Results of 12 years' treatment of chronic renal failure by dialysis and transplantation J.D.E. PRICE, B SC, MD, CM, FRCP[C], FACP; K.M. ASHBY, B Sc; CE. REEVE, BA, MD, CM, FRCP[C]

The survival of 305 patients with chronic renal failure treated at the Vancouver General Hospital by centre and home peritoneal dialysis, centre and home hemodlalysis and cadaver renal transplantation over a 12.year period was analysed. There was decreasing survival with age except in patients undergoing home dialysis. Hypertension and analgesic nephropathy as primary causes of renal disease were associated with a poor prognosis. Hence age and diagnosis appear to be two of the main determinants of survival. Cardiovascular disease was the commonest cause of death but seven deaths were due to dialysis dementia. The results compare favourably with other published statistics. On analyse Ia survie de 305 patients souffrant d'insuffisance r6nale chronique trait6s sur une p6riode de 12 ans au Vancouver General Hospital par dialyse p6riton6ale au centre de dialyse ou & domicile, par h6modialyse au centre de dialyse ou a domicile ou par greffe de rein d'origine cadav.rique. On a constat6 une diminution de Ia survie avec l'ige, sauf pour les patients sous dialyse a domicile. L'hypertension et Ia n6phropathle aux analg6siques comme causes primaires des maladies r.nales 6taient associ6es & un mauvais pronostic. L'ige et le diagnostic semblent donc itre deux des principaux facteurs d6terminants de Ia survie. Les maladies cardiovasculaires ont et6 les causes de deces les plus fr6quentes, mais sept d6c&s sont attribuables & une d6mence secondaire & la dialyse. Ces r.sultats se comparent favorablement avec d'autres statistiques deja publl6es. Treatment of chronic renal failure by means of dialysis was started at the Vancouver General Hospital in 1964 with the institution of both peritoneal dialysis and hemodialysis. Transplantation was started in 1968, home hemodialysis in 1969 and home peritoneal dialysis in 1971. The philosophy of our unit is to try to give the patient the form of therapy most appropriate for him or her; therefore the dialysis and transplantation programs are closely integrated and patients move freely from From the department of medicine, University of British Columbia and the Vancouver General Hospital Reprint requests to: Dr. J.D.E. Price, do G.E. Strong Laboratory, Vancouver General Hospital, 855 w 12th Ave., Vancouver, BC V5Z 1M9

one mode of treatment to another. The availability of all modalities of treatment at one centre provides a good opportunity to compare the results of the different types of therapy. In this paper we report our analysis of the survival of patients in our dialysis and transplantation programs over a 12-year period. (Data for limited care dialysis, begun in 1976, are not included.) Methods The records of all patients who underwent dialysis or received a transplant between November 1964 and November 1976 were reviewed. The following criteria were established for inclusion in or exclusion from the study. 1. All patients with established chronic renal failure in whom dialysis was begun with a view to its being long-term therapy were included. Excluded were patients with acute or chronic renal failure who received dialysis temporarily while being assessed for the correct diagnosis or medical suitability and did not subsequently enter a long-term program of dialysis (e.g., a patient with disseminated carcinoma and renal failure would be excluded). 2. Patients transferred from another centre and already undergoing therapy were not included until they started to receive a new mode of therapy at the Vancouver General Hospital. At that point they were included as new patients (e.g., a patient transferred to the Vancouver General Hospital who was undergoing centre hemodialysis would not be included until he received a transplant or began another form of dialysis). 3. For the first 2 years of the program, only patients between the ages of 12 and 50 years were selected for treatment. Since then there have been no age limitations for dialysis but transplantation has rarely been performed in patients over 50 years of age. 4. Only data for the first cadaver transplant received by each patient at the Vancouver General Hospital are included in the statistics since the numbers were insufficient for analysis of second or third cadaver transplants or transplants from living donors. 5. Among patients returning to a given form of therapy after receiving another type of treatment the data for the second or subsequent period of the first type of therapy were excluded (e.g., if a patient had been receiving

centre hemodialysis, then underwent home hemodialysis and finally resumed centre hemodialysis the data for the second course of centre hemodialysis would be excluded from analysis, but the data for the first course of centre hemodialysis and the course of home hemodialysis would be included). However, data for all patients, including those who received second or third cadaver transplants or transplants from living donors, as well as those receiving any type of treatment for the second or subsequent times, are included in the analysis of the overall results. 6. Patients were considered to have left any particular type of therapy upon death, transfer to another mode of treatment or withdrawal from therapy. Standard immunosuppressive therapy, consisting of irradiation and administration of azathioprine and prednisone, was given to all transplant recipients after the operation except in eight instances in which antilymphocyte globulin was given as part of the multicentre trial of the Medical Research Council of Canada. Analysis of results was performed by the life-table method with the use of an IBM-370 computer. Data were analysed for survival by increments in age of 5, 10, 15 and 20 years, as well as by sex, diagnosis, type of treatment and, for transplant recipients, graft survival. Only the results that showed significant (P < 0.05) differences are presented. Results The records of 305 patients, representing a total of 11 782 patient-treatment months, were analysed. There were 203 males and 102 females with a mean age of 37 years and 6 months (males, 38 years and 7 months; females, 35 years and 5 months) and an age range of 13 months to 70 years. Overall The results for all patients with all forms of therapy are shown by age group in Fig. 1. Of all the patients 50% survived for 5 years and 11 months, but among those over 50 years of age 50% survived for only 2 years and 8 months. Of those aged 36 to 50 years 50% survived for 5 years and 10 months, whereas of those aged 25 to 35 years 50% survived for 10 years and 5 months, and of those aged 0 to 19 years 60% were alive at 8 years. Survival according to diagnosis is

CMA JOURNAL/FEBRUARY 4, 1978/VOL. 118 263

Survival

RII ages

100 90 80 70 60 50

.. .g=g=g=g.*.*

40 30 20 10 0 1

90

2

3

4

5

6

9 10 11 12

7

8

a

Hypertesisian (23)

shown in Fig. 2. Although there is Cadaver transplantation little difference in the curves for gloThe results for 76 patients receiving merulonephritis, polycystic disease and their first cadaver transplant are given pyelonephritis, the prognosis was much worse for patients with hypertension in Fig. 6. The survival rates at 8 years were 63% for the patients and 37% and analgesic nephropathy. for the graft. There were no deaths in the group aged 19 years or less, although survival of the graft was not as good (only 10% were functioning 6 years after transplantation) as in the group aged 20 to 35 years, in which 83% of the patients were alive 8 years after transplantation and 60% of the grafts were functioning. In the group aged 36 to 50 years the number of patients was insufficient for accurate analysis 3 years after transplantation; however, at 3 years, 51 % of the patients were alive and 38% of the grafts were functioning. Only one death occurred among the 20 patients in the age group 20 to 35 years; the patient died from surgical complications in the first month after transplantation. No rejection or mishaps occurred in this age group up to 8 years after transplantation. Causes of death A total of 113 patients died during the 12 years (Fig. 7). The most frequent cause of death was cardiovascular disease and the second most common cause was infection; however, 57% of the deaths due to infection were in transplant patients. No particular organism predominated. In the third largest group of patients who died the cause was unknown; while most of these deaths were likely due to hyperSurvival

FIG. 10 1 12 1

2

3

4

5 6 7 8 Graft Survival

9 10 11 12

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. 20 0 0 0

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and a 4-year survival of 80%, compared with 79% and 63%, respectively, for our series. Comparison of our data with those from the European Dialysis and Transplantation Association2 shows better patient survival in our series for those receiving centre hemodialysis and for those receiving a transplant. Of significance is the poorer survival of patients receiving home hemodialysi. in our series (Fig. 5) as compared with others2'3 and the fact that only 50% of patients continued with home hemodialysis after 3 years and 2 months (Fig. 5). It appears that the reason for the poor survival and the failure to continue with home hemodialysis is related to the long distances (up to 1600 kin) between the centre and the homes of the patients and to the poor support facilities for patients at home. The latter situation is being remedied and it is hoped that the provision of sufficient nurses, technicians and other paramedical personnel for frequent visits to the patients' homes will improve the rates. In our province the salary of one nurse could be provided from the difference in cost between centre and home hemodialysis for one patient for 1 year. There are two reasons for the poor survival of patients in our series undergoing peritoneal dialysis. First, all patients entering our program begin with peritoneal dialysis unless a recent abdominal operation, peritonitis or atdominal adhesions preclude it. This virtually prevents the development of dialysis disequilibrium, which is not uncommon when the patient's initial therapy is hemodialysis. It also enables us to assess the patient's medical and psychologic responses to the rigors of dialysis; this is particularly important in patients who have been

40

lii\

IN

III 141

referred for dialysis because of uremic coma or precoma and have never been seen by a nepbrologist. Hence patients who do not do well with the dialysis regimen or have some other medical condition that would shorten their survival without uremia tend to continue receiving peritoneal dialysis, which accentuates the mortality. Second, patients suitable for hemodialysis (centre or home) or transplantation are transferred from peritoneal dialysis within 12 months of its commencement. Since the life-table method of analysis assumes that the mortality of those withdrawn from therapy is the same as those continuing with it,4 and since patients withdrawn from therapy (and transferred to another form of therapy) tend to be those with a better prognosis, an obvious bias against pentoneal dialysis is introduced into the statistical analysis. There were insufficient numbers of patients receiving peritoneal dialysis at home for statistical analysis. Early results suggest a better prognosis in the patients aged 35 years or less, but the number of patients in this group who had received prolonged penitoneal dialysis is also insufficient for statistical analysis. Of interest is the comparison of survival by diagnosis (Fig. 2). The patients with hypertension were those presenting with malignant hypertension for whom no antecedent renal disease could be found. While the number of them after 2 years makes any conclusions questionable, there appears to be little doubt that, initially at least, they have a prognosis as poor as those with analgesic nephropathy. This is probably related to their generalized vascular disease. We believe that the poor prognosis in patients with analgesic nephropathy is due to the basic personality defect in these patients that leads them to abuse analgesics and that makes most of them unable to adapt psychologically to the rigors of dialysis. Many of our patients continued to take analgesics, which caused them at times to have a low serum bicarbonate concentration at the start of dialysis and an elevated blood salicylate concentration. It is not unusual to find serum bicarbonate concentrations as low as 11 mmol/L. From our life-table analysis of survival data by 5-year increments we found that a significant change in survival occurred after age 35 years when we considered all types of therapy together (Fig. 1), centre hemodialysis alone (Fig. 4) and cadaver transplantation alone (Fig. 6). Not enough patients had received peritoneal dialysis for long enough in each age group to permit complete analysis, but at 3 years the survival in the age group 20 to 35

years was 93.0% ± 4.1% and in the age group 36 to 50 years it was 41.2% ± 23.0% (Fig. 3). With home hemodialysis (Fig. 5) there was no difference in survival between those aged 20 to 35 years and those aged 36 to 50 years. However, those over 50 years of age had a poor survival. The poor prognosis in general for the patients in the oldest group was related to the high prevalence of cardiovascular and cerebrovascular disease in this group, as others have noted.5'.8 The transplant data (Fig. 6) showed that, although patient survival in the age group 0 to 19 years was better than that in the age group 20 to 35 years, graft survival was much worse in the younger group. We have been unable to find an explanation for this, although the numbers in the younger group may have been insufficient to give us a true picture. Decreased survival in transplant recipients over 35 years of age was reported recently by Simmons and colleagues.9 In addition, analysis of survival in our series in the age groups 20 to 35 years and 36 to 50 years showed little difference in prognosis between the various types of treatment in the younger group, but much worse results with transplantation in the older group. It therefore seems imperative to examine survival in relation to age as well as type of treatment before any recommendations can be made concerning the best form of therapy for any individual patient when first seen. We thank Mr. Michael Perlman for invaluable and considerable help in annotating the data and programming it for the computer, Drs. H.S. Ballon, E.G. Cameron, R.W. Lauener, D.S. Lirenman and M.V. Moriarty for allowing us to include their patients in the analysis, and Mrs. Gwen Mason for typing the manuscript. References 1. MATHEW TH, MARSHALL VC, VIERAMAN P. et al: Integrated programme of dialysis and renal transplantation: results in 155 patients. Lancet 2: 137, 1975 2. PARSONS FM, BRUNNER FP, BTIRCH HG, et

3. 4. 5. 6. 7.

al: Fourth combined report of the European Dialysis and Transplant Association. Proc Eur Dial Transplant Assoc 11: 3, 1975 BAILLOD RA, MOORHEAD JF: Review of ten years' home dialysis. Ibid, p 68 CUTLER 5J, EDERER F: Maximum utilization of the life table method in analyzing survival. J Chronic Dis 8: 699, 1958 LINONER A, CHARRA B, 5HasuIAsD DJ, et al: Accelerated atherosclerosis in prolonged maintenance dialysis. N Engl J Med 290: 697, 1974 LINDNER A, CuRTIs K: Morbidity and mortality associated with long term hemodialysis. Hosp Prac 9: 143, Nov 1974 PENDRAS JP, POLLARD TL: Eight years' ex-

perience with a community dialysis center;. the Northwest Kidney Center. Trans Am Soc

Artif Intern Organs 16: 77, 1970 8. SAMUEL5 5, CHARRA B, OLHEIsRR K, et al: Twelve years' experience of treatment of chronic renal failure. Trans Am Soc Artil Intern Organs 20: 62, 1974 9. Sirvs.o.s RL, THOMPSON EJ, YuNIs EJ, et al: 115 patients with first cadaver kidney transplants followed two to seven and a half years. A multifactorial analysis. Am I Med 62: 234, 1977

266 CMA JOURNAL/FEBRUARY 4, 1978/VOL. 118

SEPYRA Clinical update in pediatric infections

In a recent multiclinic study conducted in Montreal, Lethbridge, and Moncton, Septra proved equal to ampicillin in clinical efficacy, and caused notably few undesirable side effects1 Therapeutic outcome after one week of therapy in 79 children with acute otitis media

Maximum improvementt Minimtm improvementl: No change

Septra Ampicillin (74 tars) (77 tars) 57% 59% 34% 36% 9% 4%

tcomplete clearing of localized signs; no subjective complaints tparnial improvement of drtm inflammation; no systfmic signs, hut usually some residual hearing loss . SEPTRA Rn Summary (Trimethuprim + Sulfamethunazule) INDICATIONS AND CLINICAL USES: Indicated fur the fulluwing infectiuns when caused by susceptible nrganisms: URINARY TRACT INFECTIONS - acute, recurrent and chrunic. GENITAL TRACT INFECTIONS - uncumplicated gunocuccal urethritis.

UPPER AND LOWER RESPIRATORY TRACT INFECTIONS - particularty chrnnic brnnchitis and acute and chrunic ntif is media

GASTROINTESTINAL TRACT INFECTIONS. SkIN AND SOFT TISSUE INFECTIONS. SEPTRA is nut indicated in infections caused by Pseudumonas, Mycvplasma or viruses This drug has nut yet been fully evaluated in streptococcal infect iuns. CONTRAINDICATIONS: Patients with evidence nf marked liver parenchymal damage, blond dyscrasias, knnwn hypersensitivity In trimethuprim ur sulfonamides, marked renal impairment where repeated serum assays cannut be carried nut; premature or newbnrn babies during the first few weeks uf life. Fur the time being SEPTRA is cuntraindicated during pregnancy, If pregnancy cannut he excluded, the possible risks shuuld by balanced against the enpected therapeutic efect. PRECAUTIONS: As with other sulfonamide preparations, critical appraisal of benefit versus risk should be made in patients with liver damage. renal damage, urinary vbstructiun, blond dyscrasias, allergies or bronchial asthma. The pussibility of a superinfoction with a nun-sensitive organism should be borne in mind. DOSAGE AND ADMINISTRATION: Adults and children over 12 years Standard dosage: Two Septra tablets or one Seplra OS tahIet twice daily (murning and eveningl. Minimum dosage and dusage for lung-term treatment: One Septra tablet or one-half Seplra OS tablet twice daily. Maximum dusage: Overwhelming infections: Three Septra tablets or one and one-half Septra OS tablets twice daily. Uncomplicated gonorrhea: Two Septra tablets or one Septra OS tablet four times daily for 2 days. children iz years and under.t Young children should receive a dose according to biolugical age children under 2 years 2.5 ml pediatric suspension twice daily Children 210 5 years One to Iwo pediatric tablets or 2510 5 ml pediatric suspension twice daily Children 610 12 years: Two to four pediatric tablets or 510 10 ml pediatric suspension or one adult tablet twice daily. (Septra OS tablets should not be used for children under 12 years) tIn children this currespunds to an approximate dose of 6 mg trimethoprim/kg body weight/day, plus 30 mg sulfametbuxazole/kg body weight/day, divided into two equal doses. DOSAGE FORMS: SEPTRA TABLETS, each containing 00 mg trimethupnim and 400 mg sutfamethooazule, and cuded WELICOME Y2B. Bottles of 100 and 500, and unit dose packs of 100. SEPTRA OS TABLETS, each containing 160 mg trimethuprim and 000 mg sulfamethoxazxlo, and cuded WEILCOME 02C. Bottles of 50 and 250. SEPTRA PEOIATBIC SUSPENSION, each teaspoonful (5 ml) containing 40 mg trimethoprim and 200mg suttamethxxazole. Bottles of 100 and 400 ml. SEPTRA PEDIATRIC TABLETS, each containing 20mg Irimothoprim and 100 mg sultamefhuxazule, and coded WELICOME H4B. Bottles xl 100. Pruduct monograph available on request.

REFERENCE: 1. Cameron G.G., Pomahac A.C., Johnston MT.: Canad MedAss J 112 (Special Issue): 87,1975.

. Burroughs Welicome Ltd. LaSalle, Quo. .Trade Mark

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W-6021

Results of 12 years' treatment of chronic renal failure by dialysis and transplantation.

Results of 12 years' treatment of chronic renal failure by dialysis and transplantation J.D.E. PRICE, B SC, MD, CM, FRCP[C], FACP; K.M. ASHBY, B Sc; C...
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