Human herpesvirus-8 seroconversions after renal transplantation.

BACKGROUND: Human herpesvirus-8 (HHV-8) is a new human herpesvirus that is clearly associated with Kaposi's sarcoma (KS). A previous study has reported that the prevalence of KS in a cohort of renal transplant recipients with previous HHV-8 infection was 28% and two other studies have shown that KS can be linked to HHV-8 seroconversion after graft. The aim of this study was to evaluate the HHV-8 seroconversion rate in a cohort of renal allograft recipients in Paris. METHODS: Two hundred eighty-seven patients who were HHV-8 seronegative before renal transplantation were tested for HHV-8 antibodies by an immunofluorescence assay 12 months after transplantation. RESULTS: Of the 287 patients, 6 (2.09%) seroconverted after renal transplantation. None of these 6 patients developed KS within 3 years of the first HHV-8 positive serum. None of the clinical manifestations that could be associated with HHV-8 primary infection were observed during the seroconversion. CONCLUSIONS: Our results demonstrated that HHV-8 seroconversion can be observed even in a low HHV-8 prevalence area and confirmed the need to perform systematic screening for HHV-8 antibodies in renal graft donors and recipients.

Clinical features and contribution of virological findings to the management of Kaposi sarcoma in organ-allograft recipients.

OBJECTIVES: To describe the clinical features of Kaposi sarcoma (KS) in organ-allograft recipients and to determine the contribution of human herpesvirus 8 (HHV-8) investigations to the management of KS. DESIGN, SETTING, AND PATIENTS: We examined 20 organ-allograft recipients with KS at Pitié-Salpêtrière Hospital, Paris, France, between November 1, 1991, and May 31, 1999. METHODS: We detected HHV-8 antibodies using an indirect immunofluorescence assay and the HHV-8 DNA genome using nonnested polymerase chain reaction with KS-associated herpesvirus 330(233) primers in peripheral blood mononuclear cells collected at transplantation and KS diagnosis. We detected the HHV-8 genome in involved and uninvolved tissue specimens and in 10 patients' serum samples collected 1 month before the first manifestation of KS. We determined the HHV-8 double-strand DNA sequence and subtypes of open reading frame 26. INTERVENTION: Management of KS consisted of progressively tapering immunosuppressive therapy regardless of KS dissemination. Associated infections were treated when possible. Chemotherapy was prescribed only when a functional disability persisted, and polychemotherapy was prescribed for life-threatening disease. MAIN OUTCOME MEASURES: Percentage of recipients with KS remission and stabilization, organ-graft survival, and death rates. RESULTS: Remission of KS was obtained in 9 (45%) of the 20 patients independently of disease dissemination, with a mean follow-up of 35 months. The kidney graft survived in 12 (67%) of the 18 patients. Only 1 patient (5%) died of KS progression. All allograft recipients had anti-HHV-8 antibodies before transplantation. We detected HHV-8 DNA in all involved tissue samples but not in serum samples 1 month before KS onset. The most prevalent subtype was HHV-8 C (9 [53%] of 17 patients) and was not associated with extradermatological extension of KS compared with subtypes A and B'. CONCLUSIONS: Virological investigations of HHV-8 contribute poorly to KS management. Prospective studies are needed to determine the role of HHV-8 virological investigations and to identify associated cofactors so as to prevent KS in organ-allograft recipients.

Outcome of kidney transplant recipients with previous human herpesvirus-8 infection.

BACKGROUND: The consequences of a prior human herpesvirus-8 (HHV-8) infection in kidney-transplant recipients are still partially unknown. The aim of this monocentric study was to determine the prevalence of HHV-8-seropositive patients at the time of transplantation and to identify the main clinical events of these HHV-8+ recipients. METHODS: From January 1, 1990 to December 31, 1996, antibodies to HHV-8 latent nuclear antigen were detected by indirect immunofluorescent method in serum samples collected just before kidney transplantation from 400 consecutive patients. Conventional double or triple immunosuppressive treatment was prescribed. For the group of HHV-8+ recipients, data including death rate, graft survival, and occurrence of Kaposi's sarcoma (KS) were retrospectively collected until December 31, 1998. Cofactors associated with KS were studied in univariate and multivariate analyses using a Cox model. RESULTS: Thirty-two patients (8%) had antibodies to HHV-8 in their sera at the time of transplantation. Among these 32, 3 years after transplantation, graft survival was 72%, and KS prevalence was 28% (KS incidence: 8.2/yr/100 HHV-8+ recipients). Multivariate analysis identified bacterial and/or Pneumocystis carinii infection (odds ratio: 8.6; P=0.019) and female gender (odds ratio: 5.34; P=0.047) as factors associated with KS. No KS was observed in patients without anti-HHV-8 antibodies at the time of transplantation. CONCLUSIONS: The low graft survival and the high prevalence of KS within the studied population of HHV-8+ transplant recipients are strong arguments for systematic screening of HHV-8 serologic features before transplantation, especially in patients of African origin. HHV-8+ transplant recipients should be closely monitored to severe infections.

[Renal retransplantation in adults. Comparative prognostic study]. / Retransplantation rénale chez l'adulte. Etude pronostique comparative.

UNLABELLED: For a long time, retransplanted patients were considered to be high-risk subjects, but a number of studies have shown that retransplantation can give good short-term results. OBJECTIVES: Between October 1987 and February 1997, 51 retransplanted patients (Group 1) were compared with 96 patients (Group 2), matched for age, sex and date of transplantation, receiving a first kidney, with a mean age of 41 +/- 10 years and a mean follow-up of 44 +/- 32 months. RESULTS: The patient did not differ in terms of aetiology of the renal disease, mismatches and duration of dialysis before the first transplant and the duration of dialysis before the second transplant was 53 +/- 54 months. In Group 1, transplant loss was due to an immunological [34], surgical [8], or medical [3] cause, or due to recurrence of the disease [3] and discontinuation of treatment [5]. Hyperimmunized subjects were more numerous in Group 1: 21.4% vs 5.2% (p < 0.01). Immunosuppression only differed in terms of Cyclosporin: 65% for Group 1 vs 45% for Group 2 (p < 0.05). The two groups did not differ in terms of acute rejection (33% for Group 1 vs 48% for Group 2), serum creatinine at last review (140 +/- 51 +/- 65 m mol/l) and 5-year and 8-year patient (92 vs 82% and 92 vs 76%) and graft survival curves (85 vs 75% and 59 vs 61%). CONCLUSION: This study confirms that retransplantation can be successfully performed, even in terms of long-term results.

Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Groupe Cooperatif de Transplantation d' Ile de France (GCIF).

BACKGROUND: The exact reasons for the high incidence of Kaposi's sarcoma (KS) after kidney transplantation are still unknown. Immunosuppression is classically considered as the main risk factor, but the relative risk contributed by the patient's geographic origin and by human herpes virus (HHV)-8 infection still has to be determined. METHODS: We carried out a retrospective and a prospective study among kidney transplant recipients (TP) to identify the risk factors for posttransplantation KS. Each of 30 KS patients was matched with two controls to investigate the association with geographic origin, immunosuppressive regimen, HHV-8 antibodies before and after transplantation, and other infections. Among TP with new onset of KS, we prospectively evaluated HHV-8 serology and viremia in response to decreased immunosuppression. RESULTS: African and Middle East origins, past infection with hepatitis B, hemoglobin level <12 g/dl, lymphocyte count <750/mm3 at the time of diagnosis and initial use of polyclonal antilymphocyte sera were risk factors for KS. After multivariate analysis, origin in Africa or Middle East and use of antilymphocyte sera for induction remained as independent risk factors. Sixty-eight percent (17/25) of TP with HHV-8 antibodies before or after transplantation developed KS compared with 3% (1/33) of seronegative TP (P<0.00001). HHV-8 DNA was detectable in seven of nine peripheral blood mononuclear cells (PBMC) and in six of six KS lesions at diagnosis; it became negative in PBMC in three of five patients in parallel with tumor regression. CONCLUSION: African and Middle East geographic origins, HHV-8 infection before and after kidney transplantation, and initial use of polyclonal antilymphocyte sera were independent risk factors for KS. The presence of HHV-8 antibodies before or after transplantation was highly predictive of the emergence of posttransplantation KS and conferred a 28-fold increased risk of KS (odds ratio=28.4; 95% confidence interval: 4.9-279). Detection of HHV-8 DNA within PBMC and KS lesions seems related to tumor burden and evolution.

[Use of mycophenolate mofetil (MMF) in kidney transplantation: results of a single center trial]. / Utilisation du mycophénolate mofétil (MMF) en transplantation rénale: résultats d'une expérience monocentrique.

Mycophenolate Mofetil (MMF) is a new immunosuppressant demonstrated to be effective at the dose of 2 to 3 g/day. The objective of this study was to determine whether MMF could be used at a lower dose with the same efficacy. Two patient groups were studied: 334 patients treated with azathioprine (AZA) and 60 patients treated MMF (at the dose of 750 mg/day, for patients receiving triple combination therapy or 1.5 g/day for those receiving two-agent combination therapy). The rest of the treatment was identical for the 2 groups. The main endpoint was the incidence of acute rejection at 3 months, which was 16% in the MMF group and 35% in the AZA group (p = 0.003). Multivariate analysis confirmed the impact of the type of purine synthesis inhibitor used (AZA or MMF, p = 0.007) on the acute rejection rate at 3 months. This study confirms the value of MMF, even at doses lower than those recommended in the international literature, with improved safety. MMF has now replaced azathioprine in our immunosuppressant protocols.

Impact of hepatitis B and C virus on kidney transplantation outcome.

The impact of hepatitis B (HBV) and C (HCV) on patient survival after kidney transplantation is controversial. The aims of this study were (1) to assess the independent prognostic values of HBsAg and anti-HCV in a large renal transplant population, (2) to compare infected patients with noninfected patients matched for factors possibly associated with graft and patient survival, and (3) to assess the prognostic value of biopsy-proven cirrhosis. Eight hundred thirty-four transplanted patients were included: 128 with positive HBsAg (group I), 216 with positive anti-HCV (group II), and 490 without serological markers of HBV and HCV (group III). Fifteen percent and 29% of patients were HBsAg-positive and anti-HCV-positive, respectively. Ten-year survivals of group I (55 +/- 6%) and group II (65 +/- 5%) were significantly lower than survival of group III (80 +/- 3%, P <.001). At 10 years, among overall patients with HCV screening (n = 834), four variables had independent prognostic values in patient survival: age at transplantation (P <.0001), year of transplantation (P =.02), biopsy-proven cirrhosis (P =.03), and presence of HCV antibodies (P =.02). In the case control study, comparison of infected patients with their matched control patients showed that age at transplantation (P <.05), HBsAg (P =.005), and anti-HCV (P =.005) were independent prognostic factors. HCV, biopsy-proven cirrhosis, and age are independent prognostic factors of 10-year survival in patients with kidney grafts. The case-control study showed that anti-HCV and HBsAg were independently associated with patient and graft survivals. In infected patients, a routine liver histological analysis would improve selection of patients for renal transplantation.

[Kidney transplantation from living related donors: experiences from one center]. / Transplantation rénale à partir de donneurs vivants apparentés (DVA): expérience d'un centre.

Living related donor (LRD) renal transplantation has remained underdeveloped in France up until now. The reduction of the number of available grafts and especially the superiority of the results of LRD transplants recently led us to develop this type of transplantation. We present the retrospective analysis of our experience of 63 cases from March 1973 to June 1995. The actuarial graft survival rate was 91% at 1 year and 87% at 3, 5 and 10 years. The 5- and 10-year survival rates of HLS-identical transplants (n = 17) was 100%. The donor morbidity was minimal (2 cases of parietal suppuration, 1 pulmonary atelectasis). These results emphasize the superiority of LRD transplantation, which also has the advantage of allowing transplantation of hyperimmunized patients in whom the waiting time for a brain-dead donor kidney is long and unpredictable.

[Combined renal-pancreas transplantation in the treatment for chronic renal insufficiency of diabetic origin . Results from the Pitie Urology Clinic]. / Transplantation combinée rein-pancréas dans le traitement de l'insuffisance rénale chronique d'origine diabétique. Expérience de la Clinique Urologique de la Pitié.

Between 1989 and 1995, 32 patients underwent combined kidney-pancreas transplantation for diabetic chronic renal failure. Only one of these patients received an isolated pancreas following cessation of function of a previously implanted segmental pancreas. The surgical technique always consisted of pure retroperitoneal transplantation into the right iliac fossa of a total pancreas transplant with duodenovesical anastomosis. The postoperative complications included one death on D10 from pulmonary vein thrombosis in a patient with sickle cell anaemia and early loss of the transplanted pancreas due to venous thrombosis. Nine patients underwent at least one surgical revision, due to a leaking duodenovesical anastomosis in 8 cases. With a mean follow-up of 33 +/- 20 months, the results demonstrate, apart from the early death indicated above, another death at 50 months of a patient who had lost his pancreas due to early venous thrombosis and who died with a functioning kidney. 23 of the 30 surviving patients have a functioning kidney and pancreas (79%), i.e. 74% of the total population of 32 patients. Loss of pancreatic function was surgical in two cases (one case of infection of the transplant site, one case of thrombosis), vascular in one case due to rupture of a mycotic aneurysm into the duodenum and immunological in three cases: two of these pancreases retained partial function allowing perfect blood glucose control with less than 10 units of ordinary insulin per day. Lastly, a perfectly functioning pancreas was removed 13 months after transplantation because of renal rejection not controlled by reinforced immunosuppression. Compared to the data of the international registry, these results demonstrate the value of the retroperitoneal approach used in this series and the improvement of the results obtained with increasing experience of the transplant team.

[Human papilloma virus infection and renal transplantation. Two personally observed cases and a review of the literature]. / Infection à virus papilloma humain et transplantation rénale. A propos de 2 observations personnelles et d'une revue de la littérature.

Two cases of recurrent genital infection due to human papilloma virus (HPV) infection with preneoplasic lesions were observed in kidney transplant recipients. The neoplasic component appears to be very frequent in this immunosuppressed population with a risk estimated at 7%. According to the different authors in the literature [correction of litterature], genital lesions due to HPV, with or without dysplasia are found in 15 to 30% of the transplant population. The factors of risk are not different from the general population and are a function of sexual activity. The clinical expression of the lesions, their clinical course and recurrence are probably related to the immunosuppressor treatment. All such patients should be carefully screened to allow prevention and treatment, which, as seen in these cases, may be insufficient to irradicate the lesions. New therapeutic approaches should be studied in this group of patients at risk.

[Prevalence of severe arterial hypertension in patients with renal grafts and surgical indications. Experience of the La Pitié Hospital]. / Prévalence de l'hypertension artérielle sévère chez le greffé rénal et indications chirurgicales. Expérience de La Pitié.

Five hundred eighty five renal transplantations were performed in our group from January 1982 to December 1992. The observed incidence of hypertension in this group is 45%. Invasive treatment was indicated in 20 hypertensive patients (3.4%): 4 patients had bilateral-nephrectomy and 16 patients were treated for renal artery stenosis. This last group consisted of 12 men and 4 women (mean age of 36 years), who received a cadaveric transplant. 7 patients were hypertensive prior to transplantation. Only 25% of the patients received cyclosporine. Initial nephropathy was a glomerular in 9 cases. Before surgical treatment, an average of 3.2 anti-hypertensive drugs were necessary to control arterial pressure. Percutaneous transluminal angioplasty was indicated in 11 patients, whereas surgical correction of arterial stenosis was realized in 6 cases. Angioplasty was associated with poor results (persistent HTA and renal failure in 7 out of 11 patients). After surgery of renal artery, all patients had normal blood pressure. Renal artery stenosis would require surgical treatment, when possible. If not, percutaneous transluminal angioplasty will be proposed. The most efficient surgical procedure seems to be resection of the structure and termino-terminal anastomosis. When usable, internal iliac artery can be sutured beyond the stenosis.

[Repeated renal transplantation]. / Transplantation rénale itérative.

From October 1987 to June 1992, 359 renal transplantations were performed, while, over the same period, 25 patients with a follow-up of more than six months underwent repeat renal transplantation: 23 for a second transplant and 2 for a third transplant. The initial disease was glomerular for 17 patients and interstitial for 6 patients. The mean age of the patients at the time of the repeat transplantation was 36.9 years (range: 20 to 53 years). The mean survival after the first transplantation was 3 years and 10 months (range: 1 week to 10 years). The reasons for loss of the first transplant can be classified as follows: acute rejection (n = 5), chronic rejection (n = 14), surgical failure (n = 5) or sepsis (n = 1). 9 patients received conventional immunosuppressant therapy, while 16 patients (64%) received four-drug therapy including cyclosporin. The actuarial one-year survival of the patients and the transplants was 100% and 92%, respectively. The mean serum creatinine was 136.4 +/- 65 mumol/l (range: 59 to 298 mumol/l). Ten patients developed rejection after a mean of 18.6 days (range: 6 to 30 days) and 2 patients suffered from 2 episodes of rejection within 4 months. These results illustrate the low postoperative surgical and immunological complication rate in this group of patients whose long-term results are at least comparable to those of first transplantations in our group.

[Primary bladder lymphoma in kidney transplant recipients: report of a case]. / Lymphome primitif vésical chez le transplanté rénal: à propos d'un cas.

The authors report the case of a type B EBC (+) primary lymphoma of the bladder occurring in a renal transplant patient 14 months after the graft. The postoperative course had been marked by three episodes of early rejection, the last of which required the use of anti-CD3 antibody, then the later addition of cyclosporin. After immune labelling showing oligoclonal proliferation, the lesion was treated with CD24 and CD21 monoclonal antibodies. Ten months after treatment, the patient is in remission with renal function at 200 mumol plasma creatinine. Azathioprine and cyclosporin have been stopped. This apparently unique case provides the authors with an opportunity to review the usual characteristics of lymphocyte tumours in transplant patients and to stress the rarity of primary lesions of the urinary tract. They conclude that the new therapeutic approach based upon monoclonal antibodies is of value in comparison with the attempts at surgery, radiotherapy and/or chemotherapy used in the past.

Anesthesia for creation of a forearm fistula in patients with endstage renal failure.

The effects of local infiltration anesthesia, brachial plexus blockade, isoflurane, or halothane anesthesia on blood flow through the brachial artery and through a newly created forearm arteriovenous fistula (AVF) were compared in 36 patients with endstage renal failure. Brachial artery blood flow was measured at two different times, before anesthesia and during anesthesia but before surgery, using a pulsed Doppler flowmeter. AVF flows were calculated from brachial, radial, and ulnar blood flows at the end of surgery, 2 h after surgery, and 3 and 10 days after the procedure. Mean arterial pressure was lower in patients receiving isoflurane or halothane than in those receiving local anesthesia or brachial plexus blockade (BPB). There was a significant increase in brachial artery blood flow following BPB (43.7 +/- 18.7 to 186.9 +/- 98.2 ml.min-1) during isoflurane anesthesia (46.2 +/- 15.9 to 153.1 +/- 80.5 ml.min-1) and during halothane anesthesia (49.9 +/- 24.1 to 97.6 +/- 62.1 ml.min-1). During anesthesia, the difference in brachial artery blood flow between patients in the BPB and halothane groups was significant. Local anesthesia failed to increase brachial artery blood flow (44.0 +/- 12.7 to 45.6 +/- 11.3 ml.min-1). In the immediate postoperative period, the AVF blood flow was lower in patients in the halothane group than in the other groups, but this difference was only significant when compared with BPB group.(ABSTRACT TRUNCATED AT 250 WORDS)

[Transurethral surgery and persistent urinary infection: effect of a single preoperative dose of cefuroxime]. / Chirurgie transuréthrale et infection urinaire persistante: effet d'une dose unique preéopératoire de céfuroxime.

To evaluate the efficacy of cefuroxime, a second generation cephalosporin, in minimizing the risk of per and postoperative infection complications in patients with urinary tract infection undergoing transurethral surgery, 86 patients (ASA I, II) with persistent urinary tract infection despite antibiotic therapy were studied. A double blind protocol was followed. Patients were randomly assigned to receive 10 minutes before surgery either I.V. cefuroxime (1.5 g) (group C, n = 39) or placebo (group P, n = 47) the incidence of positive peroperative systematic blood cultures was lower in group C (9.7%) than in group P (25.2%) (p less than 0.001). The incidence of postoperative blood cultures taken when clinical septic signs were present, was significantly lower in group C (0%) than in group P (21.7%) (p less than 0.05). However neither the incidences of both postoperative urinary tract infection at the 48th postoperative hour and the clinical signs of bacteraemia including fever nor the average length of hospitalization were significantly different in the 2 groups. This lack of significant clinical benefit was not explained by the pharmacokinetic properties of this antibiotic. Thus, preoperative administration of a single dose of cefuroxime, reduces the incidence of per and postoperative bacteraemias in ASA I-II patients with persistent urinary tract infection.