Risk factors on graft survival of living donor kidney transplantation

Living donors have always been the basic resources of transplantation in our country, where cadaveric harvesting is still hampered for various reasons. OBJECTIVE: The aim of this study was to compare graft survival rates between living unrelated donor (LURD) and living related donor (LRD), to assess the potential risk factors for the graft survival, and to discuss the role of LURD. METHOD: From October 1991 to February 2003, 77 living donor renal transplants were performed: 41 were LURD and 36 were LRD transplants. The analyzed variables were donor relationship, recipient age and sex, donor age and sex, HLA-DR mismatching, nonspecific blood transfusion history of donor, acute rejection episodes, repeated rejection episode (more than 3 times), delayed graft function, recurred primary disease, and immunosuppressive regimen. Graft survival rate was assessed with the Kaplan-Meier method and the significance of possible variables with the Cox proportional hazard model. RESULTS: Eleven recipients lost their grafts (6 from LURD and 5 from LRD), most of them are due to chronic rejection (n = 7). Overall 3-, 5- and 10-year graft survival in live donors were 92.8%, 86.6%, and 76.9%, respectively. Graft survival at 3, 5, and 10 years being 91.9%, 88.5%, and 74.7% for the LURD versus 94%, 84%, and 78.8% for LRD transplants (P > .05). Acute rejection episodes, especially more than 3 times (risk ratio [RR] = 11.1) and preoperative multiple transfusion history (RR = 4.2) were significant factors on graft survival in our series. CONCLUSION: Acute rejection episodes markedly decreased the long-term graft survival in live donor renal transplants. The use of LURD transplants provides graft survival comparable with LRD transplants and proper management to acute rejection is essential for long-term graft survival.     

Donor-recipient age difference and graft survival in living donor kidney transplantation

Background

In paired living kidney exchange donation from an old donor to a young recipient, it may be argued that elderly donors provide an inferior quality kidney. However, the impact of donors older than recipients on transplant outcomes remains unclear.

Methods

We retrospectively reviewed the charts of primary living kidney transplantation patients who were divided into two groups based on the age difference between donor and recipient (recipient age subtracted from donor age, donor-recipient < 20 vs ≥ 20). The donor-recipient age difference < 20 group comprised 75 and donor-recipient age difference ≥ 20 group, 25 subjects. Outcome measures included serum creatinine, acute rejection episodes as well as graft and patient survivals at 1 and 5 years after transplantation.

Results

The mean donor age difference cohorts of < 20 and ≥ 20 years showed donor ages of 33 ± 8 and 54 ± 8 years, respectively. The mean recipient age in both groups averaged under 40 years. The acute rejection rate within the first year posttransplantation was greater among age difference ≥ 20 years. The mean serum creatinine values of the donor-recipient age difference < 20 group was lower than the ≥20 years group at 1 and 5 years posttransplant. The 1-year difference was associated with an increased creatinine value at 5 years. However, death-censored graft survival of the age difference of the ≥ 20 years group was not different (hazard ratio [HR] = 0.1, 95% confidence interval [CI] = 0.01-1.37, P = .08). Patient survival of the age difference ≥ 20 years group showed no difference compared with the age difference < 20 years group (HR = 0.25, 95% CI = 0.01-6.35, P = .4).

Conclusion

Although the cohort of a donor-young recipient age difference ≥ 20 years showed a greater risk of an acute rejection episode early posttransplantation, it did not affect graft or patient survivals. When considering paired kidney donation, older age donors should not necessarily be limited.     

ABO-incompatible living kidney transplantation

ABO-incompatible living kidney transplantation is nowadays a routine procedure to expand living donor pool. The past decades have seen the evolution of desensitization protocol and immunosuppression regimen. Despite increased bleeding events, infectious complications, and rejection episodes reported in some studies, favorable graft and patient survival rate are now achieved, regardless of various protocols among transplant centers. Several issues such as the usage of rituximab and standardization of blood group antibody titration remain to be settled. The deposition of C4d is no longer the histopathologic hallmark of antibody-mediated rejection, which have inspired innovative strategies of peripheral molecular screening and the improvement of histological diagnosis of AMR (antibody-mediated rejection). The better understanding of the underlying mechanism might facilitate the distinction and therapeutic schemes of AMR.     

ABO-incompatible living related donor kidney transplantation: report of two cases

The courses of two recipients of ABO-incompatible HLA-identical living related donor kidney transplants are described, the first an A into O and the second a B into A. Both patients were prepared by a month of preoperative azathioprine and a week of plasmapheresis to reduce isohemagglutinin titers in one to 1:2 and in the other to 0 at the time of transplant. Both had early mild steroid-reversible rejections, and the first patient has had an uneventful subsequent course 20 months postgrafting on low-dose cyclosporine and prednisone. The second patient developed a further immunologic event at 1 month that may have been isohemagglutinin mediated or may have been rejection but subsided with OKT3 therapy and plasmapheresis. She lost her graft at 5 months despite normal function during attempts to repair a ureteric fibrosis. Neither patient had donor-specific transfusion or splenectomy. This approach is feasible and should be considered for those patients having related but ABO-incompatible donors.     

Long term results of living donor kidney transplantation: graft and patient survival

Donor kidney transplantation's graft and patient survivals are better than cadaver donor's. In Spain, living donor kidney transplantation hardly accounts for 1% of transplant activity in comparison to 60% in United States. Accordingly to bibliography, the experience of the Renal Transplant Unit of the Hospital Clinic de Barcelona has demonstrated better graft and receptor survival for living donor recipients. The analysis of 184 living donor kidney transplants and 1678 cadaver donor transplants performed between 1978 and 2002 showed that graft survival was higher in the group of living donors (p < 0.01). At the same time, graft survival was clearly better in receptors of HLA haploidentical grafts (n=142) (p < 0.05). The introduction of new and better immunosuppressive drugs, as well as better diagnostic and therapeutic management of acute rejection, prophylaxis for infections, and control of complications have contributed to better results. The absence of acute rejection between 1978 and 1983 was 45.1%, between 1984 and 1998 was 57.3% and 84.7% between 1999 and 2003. In conclusion, these results demonstrate better graft and patient survival for living donor kidney transplants in comparison with cadaver donor receptors. Altogether with the low risk involved for donors should incentivate authorities, professionals, and patients to promote these therapeutic option by means of adequate information and wider diffusion. Living donor kidney transplantation should contribute together with cadaver kidney transplantation to lessen our long waiting lists, because they are not excluding options.     

Lessons learned from ABO-incompatible living donor kidney transplantation: 20 years later

From June 1982 to November 1989, 39 ABO-incompatible living kidney transplants were performed in 38 recipients. Pretransplant therapies included platelets donor transfusion (21/39), 2 to 5 plasmapheresis sessions (39/39), cyclosporin A with or without azathioprine (33/39) along with polyclonal Abs (36/39) and splenectomy at the time of transplantation (37/39). The last patient who received 2 ABO-incompatible transplants was previously splenectomized (end-stage renal failure due to a cortical necrosis following a traumatic spleen rupture). Three other patients who did not undergo a splenectomy at the time of transplantation were not included in that series but hyperacutely rejected their transplants during the first postoperative week. The 31 ABO-incompatible living related donor graft recipients are alive. Graft loss occurred from acute and/or hyperacute rejection in 5 cases (none below 15 years of age) and from chronic rejection in 8 cases. By contrast, among the 8 ABO-incompatible living unrelated donor graft recipients, only one renal graft is still functioning 20 years later. Graft survival rates are better in the group of patients < 15 years (100%, 89%, 78%, and 78% at 2, 5, 10, and 15 years respectively) compared with the group > 15 years (77%, 77%, 64%, and 59% respectively; NS). Today, 20 years later, prospective randomized studies testing different steps in the preparation protocol are still lacking. Plasmaphereses were replaced by double filtration plasmapheresis and immunoadsorption. Splenectomy seems to be a prerequisite for successful ABO-incompatible living kidney transplantation but IV Ig globulins and rituximab are currently being successfully used without splenectomy along with the new immunosuppressive drugs. As the procedure remains unchanged, it might be reserved to patients where cadaver graft could not be a valuable alternative, especially for recipients < 15 years of age with a living related ABO-incompatible donor.     

Kidney transplantation from an ABO-incompatible living donor

Living donor kidney transplantation is the preferred therapeutic option for patients with end stage renal disease because it provides a superior immunological compatibility, it lessens the preservation-mediated graft injury and it shortens waiting time on dialysis. Unfortunately, about 30-35% of potential living kidney donors are rejected because of incompatible immunological barriers such as ABO-incompatibility or a positive crossmatch. The newest desensitization protocols based on both therapeutic apheresis and perioperative immunosuppressive drugs allowed to overcome antibodies barriers. The aim of those protocols is to wash-out and suppress as much anti-A or anti-B antibodies as possible and to prevent the rebound phenomena after transplantation. Standard plasmapheresis, double-filtration plasmapheresis and selective immunoadsorption are among the most common apheretic modalities applied in ABO-incompatible transplantation. Furthermore, selective immunoadsorption appears to be much safer and to have markedly increased efficacy comparing with plasmapheresis being able to eliminate almost exclusively blood-group antibodies avoiding plasma and coagulation abnormalities. According to literature, long-term patient and graft survival rates are similar to those achieved by ABO-compatible kidney transplants. The comparable outcome seems related to more effective desensitization protocols as well as the protective immune mechanisms of "accommodation". We have been using selective immunoadsorption in the two ABO-incompatible kidney transplants performed in our institution. No acute rejection was experienced at 6 and 26 month follow-up and both grafts are functioning well. Despite the ABO-incompatible kidney transplant widespread use, the best desensitization protocol, the upper baseline and perioperative isoagglutinin titer limit and the most accurate isoagglutinin measurement assay are still to define.     

Factors affecting graft survival after living donor liver transplantation

Living donor liver transplantation (LDLT) has been considered as an alternative option to resolve the shortage of cadaveric donor organs, despite the ethical aspects of the donor procedure. The objective of this study was to analyze the risk factors affecting graft survival in LDLT. From June 1996 to December 2002, 141 patients who underwent LDLT were retrospectively analyzed. Graft survival rates were 82.5%, 80%, 77.3%, and 77.3% at 6 months, 1 year, 3 years, and 5 years, respectively. The factors influencing graft survival in univariate analysis were graft-to-recipient body weight ratio (GRWR) less than 0.8% (P = .0009), intraoperative transfusion of more than six packed RBC units in addition to the use of cell saver amounts (P = .0001), left lobe grafts in adults causing small-for-size situations (P = .0135), and donor age (P = .0472). The multivariate analysis demonstrated that GRWR less than 0.8% (P = .002) and intraoperative transfusion of more than six packed RBC units (P = .014) were independent factors that decreased graft survival rates. The graft selection of greater than 0.8% of GRWR and reduction of intraoperative RBC transfusion improve graft survival.     

ABO-incompatible kidney transplantation with donor-specific skin graft

From November 3, 1975, to May 31, 1989, 711 (548 living-related and 163 cadavers) kidney transplantations were performed in our centers. In the final 2 years, 15 ABO-incompatible living related kidney transplantations were performed. In 4 cases, the recipient's blood groups was O and the donor's A1. In 3 cases the blood group of the recipient was A1 and the donor's AB, two patients were B with the donors A1 and the other 2 were O with donors B. The other 3 recipients group was B and the donors' were AB. The donors' and recipients' HLA-AB typing showed one haplotype matching in 12 and two haplotypes matching in 3 patients. The donors were mothers in 7 cases, sibling in 5, and father in 3 cases. At least 3 weeks before the renal transplantation, donor-specific skin grafts and subsequently splenectomy were performed on 9 recipients, but on 6 recipients without splenectomy. Following the skin graft, cross-match was done starting from the 15th day and then continued every week. The immunosuppression, which consisted of triple drugs (0.5 mg/kg prednisolone, 2 mg/kg cyclosporin-A and 2 mg/kg azathioprine) was followed by skin graft. Renal transplantation was performed according to cross-match and skin graft results, and all recipients prior to surgery received at least two sessions of plasmapheresis. Regular dose of immunosuppression that included triple drugs were used after the kidney transplantation and then Orthoclone OKT-3 and plasmapheresis were applied during the rejection episodes without bolus therapy. All patients were followed for 5 to 24 months (ave. 14,13 months).(ABSTRACT TRUNCATED AT 250 WORDS)     

A donor risk index for graft loss in pediatric living donor kidney transplantation

Pediatric kidney transplant candidates often have multiple potential living donors (LDs); no evidence‐based tool exists to compare potential LDs, or to decide between marginal LDs and deceased donor (DD) kidney transplantation (KT). We developed a pediatric living kidney donor profile index (P‐LKDPI) on the same scale as the DD KDPI by using Cox regression to model the risk of all‐cause graft loss as a function of living donor characteristics and DD KDPI. HLA‐B mismatch (adjusted hazard ratio [aHR] per mismatch = _1.041.27_1.55), HLA‐DR mismatch (aHR per mismatch = _1.021.23_1.49), ABO incompatibility (aHR = _1.203.26_8.81), donor systolic blood pressure (aHR per 10 mm Hg = _1.011.07_1.18), and donor estimated GFR (eGFR; aHR per 10 mL/min/1.73 m² = _0.880.94_0.99) were associated with graft loss after LDKT. Median (interquartile range [IQR]) P‐LKDPI was ?25 (?56 to 12). 68% of donors had P‐LKDPI <0 (less risk than any DD kidney) and 25% of donors had P‐LKDPI >14 (more risk than median DD kidney among pediatric KT recipients during the study period). Strata of LDKT recipients of kidneys with higher P‐LKDPI had a higher cumulative incidence of graft loss (39% at 10 years for P‐LDKPI ≥20, 28% for 20> P‐LKDPI ≥?20, 23% for ?20 > P‐LKDPI ≥?60, 19% for P‐LKDPI <?60 [log rank P < .001]). The P‐LKDPI can aid in organ selection for pediatric KT recipients by allowing comparison of potential LD and DD kidneys.     

Complications, resource utilization, and cost of ABO-incompatible living donor kidney transplantation

BACKGROUND: The transplantation of living donor renal allografts across blood group barriers requires protocols to reduce and maintain anti-blood group antibody at safe levels. These protocols lead to an increase in resource utilization and cost of transplantation and may result in increased complications. METHODS: In this retrospective study, we compared 40 ABO-incompatible to 77 matching ABO-compatible living donor renal allografts with respect to complications, resource utilization, and cost from day -14 to 90 days after transplantation. RESULTS: Overall, surgery-related complications and resource utilization were increased in the ABO-incompatible group, primarily due to the desensitization protocol and antibody-mediated rejection. In the absence of rejection, the mean number of complications was similar for both groups. ABO-incompatible kidney transplantation was approximately 38,000 US dollars more expensive than ABO-compatible transplants, but was cost effective when compared to maintaining the patient on dialysis while waiting for a blood group compatible deceased donor kidney. Actuarial graft and patient survival was similar in the two groups. CONCLUSIONS: We conclude that ABO-incompatible living donor kidney transplantation is a viable option for patients whose only donor is blood group incompatible despite the additional resource utilization and cost of therapy.     

ABO-incompatible adult living donor liver transplantation for hepatocellular carcinoma

Living donor liver transplantation (LDLT) offers timely transplantation for patients with hepatocellular carcinoma (HCC). If ABO-incompatible LDLT is feasible, the need for pretransplantation treatment may be eliminated, which may reduce overall morbidity. In this article, we have described 8 adult HCC patients who successfully underwent LDLT from ABO-incompatible donors. Antirejection therapy included multiple preoperative plasmaphereses, splenectomy, and an immunosuppressive regimen with tacrolimus, methylprednisolone, and mycophenolate mofetil. The maintenance dose of immunosuppression did not differ from that of the ABO-identical cases. In addition, we also performed intrahepatic arterial infusion of prostaglandin E1. In 5 patients, we administered a single dose of rituximab, a chimeric CD20 monoclonal antibody. As a result of this treatment, 6/8 patients are still alive. Our experience has shown that it is possible to control antibody-mediated humoral rejection and other complications in adult ABO-incompatible LDLT.     

Unrelated living donor kidney transplantation

Since 1966, we have performed 41 renal transplants from unrelated living donors (ULD), 39 of which were emotionally related. All donor-recipient pairs included in the present series were AB0-compatible. Recipients included 37 with primary and 4 with secondary transplants; 2 of the latter were diabetics. We compared these results to those of 41 recipients of cadaver donor kidneys matched for age, sex, immunosuppressive regimen, rank, and year of transplant, focusing our attention of the subgroups of patients under cyclosporin A (CyA) therapy (n=24). We found that ULD transplantation was as successful as cadaver transplantation with good HLA matching: at 3 years, graft survival rates were 81% in ULD versus 86% in the control group under CyA. Moreover, grafts from ULD functioned more rapidly (no post-transplant dialysis and 70% of the patients with serum creatinine below 2 mg/dl within 3 days post-transplant). Graft tolerance was equivalent in both groups (50% of the patients experienced no rejection). We conclude that despite poor HLA matching, ULD transplantation with CyA as the basic immunosuppressive agent offers good results: benefiting from the quality of living donor kidney grafts, it helps to alleviate the persistent shortage of cadaver donors.     

Poor early graft function impairs long-term outcome in living donor kidney transplantation

Background

Poor early graft function (EGF) after living donor kidney transplantation (LDKT) has been found to decrease rejection-free graft survival rates. However, its influence on long-term graft survival remains inconclusive.

Methods

Data were collected on 472 adult LDKTs performed between July 1996 and February 2010. Poor EGF was defined as the occurrence of delayed or slow graft function. Slow function was defined as serum creatinine above 3.0 mg/dL at postoperative day 5 without dialysis.

Results

The incidence of slow and delayed graft function was 9.3 and 4.4%, respectively. Recipient overweight, pretransplant dialysis and warm ischemia were identified as risk factors for the occurrence of poor EGF. The rejection-free survival was worse for poor EGF as compared to immediate graft function with an adjusted hazard ratio (HR) of 6.189 (95% CI 4.075–9.399; p < 0.001). Long-term graft survival was impaired in the poor EGF group with an adjusted HR of 4.206 (95% CI 1.839–9.621; p = 0.001).

Conclusions

Poor EGF occurs in 13.7% of living donor kidney allograft recipients. Both, rejection-free and long-term graft survivals are significantly lower in patients with poor EGF as compared to patients with immediate graft function. These results underline the clinical relevance of poor EGF as phenomenon after LDKT.