Comparison of Survival in Recipients of Marginal and Standard Cadaveric Donor Kidneys

Increasing the Use of Kidneys From Unconventional and High-Risk Deceased Donors.

Determination of EBV serostatus prior to kidney transplantation: Comparison of VIDAS®, LIAISON® and immunofluorescence assays

Renalase is a recently described enzyme secreted by the kidney into both plasma and urine, where it was suggested to degrade catecholamines contributing to blood pressure control. While there is a controversy regarding the relationship between renal function and plasma renalase levels, there is virtually no data in humans on plasma renalase activity as well as on both urine renalase levels and activity. We prospectively examined the time course of plasma and urine renalase levels and activity in 26 end-stage renal disease (ESRD) patients receiving a cadaver kidney transplant (cadaver kidney recipients [CKR]) before surgery and during the recovery of renal function up to day 90 post transplant. The relationship with sympathetic and renal dopaminergic activities was also evaluated. The recovery of renal function in CKR closely predicted decreases in plasma renalase levels (r = 0.88; P < 0.0001), urine renalase levels (r = 0.75; P < 0.0001) and urine renalase activity (r = 0.56; P < 0.03), but did not predict changes in plasma renalase activity (r = -0.02; NS). Plasma norepinephrine levels positively correlated with plasma renalase levels (r = 0.64, P < 0.002) as well as with urine renalase levels and activity (r = 0.47 P < 0.02; r = 0.71, P < 0.0005, respectively) and negatively correlated with plasma renalase activity (r = -0.57, P < 0.002). By contrast, plasma epinephrine levels positively correlated with plasma renalase activity (r = 0.67, P < 0.0001) and negatively correlated with plasma renalase levels (r = -0.62, P < 0.003). A significant negative relationship was observed between urine dopamine output and urine renalase levels (r = -0.48; P < 0.03) but not with urine renalase activity (r = -0.33, NS). We conclude that plasma and urine renalase levels closely depend on renal function and sympathetic nervous system activity. It is suggested that epinephrine-mediated activation of circulating renalase may occur in renal transplant recipients with good recovery of renal function. The increase in plasma renalase activity observed in ESRD patients and renal transplant recipients can be explained on the basis of reduced inhibition of the circulating enzyme.

The progressive deterioration of kidney allograft function leads in most cases to transplant failure. Polymorphisms in genes encoding for inflammatory and apoptosis molecules may be one possible explanation for interindividual differences in kidney transplant outcomes. The objective of our work was to identify the possible effect of interleukin 6 (IL-6), transforming growth factor beta 1 (TGFB1), and Fas on graft function. A case-control study was carried out to assess potential associations between polymorphisms in inflammation- and apoptosis-related genes and the risk for chronic impairment of kidney graft function. The study included 376 cadaveric kidney recipients, 256 of them with stable graft function and 120 who experienced renal deterioration during the follow-up period of 2.6 ± 1.4 years. Genotyping of IL-6/G-174C, TGFB1/L10P, TGFB1/R25P, and Fas/G-670A polymorphisms was performed by PCR-RFLP and direct sequencing. Considering the single IL-6, TGFB1, and Fas polymorphisms, we found similar allelic and genotype frequencies between the 2 groups. To test the hypothesis of mutual effects of polymorphisms, multiple logistic regression was performed incorporating data for all the possible dual genotypic associations. The association of IL-6 high producer and Fas low producer genotype resulted in a protective effect against graft dysfunction (OR=0.79; 95% C.I.=0.72-0.86). This study did not find significant associations of apoptosis and inflammation gene polymorphisms with transplanted kidney function in Italian renal transplant recipients. However, our data seem to indicate that the carriage of IL-6 high producer/Fas low producer genotype has a protective effect against graft function loss.

Acute antibody-mediated rejection is the major cause of graft failure in the early stage of kidney transplantation. Preoperative treatment and early diagnosis of acute rejection is very important to prevent graft loss in sensitized patients. High panel reactive antibody (PRA) means a likelihood of acute rejection, and the recipient of high PRA needs adequate pretreatment for kidney transplantation. However, there is not sufficient time and chances for desensitization in deceased kidney transplants. We report a successful renal transplant outcome in a 47-year-old-woman with high PRA levels (Class I 97.5%, Class II 36.7%). The cross match was negative on the CDC (ELISA) and flowcytometric methods. Plasma exchange was performed on the recipient before transplantation (fresh frozen plasma replacement, 1.3 plasma volume) and immediately after plasma exchange she was given 200 mg of rituximab. She received basiliximab and methyl prednisolone induction therapy and was maintained on steroids, mycophenolate mofetil, and tacrolimus. Graft function was normal immediately after transplantation, but decreased urinary output and elevated serum creatinine was noted on POD 5. On POD 6, a graft biopsy revealed acute cellular rejection (Type IIa) and antibody-mediated rejection (Type II). On 9∼13 days after transplantation, additional plasma exchange was performed every other day, and steroid pulse therapy was performed 3 times. After normalization of urinary output and serum creatinine, the patient was discharged and is being followed up on. In conclusion, immunologically careful preparation and pretransplant treatment may be needed on the negative cross match in cadaveric kidney recipients with high levels of PRA.

Cadaver Donor Kidney Retransplantation in the Pediatric Patient: Complications and Long-Term Outcome

The outcomes of single kidneys transplanted from pediatric donors into standard adult recipients (>60 kg) are unknown. Furthermore, the outcomes of single kidneys transplanted from pediatric donors less than or equal to 10 kg are also unknown. We retrospectively compared 27 recipients of single kidneys from pediatric donors younger than or equal to 5 years with 69 recipients of adult cadaveric kidneys. The mean pediatric kidney recipient weight was 69 kg. Two-year patient and graft survival in pediatric kidney recipients was 100% and 92.5% respectively, compared with 98.5% and 89.8% in adult kidney recipients (P=NS). Mean time (days) to achieve creatinine less than 3 mg/dL was 14+/-9 compared with 14+/-20 in adult kidney recipients (P=NS). Estimated glomerular filtration rate at discharge, 6, 12, 18, and 24 months was equivalent in both cohorts. Stratifying pediatric kidney recipients by donor weight, there were no differences in acute rejection or graft loss in recipients of kidney from donors less than or equal to 10 kg (n=11; mean weight=8.85 kg), but there was a higher incidence of delayed graft function (7 of 11 vs. 1 of 16; P=0.002). Estimated glomerular filtration rate at discharge, 6, 12, 18, and 24 months was equivalent in both cohorts. Single pediatric kidneys from donors younger than or equal to 5 years can be transplanted into standard adult recipients without compromising outcomes. Transplanting single kidneys from pediatric donors less than or equal to 10 kg into standard adult recipients is associated with an increased risk of delayed graft function; however, this does not compromise 2-year graft survival or function.

Insertion/Deletion Polymorphism of Angiotensin-Converting Enzyme as a Risk Factor for Chronic Allograft Nephropathy

Urinary Tract Infections in Solid Organ Transplant Recipients

Long Graft Cold Ischemia Time Is Associated With Increased Arterial Stiffness in Renal Transplant Recipients

Angiotensin-Converting Enzyme Inhibitors After Renal Transplantation

Increased aortic stiffness is a major factor responsible for the high cardiovascular mortality in patients with end-stage renal disease, but the impact of kidney transplantation on recipient aortic stiffness remains poorly defined. The use of expanded-criteria kidney donors is associated with decreased recipient survival compared with the use of standard-criteria donors, although the underlying mechanisms are incompletely understood. It was hypothesized that donor characteristics may affect recipient aortic stiffness, which may contribute to cardiovascular mortality in these patients. Aortic stiffness was evaluated by measurement of carotid-femoral pulse wave velocity in 74 cadaveric kidney recipients at 3 and 12 mo after transplantation. At 3 mo, aortic stiffness was associated exclusively with recipient-related factors: Age, gender, and mean BP. At 12 mo, age of the donor kidney emerged as an additional determinant. The change in aortic stiffness between 3 and 12 mo strongly correlated with donor age; stiffness improved in recipients of young kidneys (first tertile of donor age) and worsened in recipients of older kidneys (upper tertile of donor age). At 12 mo, the carotid-femoral pulse wave velocity was >1 m/s higher in recipients of the oldest kidneys than in the recipients of younger kidneys. The association between donor age and aortic stiffness was independent of recipient age, gender, mean BP, pretransplantation dialysis duration, conventional cardiovascular risk factors, medication, posttransplantation events, and GFR. These results demonstrate that the impact of kidney transplantation on recipient aortic stiffness is dependent on donor age and suggest that ongoing damage to large arteries might contribute to the mechanism underlying the association of old-donor kidneys and increased cardiovascular mortality.

To evaluate the clinic relevance of anti-HLA-II antibodies on allograft long-term survival. Perioperative sera of 118 cadaveric kidney recipients were tested by ELISA for anti-HLA-II antibodies in our prospective cohort study. All recipients who divided into different groups according to HLA antibody production were followed-up. (1) Anti-HLA-II antibody-positive recipients were associated with significantly lower graft survival (78.6% vs 84.4%; 71.4% vs 80.0%; P = 0.002) and death-censored graft survival (85.7% vs 92.2%; 82.1% vs 90.0%; P = 0.003) at 3 and 4 years compared to antibody-negative recipients. (2) Anti-HLA-II antibody-positive recipients were associated with a significantly increased risk for decline in renal function at 3 and 4 years (39.3% vs 33.3%; 46.4% vs 38.9%, P = 0.001). (3) There was statistically non-significance difference in late-acute rejection rate between two groups (10.7% vs 13.3%, P > 0.05). Posttransplant HLA-II antibodies perhaps are one of the most important influential facts on allograft long-term survival and could be used to predict the prognosis of allograft.

The effect of sirolimus- or cyclosporine-based immunosuppression effects on T-cell subsets in vivo

Effect of Panel-Reactive Antibody in Predicting Crossmatch Selection of Cadaveric Kidney Recipients

The incidence of postischemic acute renal allograft failure (ARF) occurs in roughly 25% of cadaveric donor kidney recipients. This high rate remained virtually unchanged over the last decades despite modification in recipient management and modern immunosuppressive strategies. It has recently been shown that among other reasons, the systemic inflammation in the brain death cadaveric organ donor contributes to subsequent ARF in the recipient. This review focuses on the consequences of ischemia and reperfusion on the cellular level and offers potential solutions for the reduction of ARF. Genome-wide gene expression analysis together with sophisticated biostatistical analysis made it possible to identify several candidate gene products and proteins that may act as specific and sensitive biomarker for renal inflammation and ischemia. These markers may be very helpful in the clinical management of patients with a high a priori risk of subsequent ARF such as recipients of marginal donor kidneys. Ongoing clinical trials will evaluate whether immunosuppression of the cadaveric organ donor before organ harvest will have the potential to reduce inflammation in the transplant kidney and subsequently lead to a reduction in the rate of ARF.

C2 monitoring of cyclosporine (CsA) has been promoted as improving the results of organ transplantation. No randomized, controlled studies in de novo kidney transplant recipients are available. Between June 2003 and August 2004, 160 consecutive cadaveric kidney recipients allocated to CsA, mycophenolate and steroids were randomized to either C0 or C2 monitoring of CsA for the first 3 weeks posttransplant. Both levels were measured, keeping the other level blinded until 3 weeks. Altogether, 1451 double measurements were done. The target C0 was 200-300 microg/L and C2 1500-2000 microg/L. From the fourth week on, only C0 monitoring was used. Median follow up time was 505 days. The overall 3-month rejection rate was 7.5% in Group C0 vs. 10.8% in Group C2 and the one-year graft survival rates were 92.5% vs. 94.6% (NS). Rate of delayed graft function was similar in the groups. Plasma creatinine tended to be higher in group C2 at 3 weeks, but not thereafter. During the first three weeks posttransplant, the mean CsA dose was 57%, mean C2 levels were 55%, and mean C0 levels were 98% higher in group C2 than in group C0 (P < 0.00001). This pilot study showed no advantages of C2 monitoring but led to significantly higher CsA doses and blood levels than C0 monitoring.

In kidney transplantation, pretransplant serum sCD30 testing has been proposed in immunological risk estimation together with anti-HLA antibodies. We evaluated the risks associated with high pretransplant serum sCD30 in well HLA-matched cadaveric kidney recipients recruited in a clinical study comparing different immunosuppressive regimens. Rejection rate was similar in 37 recipients with high pretransplant serum sCD30 compared to 117 recipients with low serum sCD30 (16% vs. 15%, P=NS). Compared to pretransplant levels, the posttransplant sCD30 levels generally decreased, also in patients with rejection, although on day 21 posttransplant, rejecting patients had significantly higher relative sCD30 than nonrejecting patients (P<0.01). However, steroid-resistant rejection was associated with increasing posttransplant sCD30 levels. High pretransplant sCD30 values were associated with tubulointerstitial rejection. There was no correlation of sCD30 with delayed graft function. Good HLA matching seems to be effective in neutralizing the negative effect of a high pretransplant serum sCD30.

National registry data are often a suitable basis for examination of transplant outcomes. Using data supplied by the Italian National Transplant Registry, established in 1995, we performed the first nationwide analysis of this kind. A retrospective analysis of 4893 recipients of cadaveric kidneys transplanted in all Italian centers from 1995 through 2000 was done to study 5-year graft survival. The association between some donor and recipient variables and outcomes in renal transplantation was analyzed. Graft survival was 93% at 3 months, 89% at 1 year, 82% at 3 years, and 80% at 5 years after transplantation. A significant association between graft survival and donor age (old vs young, relative risk [RR] = 1.62, 95% CI 1.27-2.06) and recipient age (old vs young, RR = 1.25, 95% CI 1.02-1.53). Graft survival was also associated with cold ischemia time (24-36 hours, RR= 1.39, 95% CI 1.05-1.85 and >36 hours, RR= 1.94, 95% CI 1.32-2.86 vs 0-24 hours) and donor/recipient sex mismatch (female/male vs male/male, RR= 1.50, 95% CI 1.17-1.93). The quality of kidney transplantation in Italy is satisfactory and is comparable to that in other developed countries. Furthermore, our experience confirms that both donor and recipient factors are major determinants of renal allograft function.