He had guessed the sender from the handwriting on the envelope immediately. It would have ‘decorated’ his undergraduate physiology essays.

The card within had confirmed his surmise.

        Prof H. Methuselah DSc

    Emeritus Professor of Human Physiology

Dear Homer,

There is something personal I would very much like to run by you. How would this Saturday morning suit? Say 10.30? I’ll have the Fair Trade coffee percolating.

Yours ever,

Henry

Homer is not his real name but he had been allocated this soubriquet (in honour of Homer Smith the famous renal physiologist) by Henry, his physiology tutor, because he had expressed a special interest in the kidney. He now practises as a clinical nephrologist.

This had not been an invitation but a summons.

The coffee poured, Henry had come straight to the point.

‘It's about Hetty (his wife). Seems she has a problem in your department. Our new GP, a Dr Quoff or some such name, wrote to say she has Stage 3 Chronic Kidney Disease. This came as terrible shock to us both, especially as she feels absolutely fine. Lord knows how he managed to make the diagnosis – he had not even seen her. Apparently it was detected when she had a blood test for her annual TSH check. She wants to cancel our trip to Australia to see the grandchildren for fear of falling ill away from home. Of course the travel insurance will not cover “kidney disorders” unless I pay an exorbitant premium. She is talking about “getting her affairs in order” and living wills, and has become really quite depressed. She was called back for further blood tests but she had to remind them, on my say so, to take her blood pressure and test her urine.’

His heart had sunk. Henry is a genial chap but when he detected humbug or sloppy science he could be acerbic and forensic.

Henrietta (Hetty) Methuselah is a formidable and cheerful woman, and could be described, euphemistically as ‘big boned’. Although now 80 years of age she is an enthusiastic and muscular gardener and had swum for the University (which is how she met Henry). Apart from hypothyroidism diagnosed after her fifth pregnancy she had been entirely healthy.

Homer had asked for the actual biochemical values.

‘Her plasma creatinine is 90umol/L and her eGFR is 56 ml/min. So what is CKD Stage 3? It sounds pretty advanced to me. NYHA Grade 3 heart failure and cancers at Stage 3 are usually very bad news.’

‘It just means she has an abnormally low GFR, somewhere between 30 and 59 ml/min.’

‘But nobody has measured her GFR.’

‘It has been calculated automatically from her plasma creatinine.’

‘Surely you mean it was estimated? How accurate is the estimate? They did not even weigh her in the surgery! As you know Hetty is not a small woman. How did they estimate her surface area and muscle mass?’

‘Yes – it was an estimate and to tell you the truth, it is rather inaccurate and has quite wide confidence intervals. We call it eGFR the “e” is for estimate but some of the wags in the department say “e” stands for error-prone!’

The attempt at humour had been ignored.

‘So it may be even worse? She might even have Stage 4?’

‘Unlikely.’

‘This cut off of 60ml/min comes; I take it from the classic Davies and Shock paper in JCI in 1950? They used inulin clearances you know, and only studied men– this eGFR had not been invented. I had quite a struggle getting the volume from the library, and looked at the tables again – it shows what we all know - GFR declines with age. Incidentally did they calibrate this eGFR formula across the full range of creatinines values?’

‘They did refer to Davies and Shock. Actually the formula was derived from patients known to have renal failure. It does tend to underestimate the GFR a bit when the creatinine is in the lower range.’

‘How much is a bit?’

‘Er – as much as 20% actually.’

‘So she might not have CKD Stage 3 at all? This formula seems to be, as old Fred used to say in the lab, “subject to methodological vicissitudes.” How can these experts define a normal range using one technique for measuring GFR, make no allowance for gender or age, then use a different and inaccurate technique for diagnosing and then staging disease? They would have been given a very hostile time at the Renal Association. Actually I plugged her results into the Cockroft-Gault formula and got an estimated creatinine clearance of 62 ml/min which is within the normal range for a woman of her age according to the data from Belgium published in the Lancet back in the 1980s. Incidentally, her blood pressure is fine and her urine is completely free of protein. They have requested a kidney ultrasound, a PTH, a Vitamin D, a Full Blood Count and ferritin, and have put her on a register. This is going to cost a bit but I gather the GP is obliged to do this to collect his points’

‘The current view, Henry, is that any change in GFR with age is explained by some form of kidney injury probably subtle changes to the vasculature. The Cockroft-Gault formula is no longer used – doctors cannot be relied upon to record body weight on the request forms.’

‘So, let me get this straight, you are saying that her GFR is abnormal. If we were to check it after she gave up meat, swimming and digging the vegetable bed, for a while, and the creatinine dropped to 84umol/L, the eGFR would be computed as 60 ml/min. She would no longer be classified as having CKD at all. With a fall in creatinine of 6umol/L she would jump from Stage 3 to Stage 0!’

He had obviously done his homework before inviting Homer for this viva examination.

‘Homer, despite my age I have mastered the internet and found this paper in Kidney International last year from the Netherlands. This gives the 95% confidence intervals of eGFR in healthy women and Hetty is safely above the 5th centile. It seems rather a lot of healthy women of her age will be classified as having Stage 3 Chronic Kidney Disease. Tell me honestly, do you as a clinical nephrologist really believe that they and Hetty have a kidney disease? What is her risk of needing dialysis?’

‘Actually I don't think she has kidney disease and her chance of becoming dialysis dependent is, according to the Norwegians, about 0.4% per year so you can reassure Hetty that she is very unlikely to run into trouble.’

‘Homer, from Hetty's point of view I have found our little chat very reassuring. However, in another way I have found it very dispiriting. It seems that this, for want of a better word, I will call, a construct, has emanated from the grand Academy of Lagado. Do the architects believe the human race has evolved into Struldbrugs?’*

To understand Henry's allusions* the reader is directed to Gulliver's Travels.

The author has taken the same liberties as Jonathan Swift.