Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study.

We previously reported a randomized controlled trial in which 227 de novo deceased-donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy-proven acute rejection (BPAR) and steroid-resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG-treated patient (0.9%) and one daclizumab-treated patient (1.0%) developed BPAR after 1 year. Five-year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high-immunological-risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low-risk cohorts.

Significant risk factors for occurrence of cancer after renal transplantation: a single center cohort study of 1265 cases.

Occurrence of cancer after renal transplantation remains a major problem, and the second cause of death. We performed a retrospective analysis of first cancer, first skin cancer, and first organ cancer (including posttransplant lymphoproliferative disease [PTLD]) among 1265 cases from 1979 to 2006. The occurrence of cancer was clearly a time-dependent event justifiying the use of Kaplan-Meier survival and Cox regression methods. The 10-year cumulative incidences of first cancer, first skin cancer, and first organ cancer were 24.6%, 14.5%, and 14.5%, respectively. Recipient age was a major, independent risk factor for the 3 endpoints with a 6% increased relative risk for each year increment (P < .0001). Female gender was also a major, independent risk factor, but only for skin cancer (P = .0002). We could not demonstrate any difference between the immunosuppressive drugs used for induction or maintenance therapy, especially between antithymocyte globulin (ATG) vs anti-CD25, cyclosporine vs tacrolimus, and azathioprine vs mycophenolate mofetil. Large cohorts are needed with strict stratifications for recipient age and gender to detect any difference, if any, among the drugs.

A trial comparing local pain after subcutaneous injection of epoetin-beta versus darbepoetin-alpha in healthy volunteers.

BACKGROUND: The aim of this study was to compare local pain experienced with subcutaneous (s.c.) injection of epoetin-beta vs. darbepoetin-alpha. METHODS: 40 healthy volunteers were enrolled into this single-blind, crossover study. After receiving an injection of placebo, individuals were randomized to receive s.c. injections of epoetin-beta 6,000 IU (0.3 ml) or darbepoetin-alpha 30 mg (0.3 ml), with a 1-week washout period between injections. Local pain was evaluated using a Visual Analog Scale (VAS) and a 6-item Verbal Rating Scale (VRS) immediately after (T0) and 1 h after injection (T1). RESULTS: The respective mean (standard deviation) and median (range) VAS values at T0 were 1.2 (1.7) and 0.5 (0.0 - 6.9) for epoetin-beta vs. 2.8 (2.4) and 1.9 (0.0 - 9.0) for darbepoetin-alpha (p < 0.0001). At T0, VRS scores demonstrated that 51% of individuals experienced no pain after epoetin- injection compared with 16% of those receiving darbepoetin-alpha. The percentage of individuals perceiving moderate or important pain was significantly greater with darbepoetin-alpha (38%) compared with epoetin-beta (5%, p = 0.0005) and placebo (14%). Pain evaluation at T1 showed no difference between treatment groups. Local tolerance was excellent except for a small hematoma with epoetin- at T1 and with darbepoetin-alpha at T0 which persisted at T1. CONCLUSION: In healthy volunteers, s.c. injection of epoetin-beta was significantly less painful than with darbepoetin-alpha and comparable with placebo. No significant pain was apparent at T1 in any group.

Tolerability of enteric-coated mycophenolate sodium to 1 year in combination with cyclosporine and corticosteroids in renal transplant recipients.

Enteric-coated mycophenolate sodium (EC-MPS) is therapeutically equivalent to mycophenolate mofetil, but delays release of mycophenolic acid until it reaches the small intestine. De novo renal transplant patients taking part in a 12-month, multicenter, randomized study received cyclosporine microemulsion (CsA-ME, early or delayed to day 6), EC-MPS, steroids, and interleukin-2 antagonist induction. Tolerability data relating to EC-MPS are reported. Ninety-seven patients were randomized to early CsA-ME and 100 patients to delayed CsA-ME. Median daily dose of EC-MPS was 1440 mg at all time points throughout the 12-month period. The most frequently reported adverse events were constipation, anemia, urinary tract infection, abdominal pain, leukopenia, and cytomegalovirus infection; there were four malignancies. Fifty patients (24.6%) discontinued EC-MPS prematurely by 12 months, including 42 patients (84%) who discontinued owing to adverse events. No patient discontinued treatment because of gastrointestinal adverse events. Two-thirds of patients (137 [67.5%]) maintained full EC-MPS dose throughout the 12-month study and did not require any dose reduction or dose interruption. EC-MPS is well tolerated in de novo renal transplant recipients when administered in combination with CsA-ME and steroids, with low rates of dose reductions or interruptions. Gastrointestinal adverse events were responsible for dose reduction or interruption in only 5% of patients.

The influence of prophylactic immunosuppressive regimens on natural killer and lymphokine-activated killer cells in renal transplant recipients.

We investigated natural-killer cells in 81 renal transplant recipients (RTR) in order to define what kind of in vivo prophylactic immunosuppression could be responsible of the impairment of these NK cells. Cell-surface phenotyping was performed by direct immunofluorescence with Leu7 (CD57), Leu11 (CD16), and Leu19 (CD56) antibodies, in one- and two-color stainings. Functional properties were analyzed with freshly isolated nonadherent mononuclear cells (NK activity) and after in vitro activation with r-IL-2 (LAK activity), in cytotoxicity assays using K562 and Daudi tumor lines as specific targets. A flow cytometry technique using carboxy-Fluorodiacetate was applied to monitor the cytotoxicity of NK cells. Our data emphasize the already known deficiency of NK cells: both NK subsets (CD16+ and/or CD56+) and NK activity were decreased in RTR. Moreover, we demonstrated that the in vitro IL-2-induced LAK cytotoxicity was also diminished in RTR. NK cells and functions were normal in RTR treated with cyclosporine only, decreased in RTR treated with both cyclosporine and azathioprine, and at the lowest level in RTR treated with azathioprine without cyclosporine. A multivariate statistical analysis found a negative linear regression between the doses of azathioprine and the number of functions of NK cells, confirming that azathioprine was responsible for the deficiency of NK cells in our RTR.

High frequency of IL-10-secreting CD4+ graft-infiltrating T lymphocytes in promptly rejected kidney allografts.

IFN-gamma and IL-10 secretion by sorted T cell subsets of irreversibly rejected kidney graft-infiltrating cells (GIC) and normal PBMC was studied by ELISPOT. The low spontaneous frequency of IFN-gamma-producing cells (IFN-gamma-PC) was strongly increased by anti-CD3 activation within unsorted, CD3+CD4+, and CD3+CD4- subsets of GIC and PBMC. In contrast with PBMC, IL-10-PC from GIC were at higher frequency within CD4+ cells than among CD4- ones (P < 0.03). Four kidneys removed after 3.7 +/- 0.8 months showed acute vascular rejection, high frequency of activated CD4+ IL-10-PC (118 +/- 68 per 10(4) cells), and high percentage of anti-class II antibody reactivity (87.6 +/- 6.3%). In contrast, four patients with kidneys removed later (53.7 +/- 1.6 months, P = 0.02) displayed chronic rejection with superimposed acute cellular rejection, low frequency of CD4+ IL-10-PC (7.0 +/- 3.0 per 10(4) cells, P = 0.02), and low percentage of anti-class II antibody reactivity (12.9 +/- 6.1%, P = 0.02). Thus, accelerated vascular rejection appears to be associated with preferential production of IL-10 by activated CD4+ GIC, which may act by shifting the effector arms of alloreaction toward humoral responses.

Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients.

INTRODUCTION: A previous trial in renal transplantation comparing sirolimus (rapamycin) to cyclosporine (CsA) in a triple-drug therapy regimen with azathioprine and corticosteroids found that the incidence of acute rejection was similar (approximately 40%) with a trend for better renal function with sirolimus. METHODS: In 14 European centers, first cadaveric renal allograft recipients were randomized to receive sirolimus (n = 40) or CsA (n = 38) in an open-label design. All patients received corticosteroids and mycophenolate mofetil 2 g/day. Sirolimus and CsA were concentration controlled; trough levels of mycophenolic acid and prednisolone were also measured. RESULTS: At 12 months, graft survival (92.5% sirolimus vs. 89.5% CsA), patient survival (97.5% sirolimus vs. 94.7% CsA), and the incidence of biopsy-proven acute rejection (27.5% sirolimus vs. 18.4% CsA) were not statistically different. The use of antibodies to treat suspected rejection episodes was also similar (7.5% sirolimus vs. 5.3% CsA). More sirolimus patients received bolus steroid therapy (20 vs. 11, P = 0.068). From month 2 onward, the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients. The adverse events reported more frequently with sirolimus were thrombocytopenia (45% vs. 8%) and diarrhea (38% vs. 11%). In the CsA group, increased creatinine (18% vs. 39%), hyperuricemia (3% vs. 18%), cytomegalovirus infection (5% vs. 21%), and tremor (5% vs. 21%) were observed significantly more often. DISCUSSION: Patient and graft survival and the incidence of biopsy-proven acute rejection at 12 months were comparable between sirolimus and CsA, whereas safety profiles were different. These data suggest that sirolimus may be used as primary therapy for the prevention of acute rejection.

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis.

Experimental evidence suggests a role for obesity in the formation and progression of some glomerular lesions, but data for human glomerulonephritis are lacking. In a cohort of 162 incident patients with biopsy-proven immunoglobulin A (IgA) nephropathy, we assessed whether the presence of an elevated body mass index (BMI >/= 25 kg/m(2)) at the time of the first renal biopsy (RB1) correlated with clinical data at RB1 (24-hour proteinuria, arterial hypertension, and renal function), pathological data (global optical score [GOS] with detailed pathological indices), and clinical progression to both arterial hypertension and chronic renal failure (CRF). In both univariate and multivariate analyses, the presence of an elevated BMI at RB1 was significantly associated with the severity of pathological renal lesions (GOS and vascular, tubular, and interstitial indices). Hypertension-free survival was significantly less in overweight patients (P: < 0.0001) compared with those with normal weight. In a Cox regression analysis for hypertension-free survival including 24-hour proteinuria greater than 1 g, GOS, and metabolic parameters, only elevated BMI and GOS were independent factors for the development of arterial hypertension. CRF-free survival was also significantly less in patients with an excessive BMI. In a multivariate Cox regression analysis for CRF-free survival, hypertension, GOS, and BMI at RB1 were independent risk factors for CRF. In IgA nephropathy, excessive body weight and/or BMI are underestimated predictive factors for the development of arterial hypertension and, ultimately, CRF.

Comparison of pathological lesions on repeated renal biopsies in 73 patients with primary IgA glomerulonephritis: value of quantitative scoring and approach to final prognosis.

In order to improve our possibility of establishing a long-term prognosis in IgA nephritis, 73 patients out of a cohort of 282, followed over a mean period of 12 years at the same institution for an IgA nephritis, had a prospective second renal biopsy 5 years later. For all biopsies (RB1 and RB2), we developed a quantitative scoring for all elementary lesions with a glomerular, an interstitial, a tubular and a vascular index. The sum of these 4 indexes gave a global optical score (GOS). Pathological improvement on light microscopy (delta GOS less than or equal to -2) was noticed only in 3 patients (4%), stability (-2 less than delta GOS less than +2) in 30 patients (41%), mild deterioration (+2 less than or equal to GOS less than 5) in 23 patients (32%) and major progression (delta GOS greater than or equal to 5) in 17 patients (23%). We observed no pathological remission, even in the 14 patients with complete clinical remission. The pathological progression was characterized by an increase in all elementary lesions, mainly the tubulo-interstitial and vascular ones. By immunofluorescence mesangial IgA deposits remained stable with no disappearance; however, the number and intensity of vascular C3 deposits were significantly greater on RB2. Chronic renal failure (serum creatinine greater than 1.5 mg/dl) correlated best with major pathological progression and mainly with the progression of extraglomerular lesions. IgA nephritis is a slowly progressive disease with no pathological remission, and its evolution is characterized by progression of extraglomerular lesions, mainly vascular, which might play a major role in the ultimate development of chronic renal failure.

Mesangial IgA glomerulonephritis in HLA-identical brothers.

Two HLA identical brothers with mesangial IgA glomerulonephritis are reported. Patient 1 developed gross hematuria at age 12 and required chronic hemodialysis at age 20. Patient 2 presented at age 21 with gross hematuria and normal renal function, the follow up period is only 9 months. Neither of these patients had nerve deafness, ocular defects or complement abnormalities. The family history did not support a diagnosis of classical hereditary nephritis, but a genetic linkage is strongly suggested by the identical HLA phenotypes of these brothers (A10 - A32 - B13 - B35). The B35 antigen has previously been suspected to be linked to this disease. These observations strongly support the hypothesis of an aberrant, genetically controlled, immune response, in patients with mesangial IgA glomerulonephritis.

Live poliovirus vaccine in patients with chronic glomerulonephritis: effects on renal function and specific antibody response.

Twenty-one patients with chronic glomerulonephritis (GN) (5 with renal failure) received three doses of live trivalent poliovirus vaccine administered orally. The effect of the polio vaccination on the renal function and the titers of antibodies to poliovirus were studied. No significant consequence was observed in renal disease. Before vaccination, titers of poliovirus type 1 and 3 antibodies were significantly decreased as compared to healthy adult subjects. After vaccination, the patients exhibited a significant rise in poliovirus antibody titers for the three serotypes, although some of them failed to develop a fourfold or greater antibody rise to at least one of the three serotypes, especially in the group of patients with renal failure. These results indicate that live poliovirus vaccination is not deleterious in patients with GN and can provide a good protection.

Immunogenetics and immunopathology of human primary membranous glomerulonephritis: HLA-A, B, DR antigens; functional activity of splenic macrophage Fc-receptors and peripheral blood T-lymphocyte subpopulations.

In most of our patients with idiopathic membranous nephritis (MGN), we have studied the HLA-A, B, DR phenotype, the clearance of anti Rhesus D coated-51 Cr-labeled-autologous erythrocytes, and the peripheral blood T-lymphocyte subpopulations as ascertained by monoclonal antibodies (OKT3, OKT4, OKT8). The frequency of HLA-B8 antigen is 57.14% in 28 primary MGN versus 14.4% in 104 local controls (Pc less than 0.00018). The frequency of HLA-DR3 antigen is 65.38% in 26 primary MGN patients versus 20.27% in 74 local control individuals (Pc less than 0.00008). The half-life of sensitized erythrocytes is 37.30 +/- 9.55 min in 10 controls, 1963 min and 1601 min in 2 splenectomized controls, 12 min in a patient with hypersplenism, and 67.05 +/- 69.64 min in 18 idiopathic MGN patients respectively. The half-life is significantly prolonged in 6 out of 18 MGN patients. This prolongation correlates with exacerbation of the disease while normal values are obtained with remission. The OKT3 positive subpopulation (total T-lymphocytes) is 63.77 +/- 10.37% in 31 controls versus 53.74 +/- 13.81% in 22 MGN (P less than 0.002). The OKT4 positive subpopulation (helper T-cells) is 37.90 +/- 8.21% in controls versus 32.79 +/- 10.89% in MGN (P less than 0.03). The OKT8 positive subpopulation (suppressor T-cells) is 21.60 +/- 5.28% versus 20.03 +/- 5.76% respectively. The OKT4/OKT8 ratio is 1.85 +/- 0.58 in controls versus 1.74 +/- 0.69 in MGN. During exacerbation, the T-lymphocyte subset fractions are normal, whereas OKT3 and OKT4 are decreased during remission. MGN is a strongly HLA-linked disease.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of diltiazem on arterial pressure and renal function in renal transplanted and cyclosporin A treated subjects. Results after 3 months of a prospective study]. / Effets du diltiazem sur la pression artérielle et la fonction rénale du transplanté rénal sous ciclosporine A. Résultats à trois mois d'une étude prospective.

With the aim to improve renal graft function and to prevent hypertension, we used the calcium-antagonist diltiazem in a prospective randomized study in 30 consecutive cadaveric renal transplanted patients from september 1987 to may 1988. The diltiazem (D+) group comprised 14 patients receiving a loading dose of 0.3 mg/kg followed by a 2 micrograms/kg/d continuous IV infusion of D started as soon as possible after clamp on renal artery removal. D was then given orally (120-180 mg/d) throughout the study. 16 patients without D composed the D- group. Cyclosporine A (csa) was started either just before transplantation (15 mg/kg/d orally) in 18 patients (9 D+ and 9 D-) or after 2-3 weeks of poly or monoclonal antibodies (5 D+ and 7 D- at 10 mg/kg/d. In addition to the usual monitoring, inulin (for GFR) and PAH (for ERBF), clearances were performed 7 days and 3 months after transplantation. If hypertension (blood pressure greater than 160/90 mm Hg) occurred, all but calcium-antagonists antihypertensive agents were used in both groups. Between D+ and D-, the number of patients requiring haemodialysis during the first week was not different (7/14 vs 5/16) like the number of dialysis session per patient (1.4 vs 1.1) day 7 GFR (19 +/- 22 vs 23 +/- 20) and day 7 ERBF (146 +/- 147 vs 226 +/- 224) ml/mn/1.73 m2; at 3 months 13/14 (93 p. 100) vs 12/15 (80 p. 100) of the grafts are functioning (NS), GFR (34 +/- 17 vs 33 +/- 10) and ERBF (242 +/- 90 vs 236 +/- 117) are not different.(ABSTRACT TRUNCATED AT 250 WORDS)

[Phenotypic and functional study of natural killer lymphocytes in flow cytometry: application to renal transplantation]. / Etude phénotypique et fonctionnelle des lymphocytes natural killer en cytométrie de flux: application à la transplantation rénale.

In order to define the best appraisal of Natural Killer cells, the authors performed a dual study, including both phenotypes and functional activities, and all the analyses were achieved with flow cytometric techniques. Results were applied to renal transplantation. Among the numerous clusters of differenciation, only CD16 and CD56 appeared to be well correlated with the functional properties of Natural Killer cells, and especially for CD3- cells. On the other hand, CD57 should no longer be considered as a NK marker. Functional properties of Natural Killer cells were evaluated by cytotoxicity assays of peripheral lymphocytes against K562 and Daudi tumor cells, either spontaneously, or after a 3-day activation with Interleukin 2 (LAK). The authors use carboxyfluoro-diacetate to label viable cells and avoid radioisotopes. They confirm the Natural Killer cells deficiency in renal transplant recipients, and show that this impairment also involves the LAK cytotoxicity. Azathioprine appeared to be responsible of such deficiency. During viral infections, Natural Killer cells raised and reached the normal values, while they were incapable of any response to fight against cancer. They suggest that the Natural Killer deficiency could explain the high incidence of malignancies during renal transplantation.

[Renal insufficiency and severe genital prolapse. 2 cases]. / Insuffisance rénale et prolapsus génital majeur. Deux cas.

The authors report two patients with renal failure due to total procidentia. Surgical repair led to an improvement in renal function. Mild chronic renal failure persisted. Thus the renal status must be assessed in cases of uterine prolapse.

[Antibodies and immunomodulation]. / Anticorps et immunomodulation.

CURRENT SITUATION: When examining immunosuppressor induction one important question is to determine the efficacy of anti-CD25 antibodies or the new compound efalizumab compared with anti-lymphocyte globulins and anti-OKT3 agents known to be very effective but with important side effects. DACLIZUMAB: Recent work has shown that 2 injections at 1 mg/kg (one on day 1 the other between day 10 and day 14) completely block interleukin-2 receptor for more than 10 weeks in 98% of the recipients. Instead of the 5 injections every 15 days as indicated by the recommendations, this new protocol is easier to institute and less costly. The efficacy remains to be demonstrated. BASILIXIMAB: This chimeric monoclonal antibody has affinity for the IL-2 receptor. Balisiximab is administered in 2 doses at 20 mg, one on day 0 and the other one on day 4. A unique 40 mg dose on day 1 has a comparable efficacy. OTHER PROTOCOLS: Among the different induction molecules with promising properties, particular attention should be given to efalizumab. The antisense oligonucleotide (ICAM-1; ISIS 2302) appears to show relatively poor tolerance and no therapeutic efficacy. In association with plasmapheresis and intravenous immunoglobulins, it has been shown to be very effective when given to graft candidates with a positive cross match or after transplantation in case of acute rejection.

[Oncological complications after renal transplantation]. / Complications carcinologiques après transplantation rénale.

Oncological complications were studied in 420 renal transplantations performed in 389 patients. Seven patients with a history of neoplasia were transplanted, and 2 tumours were transmitted by the graft. However, the main problem was that of de novo tumours induced by immunosuppression: 26 patients developed such tumours which resulted in death for 7 of them. The risk of tumour seems to be relatively selective. Seven lymphoproliferative syndromes, 6 Kaposi's sarcomas and 4 spinocellular epitheliomas were observed and together accounted for 65.3 percent of de novo tumours. Excessive immunosuppression could be blamed in only one third of the patients. On the other hand, some geographical and/or ethnic factors seemed to facilitate tumour development, and infections with viruses of the herpes group were found in 76 percent of these subjects.

[Natural killer lymphocytes in kidney transplantation]. / Les lymphocytes natural killer en transplantation rénale.

We conducted a dual study of phenotype and function of natural killer cells (NK) using flow cytometry, this study being applied to renal transplantation. The CD 16 and CD 56 clusters correlated well with NK cytotoxicity, especially for CD 3 lymphocytes, whereas CD 57 should no longer be considered a NK marker. NK activity was determined on K 562 or Daudi cells, either spontaneously or after in vitro activation with r-interleukin 2 (LAK). Cytotoxicity was analyzed after labeling of target cells by carboxyfluoro-diacetate and measured by flow cytometry. We found that in renal transplant recipients NK cells were deficient in numbers and functions and showed that LAK activity was also diminished. Azathioprine appeared to be the main immunosuppressant impairing NK cells. Viral infections increased the numbers and functions of NK cells, whereas during malignancies they remain as low as in uncomplicated recipients. NK cells deficiency might be involved in the high incidence of de novo malignancies in renal transplant recipients.

[Update on hepatitis G virus]. / Le point sur le virus de l'hépatite G.

HEPATITIS G VIRUS: The hepatitis G virus is an RNA virus with a genomic organization and variability similar to the hepatitis C virus but with a much different pathogenic power which remains to be elucidated. HEPATITIS G: No cases of chronic hepatitis have been observed. Coinfections with HCV and HIV do occur but do not aggravate the prognosis. Anti E2 antibodies are found in the serum and correspond to elimination and neutralization of the HVG genome. There is a high prevalence in transplant recipients (31%), but no modification in liver or kidney grafts has been reported.