Pretransplant Immune Interplay Between Donor and Recipient Influences Posttransplant Kidney Allograft Function.

BACKGROUND: Renal transplant candidates present immune dysregulation caused by chronic uremia, and deceased kidney donors present immune activation induced by brain death. Pretransplant donor and recipient immune-related gene expression were examined in the search for novel predictive biomarkers crosslinking recipient and donor pretransplant immune status with transplant outcome. MATERIALS AND METHODS: This study included 33 low-risk consecutive renal transplant recipients and matched deceased donors. The expression of 29 genes linked to tissue injury, T-cell activation, cell migration, and apoptosis were assessed in postreperfusion kidney biopsies, as well as 14 genes in pretransplant peripheral blood of the kidney recipients. Gene expression was analyzed with real-time polymerase chain reaction on custom-designed low-density arrays. RESULTS: Donor MMP9 expression was related to delayed graft function occurrence (P = .036) and short term kidney allograft function (14th day rs = -0.44, P = .012; 1st month rs = -0.46, P = .013). Donor TGFB1 expression was associated with short- and long-term graft function (14th day rs = -0.47, P = .007; 3rd month rs = -0.63, P = .001; 6th month rs = -0.52, P = .010; 12th month rs = -0.45, P = .028; 24th month rs = -0.64, P = .003). Donor TGFB1 expression was not related to donor age (rs = 0.32, P = .081), which was also an independent factor influencing the outcome. Recipient gene expression was not related to graft function but determined the acute rejection risk. Recipient IFNG and, to a lesser extent, IL18 expression were protective against acute rejection (area under the curve [AUC] 0.84, P < .001, and AUC 0.79, P < .001, respectively). CONCLUSION: Kidney transplant outcome depends on the interplay between donor-related immune factors, which mostly affect allograft function and recipient immune milieu, influencing an alloreactive response.

Functional Activity of the Complement System in Deceased Donors in Relation to Kidney Allograft Outcome.

Complement activation is considered one of the mediators of renal ischemia-reperfusion injury. Elevated levels of C5b-9, C3a, and C5a are detected in sera of deceased kidney donors. The goal of the study was to characterize the functional activity of complement pathways in donor sera and to assess their influence on transplant outcome. MATERIALS AND METHODS: Sixty-four deceased kidney donors (age 45 ± 16 years; 28 female, 36 male) and 27 healthy controls (age 42 ± 12 years; 14 female, 13 male) were enrolled in the study. The results of transplantation for the respective 122 kidney recipients were included in the analysis. The functional activities of classical (CP), lectin (LP), and alternative (AP) pathways were measured using Wielisa-kit (reference normal level = 100%). In most cases, decreased functional activity reflects the activation status of the pathway. RESULTS: The median (interquartile range) functional activities of the pathways in donor sera were CP 118 (89-150)%, LP 80 (20-127)%, and AP 74 (50-89)%, and did not differ from the control values CP 110 (102-115)%, LP 81 (26-106)%, AP 76 (61-88)%. The frequency of pathway activation observed in controls was CP 0%, LP 11%, and AP 0%. Deceased donors did not differ in activation of classical (11%) and lectin (13%) pathways, but presented a higher rate of alternative pathway activation (19%, P = .03). No significant influence of any pathway functional activity or its activation was proved to influence the transplant outcome. CONCLUSION: Complement activation via alternative pathway was observed in diseased donor sera. No predictive potential of donor complement functional activity on the transplant outcome could be proved.

Kidney Transplantation From Old Deceased Donors: Impact of Uric Acid Level-A Quarter-Century of Experience in One Transplant Center.

BACKGROUND: The long-term burden of higher donor age on graft function and survival after kidney transplantation remains uncertain. Because both recipient and donor characteristics have evolved and the general population age is on the increase, we looked at the causes of kidney graft outcome. AIM: The aim of this study was to evaluate the impact of different clinical parameters on long-term outcome of older-donor kidney transplantation. This retrospective study included 345 adult patients (58 patients received kidney from donors at least 55 years old) transplanted between January 1993 and December 2005 and were followed in one center throughout the post-transplant course (median, 9.4 years). Data included recipient and donor age, cold ischemia time, delayed graft function, panel reactive antibodies, HLA mismatch, time on dialysis, graft function at different time points, uric acid level, proteinuria, immunosuppression, and biopsy-proven rejection. RESULTS: Improvement of estimated glomerular filtration rate at 36 months after transplantation was a good prognostic factor for long-term kidney function. Higher donor age decreased the chance for improvement of kidney function by 2.8% per year of life (P = .0244). Hyperuricemia was found in 46% of the study population; estimated glomerular filtration rate less than 50 mL/min/1.72 m2 was associated with hyperuricaemia. A higher uric acid level was associated with inferior kidney function in recipient of older kidneys. Graft failure occurred late (median, 6.3 years post-transplantation) in 26 (44.8%) of older-donor recipients and in 87 (30.3%) of the remaining patients. CONCLUSIONS: Our results suggest an important association between older donor age and decreased allograft function in kidney recipients with elevated uric acid level. Recipients of older kidneys with normal uric acid level presented satisfactory outcomes.

Issues of Immunological and Hemodynamic Monitoring Before and During Kidney Transplantation in Sensitized Heart Transplant Recipient.

Previously transplanted highly sensitized patients experience problems with subsequent transplantation. It is also difficult to provide optimal hemodynamic conditions during successive kidney transplantation in heart transplant recipients. PATIENT AND METHODS: We present a case of a 56-year old patient with end-stage renal failure after heart transplantation performed 21 years ago and hemodialyzed using arteriovenous fistula. The patient had 69% panel-reactive antibodies, had been on the active waiting list since 2013, and presented 335 positive crossmatches with deceased donors. He also positively crossmatched with a potential living donor. Detailed examination of anti-HLA antibodies revealed the absence of IgG donor-specific antibodies and negative crossmatch with dithiothreitol-treated serum. The transplantation from his wife was performed with positive crossmatch after 4 plasma exchanges and thymoglobulin induction. Because sympathetic and parasympathetic denervation of the transplanted heart and the presence of arteriovenous fistula induced volume overload of the right heart, we used central venous pressure (CVP) and the PiCCO2 for postsurgical assessment of cardiac output. RESULTS: Monitoring, like CVP and other static exponents of preload obtained by PICCO (extravascular lung water, global end-diastolic volume index) as well as the dynamic parameters obtained by PiCCO2 (pulse pressure variation, stroke volume variation), was not sensitive enough to describe recipient volume status. The immediate graft function was observed, and after 11 months satisfactory estimated glomerular filtration rate is noted with the absence of donor-specific antibodies. CONCLUSION: The history of heart transplantation with existing arteriovenous fistula makes clinical tools such as continuous cardiac output monitoring and CVP parameter inadequate for describing the hemodynamic situation. The high level of panel-reactive antibodies and positive crossmatch possibly caused by IgM antibodies do not have to withdraw the recipient from kidney transplantation.

The impact of de novo donor-specific anti-human leukocyte antigen antibodies on 5-year renal transplant outcome.

Numerous studies have shown that circulating donor-specific antibodies targeting human leukocyte antigen (HLA) are associated with accelerated renal transplant failure, but many patients with these antibodies have good graft function. The aim of our study was to investigate the long-term graft function and survival in patients with de novo post-transplant donor-specific anti-HLA antibodies (DSA). Our prospective study included 78 consecutive recipients with a negative crossmatch before transplantation. Recipient serum samples were assayed for DSA in week 2 and 1, 3, 6, 9, 12 months after transplantation using a complement-dependent lymphocytotoxic technique with donor lymphocytes. Additionally, patients with DSA and stable renal function in the first year were tested with a more sensitive flow-panel-reactive antibody. DSA were present in 34 (44%) of our patients during the first 12 months after transplantation. Biopsy-proved acute rejection occurred in 11 DSA-positive and 10 DSA-negative patients. Seven DSA-positive patients had antibody-mediated rejection and no DSA-negative ones developed humoral rejection. The serum creatinine level in DSA-positive patients was significantly higher (2.48 vs 1.43 mg/dL) in year 5. The 13 (38%) DSA-positive patients with good graft function in month 12 were stable during a 5-year follow-up: their serum creatinine was 1.46 ± 0.4 in year 1 and 1.56 ± 0.4 mg/dL in year 5 and nobody lost their allograft. One- and 5- year graft survivals were appropriately 85% and 59% in DSA-positive patients compared to 93% and 93% in DSA-negative patients. To sum up, post-transplant DSA had a significant influence on kidney function and graft survival but in 38% of patients the presence of DSA did not decrease a 5-year renal function. A good renal allograft function in the presence of DSA in the first year after transplantation and cessation of their production in the subsequent years may be a good prognostic marker for a long-term allograft function and survival.