Importance of HLA-DR matching in polytransfused cadaveric kidney transplant recipients. A prospective one-center study.

Since August 1978 prospective HLA-DR typing has been performed in 157 donor-recipient pairs. All recipients received pretransplant blood transfusions. This study shows that HLA-DR matching can significantly improve the survival of cadaveric kidney allografts, even in polytransfused recipients. Patients receiving kidneys with no HLA-DR incompatibilities have a one-year graft survival of 97%, versus 86% for recipients with 1 HLA-DR incompatibility and 73% for recipients with 2 HLA-DR incompatibilities. The cumulative dose of corticosteroids during the first year after transplantation is significantly lower in patients with no DR-incompatibilities. HLA-A and B matching have no additional effect on graft survival.

Inferior outcome of cadaveric kidneys preserved for more than 24 hr in histidine-tryptophan-ketoglutarate solution. Leuven Collaborative Group for Transplantation.

BACKGROUND: During recent years, an increasing number of transplant centers within the Eurotransplant organization have used histidine-tryptophan-ketoglutarate (HTK) solution instead of University of Wisconsin (UW) solution as their preferred cold storage solution for abdominal organ preservation. We report on our single-center experience on the outcome of imported kidneys preserved with either HTK or UW solution in relation to the duration of cold ischemia time (CIT). METHODS: Between July 1989 and July 1997, 323 cadaveric kidneys preserved with UW or HTK and imported as a result of an exchange within the Eurotransplant organization were transplanted at our institution. CIT was <24 hr in 216 kidneys (UW: n=174, HTK: n=42) and > or =24 hr in 107 kidneys (UW: n=67, HTK: n=40). Renal functional outcome was evaluated by comparing delayed graft function and initial non-function rates, daily urinary output, the evolution of serum creatinine, and creatinine clearance at 1, 3, 5, 7, and 14 days and at 1, 3, 6 and 12 months, and graft survival at 1 year after transplantation in relation to the type of cold storage solution and CIT < or > or =24 hr. RESULTS: Whereas the incidence of delayed graft function did not differ significantly between kidneys preserved for less than 24 hr in UW (18.6%) or HTK (26.2%), this rate increased to 50% in HTK kidneys compared to 23.9% in UW kidneys when CIT exceeded 24 hr (P=0.006). Mean serum creatinine and creatinine clearance values were better at 1 and 5 days postoperatively in kidneys preserved <24 hr with UW as compared to HTK (P<0.05). After 24 hr of CIT, HTK-preserved kidneys showed an impaired renal function, not only in the immediate postoperative phase but also at 1, 3, 6, and 12 months after transplantation (P<0.05). Graft survival at 1 year was 92.9% in UW vs. 87.5% in HTK kidneys preserved for <24 hr (NS), and 91% vs. 77.4% when CIT exceeded 24 hr (P=0.059). CONCLUSIONS: From these single-center findings, it can be concluded that UW is superior to HTK in kidney preservation, particularly when CIT exceeds 24 hr.

Immunological and clinical observations in diabetic kidney graft recipients pretreated with total-lymphoid irradiation.

In a feasibility study, twenty patients with end-stage diabetic nephropathy were treated with fractionated total-lymphoid irradiation (TLI, mean dose 25 Gy), before transplantation of a first cadaveric kidney. During radiotherapy, only one patient had a serious side effect (bone marrow depression). After transplantation four patients died (one of a myocardial infarction, one of ketoacidosis, and two of infections occurring during treatment of rejection crises). One graft was lost because of chronic rejection. The other 15 patients have a functioning graft (mean follow-up 24 months) and receive low-dose prednisone alone (less than 10 mg/day, n = 11) or in conjunction with cyclosporine (n = 4) as maintenance immunosuppressive therapy. A favorable clinical outcome after TLI (no, or only one, steroid-sensitive rejection crisis) was significantly correlated with a high pre-TLI helper/suppressor lymphocyte ratio, a short interval between TLI and the time of transplantation, and the occurrence of functional suppressor cells early after TLI. The most striking immunological changes provoked by TLI consisted of a long-term depression of the mixed lymphocyte reaction and of the phytohemagglutinin, and Concanavalin A or pokeweed-mitogen-induced blastogenesis. A rapid and complete recovery of the natural killer cell activity was observed after TLI. A permanent inversion of the OKT4+ (T helper/inducer) over OKT8+ (T suppressor/cytotoxic) lymphocyte ratio was provoked by a decrease of the OTK4+ subpopulation, together with a supranormal recovery of the OKT8+ lymphocytes. A majority of the latter lymphocytes did also express the Leu 7 and the Leu 15 phenotype.

Chronic renal allograft failure: clinical overview. The Leuven Collaborative Group for Transplantation.

The factors that have led to a steady improvement of one-year renal allograft survival, have not resulted in better long-term outcome. Main causes of chronic renal allograft failure are patient death with a functioning transplant, chronic rejection and non-compliance with immunosuppressive therapy. The role of hyperfiltration as a cause of graft failure is at present unclear. Among the risk factors associated with allograft outcome are donor- and recipient characteristics, HLA matching, delayed graft function and acute rejection episodes. As with short-term results there are considerable differences between transplant centers. The effect of cyclosporine-based immunosuppression on late graft outcome is still controversial. Possibly, the potential benefit of cyclosporine is obscured due to suboptimal dosing in the fear of chronic nephrotoxicity.

Prognostic factors in a transplantation center with good results.

In a homogeneous group of 299 first cadaver kidney allograft recipients transplanted within one single center between 1973 and 1983, we analyzed the influence of several factors on graft survival. All recipients received at least one blood transfusion before transplantation. Criteria of donor-recipient selection as well as immunosuppressive treatment policy have never changed significantly within the studied period. In contrast to matching for HLA-A and B antigens, DR-matching has a significant influence on early graft survival. Kidneys with zero DR-mismatches have a one year graft survival of 96.2% versus 75.6% for kidneys with 2 DR-mismatches (P less than 0.05). The presence or absence of DRW6 in the recipient as well as in the donor has no effect on graft survival. A preservation time less than 12 hours is accompanied by a decreased early graft survival. The long-term survival of kidneys from donors older than 30 years is significantly reduced. At 5 years graft survival of kidneys from donors younger than 30 years is 75% versus 53% for kidneys from donors older than 30 years.

Treatment of chronic glomerulonephritis with a combination of indomethacin and cyclophosphamide.

33 cases of chronic glomerulonephritis who responded unsatisfactorily to treatment with indomethacin alone were treated in addition with a low dose of cyclophosphamide. The five patients with focal glomerulosclerosis responded poorly. The remaining 28 patients showed a statistically significant improvement in renal function and proteinuria.

Significance of urinary excretion of fibrin degradation products during treatment of glomerulonephritis.

189 patients with various types of glomerular disease were studied. Creatinine clearance, protein excretion and urinary excretion of fibrin degradation products (FDPs) were measured before and at various intervals (up to 42 months) after starting treatment with indomethacin, alone or in combination with other drugs. The following observations were made: a. Patients with a urinary FDP in excess of 2 mg/24 hours before treatment had a significantly lower creatinine clearance and a significantly higher protein excretion than patients excreting less than 2 mg FDP/24 hours, indicating that FDP excretion reflects the severity of the renal disease. b. During treatment, the incidence of high FDP excretion decreases progressively, but remains high in patients who ultimately develop renal insufficiency. c. There is no correlation between the initial value of FDP excretion and the subsequent changes in creatinine clearance and proteinuria during treatment. This implies either that the initial FDP excretion has no prognostic value or, perhaps more likely, that disease activity is modified by treatment. d. The best correlation between FDP excretion and evolution is found in proliferative glomerulonephritis. There are reason to suppose that, in this group at least, the treatment influenced the evolution of the disease.

Donor Action: an international initiative to alleviate organ shortage.

CONTEXT: Donor Action, an international initiative to alleviate organ shortage, provides a comprehensive state-of-the-art methodology that helps critical care units develop a tailor-made approach to optimize donation practices and performance. OBJECTIVE: To report the impact of the Donor Action methodology on organ donation rates in 8 countries (70 critical care units) in North America and Europe. DESIGN: Baseline data on the clinical potential for donation, staff attitudes, knowledge toward donation, self-reported confidence in performing a range of donation roles, and educational requirements were gathered. These data were analyzed using the Donor Action database and improvement measures were introduced to address identified weaknesses. RESULTS: Following introduction of the program's improvement measures, which addressed identified weaknesses, donations increased on average by 53% (P = .0017) per country at 1 year. Sustained improvements settled at 70% to 160% increases at 3 years. Although Donor Action is at various stages of implementation in different countries, the number of centers and countries demonstrating an immediate awareness effect is increasing and sustained effects in centers with the longest follow-up promise a significant impact on donation rates as more countries implement this methodology.