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Genesis of Analgesic Nephropathy in the United Kingdom

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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, C C 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.
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