Gout, with a section on ocular disease in the gouty

by Llewellyn J. Llewellyn

To what may be Ascribed the Deficient Eliminating Capacity of the Kidney for Uric Acid?

Naturally the advocates of the renal theory had to account in some way for the alleged functional disability of the kidney. Thus, Sir Dyce Duckworth, recalling the occasional occurrence in hysteria of anuria, held that, judging from the general phenomena of acute gout, “the influence of the nervous system ... must not be left out of account as a possible determining factor for renal inadequacy.”

Others, with whom Duckworth disagreed, propounded the view that the deposition of urates in the renal tissues was essential for the initiation of a nephritis in the gouty. Duckworth, on the other hand, held that nephritis could develop in their absence.

Croftan considers the renal changes in gout identical with those of chronic plumbism. From experiments with hypodermic injections of xanthine and hypoxanthine over a prolonged period, he concludes that the presence of minute quantities of purin bases in the circulation is capable of producing marked renal changes. On the other hand, uric acid, injected into the circulation of healthy animals for a period of over three months, produced no renal change whatever.

As to this possibility, viz., that the circulating uric acid might lead to nephritis in the gouty, some reflections of Folin and Denis are instructive. Normal blood, according to these observers, contains not less than from 1-2 or 2-5 mg. per 100 grams, while that of gouty blood does not, in their experience, exceed 6 mg. Continuing, they observe, “There is, however, no reason to suppose that a uric acid concentration of 4-6 mg. per 100 grams of blood is very much more irritating or stimulating to the kidney than the somewhat more dilute solution represented by normal blood. Disregarding the insolubility of uric acid, the elevation of its threshold of elimination from 2-4 or 6 mg. (per 100 grams of blood) is certainly a small one. Kidneys in which the threshold of elimination for urea has risen by 10-20 mg. (per 100 grams), or even more, are extraordinarily common.”

While they consider that such urea and total nitrogen retention may possibly bespeak latent or incipient nephritis, they recognise that no appreciable effects on health have as yet been determined in connection therewith. But more pertinently to our point, they make the further pregnant observation, “In the case of uric acid it seems to be purely a matter of insolubility that corresponding or even smaller degrees of kidney insufficiency with slight uric acid accumulation should result in all the serious consequences involved in the development of gout”!

Again, some have attempted to account for the assumed renal incapacity as being part of the tissue peculiarity of the gouty subject. “Without doubt,” says Duckworth, “there are peculiarities of tissue in the gouty, and with this may very possibly be associated peculiarities of tissue function and metabolism.”

Naturally this suggests the further question, Are there any distinctive histological changes in the gouty kidney? On this point Walker Hall has some apposite reflections. Taking Folin’s figures as a basis, it transpires that in acute and chronic nephritis, also in arterio-sclerosis, there is an average content of 2·5 mg. uric acid per 100 grams of blood. Now, notwithstanding the fact that in these conditions an appreciable quantity of the renal tissues is, functionally speaking, temporarily or permanently out of action, nevertheless “the extraction of uric acid from the blood and its subsequent excretion are practically normal.” The inference is that a relatively small moiety of renal tissue suffices for the excretion of the daily quantum of uric acid in the urine.

Now in contrast thereto, the blood content in gout and lead poisoning is about 4·5 mg. uric acid per 100 grams of blood, or “an increase of about 50 mg. in the total blood-stream at any one moment (an increase from the normal 70 up to 120 mg.).” Continuing, Walker Hall observes that “the gouty kidney per se, even when arterio-sclerotic conditions prevail, does not show anything like the amount of cellular damage which occurs in acute or chronic diffuse nephritis.” Thence he argues if histological changes be taken as a criterion of functional efficiency, then the gouty kidney should be more capable of excreting freely than the diffuse nephritic organ.

How does this work out in actual daily life? he asks. “0·5 gram, in a normal adult, represents the average daily endogenous uric acid excretion in the urine, while that of a gouty subject is about 0·45 gram. Now, assuming that the type and extent of the endogenous metabolism is identical in each instance, then the balance, i.e., 0·05 gram, is distributed between the uric acid pent up in the tissues and the uratic deposits, i.e., tophi.” Walker Hall tells us it has been stated that about 0·01 gram suffices to cover the amount deposited as tophi every twenty-four hours. The residual 0·04 gram runs to swell the amount in the blood and lymph-streams. “The increase is 0·0114 to 0·0118 gram per litre of blood; in other words, the actual increase of uric acid circulating through the kidneys is about 0·00047 per hour,” which, as Walker Hall contends, “seems to be a very trifling difference, especially as it is one of amount and not a type.” In other words, it is quantitative, not qualitative. But, trivial as the disparity is, to what may it be referred? To Walker Hall’s mind, if we are to appreciate the standpoint of those who maintain that the gouty uricæmia is referable to renal inadequacy, it is necessary to postulate the presence of a poison acting upon the renal tubules specifically.

In the gouty uric acid excretion is maintained at a “low physiological level to the very end,” and it is easier, he thinks, to adopt the above hypothesis as to its cause than “to conceive of a poison acting upon the nuclear processes in such a way as to induce a persistently low uniform level” of purin excretion.

This view, viz., of a toxin acting specifically upon the uric acid excreting cells of the kidney, seems to be the only reasonable assumption available. But even this is difficult of adherence when we recall the fact that the effect of the toxin is so readily neutralised by a few grains of atophan. Always we have to recollect, too, that under normal conditions, even given a constant diet, the elimination of uric acid displays wide variations. Also the uric acid output in the subjects of chronic gout, when placed on a fixed diet, differs but little from that of normal individuals on a like dietary. At most the excretion but tends to fall to, or slightly below, the lower normal limits of uric acid elimination.

From the foregoing considerations it is but too obvious that those who render obeisance to the primary renal origin of gout have not only yet to prove that the functions of the kidney are defective, but also upon them lies the onus probandi why gouty subjects should exhibit, or acquire, such a disability.