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Erythropoietin treatment in the sixth posttransplant month as a prognostic factor for renal allograft survival.

The purpose of this work was to assess the prognostic value of the need for erythropoietin (EPO) treatment at 6 months after transplantation. We retrospectively reviewed the outcomes of 143 consecutive cadaveric kidney transplants performed between January 2000 and April 2004, functioning at 6 months postransplantation. Patients were divided into two groups: group EPO6m (n = 24) received EPO treatment in the sixth month, and a control group (n = 119) did not receive EPO. Renal function deterioration (RFD) was considered to be a sustained decrease in creatinine clearance (CrCl) greater than 20% between the sixth month postransplant and the last visit. Mean follow-up was 38 +/- 16 months. The mean ages of the donor (57 +/- 9 vs 49 +/- 12 years; P = .001) and the recipient (59 +/- 12 vs 47 +/- 17 years; P = .000) were greater in the EPO6m group. Delayed graft function (83% vs 48%; P = .001) was more frequent in the EPO6m group. At 6 months after transplantation the EPO6m group showed lower hemoglobin (11.52 +/- 1.71 vs 13.32 +/- 1.69 g/dL; P = .000), higher serum creatinine (2.31 +/- 0.72 vs 1.65 +/- 0.53 mg/dL; P = .000), lower CrCl (33.53 +/- 10.83 vs 53.6 +/- 17.58 mL/min; P = .000), and similar proteinuria. RFD was more common in the EPO6m group (38% vs 10%; P = .026), with a different pattern of evolution of CrCl (-0.098 +/- 0.176 vs +0.093 +/- 0.396 mL/min/mo, P = .000). Multivariate analysis demonstrated that treatment with EPO at 6 months was the only predictor of RFD (RR 4.46; 1.58 to 12.58; P = .005). The need for EPO at 6 months postransplant was a good predictor of later renal allograft deterioration, more sensitive than serum creatinine or proteinuria.

Aged↗

Patients with a low income have reduced renal allograft survival.

The impact of socioeconomic factors on long-term outcome after renal transplantation is unknown. We examined the effects of family income among 202 patients transplanted between 1976 and 1982 who had an allograft that functioned for at least 1 year. Compared with patients with an adequate income, recipients of medical assistance at the time of transplantation were more likely to return to dialysis after 1 year (16/45 [36%] v 26/157 [17%], P less than 0.01), or after 5 years of graft function (10/38 [26%] v 12/116 [10%], P less than 0.01). Patients who complied with fewer than 85% of visits during the first 2 years were also more likely to return to dialysis after 1 year (17/49 [35%] v 25/153 [16%], P less than 0.01), or after 5 years (8/31 [26%] v 14/123 [11%], P less than 0.05) than were more compliant patients. However, noncompliance was not different in patients with and without a low income (37/157 [24%] v 12/45 [27%], P greater than 0.05). The relative risk for returning to dialysis after 5 years was 2.4 (P less than 0.05) for low income and 3.0 (P less than 0.05) for less than 85% compliance using a Cox proportional hazards model. These effects were independent of prior transplantation, mismatches, pre-formed antibodies, delayed graft function, age, sex, diabetes, alcohol or drug abuse, education, race, distance from the transplant center, and living in an urban environment (relative risk = 2.5, P less than 0.05). Neither income nor compliance could be linked to death.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Estimated one-year glomerular filtration rate is the best predictor of long-term graft function following renal transplant.

BACKGROUND: Long-term success of renal transplantation depends upon the quality of the donor organ, avoidance of peritransplant and early posttransplant damage (rejection), and optimal maintenance of graft function after the first 6-12 months. Glomerular filtration rate (GFR) at 1 year is a standard way to evaluate short-term success, whereas calculated GFR at 5 years gives a better appreciation of long-term outcomes. The objective of this study was to assess the effect of various demographic and transplant-related parameters on renal function via GFR at 1 year and 5 years post transplantation, using univariate and multivariate data analysis. METHODS: Data on 1-year GFR were available from 10,397 patients, whereas 2,889 patients provided data on both 1-year and 5-year GFR. All patients were enrolled in the Neoral Multinational Observational Study in Transplantation (Neoral-MOST), an ongoing, prospective, observational study of adult renal transplant recipients. RESULTS: One-year GFR was the most relevant predictor for 5-year GFR. In a multifactorial analysis (ANCOVA) using 1-year GFR as a continuous variable, the effects of several highly relevant parameters from univariate analysis (such as acute rejection and delayed graft function) on 5-year GFR appeared to be fully mediated by their influence on 1-year GFR, whereas immunological risk factors like HLA match or previous transplantation had an ongoing effect on graft function beyond year 1. CONCLUSIONS: The findings of this study corroborate and augment data from previous registry surveys, and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome.

Adult↗

Nephrological indications in combined liver-kidney transplantation.

In isolated liver transplantation pretransplant renal failure is a major mortality risk, there are no guidelines at the moment to establish the indications for a combined liver-kidney transplantation (LKT). In irreversible chronic renal failure (CRF) not on dialysis, nephrological evaluation is required to assess the need for a simultaneous kidney transplantation. There are no experiences about the functional contribution of native kidneys post-LKT. Herein we have reported the case of two patients who underwent LKT in 2004 due to CRF, not yet on dialysis. At the moment of LKT, the first patient (polycystic kidney disease) had a glomerular filtration rate (GFR) = 29 mL/min, and the second recipient (vascular nephropathy and diabetes), a GFR = 33 mL/min. In both cases we did not observe delayed graft function. At discharge the serum creatinine was 1.1 and 1.0 mg/dL, respectively, which was maintained during follow-up. In both cases renal scintigraphy with Tc-99 DMSA was performed to evaluate the functional contributions of transplanted versus native kidneys. In the first case scintigraphy at 9 months after LKT demonstrated an 81% contribution from the transplanted kidney, 9% from the right and 10% from the left native kidneys. In the second case, at 3 months after LKT, the functional contributions were 76%, 10%, and 14%, respectively. The transplanted kidney nephron mass may avoid the need for hemodialysis in the early posttransplant period; in the midterm it may help to maintain residual renal function. As in other combined transplant programs (heart-kidney, kidney-pancreas) with irreversible CRF, a GFR < or = 30 to 35 mL/min may be an indication for LKT, but we need more experience.

Adult↗

Combined analysis of cytokine genotype polymorphism and the level of expression with allograft function in African-American renal transplant patients.

Cytokine gene polymorphism and expression levels were evaluated in a group of African-American patients who had undergone renal transplantation. It was hypothesized that possession of specific cytokine alleles might be influential in predisposing the recipient to allograft rejection. Thus, we sought to establish a relationship between cytokine gene polymorphism, the levels of cytokine expression, and the outcome of allograft function. Cytokine genotypes and mRNA transcript levels of IL-2, TNF-alpha, TGF-beta1, IL-10, IL-6 and IFN-gamma were determined using peripheral blood cells. Genomic DNA samples from 77 transplant recipients and 77 controls were tested by a multiplex PCR with specific primers for the above cytokines. The frequency distributions of cytokines were analyzed in respect to the clinical characterization, including delayed graft function (DGF), rejection episodes (REs) and stable graft function (SGF). The mRNA transcript level was tested both at pre- and early post-transplantation (day 1 and day 4) with primers for coding regions of the above cytokines in a RT-PCR assay. The majority of recipients with successful graft function were matched with their donors for only three out of the six HLA alleles. We have shown that the TGF-beta1 T/C G/G high producer and IFN-gamma T/A intermediate producer genotypes were associated with allograft rejection, whereas low IFN-gamma producer and high IL-10 producer genotypes were significantly protective of the allograft. There was some correlation between the TGF-beta1 high producer genotype and DGF, but it was not statistically significant. Overall, 77% of those who experienced REs carried the TGF-beta1 T/C G/G, high producer genotype as compared with 52% who experienced DGF, 39% with SGF (P<0.01, RR=2.0), and 27.3% of controls (P<0.003, RR=2.6). The IFN-gamma T/A intermediate producer genotype was found in 69.2% of patients with REs as compared with 26.8% of patients with SGF (P<0.008, RR=2.85). The IL-10, ATA/ATA low producer genotype was found in 38.5% of recipients with REs and 14.6% of recipients without REs (P<0.04, RR=0.53). Expression levels of mRNA transcript were correlated with genotype data, except for the TGF-beta1 high producer genotype where there was no significant difference between the level of mRNA transcript at pre- and post-transplantation. Low DRbeta1 and high DPbeta1 expression by recipient peripheral blood mononuclear cells before transplantation was associated with more SGF, whereas high DRbeta1 and low DPbeta1 expression at pretransplantation was associated with more REs (DRbeta1, P<0.001 and DPbeta1, P<0.05, respectively). We concluded that, dual analysis of cytokine genotype and expression levels by peripheral cells may be an important clue to understanding the contribution of the recipient's immune response to an allograft pre- and post-transplantation. Identification of peripheral markers diagnostic of rejection could allow advance anticipation of clinical outcome, and might reduce the need for tissue biopsy.

Black or African American↗

Diapedesis of leukocytes: antisense oligonucleotides for rescue.

Ischemia-reperfusion injury is an acute inflammatory process during which leukocytes are intimately involved. In this review, we summarize the current data on the leukocyte cell adhesion cascade in ischemia-reperfusion injury, focus upon studies which have demonstrated specific cell adhesion molecule interactions which mediate the leukocyte involvement in ischemia-reperfusion injury, and suggest future avenues of therapeutic interventions. The increased adhesion between activated vascular endothelium and peripheral blood leukocytes is central to the structural and the functional impairment in ischemia-reperfusion injury. Several families of adhesion molecules, namely the selectins, the intercellular adhesion molecules (ICAMs), and the integrins expressed either on the endothelium or on the leukocytes, are involved the cascade of events. Sequential and overlapping cellular interactions between the members of the three gene families of adhesion receptors result in adhesion of the leukocytes to the endothelium and extravasation at the site of ischemia. The functional importance of ICAM-1 and its beta2 integrin ligands in ischemia-reperfusion of the kidney has been demonstrated by monoclonal antibody blockade studies, in knockout mice and by treatment with antisense oligodeoxynulceotides (ODN). We have shown that antisense ODN for ICAM-1 protected the kidney against ischemic renal failure. In addition, in transplanted kidneys, ICAM-1 inhibition by antisense ODN ameliorates ischemia-reperfusion injury and prevents delayed graft function. Recent developments in antisense ODN technology make this a promising therapeutic approach, and antisense ODN treatment of donors or donor organs for ICAM-1 may be useful for the prevention of reperfusion injury in human renal transplantation and could influence acute and chronic graft function.

Animals↗

A comparison of traditional open, minimal-incision donor nephrectomy and laparoscopic donor nephrectomy.

Laparoscopic donor nephrectomy (LDN) and minimal-incision donor nephrectomy (MILD) are less invasive procedures than the traditional open donor nephrectomy approach (ODN). This study compares donor and recipient outcome following those three different procedures. Sixty consecutive donor nephrectomies were studied (n = 20 in each group). Intra-operative variables, analgesic requirements, donor recovery, donor/recipient complications and allograft function were recorded prospectively. Operating and first warm ischaemia times were longer for LDN than for ODN and MILD (232+/-35 vs 121+/-24 vs 147+/-27 min, P < 0.001; 4+/-1 vs 2+/-2 vs 2+/-1 min, P < 0.01). Postoperative morphine requirements were significantly higher after ODN than after MILD and LDN (182+/-113 vs 86+/-48 vs 71+/-45 mg; P < 0.0001). There was no episode of delayed graft function in this study. Donors returned to work quicker after LDN than after ODN and MILD (6+/-2 vs 11+/-5 vs 10+/-7; P = 0.055). Donor and recipient complication rates and recipient allograft function were comparable. We concluded that MILD and LDN reduce postoperative pain and allow a faster recovery without compromising recipient outcome.

Adult↗

Impact of selected factors on early graft function in patients after renal transplantation.

Transplantation is the best treatment for end-stage renal diseases. For transplantologists, it is most important to know the factors that worsen graft survival prognosis. The aim of the study was to investigate factors predictive of graft loss and shortened graft survival. We retrospectively reviewed 442 renal transplant patients between 1990 and 1995 in two Szczecin units, all of whom received a triple-drug immunosuppressive regimen. One hundred thirty patients showed graft disorders such as delayed graft function or primary nonfunction. The occurrence of these disorders was examined as a function of donor and recipient age and sex, cause of ESRD, HLA compatibility, ABO and Rh compatibility, cold ischemia time, warm ischemia time, antileukocyte antibody level (PRA), and period of dialysis therapy before transplantation. The study showed that a high maximal PRA level, incompatibility for ABO group, and a longer warm ischemia time increase the probability of early graft function disorders.

ABO Blood-Group System↗

A randomized trial comparing cyclosporine induction with sequential therapy in renal transplant recipients.

Calcium antagonists may reduce the nephrotoxicity of cyclosporine (CsA), allowing CsA to be introduced immediately after renal transplantation and thereby obviating the need for sequential induction therapy with a monoclonal or polyclonal antibody. To test this hypothesis, in a pilot feasibility trial 100 cadaveric or one-haplotype-mismatched living-related renal transplant recipients were randomized to either (1) sequential therapy with anti-thymocyte globulin (ATG) (ATGAM; Upjohn, Kalamazoo, MI) 20 mg/kg/d for 7 to 14 days until renal function was established and CsA (Sandimmune; Sandoz, East Hanover, NJ) was started, or (2) CsA 8 mg/kg/d begun immediately before surgery with diltiazem (Cardizem; Marion Merrell Dow, Kansas City, MO) 60 mg sustained release twice daily. Acute rejection episodes during the first 90 days were not different with ATG versus CsA induction (42% v 28%; P = 0.142 by chi-square analysis). Graft failures (10% v 16%; P = 0.372) and the incidence of delayed graft function (28% v 34%; P = 0.516) were also similar with ATG compared with CsA. ATG caused lower platelet counts (138 +/- 59 x 10(3) v 197 +/- 75 x 10(3) at 7 days; P < 0.001) and lower white blood cell counts (9.6 +/- 4.6 x 10(3) v 12.3 +/- 4.9 x 10(3) at 7 days; P = 0.003). Diltiazem reduced the dose of CsA required to maintain target blood levels (479 +/- 189 mg/d v 576 +/- 178 mg/d at 14 days; P = 0.015). There were no statistically significant differences between the groups in serum creatinine levels at days 1, 3, 5, 7, 14, 28, 60, or 90. The results of this pilot feasibility trial suggest that prophylactic treatment with CsA and diltiazem may be equally effective and less toxic than ATG induction after renal transplantation.

Adult↗

Hydroxyethyl starch does not impair immediate renal function in kidney transplant recipients: a retrospective, multicentre analysis.

BACKGROUND: The effect of hydroxyethyl starch (HES) on early allograft function was examined retrospectively in a cohort of 119 renal transplantations realized by local organ exchange between four cooperating centres. METHODS: After exclusions, 109 transplant procedures were subdivided in three groups according to donor colloid loading: (i) HS-group (Haes steril 6%, mean volume (SD): 979 (946) ml, n = 20); (ii) PS-group [Plasmasteril, mean volume (SD): 769 (411) ml, n = 16]; and (iii) control group (gelatin albumin, n=73). RESULTS: Delayed graft function (DGF), defined as the need for dialysis during the first post-transplant week, occurred in 3/20 (15%) cases in the HS-group, in 5/16 (31%) cases in the PS-group and in 14/73 (19%) cases in the control group (P = 0.450). Uni- and multivariate analysis revealed older donor age (P = 0.001) and kidney preservation with histidine-tryptophan-ketoglutarate (HTK) (P = 0.001) as the only factors associated with a higher incidence of DGF. CONCLUSIONS: Renal function as measured by daily serum creatinine concentration and 24 h urinary output up to 14 days post-transplantation in the HS-group was comparable with that of controls. The higher serum creatinine observed during the first seven post-transplant days in the PS-group could be related to higher donor age and haemodynamic instability, and recipient male preponderance, rather than to HES itself.

Adult↗

Long-term follow-up of kidneys transplanted from elderly cadaveric donors.

This report examines the long-term results obtained in 50 patients transplanted between 1977 and 1990 with kidneys from cadaveric donors aged 55-70 (median 59) years. The recipients comprised 27 men and 23 women aged 8-68 (median 42) years. In all, 20 patients (40%) had end-stage renal disease on the basis of glomerulonephritis, whereas 8 (16%) were diabetic. Immunosuppression was induced with antilymphocyte globulin and maintained with azathioprine and prednisone in all patients in addition to cyclosporine in the 35 patients transplanted since 1985. Immediate graft function occurred in 18 patients (36%), and 36 patients (72%) were off dialysis at 1 year posttransplant. Altogether, 25 patients (50%) had functioning grafts at 5 years posttransplant, and at up to 13 years of follow-up (mean 5.8 years), 22 patients (44%) are off dialysis and their serum creatinine levels range from 0.8 to 3.8 mg/dl (mean 2.0 mg/dl). In all, 12 patients (24%) expired from 2 months to 15.5 years posttransplant (mean 4.3 years), and 5 of these patients died with functioning grafts. These 5 deceased recipients and the 22 who remain alive with functioning grafts had a mean antigen match of 2.27 with their donors. The other 23 patients whose grafts failed had a mean antigen match of 2.13 (P = 0.77). The 15 recipients who were transplanted prior to the cyclosporine era had lower 1- and 5-year allograft survival rates of 67% and 47%, respectively, as compared with their counterparts, who took cyclosporine-based immunosuppression (74% and 51%, P = 0.58 and 0.76, respectively). Likewise, the 32 recipients with delayed graft function had lower 1- and 5-year allograft survival rates of 66% and 47%, respectively, as compared with the group with immediate graft function (83% and 56%, P = 0.18 and 0.56, respectively). We conclude that acceptable long-term patient and graft survival may be achieved by transplanting these organs and that the degree of HLA matching does not affect their outcome significantly. Patients with immediate allograft function also tended to do better over the long term. Although cyclosporine-based immunosuppression was advantageous within 1 year of transplant, its beneficial effect was less marked 5 years out.

Adolescent↗

[Survival of the renal transplant: data from international registries].

In this article the authors examine which factors have the greatest influence on both renal survival and renal function by reviewing the database of the main International Registries. Both patient and renal survival rates have been continuously improving over recent years. In the case of a living donor, graft survival is similar either for related or unrelated donor. Long-lasting hypertension and low donor glomerular filtration rate are relevant factors negatively affecting the outcome. Older recipients have poorer prognosis. Graft loss due to the recurrence of the original disease actually has a higher incidence. Delayed graft function and acute rejection are the major determinants of poor prognosis. In recent studies, one year renal function proved to be the best predictor of poor outcome. Several other factors, such as recipient hypertension, dyslipidemia, smoking and recipient compliance influence graft survival.

Age Factors↗

Identification of clinical and histopathologic risk factors for diminished renal function 2 years posttransplant.

The aim of this study was to identify early clinical and pathologic variates that independently predict diminished renal allograft function at 24 mo posttransplant. A clinical pathologic data base was prospectively derived from 71 patients in whom protocol renal biopsies were performed at 1, 2, 3, 6, and 12 mo posttransplant. The major end point was the 24-mo serum creatinine. Variates correlating independently (r2 = 0.67) with the 24-mo serum creatinine were the chronic biopsy scores (months 3 and 6), late rejections (months 4 to 6), cyclosporin A (CsA) levels (months 1 to 2), and delayed graft function. The adjusted odds ratio (OR) and 95% confidence interval (CI) for having a serum creatinine > or = 130 mumol/L at 24 mo increased for every year the donor age increased (OR = 1.07; 95% CI, 1.02 to 1.13; range, 9 to 55) or for each late rejection episode (OR = 5.9; 95% CI, 1.7 to 20.1), whereas a mean CsA level > 300 micrograms/L from months 1 to 3 was protective (OR = 0.07; 95% CI, 0.01 to 0.43). Variates correlating independently (r2 = 0.53) with the change in serum creatinine from 6 to 24 mo (delta Cr6-24) were the chronic biopsy scores at months 3 and 6. The adjusted OR of the delta Cr6-24 rising > or = +20 mumol/L increased for every year the donor age increased (OR = 1.09; 95% CI, 1.02 to 1.16; range 9 to 56) or when the 6-mo chronic biopsy score was > or = 2 (OR = 6.6; 95% CI, 1.2 to 36.4). An estimate of the relative risk for diminished renal function at 2 yr can be assigned within 6 mo of transplant based on chronic pathology, late acute rejections, CsA levels, and donor age.

Adult↗

Comparison of laparoscopic and open donor nephrectomy: UK experience.

UNLABELLED: A comparison of laparoscopic and open donor nephrectomy is presented by authors from the UK. They found that the laparoscopic approach could safely be offered to patients treated in experienced units and after adequate training fo the surgeon, with no increase in complications or decrease in efficacy. OBJECTIVE: To compare our early experience of laparoscopic donor nephrectomy (LDN) with a contemporary cohort of conventional open donor nephrectomy (ODN). PATIENTS AND METHODS: Transperitoneal left-sided LDN was offered to carefully selected potential live kidney donors on the basis of vascular anatomy. The first 20 donors who underwent LDN were compared with a control group of 20 patients who had ODN. Donors and recipients were compared for demographics, intraoperative variables, postoperative complications and allograft function. RESULTS: There was no peri-operative mortality in either group. No laparoscopic procedure required open conversion. The operating time was comparable (165 vs 153 min); LDN was associated with significantly less intraoperative blood loss (200 vs 350 mL; Mann-Whitney U, P = 0.01) and hospital stay (3 vs 5 days; P < 0.001). The graft warm ischaemic time was significantly longer for LDN (5 vs 2 min; P < 0.001) but this did not appear to affect either the delayed graft function rate (5% vs 10%, not significant) or serum creatinine level at discharge (125 vs 126 micromol/L). CONCLUSIONS: UK centres with experience of advanced laparoscopy and ODN can safely offer LDN to potential live donors.

Adult↗

Comparison of sequential protocol using basiliximab versus antithymocyte globulin with high-dose mycophenolate mofetil in recipients of a kidney graft from an expanded-criteria donor.

This retrospective pilot study investigated use of high-dose mycophenolate mofetil with biological induction and sequential introduction of low-dose cyclosporine in recipients of expanded criteria donor (ECD) kidneys. Fifty-four patients received mycophenolate mofetil 3 g/day for 45 days, cyclosporine 4 mg/kg/day, prednisolone, and rabbit antithymocyte globulin (rATG, n=14) or basiliximab (n=40). Acute rejection incidence was 11.3% (7.1% with rATG, 12.6% with basiliximab). Delayed graft function was observed in 31 patients (54%). At one year, measured glomerular filtration rate was 54+/-4 ml/min, with no significant differences between induction therapies. Thirty patients (55%) required > or =1 MMF dose reduction within month 1 due to adverse events (gastrointestinal symptoms, 67%; leucopenia 33%). Leucopenia was more frequent with rATG, while gastrointestinal symptoms were more frequent with basiliximab. Cytomegalovirus replication occurred in three patients (23%) with rATG and 3 (8%) with basiliximab. In conclusion, high-dose MMF, corticosteroids, delayed low-dose cyclosporine and induction therapy offers an excellent risk-to-benefit ratio in patients receiving an ECD allograft.

Antibodies, Monoclonal↗

Improved outcomes in cadaveric renal allografts with pulsatile preservation.

BACKGROUND: Early immunologic and non-immunologic injury of renal allografts adversely affects long-term graft survival. Some degree of preservation injury is inevitable in cadaveric renal transplantation, and, with the reduction in early acute rejection, this non-immunologic injury has assumed a greater relative importance. Optimal graft preservation will maximize the chances of early graft function and long-term graft survival, but the best method of preservation pulsatile perfusion (PP) versus cold storage (CS) is debated. METHODS: Primary cadaveric kidney recipients from January 1990 through December 1995 were evaluated. The effects of implantation warm ischemic time (WIT) ( < or = 20 min, 21-40 min, or > 40 min) and total ischemic time (TIT) ( < or > or = 20 h) on death-censored graft survival were compared between kidneys preserved by PP versus those preserved by CS. The effect of preservation method on delayed graft function (DGF) was also examined. RESULTS: There were 568 PP kidneys and 268 CS kidneys. Overall death-censored graft survival was not significantly different between groups, despite worse donor and recipient characteristics in the PP group. CS kidneys with an implantation WIT > 40 min had worse graft survival than those with < 40 min (p = 0.0004). Survival of PP kidneys and those transplanted into 2 DR-matched recipients was not affected by longer implantation WIT. Longer TIT did not impact survival. DGF was more likely after CS preservation (20.2% versus 8.8%, p = 0.001). CONCLUSIONS: Preservation with PP improves early graft function and lessens the adverse effect of increased warm ischemia in cadaveric renal transplantation. This method is likely associated with less preservation injury and/or increases the threshold for injury from other sources and is superior to CS.

Adenosine↗

Long-term renal allograft outcome after simultaneous kidney and pancreas transplantation.

BACKGROUND: In selected young patients with type 1 diabetes mellitus and end-stage renal failure, simultaneous pancreas and kidney (SPK) transplantation is the treatment of choice. We conducted a retrospective, case-controlled study to compare the function, survival and pathology of renal allografts after SPK and kidney-alone (KA) transplantations. METHODS: We studied 26 consecutive SPK patients and 67 KA controls matched for time of transplantation. Renal function was assessed by routine evaluation of serum creatinine and its course by the 1/serum creatinine vs time curve. Histologic evaluation of early biopsies (0-3 months post-transplantation, n=63), intermediate biopsies (3 months-1 year, n=75) and late biopsies (after 1 year, n=35) were performed by two independent reviewers. RESULTS: SPK and KA recipients differed significantly with regard to donor and recipient age, time on the waiting list, HLA sensitization, renal cold ischaemia time (CIT) and the incidence of delayed graft function. Acute rejection was more frequent after SPK than KA (54 vs 27%; P=0.01), despite higher trough levels of calcineurin inhibitors. After SPK and KA, actuarial patient and renal allograft survival and renal function were comparable at 1 and 4 years. Severe chronic lesions, especially vascular lesions, and calcineurin-inhibitor nephrotoxicity were more frequent in intermediate and late biopsies in the SPK group. CONCLUSIONS: We confirmed that patient and graft survival is comparable between SPK and KA recipients. Despite the use of optimal organs and shorter CIT in SPK, renal graft function was not different in the two groups. Histologic chronic lesions were more severe in SPK than in KA recipients. This might be caused by acute rejection episodes or be due to more severe nephrotoxicity after SPK, because of higher doses of calcineurin inhibitors, or higher sensitivity to calcineurin-inhibitor nephrotoxicity.

Adult↗

Single-center analysis of 468 first cadaveric kidney allografts with a uniform ATG-CsA sequential therapy.

Progress in clinical management and sophistication of immunological treatment of kidney allografts depend upon continuous reassessment of the risk factors related to pre- and post-graft information according to the therapeutical strategies used. We studied predictive factors of long-term graft survival (up to 9 years) and of kidney graft function at one year after surgery in a single-center population of 468 first cadaveric kidney recipients treated with a uniform immunosuppression induction regimen of anti-thymocyte globulin, followed by cyclosporine A. The statistical analysis showed that long-term graft survival was highly correlated with the occurrence of one or more acute cellular rejections and with the timing of these episodes. In addition, this uniformly treated series of patients confirmed the potential importance of gender matching. The magnitude of anti-HLA immunization and delayed graft function were also strongly linked to low graft survival rates. We found no significant influence of HLA matching, with serological HLA typing, on graft loss. The quality of graft function at one year was found to be a strong prognostic factor of long-term graft survival. In addition, the impact of pre- and post-graft parameters were studied in terms of prediction of one-year graft function. A stepwise multivariate analysis showed that graft function at one year was a multivariate phenomenon strongly correlated with a history of acute rejection episodes and with donor and recipient age. However, these 3 factors could account for only 15% of the graft function deterioration, the remaining 85% might be explained in part by chronic cyclosporine toxicity and/or chronic rejection.

Adolescent↗