Primary Renal Calculi: Anderson-Carr-Randall Progression?

ANDR#{201}BRUWER1

Afthough numerous reports deal with the histology of renal lymphatic system plays a critical role in renal stone
medullary calcification, there has been only limited applica- formation.
tion of radiographic methods for its description. From routine Building on an earlier proposal by Carr [8] and on
autopsy material, findings on 61 kidneys studied by high more recent work by Haggitt and Pitcock [10] on the
resolution radiography are presented and related to those of
electron microscopic demonstration of renal parenchy-
Randall (1937), Anderson (1945), Carr (1954), and others.
mal calcification, the following hypothesis is stated:
Histologically Anderson found microscopic plaques formed
from coalesced calcific “droplets” in the pyramids of practi-
1 Histologically
. demonstrable calcium-containing
cally all of 168 kidneys, including some very young infants. structures are normally present in the human kidney.
Carr, using microradiographic techniques, also found calcific 2. Under abnormal conditions the normally present
deposits in nearly all of 209 kidneys from patients over 9 years calcium accumulates in larger concretions which may
of age. Anderson and Carr separately concluded that the either remain within the renal parenchyma or may mi-
calcific deposits they demonstrated could, by migration, form grate centrally, to the surface of one or more renal
the subepithelial plaques that Randall observed earlier. The papillae and may then become clinically significant.
present work illustrates some radlologic aspects of renal Under these circumstances the calcium may be radiolog-
calcification which seem to support a hypothesis that primary
ically detectable, either by clinical or experimental radio-
renal calculi result, under certain circumstances, from the
graphic methods, depending on the size of the accumu-
American Journal of Roentgenology 1979.132:751-758.

migration of calcific deposits from the substance to the sur-

face of renal papillae. In order to emphasize the pathogenetic
lation. Such abnormal conditions would include one or
sequence of the work of the previously mentioned authors, it more of many factors (e.g., biochemical, dietary, geo-
is proposed that the sequence of events be referred to as the graphic, hormonal, immunologic, etc). The extent of the
Anderson-Carr-Randall morphologic progression of primary abnormal renal calcium deposition would depend on
renal calculus formation. Proposals are made for additional whether the entire environment of the kidney (renal
experimental work. macroenvironment) or only a small segment of the envi-
ronment of the kidney (renal microenvironment) had
Although much literature relates to the role of the kidney been affected by such factors.
in the physiology and pathophysiology of calcium me- In the hope that an eponymous title will maintain a
tablism 2], the site of the formation
[1 , of primary renal focus on the pathogenetic unity of the contributions of
calculi is still uncertain. This is illustrated, for example, the original workers, the term Anderson-Carr-Randall
by some of the questions and answers given during progression of renal calculus formation is proposed.
discussions of the subject at a recent National Research There is a remarkable lack of radiographic literature
Council Conference on the physical aspects of urolithia- dealing with the demonstration of renal calcific patterns
sis [3]. To the question whether a stone is formed in the in autopsy material. I present relatively limited radio-
renal substance or at the outlet of the tubules, the graphic findings from routine autopsy material, as they
answer was that this is not known and that there are seem to lend support to the findings of those observers
several points of view [3]. To a similar question another previously mentioned and to the hypothesis presented.
speaker replied that there was no certainty whether a Certain observations suggest further work that might
stone formed in the renal papilla or in the calyces define more clearly the pathogenesis of renal calculus
or perhaps even at a higher level than the papilla formation.
‘ ‘ . . where
. stones actually originate constitutes a
problem [3]. Materials and Methods
Whereas some of the pieces of the puzzle of primary The material presented in this report was derived from 61
renal stone-formation seem to have been uncovered, a grossly normal (except for postmortem congestion) kidneys
definitive study putting them together into a recogniz- removed at an equal number of autopsies. The 61 kidneys were
from 27 female and 34 male patients aged 14-83 years. Most of
able whole is still to be done. These include the obser-
the patients had died of conditions common to most busy
vations of Randall [4, 5] suggesting an initiating “ lesion”
community hospitals: chronic pulmonary diseases, diseases
arising from a subepithelial calcium-containing plaque
associated with arteriosclerosis, leukemia, and also following
(Randall’s plaque); the finding by Anderson and Mc- various types of surgery and subsequent complications. The
Donald [6, 7] that microscopic calcareous deposits in the state of hydration and nutrition and the biochemical composi-
renal papilla are very common and may be normal; the tion of each patient’s blood and urine prior to death unfortu-
work of Carr [8, 9] who showed that calcium could nately were not recorded and cannot be determined in retro-
frequently be radiographically demonstrated in the kid- spect. They might have provided interesting correlations with
ney, and who theorized that the function of the renal the radiographic studies of the autopsy tissue. Although many
interrelated factors in the nutritional aspects of metabolic prob-
Received July 6. 1978; accepted after revision January 29, 1979. lems are associated with urolithiasis, the patient’s fluid intake is
Radiology, Ltd., no. 59. 601 North Wilmot, Tucson, Arizona 85711. by far the most important factor relating to the actual formation

AJR 132:751-758, May 1979 751 0361 -803Xl79ll325-0751 $0.00

© 1979 American Roentgen Ray Society
 752 BRUWER AJR:132, May 1979
American Journal of Roentgenology 1979.132:751-758.

Fig. 1.-A and B, 51-year-old woman who died of multiple sclerosis. A, Radiograph of slice of kidney. Papilla (arrow) shows fan-shaped calcific
pattern. B. Detail of A. C and D. 57-year-old woman who died of reticulum cell sarcoma. C, Radiograph of slice of tip of complex renal papilla
demonstrating fan-shaped calcific pattern. D. Detail of C. E, Alizarin red-stained full-thickness section of histopathologic preparation of renal papilla
(reprinted with permission from [11]).

or lack of formation of renal calculi according to Smith et al. 28 kVp and the slices at 16-18 kVp. Using a x7 calibrated hand
[2]. lens, we were able to see calcific particles of about 100 .tm and
The kidneys we examined were part of a larger group (160 perhaps even somewhat smaller.
kidneys) removed for the purpose of vascular anatomic injec- In only 10% of these cases were radiographs that included
tions. For various reasons the 61 cases used for this paper were the renal areas taken prior to death. In none of these could renal
found to be unsuitable for injection studies. calcification be detected with any certainty.
Radiography was first performed on the intact kidneys. Sub-
sequently the kidneys were immersed in formalin for 2-3 days. Observations
Longitudinal coronal slices about 4 mm thick were then made,
and the slices were radiographed.
Excluding calcification seen in arteriosclerotic vessels
All radiography was performed with Faxitron (Hewlett-Pack- and in one tumor, we found evidence of varying degrees
ard) equipment and Eastman Kodak industrial type film, either of parenchymal calcification in 39 of the 61 kidneys
Type M or Type R, or both. The whole kidneys were exposed at examined. This seemed to confirm radiologically a num-
 AJR:132, May 1979 PRIMARY RENAL CALCULI 753
American Journal of Roentgenology 1979.132:751-758.

A B C
Fig. 2.-A, 59-year-old woman who died ofemphysema and cor pulmonale. Radiograph of slice of kidney, considerably enlarged. Cortical margin on
right and pyramids at left. Numerous rounded 0.2 mm calcific densities throughout renal substance. B, 73-year-old woman who died with severe
arteriosclerosis, active pyelonephritis, and arteriolar nephrosclerosis. Radiograph of slice near renal surface, considerably enlarged. Much of the
calcification evident only under hand lens magnification. C, 66-year-old man who died with generalized arteriosclerosis. Radiograph of renal papilla.
Note many tiny globular and streaky calcifications extending throughout pyramid. Several large calcifications near tip. Because of the thickness of the
slice, some calcifications appear to lie outside contour of papilla. They are converging from bases of complex pyramid.

ber of calcific patterns previously described by others in article by Stewart [12], from a previously unpublished
histologic material. Thus, we demonstrated the following radiograph attributed to Carr.
predominant patterns: Photographic magnification of the “plaque” in my
1 A fan-shaped
. pattern of calcific streaks, focusing on case unexpectedly revealed that it was apparently com-
the tip of the renal papilla (figs. lA-iD). This pattern posed of multiple tiny spherules (fig. 3B). It is obvious
conforms to the calcific pattern shown, for instance, in that this finding is identical to that of Carr in 1954 [8]. He
the full-thickness photomicrograph of a renal papilla found that ‘ ‘radiographs of thick sections through pa-
illustrated by Cooke (fig 1 E) [1 1]. This pattern
. was found pillae with adherent stones confirm the view that in
in 25 of the 61 kidneys, occurring in patients 28-83 years reality the ‘plaque’ is composed of multiple concretions
old. aggregated together
2. A second pattern, composed of spherical stipples of A kidney from another patient showed a semispherical
calcification varying in size from being barely perceptible calcific mass located along the lateral aspect of a papilla.
through a x7 hand lens to about 0.2 mm, occurred in 23 This 4.5 x 3 mm density also had a mulberry appearance.
kidneys of patients 14-77 years old These calcific . depos- A kidney of a third patient showed a 4-mm-diam
its varied widely in number, from a few scattered or calcific deposit at the tip of a papilla (fig. 4A). Of interest
clustered deposits to, in one case, a veritable cloud of is the fact that the main calcific mass appears to be
particles. Such particles could be seen in any part of a “followed” by several smaller globular densities of the
kidney, but appeared to be more frequent in the medulla type described by Carr [8]. Of additional interest in the
(fig. 2). latter kidneys was the appearance of a striated calcific
In 10 patients calcifications conforming to both pat- pattern in another papilla, which also contained a few
terns A and B were seen. tiny calcific spherules (fig. 4B). One can only speculate
3. Another pattern, with the impression of calcific that the renal papilla of figure 4A at one time might have
spherules clustered in a mulberry pattern, was seen in had the appearance seen in figure 4B.
three middle-aged patients. One (fig. 3A) had an appear-
Discussion
ance similar to a case described by Randall in 1 937 [4] It .

was triangular, about 4 x 1 .5 mm, and seemed plastered In 1937 Randall [4] first described his findings of a
against the side of a complex papilla in the region of the “milk patch” at or near the tip of one renal papilla in 12
fornix. An almost identical calcific density, identified as kidneys from 104 routine autopsies. These plaques were
a “Randall’s plaque,” was illustrated in figure 4 of the visible by a hand lens and microscopically were seen to
 754 BRUWER AJR:132, May 1979

Fig. 3-58-year-old man who died

of bronchogenic carcinoma. A, Radio-
graph of slice of kidney. Calcification
(arrow) near fornix of complex papilla.
B, Detail of calcification. Actual size
of calculus about 1.5 x 3 mm. Note
mulberry contour.
American Journal of Roentgenology 1979.132:751-758.

Fig. 4.-A, Radiograph of papillary

tip and calyx. Calculus at tip of papilla.
Note small, separate globular calcifi-
“l. cations migrating (?) toward tip. Also
fine calcific streaks in body of pyra-
mid. B, Another papilla from same
patient. Note striated pattern of cal-
cific stipples and streaks in pyramid
and calyceal wall.

A B

be subepithelial. In one kidney such plaques had eroded recognizable Randall’s plaques. Figure 5 is reproduced
through the papillary epithelium and had become the from their article, a beautiful illustration of the entity
‘ ‘initiating lesion” for the formation of a triangular mul- known as a Randall’s plaque.
berry calyceal calculus plastered against the side of its The work of Anderson and McDonald [6, 7] gave a
papilla. reasonable clue to the nature and origin of Randall’s
Subsequently, Randall [5] reported such plaques as “initiating lesion.” In studying 148 surgically removed,
occurring in 19.6% of kidneys examined in 1 154 autop- diseased kidneys and 20 apparently normal autopsy
sies. He proposed that they developed in a small area of kidneys, Anderson found microscopic evidence of cal-
degenerated papillary tissue. careous plaques or tiny stones in the parenchyma of
In a recent microscopic study of renal med uliary calci- renal pyramids in almost all specimens [6]. In only three
fications involving 200 kidneys from 100 randomly se- grossly diseased kidneys, all from patients under age 2,
lected autopsies, Haggitt and Pitcock [10] noted that the he did not find such calcific deposits. Anderson pointed
renal papillae of 23 of the patients contained grossly out that his determinations were made from an average
 AJR:132, May 1979 PRIMARY RENAL CALCULI 755

‘.

i:
v’-. ...‘

Fig. 5.-Subepithelial calcium deposit (Randall’s plaque) at lateral Fig. 6.-Photomicrograph from section of pyramid of pyelonephritic
margin of renal papilla reduced from x35 (reprinted with permission kidney (x700). Clearly apparent coalescence of microscopic “droplets”
from [10]). and of such droplets into calcific plaques. (Reprinted with permission
from [7].)

of only three microscopic sections per kidney. He esti- magnification of 200-300 diameters was used. He found
American Journal of Roentgenology 1979.132:751-758.

mated that it would take 10,000 microscopic sections to that, in practically all kidneys from patients over age 9,
completely examine a kidney with 10 pyramids. small concretions just visible to the naked eye could be
Anderson [6] cited two “generally accepted postulates demonstrated. Usually one or two could be seen, but
regarding kidney physiology’ and correlated
‘ them with some kidneys contained a dozen or more. The majority
his microscopic findings, proposing as a result ‘a some- ‘ of these concretions, when they reached a diameter of
what different interpretation of the etiology of kidney about 0.2 mm, were spherical. Some were as large as 1-2
stones” from the one proposed by Randall. The postu- mm in diameter.
lates to which Anderson referred were: (1 ) the concentra- Carr’s concretions were primarily located in three
tion of calcium and related ions is high in the tissue regions: (1) just outside the calyceal fornices or at the
fluids about the renal tubules, and (2) phagocytic cells, sides of the renal pyramids in line with the interlobar
probably macrophages, are abundant about renal tu- vessels; (2) in the corticomedullary junction zone; and
bules, and macrophages have an affinity for calcium. (3) immediately beneath the renal capsule.
The interstitial calcareous plaques (microplaques) An aggregation of these concretions could in some
demonstrated by Anderson seemed to be the result of kidneys be seen in the region of the fornix or adherent to
coalescence of innumerable microspherules of calcar- the side of a papilla, and such ‘plaques” ‘ could be seen
eous material. Anderson referred to the microspherules to be composed of numerous macroscopic round con-
as ‘droplets.”
‘ These “droplets” were apparently formed cretions, much as Anderson’s microliths were composed
as a result of calcareous material being absorbed by of numerous microscopic “droplets.” Even when a large
phagocytic cells, these cells subsequently dying and stone formed at the tip of a papilla, smaller ones were
leaving calcareous “droplets” in the interstitial tissues seen behind its base. This would seem to match our
(fig. 6). figure 4A.
Location of these ‘droplets’ ‘ beneath the epithelial
‘ So consistently did Carr, radiologist, and Stewart, his
covering of the renal papilla might be followed by ero- surgical colleague, find small concretions in the region
sion of the epithelium. Anderson proposed that Randall’s of the fornix (just extrinsic of the forniceal lumen) that
plaques were probably the result of aggregation of mi- they have used, respectively, the terms Stewart’s nest [9]
crocalculi which he had described and not due to pri- and Carr’s pouch [12] in their publications.
mary degenerative changes in the papilla. Carr suggested that because the microliths demon-
Carr’s work [8] offers the best radiographic studies to strated by Anderson are apparently a normal phenome-
date. Unfortunately Randall, Anderson, and Haggitt and non, one must account for the way in which the body
Pitcock [10] did not use radiography in conjunction with disposes of them. He proposed that this function is
histologic methods. Carr examined by extremely , sophis- performed by the lymphatic system. Carr cites the work
ticated radiographic techniques, 98 partial nephrectomy of Goodwin and Kaufman (cited [9]) and of Rawson [13]
specimens and 1 1 1 kidneys obtained at autopsies from on the lymphatic system, and indicates that the renal
patients dying of nonrenal causes. Intact kidneys and lymphatic system undoubtedly plays an enormously vital
slices of kidneys were radiographed. Extremely thin “cleansing” role in the kidney. To quote Carr [9]:
slices were examined at voltages so low that a vacuum We know that in the lungs particulate matter
had to be used between the tube and the specimen, inhaled gets into the alveoli, and then it is
some exposures lasting 24 hr. Fine-grain film allowing taken up in the lymphatics and transported to
 756 BRUWER AJR:132, May 1979

where it can do no more harm, as long as the be shown to involve the renal papillary substance exten-
mechanism is working properly. I believe that sively and these deposits were described as being ‘ ‘ in
the kidney functions in the same way. I think the collecting ducts” [15], that is, quite unlike the find-
that effete cells, debris of all sorts, calcium ings of Anderson and Cooke in humans. Vermeulen et
which has been re-absorbed and come out of al. speculated that such accumulations usually “abort
solution in the interstitial fluid where there is into the pelvis” and, being small enough, presumably
always debris available to act as a nucleus to usually wash out. But occasionally a small piece might
precipitation all get removed with the protein be caught at the ostium of a duct of Bellini, thus
and interstitial fluid into the lymphatics. providing an “embryo” upon which, under the right
Carr postulated that any abnormality that can result in circumstances, crystallization would result in the devel-
overload of calcium in the kidney, or interference with opment of a calculus.
lymphatic drainage, could result in overproduction of Carr [9] does not believe that the work of Vermeulen et
microliths and the development and accumulation of al. is relevant to the process of so-called primary renal
larger concretions. The rounded shape of the latter, he calculus formation. He believes that their experimental
postulated, can be attributed to their being molded in results relate to nephrocalcinosis (i.e. , “a totally different
lymphatic channels. Any of these concretions (macro- disease process to that of calculus formation”).
liths formed from microliths) could eventually erode into Spheroidal morphology may have special significance.
the calyceal lumen. They may be washed out or, by being I was struck by the fact that many of the calculi demon-
adherent, grow in size in a calyx. Because of microre- strated in the study material conformed to the spheroidal
gional pathologic changes in the kidney, calculi would pattern described by Carr [8]. I also noted, as did Carr,
tend to re-form in the same region after having passed or that concretions might lie in a line or a chain. Another
having been removed without resection of the involved appearance that I noted was that spherules tend to
American Journal of Roentgenology 1979.132:751-758.

area. cluster in the region of the papillary tip, sometimes

Epstein [1] pointed out that the glomeruli of a healthy seeming to follow a large calculus which appeared to be
adult filter about 9-1 0 g of calcium per day and that 98% composed of multiple macrospherules in a mulberry or
of this is reabsorbed by the renal tubules. Ullrich and botryoidal pattern (figs. 3 and 4). Spheroidal geometry
Jarausch (cited in [1]) believed that the calcium content seems to play a basic role in the life cycle of primary
of the kidney manifests a gradient, the concentration renal calculi, from the microspheroidal stage to macro-
being progressively higher toward the papillary tip. Such spheroidal agglomerations.
a chemical gradient was confirmed by the work of Cooke Haggitt and Pitcock [10] performed light and electron
and Rosenzweig [14]. They found, by chemical analysis microscopic studies of renal medullary tissue obtained
of calcium content in samples of kidney tissue, evidence at necropsy from 100 patients aged 18-91 years. In
of a calcium gradient in the human renal medulla, the all 100 pairs of kidneys examined, they were able to
highest values being in the region of the papilla. demonstrate minute laminated spherules which stained
Cooke [11], in a careful histologic examination of 62 for calcium in the medullary interstitium and in the
apparently normal kidneys, found calcification in 43 basement membranes of collecting ducts (fig. 7A). One
cases (69 %). Calcium was seen in the papilla in all these of their illustrations of a typical spherule, enlarged
cases, usually in substantial amounts, and occasional x54,000, demonstrates the lamination of these bodies
deposits were seen in the outer medulla in 20 cases. In beautifully (fig. 7B).
nine cases calcification was seen in the cortex. Cooke’s Doyle et al. [16] recently demonstrated concentric
study showed that the location of papillary calcification layering in concretions smaller than 50 m obtained
was invariably in the basement membrane of the long from mollusk kidneys (fig. 8).
loops of Henle, which descend for variable distances Boyce [17] observed calcium and phosphate-contain-
into the medulla, sometimes as far as the papilla. Al- ing microspherules and macrospherules by light, elec-
though some showed evidence of calcium in all parts of tron, and scanning electron microscopic analysis of
the kidney, all showed calcium in the papilla. Cooke did calculi recovered from 28 patients classified as “idio-
not find calcium to lie free in the tubular lumens. Figure pathic oxalate or phosphate stoneformers.” Lamination
1E, reproduced from Cooke’s article, shows the fan- was a common finding in their material.
shaped calcific pattern, similar to that which we fre- Anderson and McDonald [6, 7] and Haggitt and Pitcock
quently encountered in our radiographs. [10] found a strong tendency for aggregations of the
Anderson [6], too, concluded that the microscopic concretions which they had described to migrate into a
collections of calcium ‘seemed to occur
‘ anywhere ex- subepithelial location in the renal papillae, that is, for the
cept within the lumen of the tubule. A few specimens formation of Randall’s plaques, with a consequential
were found with the deposits within the tubules, but it proclivity to erode through the epithelium and initiate
seemed to me that they had eroded into the tubules from the development of a free calculus.
the surrounding parenchyma.”
We should make reference to the work of Vermeulen
Conclusions
et al. [15] on experimental calculogenesis. For example,
by mixing oxamide in the diet of rats, they could rapidly Hypothesis of Anderson-Carr-Randall progression of
produce spectacular oxamide deposits that extruded primary renal calculus pathogenesis. Anderson’s histo-
from the papillary tip. Streaks of oxamide crystals could logic studies demonstrated the ‘ ‘normal” presence of
 AJR:132, May 1979 PRIMARY RENAL CALCULI 757

Fig. 7.-A, Reproduction of lami-

nated electron-dense bodies in base-
ment membrane of collecting duct.
Duct epithelium shows postmortem
degeneration. Reduced from x21 .000.
(Reprinted with permission from [10].)
B, Laminated electron-dense body in
interstitium, surrounded by collagen
fibrils. Reduced from x54,000. (Re-
printed with permission from [10].)
American Journal of Roentgenology 1979.132:751-758.

A B
Fig. 8.-A, Tissue section (6 Mm thick) of Argopecten irradians kidney choked with phosphorite concretions. Note concentric layering of
concretion (A). H and E stain. (Reprinted with permission from [16]. B, Close-up of concretion from kidney of mollusk Mercenaria mercenaria,
showing microbotryoidal texture (compare human “mulberry” texture). (Reprinted with permission from (16].)

calcium in the tissues of the renal papilla, work that has Much more correlated information is needed concern-
been confirmed by others [10, 11]. Carr’s radiologic ing histopathologic and radiographic findings on much
studies have substantiated, at the microradiographic larger ‘ ‘normal” populations, under known conditions of
level, Anderson’s original work. Only the impossible- hydration and nutrition. Investigations such as those
moving pictures of the drift of Anderson’s and Carr’s being performed on the renal lymphatic system by Clark
calcific deposits from a locus within the substance of a and Cuttino [18] are also of interest. For example, can
papilla to a subepithelial location near or at the surface methods of “sifting” the main renal lymphatics for cal-
ofthe papilla-could “prove” that Randall’s subepithelial careous microspherules under varying conditions of diet
plaques and “initiating lesions” originate from deeper and hydration be developed? Or can the main renal
calcific deposits. I believe that the circumstantial evi- lymphatics be obstructed with a view to subsequent
dence is overwhelming and there is useful logic in radiologic and microscopic evaluations of the renal pa-
thinking of the formation of primary renal calculi as pillae for evidence of Carr’s concretions and Randall’s
being initiated by a pathogenetic progression that I plaques?
propose to call the Anderson-Carr-Randall progression Because of the common finding of calcific microspher-
of primary renal calculus formation. ules in the tissues of the renal papilla histologically and
 758 BRUWER AJR:132, May 1979

radiographically, might one speculate, for example, that Academy of Sciences, Washington, D.C. 1972, pp 41 61- , ,

some or many cases of microhematuria might be due to 62

erosion of these tiny plaques into the lumen of the 4. Randall A: The initiating lesions of renal calculus. Surg
Gyneco! Obstet 64:201-208, 1937
urinary tract, and might electron microscopy of the
5. Randall A: Papillary pathology as a precursor of primary
urinary sediment from such patients be worthwhile?
renal calculus.J Uro! 44:580-589, 1940
Furthermore, because the degree of physioloic hydra-
6. Anderson LE: The Significance of Microscopic Ca!careous
tion apparently affects the extent of the presence of Deposits in the Rena! Thesis (Master of Science in
Pyramid.
calcium within the renal papilla and presumably, there- Surgery), University of Minnesota, 1945
fore, the chance of calculus formation [2] might electron
, 7. Anderson L, McDonald JR: The origin, frequency, and
microscopy of urinary sediment under various conditions significance of microscopic calculi in the kidney. Surg
of hydration perhaps be expected to yield, or not to Gyneco! Obstet 82 : 275-282, 1946
yield, microcalculi? 8. Carr RJ: A new theory on the formation of renal calculi. Br
We know that calcific “droplets” and microcalculi J Uro! 26:105-117, 1954
9. Carr RJ: Etiology of renal calculi: Micro-radiographic stud-
commonly exist in the renal pyramids. We also know that
ies, in Proceedings of Rena! Stone Research Symposium,
small , subepithelial calcific plaques composed of calcific
edited by Hodgkinson A, Nordin BEC, Churchill, London,
microspherules are not uncommonly found in renal pa- 1969, pp 123-132
pillae, and that the epithelial cover of these plaques can 10. Haggitt RC, Pitcock JA: Renal medullary calcifications: a
erode to allow them to become ‘initiating
‘ lesions’ for ‘ light and electron microscopic study. J Uro! 106:342-347,
free primary calculi. Short of proving a central-to-surface 1971
drift of microcalculi by serial imaging, it is possible that ii . Cooke SAR:
The site of calcification in the human renal
additional pieces of circumstantial evidence in the form 57:890-896,
papilla.BrJSurg 1970
of investigation of the lymphatic system and urinary 12. Stewart HH: Calcifications and calculus formation in the
American Journal of Roentgenology 1979.132:751-758.

sediment under various conditions of controlled hydra- upper urinary tract. Br J Uro! 27 :352-366, 1955
13. Rawson AJ: Distribution of the lymphatics of the human
tion and nutrition and other variables, might prove”
“ the
kidney as shown in a case of carcinomatous permeation.
Anderson-Carr-Randall progression hypothesis.
Arch Patho! 47:283-292, 1949
14. Cooke SAR, Rosenzweig 0: The concentration of calcium
ACKNOWLEDGMENTS
in the human renal papilla and the tendency to form calcium
I thank Dr. Mary-Ellen Shields for assistance with this project; containing stones. Nephron 8:528-539, 1971
and Richard Durbin, Dr. Richard Armstrong, and Dr. Gerd 15. Vermeulen CW, Lyon ES,
Ellis JE, Borden TA: The renal
Schloss, Tucson Medical Center. papilla and calculogenesis. J Urol 97 : 573-582, 1967
16. Doyle U, Blake NJ, Woo CC, Yevich P: Recent biogenic
phosphorite. Concretions in mollusk kidneys. Science 199:
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