Two related posts, for patients and for physicians, emphasize the fundamental importance of the kidney stone crystal composition in management of kidney stones and by direct extension the importance to patients and their physicians of sending stones for analysis. Here, in a scientific forum, one needs to raise the obvious and complementary issue of quality: can patients and their physicians rely on the results of stone analyses?
There is a gold standard
Basiri et al recently reviewed all available papers concerning analysis of kidney stone crystals. Like many others, some of whom they reference, X-ray diffraction does indeed reveal the crystal structures and if applied to several regions of a stone is perhaps the ideal method on which to base research or with which to create reference standards against which other methods may be compared. My own co-workers regularly use high resolution CT scanning of individual stones which, while not giving the diffraction patterns by which a crystal can be absolutely identified give instead highly calibrated density measurements that can, within the rather narrow ensemble of kidney stone material identify its components with considerable accuracy. Moreover, the CT technique shows not only some selected part of a stone but can show the whole stone and reveal separate components which are not rarely mixed together to form regions of high complexity.
Commercial laboratories provide variable quality
Using stone fragments whose composition they had determined with considerable precision and accuracy, Krambeck et al found that among 5 commercial laboratories reporting of struvite components was missed about half the time, apatite was missed 20% of the time, and atazanavir was missed by all 5 labs. The featured image shows by + signs when struvite was reported in stones which were not thought to contain struvite when analysed in a research quality manner; the – signs show struvite was not reported in stones that contained that crystal. In general, the labs identified the main stone materials well enough. However the failures concerning struvite are worrisome as that crystal arises from infection and demands a different approach to treatment from metabolic stones.
Is there a problem?
I would always want the highest accuracy in stone analysis, yet realize that at $25 or so per test there is only so much that can be accomplished. For another reason altogether I vote that stone analyses cannot be too lacking in discrimination. Our own research group has pioneered in tissue biopsy of renal papillae of stone forming patients during the course of stone removal surgery and found a remarkably stable relationship between the average stone composition and tissue changes among patients whose stones were not due to systemic disease but where ‘idiopathic’.
For example, in patients whose stones were >50% calcium oxalate on average, stones were found growing outside the kidney on the papillary surface over deposits of interstitial apatite plaque. Among patients whose stones are predominantly calcium phosphate crystals terminal collecting ducts are plugged with hydroxyapatite deposits. Their phosphate stones are rarely found on plaque but rather seem either to form in free solution or as overgrowths on the open surface of ductal plugs – the end exposed to the urine. Most remarkably, even the distinction between stone formers whose stones did or did not contain brushite seemed to matter. Those whose stones were entirely hydroxyapatite in their phosphate component formed numerous small tubule plugs whereas those whose stones contained brushite formed few but very large ductal plugs.
The analyses for these studies did sometimes arise from the sophisticated methods I have already mentioned but often, perhaps even usually, arose from a variety of commercial sources over a period of many years of stone passage. If random commercial laboratory reports are adequate to support distinctions of such subtlety, how bad can they be?
Likewise, we have published that the percent of phosphate in kidney stones correlates very well with the urine calcium phosphate supersaturation of the patients who produced these stones.
However, these observations concern mainly the calcium oxalate and calcium phosphate crystals, whereas the problem with struvite identification is seemingly large and important.
Do we need more research on this issue?
I would think perhaps we might. The quality of stone analyses is not exactly easy to assess. If the issue is whether results are good enough to practice by, then variability or error needs to be assessed in terms of which, if any, therapeutic actions might be misled. For example, missing minor apatite components in a stone would make no difference, at least to me. On the other hand, missing apatite when abundant might well be a problem. Likewise, failure to report struvite is very important as it reflects infection which needs its own specialized treatment, and the same for uric acid.
If I were doing research in this area I might seek some design that captures the clinical consequences of errors that are made. Judging from the several references I have shown errors will be found, but the frequency of consequential errors is not clearly known.