 yr); sex; transplant number; antigen mismatch; peak PRA; PRA at transplant (< 11, 11-50, > 50); diabetic status; pretransplant dialysis (vs. pre-emptive transplant); pretransplant cardiac, peripheral vascular, or respiratory disease; and delayed graft function (DGF) (dialysis in the first week vs. no dialysis). Risk factors were analyzed separately for living donor and cadaver donor recipients. For cadaver donor recipients, DGF was the major risk factor (p < 0.0001); others were age 55 yr (p = 0.03) and diabetes (p = 0.02). For living donor recipients, DGF was also a risk factor (p = 0.003); others were diabetes (p = 0.01), retransplant (p = 0.006), PRA at transplant > 50 (p < 0.0001), age > 55 yr (p = 0.02), pretransplant respiratory disease (p = 0.005), and pretransplant dialysis (p = 0.005). Because DGF was the major risk factor for a prolonged stay, we then studied risk factors for DGF using multivariate analysis. For cadaver donor recipients, risk factors were recipient weight > 90 kg (p = 0.004), preservation time 24 h (p = 0.03), PRA at transplant > 50 (p = 0.03), and donor age < 15 or > 50 yr (p = 0.002). For living donor recipients, risk factors were recipient age < 18 yr (p = 0.01), donor age > 50 yr (p = 0.03), female sex (p = 0.05), pretransplant respiratory disease (p = 0.1), pretransplant peripheral vascular disease (p = 0.05), and recipient weight > 90 kg (p = 0.1). From our data, a profile emerged of recipients likely to have a longer hospital stay. Important variables, either simultaneous with or related to DGF, include donor and recipient age, diabetes, pretransplant recipient weight, PRA at transplant, preservation time, and pretransplant respiratory or peripheral vascular disease.

Adolescent↗
PubMed1997

Relationship between blood pressure and renin, angiotensin II and atrial natriuretic factor after renal transplantation.

The objective of the study was to assess the evolution of renin, angiotensin II, atrial natriuretic factor (ANF) and blood pressure (BP) in the first trimester following renal transplantation in man Thirty-two recipients were investigated for 3 months post-transplantation. Twenty had a history of hypertension with moderate cardiac hypertrophy. Thirty-one retained their native kidneys. Five kidney donors had a history of mild hypertension. The recipients were perioperatively volume-expanded with 0.9% saline and diuresis was maintained for 48 h with furosemide and dopamine. The sodium intake was 25 mEq/24 hours. Prophylactic immunosuppressive therapy was antilymphocyteglobulins (25 cases), or anti-LFA1 (7 cases) and maintenance therapy was cyclosporine-prednisone (8 cases), or cyclosporine-prednisone-azathioprine (24 cases). Mean BP, serum creatinine, urinary sodium excretion (UNA) and hormonal (renin, angiotensin II and ANF) parameters were collected every other day for the first week after transplantation and then twice monthly. Twenty (62.5%) patients developed hypertension and hypertension was more frequent in patients with a delayed graft function, than in patients with immediate good graft function (10/20 vs. 4/12, p < 0.05%). Both hypertensive (group HBP) and normotensive (group NBP) patients had similar very low renin and angiotensin II plasma levels, after an initial early peak. Analysis of covariance with multiple regression analysis showed that in the HBP patients, BP was negatively correlated with UNA (p = 0.02) and positively with plasma ANF (p < 0.01). The normal BP patients also showed a correlation between BP and UNA, although it was limit of statistical significance (p = 0.05); there was no correlation between ANF and BP. We conclude that the RAS is rapidly depressed after renal transplantation and does not interfere with BP regulation. The hypertension in the early stage of post-transplantation varies inversely with the urinary sodium excretion. The defective sodium excretion, which dominates the effect of the low sodium diet, results in volume overload, increased ANF and volume-dependent hypertension.

Adult↗
PubMed1996

Kidney sharing by centers of the South-Eastern Organ Procurement Foundation.

1. SEOPF centers historically have shared kidneys at a higher rate than the rest of the United States. 2. SEOPF centers transplanted better-matched kidneys than the rest of the nation despite transplanting a significantly larger percentage of "hard-to-match" black recipients. 3. Within SEOPF centers, a shared kidney was almost twice as likely to be a good match (zero-3 HLA antigen mismatches) as was a local kidney. 4. Within SEOPF centers, well-matched kidneys (zero-3 HLA antigen mismatches) had significantly better graft survival than did poorly-matched (4-6 HLA antigen mismatches) kidneys. 5. SEOPF centers had one-, 2- and 3-year graft survival rates comparable to those of the rest of the nation. 6. SEOPF centers have proven the efficiency of ROP trays in predicting final crossmatch results for shared kidneys. 7. The SEOPF High Grade Match (HGM) algorithm has been successful in transplanting highly sensitized (current PRA > 40%) recipients. 8. The use of ROP trays in well-matched, highly sensitized recipients resulted in improved kidney availability. 9. Graft survival of HGM recipients was comparable to that of non-HGM recipients. 10. Despite longer cold ischemia times for HGM kidneys, there was no increased incidence of delayed graft function in these kidneys. 11. The HGM program accounted for 8.1% of the participating centers' activity and, thus, has not adversely impacted the majority of the centers' other patients. 12. The one- and 2-year graft survival data for HGM transplants were in accordance with the expected rates and were not statistically different from those of non-HGM transplants.

Actuarial Analysis↗
PubMed1996

Immunosuppressive regimens and their effects on renal allograft outcome.

The distribution and effectiveness of different immunosuppression protocols among recipients of first cadaver donor renal transplants reported to the UNOS Scientific Renal Transplant Registry whose graft survived at least 14 days after transplantation were analyzed. The results showed that between 1988-1993, 50-60% of recipients received triple therapy regimens including cyclosporine, azathioprine and prednisone (CAP). An additional 20% received CAP with antibody induction therapy (OKT3 or ALG). After 1993, there was an increase in the use of other drug combinations which include FK506 and, more recently, Neoral and mycophenylate mofetil. Patient survival was 90% at 3 years regardless of the immunosuppressive protocol. The 3-year graft survival rate was 75% under cyclosporine-based protocols, but was 79% for more recent recipients treated with FK506 (p = 0.015). Antibody induction protocols were not used more frequently for high-risk patients, including those with broadly reactive anti-HLA antibodies, pediatric recipients, transplants with delayed graft function and those with prolonged cold ischemia times. When induction therapies were reported for these higher risk transplants, there was no noticeable improvement in graft survival rates after excluding failures within the first 2 weeks. Any benefit of antibody induction must therefore be manifest with the first 2 weeks after transplantation. Induction protocols significantly reduced the incidence of rejection episodes (prior to hospital discharge) from 31% for those treated with CAP to 12% for those with antibody induction (p < 0.01), however, 24% of those given induction had at least one rejection between discharge and 6 months compared with only 18% of those treated with CAP without induction (p < 0.01). Although graft outcomes might be significantly influenced by the dosing and timing of immunosuppressive drugs, among the different combinations of drugs analyzed, only FK506 resulted in improved graft survival and half life. With the rapid proliferation of newer drugs and immunosuppressive strategies during 1996, it will be interesting to follow the course of these very recent transplants with regard to the effectiveness of changing immunosuppression.

Cadaver↗
PubMedDate not supplied

Peritoneal dialysis is not a risk factor for primary vascular graft thrombosis after renal transplantation.

OBJECTIVE: To find out if patients undergoing peritoneal dialysis (PD) have an increased risk of primary vascular thrombosis of the renal allograft, compared with patients on hemodialysis (HD). DESIGN: Observational, retrospective cohort study. SETTING: Tertiary care hospital, covering an approximate population of 2,000,000. Extensive use of suboptimal donors for renal transplantation. PATIENTS AND METHODS: The study included 827 patients receiving a cadaveric renal transplantation (RTx) in our center between 1988 and 1997 (700 on HD and 127 on PD). We searched for a potential difference in the incidence of graft thrombosis, according to the pretransplant dialysis modality and taking into consideration the main reported risk factors for this complication of RTx. RESULTS: The accumulated incidence of primary graft thrombosis was 4.7% in PD patients, and 6.1% in HD patients (NS). Arterial and venous thrombosis were also similar in both groups. Logistic regression analysis demonstrated that extremes of age of the donor, use of the right kidney, protracted cold ischemia, delayed graft function, and transplantation to a hypersensitized recipient independently predicted graft thrombosis. Peritoneal dialysis was not independently associated with the complication under study (adjusted odds ratio HD/PD = 2.5, 95% CI = 0.8-7.7). CONCLUSIONS: Peritoneal dialysis is not associated with an increased risk of primary vascular thrombosis of the renal allograft.

Adult↗
PubMed1998

Two low-dose OKT3 induction regimens following renal transplantation--clinical experience at a single center.

Experience with quadruple-drug induction therapy with two regimens of low-dose OKT3 in renal transplant patients was evaluated. Group I received 5.0 mg OKT3 in the operating room and on day 1, followed by 2.5 mg/d for a total dose and duration of 40 mg and 14 d, respectively, and group II received 14 d of OKT3 2.5 mg/d (a total dose of 35 mg). Rejection episodes developed in 21% of patients: 29% of group I vs. 17% of group II. In groups I and II, the mean number of days until first rejection was 134 and 119 d, respectively, and delayed graft function was observed in 24 vs. 13% of patients, respectively. Cytokine release syndrome was noted in 95% of group I patients and in 78% of group II patients. The overall incidence of infections did not differ significantly between the two groups; however, the incidence of oral candidiasis was higher in group II (30 vs. 11% in group I, p = 0.021) and the incidence of herpes simplex virus infection was higher in group I (13 vs. 1% in group II, p = 0.015). The average length of hospital stay was 6.7 d in group I and 6.2 d in group II. The current pharmacy charge for a 2.5-mg vial of OKT3 is 28% lower for a 5.0-mg vial. Our study suggests that by using either low-dose OKT3 regimen renal transplant patients can be safely treated with shortened hospital stays, lower pharmacy costs, and without increased incidence of graft loss or patient morbidity.

Adult↗
PubMed1998

[Treatment of the nephrotoxicity of immunosuppressive drugs with insulin-like growth factor-I].

BACKGROUND: Delayed graft function is a common and severe complication after cadaveric kidney transplantation. Besides a more complicated postoperative course, DGF can worsen the overall graft survival. In particular, DGF enhances the nephrotoxicity of mainstream immunosuppressants cyclosporine and FK506. This study evaluates a new therapeutical approach to the treatment of DGF related nephrotoxicity, based on the administration of IGF-I. METHODS: Sixty inbred Lewis rats underwent a bilateral clamping of the renal pedicles (20') as standard damage. The animals were stratified in six groups, according to the postoperative treatment. Group 1 served as control and received only the standard ischemic injury. Cyclosporine and FK506 were added in groups 3 and 5. Groups 2, 4 and 6 had the same treatment of groups 1, 3, 5 respectively, plus the administration of IGF-I. Blood samples were drawn daily to evaluate creatinine and BUN for 7 days. RESULTS: The rats treated with IGF-I had significantly better values compared to the respective controls (2-way ANOVA, p < 0.05). CONCLUSIONS: In conclusion, IGF-I improves the nephrotoxicity of mainstream immunosuppressants in this model. Its use is potentially beneficial for transplantation.

Animals↗
PubMed1992

Acute rejection in kidney grafts with delayed onset of graft function. A duplex-Doppler study.

Forty-five kidney transplant recipients with delayed onset of diuresis due to acute tubular necrosis (ATN) were examined with duplex ultrasonography (DU). Resistive index (RI) was measured on the 4th post-transplant day. Eleven grafts (24%) developed acute rejection. Mean RI prior to rejection of the 4th postoperative day in these grafts was 0.97 and in the 34 grafts which did not develop rejection mean RI was 0.82. There were 2/26 rejections (8%) in the group of grafts with an initial RI below 0.9 and 9/19 rejections (47%) in the group of grafts with RI of 0.9 or above on the 4th post-transplant day. Six months postoperatively there were 2/26 nonfunctioning grafts in the group with lower initial RI values (less than 0.9) and 6/19 nonfunctioning grafts in the group with higher indices (greater than or equal to 0.9). In nonfunctioning grafts a high initial RI (greater than or equal to 0.9) indicates that these grafts will be prone to developing acute rejection.

Adult↗
PubMed1999

A randomized multicenter trial of the anti-ICAM-1 monoclonal antibody (enlimomab) for the prevention of acute rejection and delayed onset of graft function in cadaveric renal transplantation: a report of the European Anti-ICAM-1 Renal Transplant Study Group.

BACKGROUND: T-cell activation through T-cell receptor engagement requires co-stimulatory molecules and also adhesion molecules such as ICAM-1. Moreover ICAM-1 mediates leukocyte invasion from the blood into tissue during inflammatory processes. In animal studies using mouse monoclonal antibodies against ICAM-1 (enlimomab), renal allograft survival has been improved and reperfusion damage from ischemia reduced. The European Anti-ICAM-1 Renal Transplant Study (EARTS) was a randomized, double-blind, parallel-group, placebo-controlled study lastingl year and performed in 10 transplant centers in Europe. METHODS: A total of 262 recipients of cadaveric kidneys were given either enlimomab or a placebo for 6 days and were given triple immunosuppressive therapy of cyclosporine, azathioprine, and prednisolone. The primary efficacy endpoint was the incidence of the first acute rejection within 3 months, and each event was assessed by a committee including investigators and independent pathologists. RESULTS: There was no significant difference in the incidences of first acute rejection at 3 months between the placebo and enlimomab groups (39% vs. 45%), and enlimomab did not reduce the risk of delayed onset of graft function (DGF) (26% vs. 31%). Neither was there a difference in patient survival (95% vs. 91%) or graft survival (89% vs. 84%) at 1 year. Fatal events occurred in 19 (7%) patients (7 placebo, 12 enlimomab). Clinically, the most important non-fatal adverse events were infections; however, there was no statistically significant difference between the incidences in the two groups (70% vs. 79%). CONCLUSION: Short term enlimomab induction therapy after renal transplantation did not reduce the rate of acute rejection or DGF.

Acute Disease↗