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RENAL TRANSPLANTATION IN INSULIN-DEPENDENT DIABETICS *1A Joint Scandinavian Report

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915 It is quite possible that hyposensitisation might some- times 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 aller- gic 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 sympto- matic measures with proven bronchial allergy to D. pter- orcyssinus. We thank Dr A. P. Norman for continuing encouragement and permission to study his patients; Bencard Limited, for the antigens and for much help in the planning; and the department of statistics, Beechams Research Laboratories. 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 Price, J. F. Unpublished. 15.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. W., Soothill, J. F. Lancet, 1973, ii, 111. RENAL TRANSPLANTATION IN INSULIN-DEPENDENT DIABETICS A Joint Scandinavian Report* Summary Since 1970 renal transplantation has been carried out in 146 insulin-depen- dent diabetic patients with renal failure. Patient-survi- val 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. Sur- vival was not influenced by sex, age, neuropathy, or pre- transplantation dialysis. Diabetic retinopathy pro- gressed 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 necessit- ate amputation(s) in 18 patients. One and two years after successful transplantation less than 10% of the pa- tients with a functioning graft needed constant hospital care, and more than 50% were able to work. *This report was prepared by: J. JERVELL, B. O. DAHL, and A. FLAT- MARK, 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. WIK- STRØM, Akademiska Sjukhuset, Uppsala, Sweden. 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 Minnea- polis are excluded, the latest A.C.S./N.I.H. registry report records only 104 transplantations in diabetics.8 In Scandinavia (comprising Denmark, Finland, Nor- way, and Sweden) the first renal transplantation in a diabetic patient was done in 1970. Since then an in- creasing number of such patients have been accepted for transplantation, and experience from individual centres was reported at the Scandinavian transplantation meet- ing 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 ter- minal 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 neph- ropathy was considered to be the cause of renal failure in most patients; in only 5 patients were other renal diseases (glomeru- lonephritis 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 pa- tients (56%) had symptoms or signs of heart-disease. 16 pa- tients also had symptoms of peripheral arterial disease. 86 pa- tients had undergone hxmodialysis or peritoneal dialysis before transplantation. Recipients of living-donor kidneys did not differ significantly from the rest with regard to cardiovas- cular disease, vision, neuropathy, age, sex, and duration of dia- betes before transplantation. Treatment The patients were treated at eight Scandinavian centres. Renal transplantation procedures, including immuno- suppressive therapy, are fairly standard, although minor varia- tions may exist between different centres. 25 patients received a graft from a living related donor (6 from HLA-identical sib- CLINICAL CONDITION OF 146 INSULIN-TREATED DIABETICS AT TRANSPLANTATION *Orthostatic hypotension (6%), diabetic diarrhoea (8%), bladder dys- function (8%), and/or other symptoms. tAngina pectoris (9%), previous myocardial infarction (2%), radiologi- cally enlarged heart (47%), and heart-failure (38%). $Intermittent claudication, "diabetic foot" (gangrene, ulcers), and/or pre-transplant amputation.
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Page 1: RENAL TRANSPLANTATION IN INSULIN-DEPENDENT DIABETICS *1A Joint Scandinavian Report

915

It is quite possible that hyposensitisation might some-times make the patient worse. Undoubtedly the lung isthe most important target organ for D. pteronyssinussensitivity, so in spite of the coincidental benefit of aller-gic rhinitis in these patients we feel that this treatment,for the present, should be confined, in children, to thosewith perennial asthma imperfectly controlled by sympto-matic measures with proven bronchial allergy to D. pter-orcyssinus.We thank Dr A. P. Norman for continuing encouragement and

permission to study his patients; Bencard Limited, for the antigensand for much help in the planning; and the department of statistics,Beechams Research Laboratories.

Requests for reprints should be addressed to J. 0. W. RespiratoryUnit, 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. W.,

Soothill, J. F. Lancet, 1973, ii, 111.

RENAL TRANSPLANTATION ININSULIN-DEPENDENT DIABETICS

A Joint Scandinavian Report*

Summary Since 1970 renal transplantation hasbeen carried out in 146 insulin-depen-

dent diabetic patients with renal failure. Patient-survi-val at one year was 60%, and at two years it was 50%.One-year survival among 25 patients with living donortransplants was 84%. Survival was significantly reducedin patients with heart-disease, impaired vision due todiabetic retinopathy, and a long history of diabetes. Sur-vival was not influenced by sex, age, neuropathy, or pre-transplantation dialysis. Diabetic retinopathy pro-

gressed slowly after successful transplantation, andmore than 90% had stable vision one to two years aftertransplantation. Progression of peripheral circulatoryinsufficiency was common and severe enough to necessit-ate amputation(s) in 18 patients. One and two yearsafter successful transplantation less than 10% of the pa-

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

*This report was prepared by: J. JERVELL, B. O. DAHL, and A. FLAT-MARK, 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. LARSSONand H. BRYNGER, Sahlgrenska Sjukhuset, Gothenburg, Sweden;C.-G. GROTH and G. LUNDGREN, Huddinge Sjukhuset, Stockholm,Sweden; B. HUSBERG and J. WIESLANDER, Lasarettet, Lund, andAllmänna Sjukhuset, Malmø, Sweden; and L. FRODIN and B. WIK-STRØM, Akademiska Sjukhuset, Uppsala, Sweden.

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 thosein the non-diabetic patient. 1-5 Except in Minneapolis,’ 7transplant centres have limited experience with renaltransplantation in insulin-dependent diabetics. For

example, if those who received transplants at Minnea-polis are excluded, the latest A.C.S./N.I.H. registryreport records only 104 transplantations in diabetics.8

In Scandinavia (comprising Denmark, Finland, Nor-way, and Sweden) the first renal transplantation in adiabetic patient was done in 1970. Since then an in-creasing number of such patients have been accepted fortransplantation, and experience from individual centreswas reported at the Scandinavian transplantation meet-ing in 1977.5 The present, report summarises the totalScandinavian experience over seven years.

Patients and Methods

Patients

In 1970-76 146 insulin-dependent diabetics with ter-

minal renal failure received a renal transplant. Their mean agewas 37.6 (19-63) years, and the mean duration of the diabeteswas 23 (5-47) years (see accompanying table). Diabetic neph-ropathy was considered to be the cause of renal failure in mostpatients; in only 5 patients were other renal diseases (glomeru-lonephritis 3, and medullary cystic disease 2) implicated.Urinary-tract infection may have contributed in some; in only3 patients, however, was renal failure thought to be due to acombination of infection and diabetic nephropathy. 80 pa-tients (56%) had symptoms or signs of heart-disease. 16 pa-tients also had symptoms of peripheral arterial disease. 86 pa-tients had undergone hxmodialysis or peritoneal dialysisbefore transplantation. Recipients of living-donor kidneys didnot differ significantly from the rest with regard to cardiovas-cular disease, vision, neuropathy, age, sex, and duration of dia-betes before transplantation.

Treatment

The patients were treated at eight Scandinavian centres.Renal transplantation procedures, including immuno-

suppressive therapy, are fairly standard, although minor varia-tions may exist between different centres. 25 patients receiveda graft from a living related donor (6 from HLA-identical sib-

CLINICAL CONDITION OF 146 INSULIN-TREATED DIABETICS ATTRANSPLANTATION

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

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lings, 19 from parents); the rest received cadaveric kidneys. Allpatients were followed-up until July 1, 1977.

Results

Patient survival and graft-survival (by the acturiallife method9) were 60% and 40%, respectively, at oneyear for recipients of cadaveric kidneys (fig. 1). Bothpatient-survival and graft-survival were lower than thatfor non-diabetics. Patient-survival among 25 live-donor

recipients was 85% at one year, a result similar to thatin non-diabetic patients.The main cause of death was cardiovascular disease,

which was responsible for 35 out of 79 (44%) deaths. 23patients died from infection and the cause of death inthe other 21 was ursemia 6, gastrointestinal complica-tions 3, severe hypoglycaemia 3, and other causes 9.

Patients with poor vision, heart-disease, and longduration of diabetes had a significantly higher mortality.

Fig. 1—Cumulative patient ( ) and first-renal-graft survi-val (- - - - -) in 121 insulin-dependent diabetics receivingcadaveric kidneys (888), and 25 insulin-dependent diabeticsreceiving living-donor kidneys (000).

Fig. 2-Cumulative patient-survival in diabetics receiving cada-veric kidneys.Unbroken line represents 39 patients who had combinations of

impaired or lost vision and heart-disease; broken line represents 31patients with reading vision and no signs of heart-disease at trans-plantation.

Patients with both impaired vision due to diabetes andheart-disease had an especially low survival-rate (fig.2) when given a cadaveric kidney. 7 recipients of living-donor kidneys also had impaired vision and heart-

disease, and 3 of the 6 deaths in the living-donor groupoccurred in patients with both these complications. Sex,age, neuropathy, or dialysis before transplantation didnot influence patient-survival.More than 90% of patients with successful graft and

normal vision before transplantation, retained theirvision for at least two years after the procedures. Pro-gressive peripheral circulatory insufficiency necessitatedamputation(s) in 18 patients (5 women and 13 men)after transplantation.

Rehabilitation, according to criteria used at the latestEuropean Dialysis and Transplantation Association

(E.D.T.A.) meeting,10 was reasonably good. Less than10% of survivors with functioning grafts required hospi-tal care at one and two years (E.D.T.A. group 6). 40%of cadaveric-kidney recipients and 25% of living-donorrecipients were living at home but were unable to work(E.D.T.A. group 5). The remaining patients were able towork (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

Since the results of permanent hsemodialysis indiabetic patients are inferior to those in non-

diabetics,1-5 renal transplantation seems preferable fordiabetics. Data from Minneapolis6 show that renal

transplantation increases patient-survival in diabetics.However, both patient-survival and graft-survival areworse than that for non-diabetic patients.

Our study does not allow a comparison between dialy-sis and transplantation in the diabetic patient. It does,however, show that the results of transplantation are notbetter in patients who have been dialysed and does notsupport the suggestion that pre-transplantation dialysiswill improve patient (and graft) survival .6 Our resultssuggest that the only indication for early, pre-dialysistransplantation is the patient with deteriorating vision.Terminal ursemia and dialysis often cause marked pro-gression of retinopathy, whereas successful trans-

plantation has a beneficial effect. Dialysis will not haltimpairment of vision while a successful transplantationwill.

Patient-survival and graft-survival in our study werenot as good as those reported from Minneapolis. Thetwo most important of the factors which may be respon-sible for this difference appear to be donor-selection andthe criteria for acceptance of patients for transplan-tation. In Minneapolis 73% of the transplants wereliving-donor kidneys compared with 18% in our study.Our results for those who received living-donor kidneysare similar to those reported from Minneapolis, andonce again show that the living donor is the bettersource of kidney for transplantation. Our selection ofpatients for transplantation also seems to have beenmore liberal than that in Minneapolis. 50% of ourpatients had impaired or lost vision at the time of trans-plantation, compared with 30% in Minneapolis. Thefrequency of heart-disease in our patients was 55%, butthe frequency of this complication in Minneapolis is notgiven.

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

particularly poor survival, and it is doubtful whether

transplantation is justified in these patients.Renal transplantation cannot be expected to reduce

the severity of other diabetic complications. In fact, ourresults, like those of others,6 show that the progressionof arteriosclerotic complications after transplantationleads to a high number of limb amputations. The fre-quency of cardiovascular complications is also the mainreason why deaths continue to occur after two years,even when graft function is stable (figs. 1 and 2). Thebeneficial 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-pressurecontrol.

At present about 10% of renal transplantations inScandinavia are carried out on diabetic patients. Webelieve that this is justified. Most uraemic patientssuitable for active treatment are looked after under ourtotal transplantation programme and the inclusion ofdiabetics has not excluded other patients from the

programme. Also, the rehabilitation of these patients isreasonable; most patients manage quite well out of

hospital, and several patients are at work. Recipientsshould be selected carefully, and transplantation in

patients with both impaired vision and heart-diseaseshould be avoided. Living related donors are preferred.

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

REFERENCES

1. 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, 222,1386.

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.

5. Scand. J. Urol. Nephrol. 1977, Suppl. 42, 101.6. 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 onIntermittent Dialysis and Renal Transplantation in Europe VII, 1976.14th EDTA congress, June 1977, Helsinki.

IDENTIFICATION OF UREAPLASMAUREALYTICUM (T-STRAIN MYCOPLASMA) IN

PATIENT WITH POLYARTHRITIS

MARTIN STUCKEY PATRICIA A. QUINNERWIN W. GELFAND

Departments of Immunology and Bacteriology,Research Institute, Hospital for Sick Children,

Toronto, Ontario M5G 1X8, Canada

Summary A 10-year-old boy with confirmed con-genital agammaglobulinæmia presented

with polyarthritis while on gammaglobulin replacementtherapy. Initial cultures of material aspirated from anabscess and of joint fluid were negative, and symptomsprogressed despite antibiotic therapy. Synovial-biopsy

material, cultured specifically for mycoplasmas, waspositive for Ureaplasma urealyticum as were the blood,abscess fluids, throat-swab, and nasopharyngeal secre-tions. Therapy, based on in-vitro studies of antibioticsusceptibilities of the organism, resulted in the eradica-tion of the infection and resolution of the arthritis.These findings suggest that U. urealyticum may be cap-able of inducing polyarthritis in man.

Introduction

A FORM of arthritis, clinically similar to rheumatoidarthritis, is a familiar feature in hypogammaglobulinae-mic states1--’:3 but the pathogenesis remains unknown.Some of the immunological factors involved have beenelucidated4-7 and no infective agents (bacteria, viruses,or mycoplasmas) have been consistently found.8-10Mycoplasmas may be candidates for this role becausethey are associated with chronic arthritis in mammalsand birds,11 they can persist in tissues for long periodswithout being eliminated by host defences, 12 13 and theycan elicit an immune response that results in joint-tissuedamage. The role of mycoplasmas in human arthritideshas been doubted8 11 14 because the organism has notbeen consistently isolated.

This report describes the course of polyarthritis in apatient with congenital agammaglobulinx-mia, its rela-tion to diagnosis, and treatment of infection due toUreaplasma urealyticum.

Case-reportA 10-year-old boy with congenital agammaglobulinaemia

presented with a 3-week history of pain and swelling in the lefthand while on gammaglobulin replacement therapy. A pre-vious arthritis of the knee had responded to resumption ofgammaglobulin therapy which had been temporarily discon-tinued. His history included episodes of conjunctivitis (culturesfor viruses and bacteria were negative) and bronchopneumonia(cultures’ for bacteria and Mycoplasma pneumonice were nega-tive).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

Fig. 1—Clinical course of polyarthritis.’Culture for U. urealyticum not done. Specimens were negative for

large-colony mycoplasmas.


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