L. De Pauw

The long-term effects of prophylactic OKT3 monoclonal antibody in cadaver kidney transplantation : a single-center, prospective, randomized study

We conducted a randomized, prospective study to determine the long-term effects of prophylactic OKT3 in cadaveric renal transplantation. In the first group of patients (n=56) OKT3 (5 mg/day) was administered for the first 14 postoperative days in association with azathioprine (AZA) and low-dose steroids, cyclosporine (CsA) being introduced on day 11. The other group of patients (n=52) received CsA from the first POD, together with AZA and steroids. Both protocols were identical from POD 14 on. The total number of infections was higher in OKT3 patients (124/1455 patient-months [P-M] vs. 68/1320 in CsA patients, P<0.001) without impact on patient survival (94.5% in OKT3 vs. 93% in CsA patients). OKT3 patients experienced a lower number of rejection episodes (61 per 1455 P-M of risk exposure vs. 81/1320 in CsA patients, P<0.05). In addition, the frequency of corticoresistant rejection episodes was lower in OKT3 patients (9 out of 61 vs. 24 out of 81 in CsA patients, P<0.05). This resulted in a trend toward improved overall graft survival (83% vs. 75%, P=0.12) and in a significant increase in immunological graft survival (92% vs. 79%, P=0.02) in OKT3 patients at 3 years. Taken together, these data suggest that prophylactic OKT3 therapy might have long-term beneficial effects in cadaveric renal transplantation.

Male recipients of kidneys from female donors are at increased risk of graft loss from both rejection and technical failure

The aim of the present retrospective study was to uncover the factor(s) responsible for the poor outcome of cadaver kidney grafts from female donors in male recipients.The 741 transplantations performed at our center from August 1983 to September 1997 were distributed into four groups according to recipient and donor gender: female donor to female recipient (F to F: n=117), male donor to female recipient (M to F: n=172), female donor to male recipient (F to M: n=170), and male donor to male recipient (M to M: n=282). All the patients received immunosuppressive therapy based on corticosteroids and cyclosporine, associated or not with either azathioprine or prophylactic anti‐lymphocyte globulin.Overall graft survival was lower in the F to M group than in the three other groups (p=0.009). Failures due to rejection were more frequent during the 1st post‐transplant trimester in female than in male donor grafts, irrespective of recipient gender (p=0.025). All failures due to technical problems occurred during the first 3 months post‐transplantation: they were more frequent in the F to M group than in the three other groups (p=0.040); this could be related to the older age of the donors in the former group. After the first post‐transplant year, failures due to causes other than rejection remained low in the F to F group but increased steadily in the three other groups (p=0.007). Specific survival rates were not correlated with the time‐evolution of mean serum creatinine values, daily doses and trough levels of cyclosporine in the four groups of grafts. In conclusion, the poor outcome of F to M grafts results from combined immunologic and technical factors exerting their effects early in the course of transplantation.

A case of rapidly fatal systemic capillary leak syndrome in a kidney transplant recipient.

Idiopathic Systemic Capillary Leak Syndrome (SCLS) is a rare entity characterised by idiopathic increasing of capillary permeability associated with recurrent attacks of hypovolaemic shock. We report the case of a 39-year-old man with a SCLS fourteen years after a cadaveric renal transplantation. The clinical evolution was rapidly fatal despite treatment with corticoids, aminophylline and terbutaline which are the most efficient drugs known to prevent attacks.

High or low dose steroid therapy for acute renal transplant rejection after prophylactic OKT3 treatment: a prospective randomized study

In this prospective randomized study, acute renal transplant rejections occurring in patients who received prophylactic OKT3 therapy were treated with either 3 pulses of 8 mg/kg methylprednisolone (MPS) in an alternate-day regimen (total dose 25 mg/kg in 1 week, H group, n = 24) or 5 daily pulses of 3 mg/kg MPS (total dose 17 mg/kg, L group, n = 22). Acute rejection was proven by biopsy in more than 85% of cases in both groups. No difference was observed in rejection reversal (H 88%, L 91%), graft losses in the following 3 months (H 11%, L 4%) or the time evolution of the serum creatinine levels. The number (H 14, L 21) as well as the nature and severity of infections were similar in both groups. Only one death occurred in a patient who received OKT3 rescue therapy for corticoresistant rejections and developed Epstein-Barr virus (EBV)-related lymphoma. In conclusion, low dose MPS pulses appear as effective and safe as a higher dose to reverse acute rejection occurring after OKT3 prophylaxis. Thus, we favour the use of the low dose regimen in these patients.

Detrimental role of donor-recipient HLA-DQ5 and -DQ6 disparities on cadaver kidney graft survival.

Donor-recipient incompatibility (D + R -) for HLA-DQ1, but not for -DQ2 or -DQ3, is associated with an adverse effect on cadaver kidney graft survival. Until now, however, DQ1 recipients of DQ1-negative kidneys (D - R +) have not been differentiated from DQ1-identical donor-recipient pairs (D + R +) and splits of DQ1, DQ5 and DQ6, have not been studied in that respect. From our data (480 transplantations performed from January 1980 to December 1990), three donor-recipient DQ combinations (D + R +, D - R +, D + R -) were formed for each of four DQ specificities (DQ2, DQ3, DQ5, DQ6). As DR-DQ linkage disequilibrium is well conserved in caucasoid individuals, DQ specificities were inferred from the associated DR specificities. Graft survival rate (%) was significantly lower for the DQ5 D + R - and the DQ6 D - R + combinations when compared with the other corresponding DQ combinations, whereas no significant difference was observed between the DQ2 and DQ3 combinations. In conclusion, if DQ1 plays a prominent role in kidney graft survival, the effects of its splits appear dissociated: DQ5 could be a marker of high antigenicity and DQ6 a marker of high responsiveness.