Jean-Marc Doutrelepont

Hyper IgE in stimulatory graft‐ versus‐host disease: role of interleukin‐4

Intravenous injection of 2 × 108 DBA/2 spleen cells into adult intact (C57BL/6 x DBA/2) Fl mice results in a stimulatory graft‐versus‐host reaction (GVHR) linked to the recognition by donor CD4+ T cells of Ia alloantigens on host B cells. In the experiments presented here, we found that this GVHR is associated with a major increase in IgE serum levels which was already present 7 days after the cell transfer. At 6 weeks, mean IgE levels were more than 200‐fold above the control values. Host B cells were responsible for the hypersecretion of IgE in stimulatory GVHR since it was also observed when the DBA/2 donor inoculum was depleted of B cells but not when the Fl recipients were irradiated. The induction of IgE secretion required donor CD4+ T cells as treatment of the donor inoculum with lytic anti‐CD4 monoclonal antibody (MoAb) completely prevented the occurrence of the hyper IgE whereas depletion of CD8+ cells had no influence on this parameter. The role played by interleukin‐4 (IL‐4) in this model was analysed in vivo by the administration of the 11B11 anti‐IL‐4 rat MoAb (total dose 36 mg) during the first 12 days following induction of stimulatory GVHR by 8 × 107 DBA/2 spleen cells. This treatment completely prevented the development of hyper IgE whereas the administration of a control rat MoAb had no significant effect. We conclude that stimulatory GVHR in mice is associated with a major increase in serum IgE which is mediated by IL‐4.

Renal transplantation exposes patients with previous Kaposi's sarcoma to a high risk of recurrence

It is currently estimated that about 0.5% of patients will develop Kaposis sarcoma (KS) after kidney transplantation. Tapering of immunosuppression often leads to KS remission, but also results in graft loss in more than 50% of cases. Whether retransplantation is safe in these patients is unknown. We here report on eight patients who developed KS recurrence after kidney transplantation-(A) Patients with previously treated KS: There were 4 patients who had clinical remission of KS (including three posttransplantation) for periods ranging from 5 months up to 19 years before transplantation. All 4 developed KS recurrence within months after transplantation. In 3 patients, KS regressed only when all immunosuppression was discontinued, at the price of allograft removal. Partial remission occurred in the fourth patient following reduction of immunosuppression and gancyclovir administration; (B) Patients with recurrent KS during a single transplant: 4 patients developed KS after transplantation that regressed following reduction of immunosuppressive therapy. Increased immunosuppression, in the form of steroid pulses in 3 patients was associated with recurrence of KS. Subsequent reduction of immunosuppression caused regression of KS in all 4 patients, but 2 recipients lost their allografts. These data emphasize the high risk of recurrence of KS after renal transplantation. If physicians decide to transplant patients with a history of KS, they should inform the future recipient of the possibility of KS recurrence.

Renal functional reserve of transplanted kidneys.

Michel Dhaene, CUB Hôpital Erasme, Service de Néphrologie, Route de Lennik 808, B-1070 Brussels (Belgium) Dear Sir, Protein intake has been shown to raise the glomerular filtration rate (GFR). A renal functional reserve has been defined [1, 2] as the difference between preand postprandial GFR following an oral protein load. We wonder whether the investigation of renal reserve could be of interest to transplanted patients. The renal reserve of 7 transplanted patients was evaluated after ingestion of 2 g of protein/kg body weight in the form of cooked red meat. All patients, aged from 16 to 44 years, were selected on the basis of a standard creatinine clearance superior to 50 ml/min. They had received a kidney graft 3–22 months prior to the study. Their residual renal function before transplantation was negligible. Immunosuppressive therapy consisted of prednis-olone (10 mg) and either azathioprine (50–150 mg) or cyclosporin (150–300 mg/daily). Metoprolol (100 mg) was given to 3 patients for hypertension. After drinking 20 ml/kg of water in half an hour, the patients underwent preand postprandial creatinine clearances and urinary urea nitrogen excretion measurements. Simultaneous in-ulin clearances were measured in 4 subjects. Baseline and postprandial GFR were calculated as the mean value of three and four successive clearance measurements. Detailed results are given in table I: only 3 patients exhibited a significant renal functional reserve after a protein load. The results obtained from inulin clearances were comparable and it should be noted that these 3 patients are set apart by their lower urinary urea excretion. These observations lead to several conclusions. First, they confirm that a denervated kidney is able to exhibit a protein-induced hyperfiltration. Secondly, despite the fact that baseline GFR could already have been raised by the glucocorticoids [3, 4], the response to proTable I. Creatinine clearances and urinary urea nitrogen excretion Patients Baseline Baseline Postprandial Renal

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.

HHV-8 is associated with recurrent Kaposi's sarcoma in a renal transplant recipient.

Sir: We have recently described how renal transplantation exposes patients with previous Kaposi’s sarcoma (KS) to a high risk of recurrence [2]. The cause of this phenomenon is unclear. Recently, a new herpes virus (HHV-8), initially identified by Chang et al. [1] in AIDS-associated KS, has been described in classic and endemic KS, as well as in KS occurring in immunosuppressed patients [3,4,6-91. This virus is suspected of being a widespread, latent virus that may be reactivated in certain conditions, such as immunosuppression, causing various tumors, in particular KS. We present here evidence that recurrence of KS after renal transplantation is associated with the presence of reactivated HHV-8 in KS lesions. In October 1988, a 32-year-old woman underwent a first cadaveric kidney transplantation for end-stage nephroangiosclerosis. Immunosuppression consisted of azathioprine (AZA), prednisolone (PRED), and cyclosporin A (CyA). At the end of the 5th post-transplant month, she developed multiple KS cutaneous lesions on her limbs and right breast. Skin biopsy confirmed the diagnosis of KS. There was no visceral involvement and antibodies against the HIV were absent. CyA was discontinued. Nevertheless, skin lesions progressed rapidly, leading to discontinuation of AZA. An acute rejection episode resulted in transplant loss in April 1989, but KS was found in an inguinal lymph node harvested during allograft nephrectomy. The skin nodules disappeared within 2 months after initiation of dialysis, and histological examination of an iliac lymph node 2 years later revealed no signs of KS. The patient was retransplanted in December 1993 under CyA, AZA, and PRED. Three months later, skin and then visceral (stomach) recurrence of KS were clearly demonstrated by histological examination. A reduction in immunosuppression resulted in complete regression of KS but also in allograft loss requiring nephrectomy in July 1994. The patient remains in clinical remission of KS 1.5 years later. We retrospectively searched for evidence of HHV-8 using the nested PCR method with KS 330-233 primers on all of the paraffin-embedded specimens obtained from this patient [l]. The virus was detected in initial and recurrent KS biopsy specimens (cutaneous and visceral). In contrast, using the same PCR conditions, no HHV-8 DNA could be detected in the lymph node harvested during KS clinical remission when the patient was off all immunosuppression (Fig. 1). These data strongly suggest that, firstly, KS recurrence after renal retransplantation is associated with HHV-8 and, secondly, that discontinuation of immunosuppression induces KS regression, apparently in parallel with a reduction in the number of viral copies, leading to a lack of detection by PCR. Thus, reintroduction of immunosuppression in the setting of renal retransplantation may induce HHV-8 reactivation, leading to clinical KS recurrence. Naturally, these findings must be viewed with caution because recent data suggest that HHV-8 is frequently present in otherwise healthy males [5]. However, as the detection Fig. 1 Agarose gel electrophoresis of products amplified using K 330-233 primers for HHV-8. The numbers in the ordinate refer to base pairs. Lane I : Molecular DNA weight marker VPBR 322-DNA-HAE 111; Lane 2: Negative control; Lane 3: Visceral (lymph node), HHV-&positive after the first transplantation episode; Lane 4: Lymph node harvested when patient was in clinical remission, free of immunosuppression; no HHV-8 could be detected; Lanes 5 and 6: Cutaneous and gastric KS lesions that develop after the second transplantation. Both lesions are HHV-8-positive; The 233 bp fragment corresponds to specific HHV-8 DNA sequences and the 268 bp product to p-globin gene

Tuberculosis presenting as acute hepatitis in a renal transplant recipient

Abstract We observed a kidney transplant recipient in whom acute hepatitis was the initial manifestation of tuberculosis, preceding radiological lung involvement by several weeks. The diagnosis was suspected and treatment initiated based on the finding of a granulomatous hepatitis on liver biopsy. Mycobacterial tube‐rulosis was grown and identified first in liver samples and only later in sputum and bone marrow. This case illustrates the protean manifestations of tuberculosis in immunosup‐pressed patients.

Inability of OKT3 to prevent donor-derived ABO hemolytic anemia in a kidney-pancreas transplant recipient.

Sir: Minor incompatibility for ABO antigens involves the presence on the recipient’s red cells of A and/or B blood group antigens lacking in the donor. Such donor-recipient combinations may expose the recipient to the development of an ABO hemolytic anemia in the early post-transplant period [6,7]. This anemia is due to the production by “passenger” donor B lymphocytes [2,8] of allohemagglutinins directed against recipient ABO antigens. The frequency of this complication reaches 70 % in heart-lung, 30 % in liver, and 10 % in heart and kidney transplants [7]. This is probably related to the number of B cells transferred with the graft. Minor ABO incompatibilities are, however, accepted for lung, liver, and heart transplantations because the poor vital prognosis without transplantation outweighs the risk of post-transplant hemolysis. For kidney [lo] and combined kidney-pancreas transplantations, minor ABO mismatches are allowed if HLA compatibility is considered to be favorable.

Combined pancreatic and kidney transplantation: en bloc retrieval and transplantation - a new surgical technique

Abstract We designed and performed on two patients a new surgical procedure of en bloc kidney and pancreatic transplantation. The liver, pancreas and kidneys were removed en bloc in the donor. On the bench, the liver and the left kidney were separated from the bloc, leaving the pancreas and the right kidney for combined kidney and pancreatic transplantation, The portal vein was divided near to the emergence of the splenic vein. The coeliac axis was taken with an aortic patch. The left renal vein was cut at its entrance to the inferior vena cava (IVC) and the left renal artery was taken with an aortic patch. Reconstruction of the pancreatic vessels was performed with a double anastomosis: the portal vein was anastomosed to the hole in the IVC resulting from the section of the left renal vein and the splenic artery was anastomosed to the hole in the aorta resulting from the section of the left renal artery. The proximal ends of the aorta and IVC were closed with running sutures. In the recipient, the iliac vessels on the right side were dissected. Anastomosis of the distal part of the aorta and the IVC was performed with the right iliac vessels. Duodenocystostomy and reimplantation of the ureter were done according to the usual techniques. This new surgical technique allowed an easy vascular reconstruction of the pancreatic vessels. In the recipient, only one side was used for renal and pancreatic transplantation. Moreover, the length of the transplant procedure was significantly reduced.