RENAL TRANSPLANTATION IN INSULIN-DEPENDENT DIABETICS

915

It is quite possible that hyposensitisation might sometimes make the patient worse. Undoubtedly the lung is the most important target organ for D. pteronyssinus sensitivity, so in spite of the coincidental benefit of allergic rhinitis in these patients we feel that this treatment, for the present, should be confined, in children, to those with perennial asthma imperfectly controlled by symptomatic measures with proven bronchial allergy to D. pter-

orcyssinus. We thank Dr A. P. Norman for continuing encouragement and to study his patients; Bencard Limited, for the antigens and the department of statistics, and for much help in the Beechams Research Laboratories.

permission

planning;

Requests for reprints should be addressed to J. 0. W. Respiratory Unit, Hospital for Sick Children, Great Ormond Street, London WC 1. REFERENCES

1. Noon, L. Lancet, 1911, i, 1572. 2. Freeman, J. ibid. 1911, ii, 814. 3. Lichtenstein, L. M. Am. Rev. resp. Dis. 1978, 117, 191. 4. Warner, J. O. Br. J. Dis. Chest, 1978, 72, 79. 5. Aas, K. Acta pæd. scand. 1971, 60, 264. 6. British Tuberculosis Association. Br. med. J. 1968, iii, 774. 7. Voorhorst, R., Spieksma-Boezeman, M. I. A., Spieksma, F. T. M. Allergie Asthma, 1964,10, 329. 8. D’Souza, M. F., Pepys, J., Wells, I. D., Tai, E., Palmer, F., Overell, B. G., McGrath, I. T., Megson, M. Clin. Allergy, 1973, 3, 177. 9. Smith, A. P. Br. med. J. 1971, iv, 204. 10. Smith, J. M., Pizarro, Y. A. Clin. Allergy, 1972, 2, 280. 11. Gaddie, J., Skinner, C., Palmer, K. N. V. Br. med. J. 1976, ii, 561. 12. Warner, J. O. Archs Dis. Childh. 1976, 51, 905. 13. Sarsfield, J. K., Gowland, G., Toy, R., Norman, A. L. E. ibid. 1974, 49, 716. 14. Price, J. F. Unpublished. 15. Cogswell, J. J., Hull, D., Milner, A. D., Norman, A. P., Taylor, B. Br. J. Dis. Chest, 1975, 69, 40. 16. Cogswell, J. J., Hull, D., Milner, A. D., Norman, A. P., Taylor, B. ibid.

p. 118. 17. Armsen, P. Biometrika, 1955, 42, 494. 18. McNicol, K. N., Williams, H. B. Br. med. J. 1973, iv, 7. 19. Taylor, B., Norman, A. P., Orgel, H. A., Stokes, C. R., Turner, M. Soothill, J. F. Lancet, 1973, ii, 111.

W.,

RENAL TRANSPLANTATION IN INSULIN-DEPENDENT DIABETICS A

Summary

Joint Scandinavian Report* Since 1970 renal

transplantation

has

been carried out in 146 insulin-dependent diabetic patients with renal failure. Patient-survival at one year was 60%, and at two years it was 50%. One-year survival among 25 patients with living donor transplants was 84%. Survival was significantly reduced in patients with heart-disease, impaired vision due to diabetic retinopathy, and a long history of diabetes. Survival was not influenced by sex, age, neuropathy, or pretransplantation dialysis. Diabetic retinopathy progressed slowly after successful transplantation, and more than 90% had stable vision one to two years after transplantation. Progression of peripheral circulatory insufficiency was common and severe enough to necessitate

tients with a functioning graft needed constant care, and more than 50% were able to work.

hospital

Introduction ACTIVE

treatment

of terminal renal failure in the insu-

lin-dependent diabetic patient causes many problems. The results of chronic haemodialysis are inferior to those in the non-diabetic patient. 1-5 Except in Minneapolis,’7 transplant centres have limited experience with renal transplantation in insulin-dependent diabetics. For example, if those who received transplants at Minneapolis are excluded, the latest A.C.S./N.I.H. registry report records only 104 transplantations in diabetics.8 In Scandinavia (comprising Denmark, Finland, Norway, and Sweden) the first renal transplantation in a diabetic patient was done in 1970. Since then an increasing number of such patients have been accepted for transplantation, and experience from individual centres was reported at the Scandinavian transplantation meeting in 1977.5 The present, report summarises the total Scandinavian experience over seven years. Patients and Methods Patients In 1970-76 146 insulin-dependent diabetics with terminal renal failure received a renal transplant. Their mean age was 37.6 (19-63) years, and the mean duration of the diabetes was 23 (5-47) years (see accompanying table). Diabetic nephropathy was considered to be the cause of renal failure in most patients; in only 5 patients were other renal diseases (glomerulonephritis 3, and medullary cystic disease 2) implicated. Urinary-tract infection may have contributed in some; in only 3 patients, however, was renal failure thought to be due to a combination of infection and diabetic nephropathy. 80 patients (56%) had symptoms or signs of heart-disease. 16 patients also had symptoms of peripheral arterial disease. 86 patients had undergone hxmodialysis or peritoneal dialysis before transplantation. Recipients of living-donor kidneys did not differ significantly from the rest with regard to cardiovascular disease, vision, neuropathy, age, sex, and duration of diabetes before transplantation.

Treatment

patients were treated at eight Scandinavian centres. transplantation procedures, including immunosuppressive therapy, are fairly standard, although minor variations may exist between different centres. 25 patients received a graft from a living related donor (6 from HLA-identical sibThe Renal

CLINICAL CONDITION OF

146

INSULIN-TREATED DIABETICS AT

TRANSPLANTATION

amputation(s) in 18 patients. One and two years transplantation less than 10% of the pa-

after successful

*This report was prepared by: J. JERVELL, B. O. DAHL, and A. FLATMARK, Rikshospitalet, Oslo, Norway; P. K. LUND and P. THAYSSEN, Odense Sygehus, Odense, Denmark; O. FJELDBORG and H. E. HANSEN, Kommunehospitalet, Arhus, Denmark; B. KOCK and B. LINDSTROM, Helsinki University Central Hospital, Helsinki, Finland; O. LARSSON and H. BRYNGER, Sahlgrenska Sjukhuset, Gothenburg, Sweden; C.-G. GROTH and G. LUNDGREN, Huddinge Sjukhuset, Stockholm, Sweden; B. HUSBERG and J. WIESLANDER, Lasarettet, Lund, and Allmänna Sjukhuset, Malmø, Sweden; and L. FRODIN and B. WIKSTRØM, Akademiska Sjukhuset, Uppsala, Sweden.

*Orthostatic hypotension (6%), diabetic diarrhoea (8%), bladder dysfunction (8%), and/or other symptoms. tAngina pectoris (9%), previous myocardial infarction (2%), radiologically enlarged heart (47%), and heart-failure (38%). $Intermittent claudication, "diabetic foot" (gangrene, ulcers), and/or

pre-transplant amputation.

916

lings,

19 from

parents); the rest received cadaveric kidneys. All

patients were followed-up until July 1, 1977. Results Patient survival and graft-survival (by the acturial life method9) were 60% and 40%, respectively, at one year for recipients of cadaveric kidneys (fig. 1). Both patient-survival and graft-survival were lower than that for non-diabetics. Patient-survival among 25 live-donor recipients was 85% at one year, a result similar to that in non-diabetic patients. The main cause of death was cardiovascular disease, which was responsible for 35 out of 79 (44%) deaths. 23 patients died from infection and the cause of death in the other 21 was ursemia 6, gastrointestinal complications 3, severe hypoglycaemia 3, and other causes 9. Patients with poor vision, heart-disease, and long duration of diabetes had a significantly higher mortality.

Patients with both impaired vision due to diabetes and heart-disease had an especially low survival-rate (fig. 2) when given a cadaveric kidney. 7 recipients of livingdonor kidneys also had impaired vision and heartdisease, and 3 of the 6 deaths in the living-donor group occurred in patients with both these complications. Sex, age, neuropathy, or dialysis before transplantation did not influence patient-survival. More than 90% of patients with successful graft and normal vision before transplantation, retained their vision for at least two years after the procedures. Progressive peripheral circulatory insufficiency necessitated amputation(s) in 18 patients (5 women and 13 men) after transplantation. Rehabilitation, according to criteria used at the latest European Dialysis and Transplantation Association (E.D.T.A.) meeting,10 was reasonably good. Less than 10% of survivors with functioning grafts required hospital care at one and two years (E.D.T.A. group 6). 40% of cadaveric-kidney recipients and 25% of living-donor recipients were living at home but were unable to work (E.D.T.A. group 5). The remaining patients were able to work (E.D.T.A. groups 1-4). Of the 18 patients who received a second graft, 9 were alive and had a functioning graft on July 1,1977. Discussion

Fig. 1—Cumulative patient () and first-renal-graft survival (- - - - -) in 121 insulin-dependent diabetics receiving cadaveric kidneys (888), and 25 insulin-dependent diabetics receiving living-donor kidneys (000).

2-Cumulative patient-survival in diabetics veric kidneys.

Fig.

receiving cada-

Unbroken line represents 39 patients who had combinations of impaired or lost vision and heart-disease; broken line represents 31 patients with reading vision and no signs of heart-disease at transplantation.

Since the results of permanent hsemodialysis in diabetic patients are inferior to those in nondiabetics,1-5 renal transplantation seems preferable for diabetics. Data from Minneapolis6show that renal transplantation increases patient-survival in diabetics. However, both patient-survival and graft-survival are worse than that for non-diabetic patients. Our study does not allow a comparison between dialysis and transplantation in the diabetic patient. It does, however, show that the results of transplantation are not better in patients who have been dialysed and does not support the suggestion that pre-transplantation dialysis will improve patient (and graft) survival .6 Our results suggest that the only indication for early, pre-dialysis transplantation is the patient with deteriorating vision. Terminal ursemia and dialysis often cause marked progression of retinopathy, whereas successful transplantation has a beneficial effect. Dialysis will not halt impairment of vision while a successful transplantation will. Patient-survival and graft-survival in our study were not as good as those reported from Minneapolis. The two most important of the factors which may be responsible for this difference appear to be donor-selection and the criteria for acceptance of patients for transplantation. In Minneapolis 73% of the transplants were living-donor kidneys compared with 18% in our study. Our results for those who received living-donor kidneys are similar to those reported from Minneapolis, and once again show that the living donor is the better source of kidney for transplantation. Our selection of patients for transplantation also seems to have been more liberal than that in Minneapolis. 50% of our patients had impaired or lost vision at the time of transplantation, compared with 30% in Minneapolis. The frequency of heart-disease in our patients was 55%, but the frequency of this complication in Minneapolis is not

given.

917

Heart-disease is the most important factor in patientsurvival. Blind diabetics with heart-disease have a

survival, and it is doubtful whether is transplantation justified in these patients. Renal transplantation cannot be expected to reduce the severity of other diabetic complications. In fact, our results, like those of others,6 show that the progression of arteriosclerotic complications after transplantation leads to a high number of limb amputations. The frequency of cardiovascular complications is also the main reason why deaths continue to occur after two years, even when graft function is stable (figs. 1 and 2). The beneficial effect on retinopathy, on the other hand, is remarkable, and it is difficult to explain. It must be due, at least partly, to better metabolic and blood-pressure control. At present about 10% of renal transplantations in Scandinavia are carried out on diabetic patients. We believe that this is justified. Most uraemic patients suitable for active treatment are looked after under our total transplantation programme and the inclusion of diabetics has not excluded other patients from the programme. Also, the rehabilitation of these patients is reasonable; most patients manage quite well out of hospital, and several patients are at work. Recipients should be selected carefully, and transplantation in patients with both impaired vision and heart-disease should be avoided. Living related donors are preferred.

particularly

poor

material, cultured specifically for mycoplasmas, was positive for Ureaplasma urealyticum as were the blood, abscess fluids, throat-swab, and nasopharyngeal secre-

Therapy, based

on in-vitro studies of antibiotic of the susceptibilities organism, resulted in the eradicaof infection tion the and resolution of the arthritis. These findings suggest that U. urealyticum may be capable of inducing polyarthritis in man.

tions.

Introduction A FORM of arthritis, clinically similar to rheumatoid arthritis, is a familiar feature in hypogammaglobulinaemic states1--’:3 but the pathogenesis remains unknown.

Some of the immunological factors involved have been elucidated4-7 and no infective agents (bacteria, viruses, or mycoplasmas) have been consistently found.8-10 Mycoplasmas may be candidates for this role because they are associated with chronic arthritis in mammals and birds,11they can persist in tissues for long periods without being eliminated by host defences, 12 13and they can elicit an immune response that results in joint-tissue in human arthritides damage. The role of11mycoplasmas has been doubted8 14 because the organism has not been consistently isolated. This report describes the course of polyarthritis in a patient with congenital agammaglobulinx-mia, its relation to diagnosis, and treatment of infection due to

Ureaplasma urealyticum.

Requests for reprints should be addressed to J. J., Medisinsk Avdeling B, Rikshospitalet, Pilestredet 32, Oslo, Norway.

’

Case-report A

REFERENCES

Chazan, B. I., Rees, S. B., Balodimos, M. C., Younger, D., Ferguson, B. D. J. Am. med. Ass 1969, 209, 2026. 2. Chaviamian, M., Gutch, C. F., Kopp, K. F., Kolff, W. J. ibid. 1972, 222, 1.

1386. 3. Skideman, J. R., Buselmeier, T.

J., Kjellstrand, C. M. Archs intern. Med. 1976, 136, 1126. 4. Kassisieh, S. D., Yen, M. C., Lazarus, J. M., Lowrie, E. G., Goldstein, H. H., Takacs, F. J., Hampek, C. L., Merrill, J. P. Kidney Int. 1974,

suppl. 1, 100. Scand. J. Urol. Nephrol. 1977, Suppl. 42, 101. Najarian, J. S. and others Surg. Gynec. Obstet. 1977, 144, 682. Obstet. 1977, 144, 682. 7. Najarian, J. S., Sutherland, D. E. R., Simmons, R. L. in Strategy in Renal Failure (edited by E. A. Friedman). New York, 1978. 8. A.C.S./N.I.H. Rental Transplant Registry. J. Am. med. Ass. 1975, 232, 148. 9. Dixon, W. J. (editor). B.M.D.-Biomedical Computer Program (Program 11S.) California, 1973. 465. 10. Jacobs, C., Brunner, F. P., Chantler, C., Donckerwolke, R. A., Gurland, H. I., Hathway, N. H., Selwood, N. H., Wing, A. J. Combined Report on Intermittent Dialysis and Renal Transplantation in Europe VII, 1976. 14th EDTA congress, June 1977, Helsinki. 5. 6.

10-year-old boy with congenital agammaglobulinaemia presented with a 3-week history of pain and swelling in the left hand while on gammaglobulin replacement therapy. A previous arthritis of the knee had responded to resumption of gammaglobulin therapy which had been temporarily discontinued. His history included episodes of conjunctivitis (cultures for viruses and bacteria were negative) and bronchopneumonia (cultures’ for bacteria and Mycoplasma pneumonice were negative). On admission he was afebrile, the blood-count was normal, and the erythrocyte-sedimentation rate (E.S.R.) was 4 mm/h (Westergren). X-rays of the hand showed periosteal elevation

IDENTIFICATION OF UREAPLASMA UREALYTICUM (T-STRAIN MYCOPLASMA) IN PATIENT WITH POLYARTHRITIS MARTIN STUCKEY PATRICIA A. ERWIN W. GELFAND

QUINN

Departments ofImmunology and Bacteriology, Research Institute, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada

Summary

10-year-old boy with confirmed congenital agammaglobulinæmia presented with polyarthritis while on gammaglobulin replacement therapy. Initial cultures of material aspirated from an abscess and of joint fluid were negative, and symptoms progressed despite antibiotic therapy. Synovial-biopsy A

Fig. 1—Clinical course of polyarthritis. ’Culture for U. urealyticum not done. Specimens large-colony mycoplasmas.

were

negative

for