by Christopher Winearls – Consultant Nephrologist in the Oxford Kidney Unit 1988-2016
It was the summer of 1978 and I was the renal ward SHO. The registrar told me that he had accepted a patient from the Intensive Care Unit (then in the Radcliffe Infirmary) who had acute renal failure as a consequence of accelerated phase hypertension. She was 31 and had had high blood pressure since the age of 24 but no cause had been found. She had been admitted to the ICU with a blood pressure measured by an arterial line of 300/160 mmHg, papilloedema and retinal haemorrhages, and hypoxia from pulmonary oedema. She had been difficult to ventilate; pink froth had come up the endotracheal tube. The creatinine had risen to 800 µmols/L but she had not been dialysed. She came to the ward on a medley (more accurately a muddley) of drugs and was unable to stand up because of syncope. However, without the cocktail of methyldopa, minoxidil, hydralazine, furosemide and atenolol, her lying blood pressure was very high.
Dr John Ledingham, who had a special interest in hypertension, came to see her and I could tell that he had no immediate suggestions as to what we might do to get out of this bind. The patient remained in limbo on the ward and became exasperated, especially when the minoxidil started to cause hirsuitism and she became even more depressed on the methyldopa. She felt ghastly so my twice daily ward rounds caused me shame at my/our failure to resolve the problem. J Led as we called him, came back the next week for his Friday ward round and I presented the intractable problem to him again. Suddenly his eyes lit up and he said “What she needs is the new Squibb drug.” I had no idea what he was talking about. He announced confidently, “I am going to get some from one of my colleagues in London.” He phoned an eminent professor of clinical pharmacology who told him that under no circumstances could any of this new drug, which was still at the most preliminary stage of testing in patients, be released. So, unabashed he phoned the MRC High Blood Pressure unit in Glasgow and they gave him the same answer, “The drug is just not available for compassionate or named patient use.” However, they suggested that we could refer the patient to their unit but we would have to arrange the transfer to Glasgow.
John turned to me and said, “Could you get the patient on the London Heathrow to Glasgow shuttle? I have agreed with colleagues there that they will take her tomorrow morning and”, he said, “be a good chap and write a really first rate summary and transfer letter. I don’t want us to look amateur.” This was about 4.45pm on a Friday. I asked him whether he would mind phoning the House Governor to authorise the purchase of the air ticket and the ambulance to take her to Heathrow Airport. He did so. I made my way to the secretaries’ office to find that it was deserted, apart from the Home Dialysis Organiser. I begged her to type my summary. These were the days before word processors. She said she did not really take dictation but if I just spoke clearly and slowly she would type directly onto her IBM typewriter. Corrections would be difficult and Tippex would look messy. So my summary was prepared and the patient left for Glasgow the next morning. She returned about 3 weeks later with her blood pressure immaculately controlled on SQ14225 (captopril), later to be called CapotenR. I asked her to tell me what had happened in Glasgow. After she arrived she had heard doctors saying that the Oxford Unit just did not know how to manage difficult blood pressure. So they had stopped all the drugs that we had prescribed, which caused a sharp increase in her blood pressure. They started re-introducing them in various combinations but achieved no better control than we had. They admitted to her that they, too, were defeated and offered her a trial of SQ14225. The effect had been miraculous. The BP was < 130/80. She was left with significant chronic kidney injury but it was 10 years before she eventually reached end-stage renal failure and required dialysis. She was fortunate that continuous ambulatory peritoneal dialysis was by then an established treatment and within 6 months she had had a kidney transplant. In 1988 10 years after her first presentation I returned to Oxford as a consultant, and took over her long term follow up.
She would kindly let me tell recount her medical history to any medical students who happened to be in the clinic or chat to them herself. She had a marvellous story to tell, of keeping one step ahead of her illnesses and relying on clinical pharmacology to provide the solutions. She was rescued by the ACE inhibitor in 1978 and was fortunate to have 10 years without the need for renal replacement treatment before she progressed to requiring CAPD. She had her kidney transplant later that year, three years after ciclosporin was licensed, and this has kept her transplant functioning free of rejection for 25 years. She stayed on captopril 25 mg tds until 2014 when she was advised to switch to take a “more modern ACEI”.
Having met ACE inhibitors in so dramatic a way, I followed their development and application I learnt how the clue came from the venom of the Brazilian snake, Bathrops jararaca. This had been brought to Professor John Vane’s laboratory by Sergio Ferreira in the 1970s. It was actually a bradykinin potentiator and was called “BPF” but they discovered that it also inhibited the ACE. It was in the Squibb laboratories that the “unlikely feat” of producing an oral form of the drug was achieved. Many experts felt that the effect of inhibiting the converting enzyme would be catastrophic. Indeed, only two of the twelve clinicians offered the drug for testing were interested. Prescription of ACEI was at first limited to patients with resistant hypertension. Indeed, this woman was the first case in a series of patients with resistant hypertension successfully treated with captopril. The paper was published in 1980 in the Lancet but you do not get to be an author for doing emergency discharge summaries or arranging air shuttle transfers! Not only have ACE inhibitors have become the first line and successful treatment for young patients with essential hypertension but they have transformed the management of progressive chronic renal failure by delaying progression of proteinuric nephropathies, especially in diabetics. They have become the rescue treatment for scleroderma crises and they are now a mainstay in the management of heart failure. They are a billion dollar pharmaceutical.
We were, of course, perplexed by the cough suffered by 20% of patients. It was ironic that Sir John Vane himself had to give up taking the drug he helped to invent because of cough. His personal experience is also recorded in the Lancet. He was switched to an Angiotensin Receptor Blocker, conceding that his “ACE” had been “trumped”.
To have been a trainee physician when a drug that has had such an impact on clinical practice was being tested in a patient one was looking after was an unforgettable experience. It was such an elegant example of physiology, pharmacology and clinical effect. I loved to watch the faces of the medical students as this memorable patient told her story. For those who look a bit sceptical, I print out the paper from the journal website right in the consulting room. I could not have done that in 1978 either.
When I retired in 2016 I had known her for 38 years. She was 68 and I was 67. At the last consultation I stood up to shake her hand. Instead she embraced me and neither of us could find any words.
Christopher Winearls
Last Updated on April 22, 2026 by John Feehally