RECURRENCE OF HAEMOLYTIC URAEMIC SYNDROME TRIGGERED BY CYCLOSPORIN A AFTER RENAL TRANSPLANTATION

1470

TABLE I-INCIDENCE OF REGRESSION

*Also taking propranolol 40 mg twice daily.tAlso taking antihypertensive drugs and diuretics.Expressed as no. (out of five cultures) showing regression.

activity giving increasing regression with increasing cellconcentration. Cells from patient 6 show no evidence of regressioneven at the highest cell concentration.Patients 1,4, and 5 had low total T cell numbers (under 60%) but

all had normal helper/suppressor ratios (table II). All anti-VCA titreswere normal (1:512).

TABLE II-STAINING OF PERIPHERAL BLOOD MONONUCLEAR CELLS

*UCHT" stains peripheral blood T cells.tLeu 2a and Leu 3a (Becton-Dickinson, Sunny Vale, California, U.S.A.) stain suppressor/cytotoxic and helper/mducer T cell subsets respectively.

Five of the six renal allograft patients receiving a CSA dose of upto 10 mg/kg daily thus had normally acting EB virus-specific T cells.This compares favourably with patients receiving conventionalazathioprine and prednisone therapy.9 All have anti-VCA titreswithin the normal limits and although some have low total T cellnumbers, none have the reversed helper/suppressor ratios whichhave been described in patients on higher doses. 10 These resultssuggest that in most individuals the lower dose of CSA allows thenormal elimination of EB virus-infected B cells from the circulation

by specific cytotoxic T cells. These findings may explain why nolymphomas have yet been detected in this group of patients.We thank Prof. A. Polak and Mr M. Slapak for their help in this study on

their patients

Department of Haematology,University College London,London WC1E 6JJ

Virus Reference Laboratory,Central Public Health Laboratory,London NW9

D. H. CRAWFORD

J. M. B. EDWARDS

9. Crawford DH, Edwards JMB, Sweny P, Hoffbrand AV, Janossy G. Studies onlongterm T-cell-mediated immunity to Epstein-Barr virus in immunosuppressedrenal allograft recipients. Int J Cancer 1981; 28: 705-09.

10. Sweny P, Tidman N. The effect of cyclosporin A on peripheral blood T cellsubpopulations in renal allografts. Clin Expt Immunol 1982; 47: 445-48

11. Beverley PCL, Callard RE Distinctive functional characteristics of human "T"

lymphocytes defined by E rosetting or a monoclonal anti-T cell antibody. Eur JImmunol 1981, ii: 329-34.

RECURRENCE OF HAEMOLYTIC URAEMICSYNDROME TRIGGERED BY CYCLOSPORIN A AFTER

RENAL TRANSPLANTATION

SrR,-In some patients treated with cyclosporin A (CSA) afterbone marrow transplantation, glomerular thrombosis has beenobserved.’ These lesions resembled the histological features ofhaemolytic uraemic syndrome (HUS). Since patients with HUShave decreased vascular prostacyclin (PG[2) synthesis and lackprostacyclin synthesis stimulating plasma factor (PSPF),2 Rocchiand co-workers examined the influence of CSA on vascular PGI2synthesis experimentally. They found remarkable decreases inPSPF activity due to CSA treatment and, as a consequence,suggested, that CSA might be dangerous in transplant patients whohad HUS as their underlying renal disease. In 1980 we saw a casewhich seems to support this warning.A 32-year-old man was admitted because of rapidly deteriorating

renal function. He showed all the clinical and histological featuresof HUS. In vitro tests of rat aorta incubation in the patient’s plasmarevealed complete absence of PSPF. All treatments failed to save thepatient’s renal function, and regular haemodialysis was required. Ayear later the patient was given a kidney graft. Immunosuppressionconsisted of prednisolone and azathioprine. 4 weeks after

transplantation an acute transplant rejection (fever, swelling of thegraft, and infiltration by plasma cells and lymphoblastsdemonstrated by biopsy) did not respond to high dose

methylprednisolone and transplant nephrectomy was done.In March, 1982, the patient was given a second transplant (one

mismatch in HLA-B, DR-identity) with immunosuppression byCSA (17 mg/kg body weight daily during the first 2 weeks) andprednisolone (rapidly decreasing from 160 to 20 mg/day). The first 2weeks passed without complications, while plasma creatinine fell to1 2 mg/dl. In the following week the transplant functiondeteriorated rapidly and the other laboratory findings of HUSreappeared: platelet count 40 000/1, fragmentation of red cells inperipheral blood smear, plasma bilirubin 3-8 8 mg/dl, LDH 1300U/1, fibrinogen 150 mg/dl. Gamma camera imaging (after labellingof autologous platelets with lllindium-oxime sulphate) revealedsevere platelet trapping by the graft (platelet uptake index 1 - 59).However, this picture is not pathognomonic for HUS; it is a veryuseful indicator of rejection crisis. The absence of graft swelling (inultrasonic scan) and of fever made acute transplant rejectionunlikely. PSPF activity on in vitro tests was once more absent. Apercutaneous biopsy confirmed recurrence ofHUS with glomerularcapillary thrombosis in the absence of interstitial or vascularinfiltrations by plasma cells and/or lymphoblasts. CSA wasdiscontinued and fresh plasma transfusions were started to replacePSPF. However, the disease did not respond sufficiently and thegraft was surgically removed, the patient being returned to chronicintermittent haemodialysis. (Synthetic PGI2 was not available at thetime.)This case seems to confirm the suggestion that CSA may trigger a

recurrence of HUS after renal transplantation. Where HUS is theunderlying disease renal CSA should not be given, at least untilfurther studies on this problem are done.

Supported by the Medizinisch-Wissenschafthcher Fonds des

Burgermeisters der Bundeshauptstadt Wien.

2nd Department of Internal Medicine,1st Department of Surgery,and Department of Pathology,

University of Vienna,A-1090 Vienna, Austria

C. LEITHNERH. SINZINGERE. POHANKAM. SCHWARZG. KRETSCHMERG. SYRE

1 Gluckmann E, Barrett AJ. Arcese W, Devergie A, Degoulet P. Bone marrow

transplantation in severe aplastic anaemia a survey af the European Group for BoneMarrow Transplantation (E G B.M.T.) Br J Haematol 1981; 49: 165-73

2. Remuzzi G, Marchesi D, Mecca G, Misiani R, Livio M, De Gaetano G, Donati MGHaemolytic-uraemic. syndrome Deficiency of plasma factors(s) regulatingprostacyclin activity? Lancet 1978; ii: 871-72

3. Rocchi G, Imberti L, Fumagalli F, Neild G, Remuzzi G, Cyclosporin-A inducesglomerular thrombosis possibly affecting vascular PGI2-production V

International Conference on Prostaglandins (Florence, May, 1982) abstr 7594. Leithner C, Sinzinger H, Angelberger P, Syre G Indium-111-labelled platelets in

chronic kidney transplant rejection Lancet 1980; ii: 213-14