Genesis of Analgesic Nephropathy in the United Kingdom

Kidney International, Vol. 13 (1978), pp. 50-57

Genesis of analgesic nephropathy in the United Kingdom

ROBIN M. MURRAY

Laboratory of Clinical Science, Clinical Neuropharmacology, National Institutes of Health Clinical Center, Bethesda, Maryland

Variations in the frequency of analgesic nephro- of the large number of analgesics available, only six pathy within Britain. British physicians were slow to preparations (all compound analgesics) were incrimi- appreciate the existence of analgesic-induced renal nated by more than one unit. The preparations disease, and the first case was not recorded until blamed most often varied throughout the country, 1964 [1]. Thereafter, although the disorder was and clearly paralleled the regional analgesic prefer- increasingly recognized in Britain, there was a strik- ences of the general population established in a sur- ing variation in the geographic distribution of the vey by National Opinion Polls [22]. Scots, in gener- cases reported. By 1972, a total of 225 cases had al, do not consume more analgesics than other been reported [2—191; 169 of these had come from Britons [22], and the per capita consumption of Scotland [13—191, with 70% from the Glasgow area phenacetin in Soctland is similar to that in England [16—191. In an effort to establish whether this was a and Wales [10, 231. I therefore concluded that the true reflection of the prevalence of the condition, or reason why analgesic nephropathy is more common an aberration due to the interest of Scottish physi- in Western Scotland must lie either with the particu- cians in it, I sent a questionnaire to the major renal lar preparations taken or the manner in which they units throughout Britain regarding their experience are consumed. of analgesic nephropathy. The replies demonstrated Use and abuse of analgesics by different popula- that there was considerable variation, with the few- tion within Glasgow. In Western Scotland, three est cases seen in the Midlands and North-West quarters of cases of analgesic nephropathy result England, more in Newcastle and London, but most from a compound analgesic powder called Askit® in Glasgow (Fig. 1) [20]. [181, this formerly contained aspirin, phenacetin, Confirmation of this came from two other sources. and caffeine, but the phenacetin has now been with- In 1970, Kontsaimanis and de Wardener [10] esti- drawn. Askit is manufactured in Glasgow, and 95% mated that the annual incidence of new cases in of their sales are in Scotland. Since there was no England and Wales was at least 450; this was based evidence that they were more nephrotoxic than other on the number of new cases referred to Charing analgesics, I decided to examine the possibility that Cross Hospital each year. A similar calculation they were more habit-forming. The analgesic habits based on new cases seen at Western Infirmary, Glas- of two different populations were studied. The first gow, produced an incidence four times the English was a series of 211 patients admitted to a medical one. This increased frequency in the Glasgow area unit of a Glasgow hospital. The results [24] demon- does not seem to hold for the rest of Scotland. While strated a clear relation between the frequency of 25.5% of patients admitted to the renal unit of the analgesic ingestion and the preparation taken. Aspi- Western Infirmary with chronic renal failure had rin was the most popular preparation among patients analgesic nephropathy, a survey by Pendreigh et a! who rarely took analgesics, but its popularity [211 revealed that analgesic nephropathy accounted declined among those taking analgesics daily without for only 4.8% of all cases of end-stage renal failure in medical advice. On the other hand, Askit® (which Scottish adults. had 22% of the Scottish market) was taken by only A second part of my survey concerned the analge- 17 out of the 104 who took analgesics less than sics implicated in causing the renal damage. In spite weekly, but it was taken by 10 of the 21 who took daily analgesics without medical advice; this differ- 0085-2538/78/00l3-0050$0l .60 ence was statistically significant (X2 =10.3;P < © 1978, by the International Society of Nephrology. 0.01).

50 GLASGOw WESTERN (>I Ask >Cod

GLASGOW STOBHILL (5- Ask >Be

NEWCASTLE (4-6) Cod An

.WESTMINSTER (2) Cod >A.P.C. .ST. MARY'S (<1) A.P.C. CHARING X(4) Cod H. (<1) PONTYPRIDD An >Phen 'S (6) Cod >Phen CARDIFF (2- Cod Phen ST. THOMAS'S (5-10) Cod> An BRISTOL (2 Cod> A. P.C. iHAMMERSMITH (2) Cod >An Fig. 1. Geographic distribution of analgesic nephropathy cases reported within Britain. The number of cases seen per year are shown in brackets. Abbreviations used are A.P.C. = aspirin,phenacetin, caffeine; An =Anadin;Ask =Askit;Be =Beechams;Cod =Tabs. Codeine Co. or Veganin; Phen =Phensic.(Reprinted from Health Bulletin [20] by permission of the Controller, Her Majesty's Stationery Office.)

The patients were also asked about various indica- reason for taking the drugs. On the other hand, daily tions for taking analgesics and which preparation analgesic self-medication was most common in wom- would be most effective for different indications (Fig. en in their thirties and forties who belonged to the 2). Most believed that the drugs would be of value for lower social classes. These self-medicators were headaches (91%), colds (79%), pain (68%), and peri- more likely to take Askit® powders than other prepa- od pains (69%). A smaller proportion thought they rations, and rarely had organic pain. Comparing would be helpful for nerve pains (48%), as a sedative medical patients who provided themselves daily (35%),anda hypnotic (32%), and fewer still as a analgesics with those who took them less than week- stimulant (18%). Different drugs were valued for ly revealed that the former were significantly more different symptoms. Aspirin and paracetomol were likely to have seen a psychiatrist (X2 =9.1;P < considered most useful for pain and headache, while 0.01). codeine compound (aspirin, phenacetin, and cod- An obvious step was to compare the frequency of eine) was the preparation of choice for insomnia; analgesic-taking among these two groups with that of Askit®, only one third as popular as aspirin for pain, psychiatric patients. A survey of patients admitted to was the most valued drug for nerve pains, period a local psychiatric hospital had been previously car- pains, sedation, and stimulation. Thus, the two prep- ried out [17]. Whereas only 5%ofthe general public arations most associated with analgesic nephropathy and 17% of medical patients admitted taking daily in Britain (Askit® and compound codeine [201) were analgesics, 23% of the psychiatric patients did so. particularly valued for inappropriate reasons. The latter were almost exclusively taking the drugs This study and a subsequent community survey of for nonorganic reasons, and their psychiatrists were 740 Glasgow citizens [251 demonstrated that those only rarely aware of the analgesic consumption; taking regular prescribed analgesics and those on women with reactive depression, chronic neurosis, daily self-medication formed two distinct groups: and inadequate personality appeared especially most of the former were over 60 years old, the sex prone to take large amounts. Further enquiry in that distribution was almost equal, and all had an organic hospital revealed that the staff were aware of 22 52 Murray

90 —

70 — All 0 analgesics a,

a, 50 — Q'

C a, a 0 30 - Aspirin

10 -

Pain Headache Nerve Period Colds Insomnia Agitased Depressed pains pains (2)

Fig.2. Reasons jhr taking anolgesics and preference of preparation reported by patients in Glasgow. other patients who had abused analgesics. The blood The ingestion of at least one gram of analgesic daily urea concentration was known to have been elevated for three years and the total consumption of a mini- in 14 of their patients, and four had died in chronic mum of 3 kg of aspirin or phenacetin, 2) the exclu- renal failure. Eight had undergone gastric surgery, sion of any other cause of renal disease, 3) creatinine and a further seven had been investigated for gas- clearance of 75 ml/min or less. trointestinal bleeding or peptic ulceration. During the three-year period, 51 patients met these criteria. A detailed psychological and social history A psychosocial study of patients with analgesic was obtained from these 51 patients, and information nephropathy regarding demographic details, analgesic habits, Many physicians [13, 20—281 have noted that their medical and psychiatric history, and personal and patients with analgesic nephropathy seldom had an family history was recorded in a standardized form. organic reason for taking the drugs, and have com- Wherever possible, relatives were also interviewed, mented on the frequency of psychiatric disorder [25, and case histories from other hospitals were 27, 29—311. But, in spite of the vast number of scrutinized. reports of analgesic nephropathy, there had been For the purposes of analysis of these data, the little research into its psychological and social patients were compared with 51 controls who were origins. I, therefore, determined to carry out such an interviewed in a similar fashion. These were selected investigation [32,331. from over 300 consecutive medical admissions on the The study included all patients with analgesic basis that they matched the patients for age and sex nephropathy attending the renal unit of the Western and did not take daily analgesics. Infirmary, Glasgow, between 1969 and 1971. For The ages of the 51 patients ranged from 27 to 72, such a diagnosis, three conditions had to be met: 1) with a mean SD of 52.2 10.5 yr, and females Genesis of analgesic nephropathy 53 predominated over males in the ratio of 4.1 to 1. Men that they only took the drugs for pain. Most patients presented at a significantly older age (t =2.32;P < had absolute faith in the efficacy of their favorite 0.0125) than women (mean ages, 58.9 and 50.6 yr, preparation, and would go to great lengths to obtain respectively). it. One chemist stated that, when supplies of a Renal papillary necrosis was demonstrated radio- patient's favorite powder ran out "she would get like logically or histologically in 37 patients, and the clini- a wreck," while one man described his wife as "like cal picture in the remaining 14 was typical of analge- a mad thing without a Beechams." sic-induced renal disease. There were 20 patients Reluctance to admit analgesic-taking. Few with hypertension, and the average creatinine clear- patients volunteered information about their analge- ance was 26 milmin. Nine had undergone gastric sic habits, and 19 denied analgesic consumption—in surgery, and 27 were anemic. These physical fea- some cases even after analgesic nephropathy had tures have been described in detail elsewhere [18, been proven radiologically. Patients universally min- 34]. imized the extent and duration of their analgesic Analgesic habits. Forty-five of the patients were intake. Although in a few cases analgesic taking had taking either Askit® powders or compound codeine been concealed even from spouses, relatives' esti- tablets. Apart from one patient who took simple mates of the analgesic intake were usually more aspirin, all the rest had taken preparations which accurate and were often three or four times higher contained at least two analgesics (usually aspirin and than the patients' estimates. This reluctance to admit phenacetin) plus at least one other centrally acting analgesic ingestion had often led to misdiagnosis. drug (codeine, caffeine, or bromide). Women were Patients had commonly been investigated for renal significantly more likely (X2 =4.6;P <0.05) to take disease, anemia, and peptic ulcer. Seldom, however, Askit® than men (31 out of 41, compared with 4 out had the history of analgesic ingestion been elicited; of 10). its causative role had not been appreciated, and renal The intake the patients admitted varied from two function had continued to deteriorate. to more than 15 preparations daily, and the duration At least 31 patients had continued their analgesic of ingestion from 4 to 45 years (average of six daily habit against family opposition. In some cases the for 20 years). Thirty-one patients had begun their family had hidden or destroyed the analgesics, and in analgesic consumption before 30, and 16 before 20 a few the patients were not given sufficient money to years of age. The approximate total dose admitted buy the drugs. Family opinions ranged from "she ranged from 4 kg of aspirin and 3 kg of phenacetin to seems to need them" to "she's an addict" or "she's 69 kg of aspirin and 51 kg of phenacetin (average of doped silly with Askit." 19 kg of aspirin and 14 kg of phenacetin). None of the patients obtained their drugs on pre- Stated reasons for analgesic taking. Twenty-four scription, and few of their doctors were aware of the patients recognized that they took the analgesics abuse. The analgesics were usually bought in gro- believing that they had mood-altering properties. Six cers' or corner shops rather than chemists' shops. patients believed that they were stimulating—"they Some shopkeepers continued supplying the drugs give me a lift"—while nine took them for sedation. although they realized the patients were habituated, Four patients thought the drugs had both these quali- but others had refused the patients further analge- ties—"Codeine perked me up and made me cal- sics. To circumvent this, some patients sent relatives mer' '—while a further five were unable to exactly or children to get them. describe their reason—"an Askit is heaven, Doc- Social characteristics. All the patients were Scot- tor." Sedative or stimulating properties were not tish, and their religious persuasion and civil status particularly attributed to any one preparation. did not differ from that of the controls or the general Twenty-two patients claimed that they took the population. Both patients and controls were predom- analgesics for headaches. These were usually inantly from the lower social classes, but significant- described as being like a pressure or vague fullness ly more of the patients had ceased their education at and were often precipitated by emotional stress. the minimum school-leaving age (X2 =4.05;P < Some of these patients realized that the analgesics 0.05). not only relieved their pain but also gave them a Only 15 patients were working; 21 women had feeling of wellbeing. Only two had an organic reason stopped working for normal social reasons, five for taking the drugs (arthritis), and both of these also because of psychiatric and two because of physical benefitted psychologically. illness. Of the ten men, three had retired, four were In all, 39 patients believed that their analgesic incapable of working because of psychiatric abnor- ingestion had "become a habit," while 12 maintained mality, and one because of physical illness. None of 54 Murray the patients had a profession. The women had Daily purgative-taking was much more common worked mainly as shop assistants, office, and factory among the patients than the controls (X2 =11.9;P < workers, while the men's occupations simply reflect- 0.001),and was particularly common among those ed the local patterns of employment. The totally taking compound codeine tablets (5 out of 10). unskilled were less likely to he working (X2 =6.8;P Patients not only smoked more frequently than con- <0.01). trols (X2 =5.2;P <0.05), but were also more prone Family history. Patients were much more likely to smoke more than 20 cigarettes a day (X2 =10.9;P than controls (X2 =14.7;P <0.001) to give a history <0.001). that another member of the family had abused anal- Dependence on analgesics. Thus, patients with gesics. Twenty-two patients gave such a history, and analgesic nephropathy take analgesics for inappro- in six cases more than one relative was said to have priate reasons. Drug abuse is defined [35] as "the abused the drugs. Of the 29 affected relatives, 11 consumption of a drug apart from medical need or in were the mothers and five the sisters of the patients, unnecessary quantities," and clearly my patients' and 11 were known to have analgesic-induced use of analgesics falls into this category. These disease. patients seldom volunteered information about their Patients were also much more likely (X2 =16.7;P drug habits, and in many cases persistently denied <0.001) to volunteer that a relative abused alcohol. analgesic abuse. Assessment of analgesic consump- This was particularly common among the families of tion, therefore, required an oblique approach via women patients, 21 of whom gave such a history headaches or other symptoms, and frequently fur- compared with only one man (X2 =5.6;P <0.05). ther evidence had to be sought from relatives. Fur- In 18 cases, the relative's history was suggestive of thermore, for at least 20 of the patients, knowledge alcoholism, and in four of a severe alcohol problem; of the consequences of analgesic abuse was no deter- fathers and husbands were especially affected. rent to continued consumption. A family history of psychiatric disorder was Thus, these patients exhibited many of the fea- obtained from 20 patients but only five controls; this tures of drug dependence, and, indeed, several phy- difference, too, is highly significant (X2 =11.9;P < sicians have remarked that they believed their 0.001).Although the exact diagnosis could seldom be patients were habituated or addicted [26, 28, 30, 36— established, 26 relatives were affected and four had 381. Although the World Health Organisation Expert committed suicide. Committee [39] did not consider the possibility of Personal history. Patients were much more likely dependence on minor analgesics, Wilson [40] has than controls to have had previous psychiatric treat- described this and has suggested that it is associated ment (X2 =18.8;P <0.001); 11 had had outpatient with psychic dependence, psychotoxicity, and possi- and 12 in-patient treatment, and 2 were long-term in- bly tolerance. patients. Neurotic and depressive reactions, person- My patients undoubtedly showed psychic depen- ality disorder, and anxiety states were the main diag- dence in that they had "a psychic drive for continu- noses that had been ascribed to them. Three had ous .. . administrationof the drug" [41]. Most had been treated for alcoholism or drug addiction. begun taking the analgesic for pain, but the depen- All but five of the remainder had attended their dence resulted from appreciation of effects other own doctors for nervous disorder, and only two were than the analgesic action. The amounts of caffeine psychologically normal. Again, neuroses and person- which the patients were taking would have a marked ality disorder of an inadequate nature were the rule. stimulating effect [42], and Driesbach and Pfeiffer Two-thirds had chronic insomnia, and seven had [43] have shown that the caffeine withdrawal head- previously attempted suicide. There was no relation ache, by causing further analgesic consumption, pro- between the severity of physical disease and psychi- vides "a plausible explanation for the hitherto empir- atric morbidity. ical addition of caffeine to many headache Psychotropic drugs had been taken in the previous mixtures." In addition, phenacetin has mild anxioly- three years by 47 of the patients, compared with only tic properties [44—46] and many people find it plea- 14 of the controls; this difference is highly significant surable [45], while the dependence-producing quali- (X2 =41;P <0.001). The majority had been taking ties of codeine are well known [47]. Thus, the hypnotics, but 35 had also received tranquillizers, patients' dependence can be largely attributed to the and 12, antidepressants. Six patients had abused psychoactivity of the analgesic mixtures, in which tranquillizers; four, alcohol; two, amphetamines; and the psychotropic effects of the constituents are 2, opiates. potentiated [45, 48, 49]. Nevertheless, one must also Genesis of analgesic nephropathy 55 consider the role of the extensive advertising of pro- [25, 30, 51, 531, abuse of other drugs [25, 31, 51], and prietary analgesics for neurotic complaints in rein- excessive smoking [25, 31, 371 has been previously forcing the dependence. noted; in addition, my patients often abused purga- There was, too, a tendency to increase the dose tives. There can therefore be little doubt that they taken, which was augmented by symptoms of anal- were dependence-prone. gesic intoxication, caffeine withdrawal, and eventu- ally uremia. Thus, the drugs were taken for symp- Predisposing personality factors toms which they themselves had caused, and a In an effort to further define the predisposing fac- vicious circle of decreasing health and increasing tors, I administered the Eysenck Personality Inven- intake of analgesics was set up. tory (EPI) to 45 of the patients [541. This is a 57-item Several authors 1129, 50] have noted the familial questionnaire designed to measure neuroticism (N) occurrence of analgesic nephropathy. That 43 per- and extraversion-introversion (F), and also contains cent of my patients had a relative who also abused a short lie scale (L). The reliability and validity of analgesics suggests that the disorder stems from these scales is well established [55]. abnormal attitudes to analgesics which are often fam- The EPI was also administered to two control ily transmitted, particularly by mothers introducing groups. The first consisted of 33 patients consecu- their children to excessive analgesic taking. tively seen at the renal unit with renal disease of The patients had often suffered parental depriva- severity comparable with those with analgesic tion or unhappy childhoods, and although they did nephropathy but not due to analgesic abuse. The not have the high divorce rate which others have second control group consisted of 20 patients, seen noted [27, 37], over half were unhappily married. by the author, who abused analgesics but who did Sexual difficulties and heavy drinking by husbands not have renal disease. were major causes of marital discord. Among single Of the 45 patients, 30 scored as introverted and women, two-thirds of whom were socially isolated, neurotic, six as extraverted and neurotic, five as loneliness was an important factor. Stressfull events introverted and stable, and four as extraverted and were often important in starting and perpetuating stable. The mean E score SD of the patients was analgesic abuse. 9.073.89 compared with an expected 12.074.37 The majority of my patients showed evidence of for normals. The mean N score SD of the patients either personality disorder of an inadequate nature or was 14.495.52, as against an expected 9.07 4.78. proneness to neurotic breakdown. To my knowl- The renal controls were more extraverted and less edge, there has been only one previous study of neurotic than the patients. The differences in both E psychosocial factors in analgesic nephropathy 1130], and N were fairly significant (P < 0.05). The 20 but many physicians have commented on the fre- analgesic controls were significantly more introvert- quency of psychiatric disorder in their patients. In ed than the patients (P <0.01). They also tended to particular, Gault et al [271 noted "emotional instabil- be more neurotic, but this difference failed to reach ity of an immature and dependent nature," while significance. L scores of the control groups were Gsell, Dubach, and Raillard-Peucker [51] believed similar to those of the patients. that "a depressive syndrome and temperamental Patients with analgesic nephropathy appear highly instability were the most common expressions," and introverted and neurotic. Have these traits contribut- Whitlock and Lowrey [521 concluded that analgesic ed to their analgesic abuse or are they merely the abusers often "showed features of personality consequence of their illness? There are two possible disorder." reasons why the latter might be the case. First, these My patients' frequent previous hospital atten- patients suffer from a chronic illness which restricts dances and their unnecessary gynecological investi- their lives and requires regular medical supervision. gations were a reflection of their hypochondriacal This might increase introversion and neuroticism. and pain-prone personalities, and their tendency, Second, uremia might, by a direct cerebral effect, possibly because of limited intelligence, to somatize exaggerate these traits. emotional conflict. Because of the frequency of One can exclude the second possibility, as there attempted suicide, there have been suggestions that was no relation between the EPI scores of either the patients with analgesic nephropathy wish to harm patients or the renal controls and uremia. If low E themselves. This seems unlikely, as before their ini- and high N were the result of chronic illness, the tial presentation they were seldom aware of the dan- renal controls ought to have had similar scores. But, gers of analgesic abuse. The frequency of alcoholism although the latter were mildly introverted and neu- 56 Murray

rotic, they were significantly less so than the they contain more caffeine and in their presentation patients. Thus, it seems that chronic renal disease as powders. Surveys of different populations in Glas- does have some effect on E and N, hut this is insuffi- gow suggest that while aspirin and paracetamol tend cient to account for the scores of the patients with to be taken relatively infrequently and for appropri- analgesic nephropathy. ate reasons such as pain, Askit® is more likely to be Furthermore, analgesic abusers without renal taken with excessive frequency for its supposed impairment showed low E and high N scores. mood-altering properties. Working-class women Increased introversion and neuroticism must, there- with psychiatric problems are especially prone to fore, be related to analgesic abuse as either its cause daily self-medication. or result. It is theoretically possible that analgesic Study of individuals with analgesic nephropathy abuse might cause symptoms which could influence reveals that in Westem Scotland, at least, the cause an individual completing the EPI to score certain is dependence on analgesics. The characteristics of items positively. None of the usual manifestations of this include a need to continue taking and to slowly analgesic ingestion or intoxication, however, would increase the dose of analgesics, partly owing to toler- interfere in this way, so this explanation appears ance and partly to treat symptoms the analgesic unlikely. ingestion has caused, as well as a psychic depen- An individual's experience of pain and his reaction dence resulting from appreciation of the psychotrop- to it is influenced by a wide range of factors including ic effects of the compound analgesics. When com- his personality. Eysenck [56]hasshown that intro- pared with matched controls, those who develop the verts have lower pain thresholds than extraverts, "analgesic abuse syndrome" are more likely to have while Bond [57] noted that subjects with high N a family history of analgesic abuse, alcoholism, and tolerate pain badly. Thus, introverted neurotics psychiatric disorder. They tend to be introverted and would not only experience pain as more severe than neurotic, are prone to abuse other drugs and many normals, but they would be less able to tolerate it. have had previous psychiatric treatment. They would, therefore, have a strong incentive to take analgesics. Acknowledgments Bond believes that complaint behavior is related to The author is a Lilly International Fellow. extraversion-introversion, and that extraverts com- municate their symptoms freely while introverts tend Reprint requests to Dr. R. Murray, Maudsley Hospital, London to be "non-complainers." He has shown that intro- SE5 8A2, United Kingdom. verts with pain are less likely to ask nursing staff for analgesics than extraverts. Thus, introverted neurotics such as these patients would be reluctant to seek References analgesics from their doctors, and might instead 1. SANNERKIN NO, WEAVER CM: Chronic phenacetin nephro- resort to self-medication. pathy. BrMedJ 1:288, 1964 Introverts develop conditioned reflexes more easi- 2.BRowN AK, PELL-ILDERTON R: Phenacetin and the kidney. Lancet 2:121—123, 1964 ly than extraverts t1561, and would, therefore, more 3. JACOBS HS: Phenacetin abused. Br Mcdi 1:1381, 1964 readily associate the pleasurable mood-altering 4. BEALES SJ: Deaths from prolonged ingestion of phenacetin; effects of compound analgesics with the act of anal- Br Mcdi 2: 45—46, 1965 gesic-taking. They would become conditioned to the 5. KENNEDYA:Renal papillary necrosis and phenacetin: Two regular taking of analgesics more quickly, and high N further cases. Postgrad Mcdi 41: 498—500, 1965 would provide the drive to continue reinforcing the 6. SANNERKtN JO: Chronic phenacetin nephropathy. Br J Urol 38:361—370, 1966 analgesic ingestion. In short, subjects with the per- 7. DYER NH, LEE Fl: Phenacetin nephropathy in a patient with sonality traits shown by the patients with analgesic an ileostomy. Postgrad Mcdi 43:791—793, 1967 nephropathy would be most likely to prescribe them- 8. HULME B, JONES EL: Analgesic nephropathy. Postgrod Med selves regular analgesics and to persist until they i43:173—176, 1967 became dependent on the drugs. 9. BELL D, KERR DNS, SWINNEY J, YEATES WK: Analgesic nephropathy: Clinical course after withdrawal of phenacetin. Br Mcdi 3:378—382, 1969 Summary 10. KOUTSAIMANIS KG, DE WARDENER HE: Phenacetin nephro- Analgesic nephropathy is more common in West- pathy with particular reference to the effect of surgery. Br ern Scotland than elsewhere in the United Kingdom. Mcdi 4:131—134, 1970 11. SWEIT J: Analgesic nephropathy. Practitioner 205:195—198, This appears to be a consequence of the frequency 1970 with which local people take Askit®, a preparation 12. DAVIES DJ, KENNEDYA,ROBERTSC:The aetiology of renal different from most other British analgesics in that papillary necrosis. i Pathol 100:257—258, 1970 Genesis of analgesic nephropathy 57

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