D. Fries

Membranous Nephropathy in a Bone Marrow Transplant Recipient

A bone marrow transplant recipient is described who had development of nephrotic syndrome in association with chronic graft-versus-host disease (GVHD) and on cyclosporine (CsA) treatment withdrawal. Renal biopsy revealed a membranous glomerulonephritis (MG). The possible relationship between this autoimmune disorder, the immunological features of GVHD in experimental animals, and the influence of CsA is discussed.

Gastrointestinal complications in renal transplantation

Abstract. One wonders whether the use of cyclosporin, histamine receptor antagonists, low doses of steroids, and early diagnosis and treatment actually modify the incidence, morbidity, and mortality of gastrointestinal (GI) and pancreatic complications in renal transplantation. To find out, we reviewed 614 kidney transplant recipients between January 1984 and December 1988. One hundred patients (16.2 %) were found to have GI and/or pancreatic complications in the following distribution: 9.6% gastroduodenal, 1.3% pancreatic, 4% colonic, and 0.4% small bowel. None of the patients presenting a gastroduodenal ulcer had perforation or bleeding. Fifty‐five percent of the patients with this complication had a past history of eso‐gastroduodenal disease, compared to 19.6% in recipients without gastroduodenal complications. Some 4.4 % of the patients had a small bowel or a colonic complication and four died of peritonitis due to bowel perforation. Mortality was 35 % in those having intestinal resection and/or perforation with peritonitis. Sixteen percent of patients with colonic complications had a known history of diverticula, compared to 3 % for those without colonic complications. The incidence of GI and/or pancreatic complications in renal transplant recipients remains high and has caused 1.1 % of the deaths in our series. Mortality is essentially due to upper GI bleeding, peritonitis following perforation, and infectious colitis. Better detection of gastroduodenal and colonic disease before transplantation seems to be mandatory. Prevention with histamine H2 receptor antagonists and early surgical treatment of complicated colonic diverticula help to reduce the morbidity and mortality in kidney graft recipients.

Value of antegrade ureteral dilation for late ureter obstruction in renal transplants

Abstract. We report on eight kidney‐allografted patients treated for delayed ureteral obstruction between January 1986 and January 1987. In all cases, standard endourological dilation was performed using a balloon catheter, and this was followed by insertion of a pigtail stent. All eight cases showed improvement 1 month after dilation (decrease in creatinine and caliceal dilation). At 6 months, renal function had deteriorated in six patients but remained good in two. One of the six patients was redilated with apparently good results. The remaining five were operated on using their own ureter. We conclude that while internal drainage helps in distinguishing between obstruction and other causes of creatinine increase, antegrade dilation is the treatment of choice for delayed ureteral obstruction.

Specific recipient-donor unresponsiveness mediated by a suppressor cell system in human kidney allograft tolerance.

The immunological responsiveness of a panel of 26 consecutive cadaver kidney allograft patients with good graft tolerance was studied against cells from the specific donor. Among these 26 patients, 11 underwent acute cellular rejection and were studied during the rejection episode. An additional eight transplant patients, who lost their graft as a result of cellular rejection, were nephrectomized and studied 6 months after their return to hemodialysis as the control group of patients “at equivalent risk.” A low responsiveness against the specific donor was observed in cases of good graft tolerance, but was absent during rejection and in the control group. By using mixing experiments, cells from tolerant patients were able to actively and selectively suppress the response of their autologous pretransplant cells stimulated by the specific donor cells. These suppressor cells were effective only when added during the first 48 hr of the culture and could respond at a suppressor to responder cell ratio from 1:1 to 1:4. Finally, our observations indicate that allogeneic un-responsiveness between donor-recipient pairs may be associated with the presence of suppressor cells affecting the generation of helper T cells only in a specific situation, i.e., donor-recipient, and only in cases of good graft tolerance.

Biological effects and irradiation dose induced in human lymphocytes in vitro by an intracellular radionuclide:99mTc.

Since lymphocyte radiolabeling is widely used for in vitro and in vivo studies and may interfere with the properties of the cells, the purpose of this work was to investigate the effects of 99mTc labeling on lymphocyte morphology and functions. Two ranges of 99mTc activity were used, 37 and 370 MBq, and their effects were compared to those produced by a graduated external irradiation. Electron microscopy was performed and T cells were studied using biological markers (E-Rosette formation, cell proliferation under lectin reactivity, and specific cell-mediated cytolysis). After 370-MBq labeling, an intense cytotoxic effect was observed on cell morphology, drastically impeding T-lymphocyte functions. Thirty-seven-megabecquerel labeling and sham procedure did not significantly affect cell functions. The external irradiation dose-response curve indicated a clear radiation-induced inhibitory effect, especially over 10 Gy. This effect was less intense than that obtained with 370-MBq 99mTc labeling. The labeling cytotoxic effect can then be attributed to a radiolesion due to a radiation dose which is probably higher than 10 Gy. In fact, the dose received by lymphocytes during the 370-MBq labeling procedure was estimated as 70 Gy by calculations, taking into account all emissions of 99mTc.

PHENOTYPIC COMPOSITION AND IN VITRO FUNCTIONAL CAPACITIES OF UNMODIFIED FRESH CELLS INFILTRATING ACUTELY REJECTED HUMAN KIDNEY ALLOGRAFTS

Cell surface markers of isolated graft-infiltrating cells (GIC) were studied, and functional in vitro assays performed in 8 cases of acute irreversible rejection of human renal allografts. The GIC were mostly activated T cells (OKT11+, OKT3+, Ia+), with predominance of the cytotoxic/suppressor T cell phenotype (OKT8+). A small proportion of B cells and monocytes/macrophages were also present among these GIC. The GIC were able to proliferate with lectin of allogeneic stimulation and were strongly cytotoxic toward specific donor target cells. Within the T cell subset, OKT8+ cells displayed most of the specific cytotoxicity. Despite allograft morphology typical of cellular rejection, anti-HLA complement-dependent antibodies and antibody-dependent cell cytotoxicity were found in the eluted material from rejecting kidneys. The results of our phenotypic and functional testing of unmodified GIC (no enzyme treatment, no additional culture with or without interleukin 2), show that T cells, especially OKT8+ cells, are of paramount importance in the mechanism of this type of acute irreversible rejection of human renal allografts (i.e., to the point of allograft rupture), but other potential effector mechanisms are also present in situ.

Expression Of Okt 8 Antigen And Fcγ Receptors By Suppressor Cells Mediating Specific Unresponsiveness Between Recipient And Donor In Renal-allograft-tolerant Patients

Renal allograft tolerant patients show specific unresponsiveness in mixed-lymphocyte culture assays when confronted with donor stimulating cells. Separation of posttransplant peripheral blood lymphocytes into Fe γ+ and Fc γ- by rosetting and into OKT8+, OKT8- by cytofluorometry enabled the demonstration of normal responses by Fc γ- and OKT8- cells, whereas the proliferation of OKT8+ and Fc γ+ cells was depressed specifically in the presence of donor cells. Using mixing experiments, we showed that OKT8+ and Fc γ+ posttransplant lymphocytes exert a suppressive effect specific to the donor-recipient pair on the proliferative response of the pretransplant lymphocytes.

Human Immunodeficiency Virus Infection in Transplant Recipients

Excerpt To the editor: Recent reports have focused attention on recipients of kidney allografts or transfusions from donors infected with the human immunodeficiency virus (HIV; formerly known as HT...

Multiple drug combinations with “low‐dose” cyclosporin for renal transplantation: Multivariate analysis of risk factors determining short‐term graft survival within one renal transplant center

Abstract. The factors affecting graft survival in transplant recipients receiving cyclosporin (CsA) are still being debated. Our report is based on an analysis of 202 successive transplantations performed in our institution from May 1984 to December 1986, using low‐dose CsA as the basic means of immunosuppression. A total of 142 patients received the triple combination CsA, azathioprine (AZA), and corticosteroids. Sixty patients received a prophylactic combination of CsA, corticosteroids, and antilymphocyte globulins (ALG). From January to December 1986, both regimens were compared in a prospective randomized trial. The factors that affect graft survival were analyzed using the Cox multivariate hazard analysis. The relative risks were calculated for pre‐transplant baseline risk factors and for outcome‐dependent post‐transplant risk factors for surviving grafts at 1 month. Transplants performed with a prolonged ischemia time and patients whose graft did not function immediately were statistically at higher risk of graft loss. Adding prophylactic ALG to CsA was associated with better graft survival. Patients who experienced more than 1 rejection crisis and patients whose 1‐month CsA dose was lower than or equal to 5 mg/kg per day were also at significantly higher risk of further graft loss. Neither HLA matching, peak panel reactivity, age of the recipient, occurrence of post‐transplant renal dysfunction nor 1‐month renal function affected the short‐term graft outcome.

Decreased lymphokine-activated killer cells in kidney transplant recipients. Correlation with a diminished number of CD3-/NKH1+ cells.

The activity of lymphokine-activated killer cells, measured either by a clonal or polyclonal technique, was assessed in 30 kidney transplant recipients (TX), in 13 hemodialyzed patients (HD-CRI), and in 18 normal (N) controls. A highly significant decrease of the LAK activity in TX in comparison with HD-CRI or N (P = 0.0001) was observed. Moreover, the percentage of CD3-/NKH1+ cells was decreased in TX in comparison with N (P = 0.01). LAK activity was strongly correlated (r = 0.72; P = 0.0001) with the percentage of CD3-/NKH1+ cells and not with that of double-positive CD3+/NKH1+ cells. Multivariate analysis showed that the sole independent variable that determined the LAK activity was the percentage of CD3-/NKH1+ cells: the pathological status (TX, HD-CRI, and N) variable was statistically not significant. On the other hand, two T cell-specific functions (IL-2 secretion and specific cytotoxic activity) were, on the whole, preserved in TX. Altogether, these results suggest that TX are LAK deficient predominantly because they have a decreased number of CD3-/NKH1+ cells. The normality of T cell functions suggests that the high rate of malignancies seen in TX is related to this LAK deficiency. Moreover, our study indicates that, in vivo, CD3+ cells do not significantly contribute to the LAK precursors.