Plaque is a collection of calcium phosphate crystals in the tissues of the kidneys. Plugging is deposits of crystals that fill the interior of the kidney tubules. Both are visible to surgeons during kidney stone surgery procedures.
Plaque is certainly part of common stone formation. We can see stones grow over it, and when stones break loose and pass they often carry with them bits of kidney tissue and the plaque embedded in it. Crystal plugs also can support stone formation. We can find stones growing on the open ends of plugged tubules, clearly anchored on the mass of crystals that have formed inside. But it is not common to find stones with attached plugs, so one cannot easily count the fraction of stones that have formed on them.
The large header figure shows two stones that detached from kidney papillas carrying with them fragments of plaque (RP). The images are high resolution CT scans. ‘CD’ on the right panel indicates renal collecting ducts awound which plaque has formed. The inserts show the stones as they appeared after removal. They are turned upside down to display their tissue side where they once attached. From Williams et al J Endourol 36:694-702, 2022
This site has detailed articles about plaque and tubule plugging. But I have not integrated either with one another nor with stone formation as viewed by physicians and their patients. That is my task here.
HOW MUCH PLAQUE AND PLUGGING
Relationships Between Plugging and Plaque
Using high resolution images of the renal papillum obtained during stone surgery, one can estimate the fraction of surface occupied by plaque and tubule plugs. The former is a white cloud which is how tissue calcium phosphate deposits appear to the surgeon. The latter is individual elongate yellow segments which each represent a tubule plugged with crystals.
On the adjacent graph I show the percent of area occupied by plaque on the vertical axis vs the number of yellow deposits per mm2 on the horizontal axis. The symbols give the kinds of crystals in plugs: A is hydroxyapatite, the crystal in bone and calcium phosphate stones. C is calcium oxalate. A is uric acid and urate species. Cy is cystine found only in cystinuria. N means there are no crystals. The size of the symbols gives some sense of the size of individual plugs.
Over the graph I have placed three ovals demarcating three zones. Some idiopathic calcium oxalate stone formers (ICSF) have no deposits at all (upper left). I have labelled them ICSF1A. I have called this group A.
Many kinds of stone formers produce plugs with no more than normal amounts of plaque (points below the horizontal blue line). Normals have no plaque or deposits. Bypass (obesity) surgery (Bypass), cystine stone formers (Cystine), primary hyperoxaluric stone formers (HOX), and distal renal tubular acidosis patients (RTA) are in this group. As well, some ICSF form little plaque but significant deposits (ICSF (Apatite) 1C). This position is in common with idiopathic calcium phosphate stone formers, therefore the ‘apatite’ inclusion. I have labelled this group ‘C’.
In between are 7 more diseases: small bowel resection (SBR), uric acid stone formers (UA), brushite stone formers (Brushite), medullary sponge kidney patients (MSK), primary hyperparathyroidism (HPT), and ileostomy. I have called this Group B. Included are some ICSF with both significant amounts of plaque and tubule plugging. Some ICSF also fall into this group (ICSF 1B).
Finally, there is a group of ICSF who have no significant plaque or plugging but nevertheless form calcium oxalate stones. They would lie with normals (ICSF 1D).
(Versions of this figure are in papers from our research group but this one is newly made and therefore I put it here without listing sources.)
Why I Have Made this Figure
One might say it is in the nature of an academician to make attempted orderings out of the chaos and irregularities, and there is in that idea some considerable truth and virtue. But – to speak in my own favor – this is a kind of clinical map for surgeons, physicians, and patients. People with only plaque or only plugging are otherwise distinctive so diagnosis is narrowed. Likewise for the middle group. Moreover, given a presumed disease origin for stones, extreme variation from pattern might suggest one rethink causes and treatments.
On a deeper level, one hopes that this engaging pattern might stimulate others to consider research directed toward understanding why there exists this variety of plaque and plug expression. In some cases, RTA as an example, one could say that extremely high urine pH raises saturation for calcium phosphate within tubule fluid giving rise to many plugs. Possibly true.
WHAT STONES CAN TELL US
Where Stones Formed
As the header picture shows, stones that grow on plaque often carry with them a fragment of kidney tissue with the embedded plaque on which the stone formed. This allows one to catalog patients by whether they form any stone on plaque or not. Using this criteria, some patients (filled circles) formed over half of their collected stones on plaque, and a smaller number (open circles) former up to 49% on plaque. A significant fraction formed none of their stones on plaque (diamonds).
Examples abound of stones growing on the open end of a plugged duct. But often stone have no attached ductal elements not plaque, so one cannot be sure about the role of an anchor – tissue plaque or tubule plug. This was the case for most of the people who did not form stones bearing plaque fragments. This figure is from the above paper by Dr Williams.
WHAT IMAGES OF PAPILLAE CAN TELL US
The amounts of plaque (RP) as a fraction of papillary surface is plotted against the percent of area showing yellow plugs (% plugging). As one might expect, those with many stones on plaque had the most abundant plaque and scantiest plugging (filled circles clustering along the left wall of the graph). Likewise, those with no plaque on stones seems to have the most abundant plugging (diamonds hugging the lower border of the figure from left to right). One imagines these people probably formed some stones on plugs even though direct evidence is uncommon.
Idiopathic Stone Former vs. Systemic Disease
These patients are all ‘idiopathic’ stone formers, lacking systemic disease as a cause of stones. IN them, plaque and plugs seem antithetical, one tends to have one or the other. That is what it means to see so few points in the main body of the figure and most hugging the left and bottom borders.
But the first figure I showed is utterly different. Many systemic diseases cause both abundant plugging and plaque. I have already named them. Perhaps primary hyperparathyroidism is the most interesting one because it is do like idiopathic calcium stone disease in having high urine calcium as a major risk factor.
Without delving further one might say the obvious – something about systemic diseases leads to a mix of plaque and plugs whereas absent a systemic disease the two are not usually both abundant in a given patient. The diseases with little plaque and much plugging, hyperoxaluria and renal tubular acidosis both have extreme urine saturations that are the likely cause of so much plugging. Given a lot of plugging perhaps kidney damage reduced the ability of kidneys to create plaque. I find interesting that virtually none of the systemic diseases fail to produce at least some excess plugging.
Brushite Stones
Though now arising from systemic disease, brushite stones are so odd as to attract considerable notice. Plugs are huge, stone growth very rapid, and renal damage far above that usually seen. Moreover the presence of considerable brushite is itself odd as the crystal is easily cannibalized by other crystals and rarely is found in urine.
WHY HAVE I WRITTEN THIS BRIEF ARTICLE?
As new papers come out in public we tend to forget, and I am about remembering. The excellent new work in the second figure points out a strangeness in the idiopathic calcium stone former – a tendency to be a former of stones on plaque OR plugs. Or perhaps not a strangeness but some important stringency that systemic diseases override because multiple factors all are at work in causing stones and blur out the underlying tendency for plug – plaque separation. I do not know which.
Should Physicians Care?
Yes. Abundant plugging AND abundant plaque may be found in idiopathic calcium stone formers, but is perhaps likelier in those with systemic diseases or brushite stones. Now that high resolution endoscopes are used virtually everywhere surgeons will see plaque and plugging and can make a general estimate of their abundances.
Should Patients Care?
Of course and for the same reasons. They should ask their surgeons what was found during stone surgery so as to inform themselves and use the information. If plaque and plugging are both very abundant, a diagnosis of idiopathic stones may still be correct but a patient should inquire about how other causes of stones were excluded.
I am quite fascinated by these data, and believe more research will sort out the reasons for the oddness they expose to view.