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Typical monohydrate calcium oxalate stones (type Ia, brown structures) harbouring papillary umbilication and Randall ’ s plaque made of apatite (white structures).
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Alexander Randall described eight decades ago a heterogeneous nucleation process at the tip of renal papillae giving birth to calcium oxalate stones. Kidney stones were for the first time described to originate from calcium phosphate plaques growing in the interstitial tissue, breaking urothelium and then promoting calcium oxalate crystals aggregat...
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... Randall, an American urologist, proposed in 1936 a new theory relative to “ The origin and growth of renal calculi ” [1,2]. Based upon extensive forensic studies performed between 1935 and 1938, he observed, at the tip of the renal papillae, lesions consisting of calcium phosphate and carbonate deposits accumulating in the kidney interstitium. These lesions were initially interstitial but their growth was likely to result in urothelium rupture and formation of plaque in contact with urine. He observed small kidney stones made of calcium oxalate in 65/1154 pairs of kidneys (2.8%). Overall, plaques were present in 19.6% of kidneys [2]. He also observed that calcium oxalate stones expelled by patients harboured in some cases a depression due to papilla imprinting and calcium phosphate residues, involving thereby plaques as the origin of stones (Fig. 1). Alexander Randall distinguished two ways for stone initiation: on the one hand, calcium phosphate deposits may form typical plaques in the renal interstitium leading to urothelium rupture in some cases (papillary lesion type 1); on the other hand, calcium phosphate plugs may be generated in the collecting duct, at the outlet of the tubule (papillary lesion type 2). In both scenarios, calcium phosphate initiates further a calcium oxalate stone heterogeneous nucleation process. Several authors were interested in kidney calci fi cations during the same period. Rosenow observed plaques in 22% of 239 kidneys and Vermooten in 17.2% of Caucasian patients' kidneys [3,4]. The calci fi cations were present in the interstitium but not in the tubule lumen [5]. Anderson found microscopic evidence for “ calcareous ” plaques ...
Citations
... All whewellite samples show concentric lamination due to growth layers (Figs. 2, 3) including one or two composite nuclei, surrounded by inner and outer growth layers. The concave portions of the nuclei of the composite aggregates ( Fig. 2Ba) may suggest that the nucleation developed adjacent to the renal papillary surface either as a coating of whewellite on Randall's plaque in the case of the sample KS-1 or Randall's plaque in the interstitial tissue (the sample KS-4) because of its matching to the papillary surface ( Fig. 1c3; Evan, 2010;Grases et al., 1998;Giannossi et al., 2012;Letavernier et al., 2016;Wiener et al., 2018). The heterogeneous nucleation for the sample KS-4 based on the general acceptance of multimineral COM stones (Goldfarb, 2012;Hill et al., 2017;Letavernier et al., 2016) and a small amount of hydroxyapatite content in the results of the XRD and geochemical analyses ( Fig. 4; Table 2). ...
... The concave portions of the nuclei of the composite aggregates ( Fig. 2Ba) may suggest that the nucleation developed adjacent to the renal papillary surface either as a coating of whewellite on Randall's plaque in the case of the sample KS-1 or Randall's plaque in the interstitial tissue (the sample KS-4) because of its matching to the papillary surface ( Fig. 1c3; Evan, 2010;Grases et al., 1998;Giannossi et al., 2012;Letavernier et al., 2016;Wiener et al., 2018). The heterogeneous nucleation for the sample KS-4 based on the general acceptance of multimineral COM stones (Goldfarb, 2012;Hill et al., 2017;Letavernier et al., 2016) and a small amount of hydroxyapatite content in the results of the XRD and geochemical analyses ( Fig. 4; Table 2). However, we observed the bouquet-like fibrous hydroxyapatite crystals formed on the large prismatic whewellite crystal surfaces (Fig. 5k) with a typical EDX spectrum in the outer growth zone. ...
... The calcium oxalate kidney stones are considered to precipitate from urine that is saturated in terms of the stone-forming components. It is well-documented in the literature that the factors controlling calcium oxalate stone formation are low urine volume, dietary imbalance, and genetic or acquired diseases such as hypercalciuria (calcium excretion), hyperuricosuria (uric acid excretion), hyperoxaluria (oxalate excretion), hypocitraturia (citrate excretion), hypomagnesuria (magnesium excretion), and hypercystinuria (cystine excretion) (Alelign & Petros, 2018;Cloutier et al., 2015;Khan et al., 2019;Letavernier et al., 2016;Singh & Rai, 2014). The CaOx stones can form under a wide variety of urinary pH conditions, but mostly 5.0-6.5 pH values favor the formation of CaOx stones (Alelign & Petros, 2018;Khan et al., 2019;Liu et al., 2013;Manissorn et al., 2017). ...
This study describes the primary characteristics of the selected kidney stones surgically removed from the patients at the Mersin University Hospital in the southern Turkey and interprets their formation via petrographic, geochemical, XRD, SEM–EDX, and ICP-MS/OES analyses. The analytical results revealed that the kidney stones are composed of the minerals whewellite, struvite, hydroxyapatite, and uric acid alone or in different combinations. The samples occur in staghorn, bean-shaped composite, and individual rounded particle shapes, which are controlled by the shape of the nucleus and the site of stone formation. The cross-section of the samples shows concentric growth layers due to variations in saturation, characterizing the metastable phase. Kidney stone formation includes two main stages: (i) nucleation and (ii) aggregation and/or growth. Nucleation was either Randall plaque of hydroxyapatite in tissue on the surface of the papilla or a coating of whewellite on the plaque, or crystallization as free particles in the urine. Subsequently, aggregation or growth occurs by precipitation of stone-forming materials around the plaque or coating carried into the urine, or around the nucleus formed in situ in the urine. Urinary supersaturation is the main driving force of crystallization processes; and is controlled by many factors including bacterially induced supersaturation.
... Oxalate deposits on the epithelium cover this plaque and result in calcium oxalate stone formation. [22] Hence, though limiting only oxalate rich foods helps reduce stone formation, research has shown that a better strategy would be to eat and drink calcium and oxalate rich foods together as oxalate and calcium would bind in the stomach and intestines. [23] Fluids, too, affect stone formation, and changes in intake can help prevent their incidence. ...
Background: Renal stones are a painful urological disorder resulting from the combined influence of epidemiological, biochemical and genetic risk factors. A high recurrence risk has been reported for renal stones, and 0.6%–3.2% cases may progress to end stage renal disease. Modern lifestyle, sedentary habits and unhealthy dietary practices are primary promoters of the stone boom in this millennium.
Aims and Objectives: The aim of the present study is to evaluate the percentage of the stone type according to chemical composition and their association with epidemiological factors like sex and age. A retrospective analysis of the chemical composition of the stone samples received was done.
Material and Methods: Stones samples were processed by Stone Analysis Set (BIOLABO S A, France). Qualitative chemical analysis was done for calcium, phosphorus, ammonium ion, oxalate, cystine, magnesium, carbonate and uric acid.
Results: Type of renal stone and its incidence with age and sex have been evaluated. The total number of patients reporting to the hospital with renal stones was 123. Of these, 69.11% were male and 30.89% were female, with a male to female ratio of 2.23:1. The maximum occurrence was in the third and fourth decade of life. On analysis, 72.35% of total stones comprised calcium oxalate and 23.57% of nonoxalate (phosphate, magnesium, carbonate, ammonium ion) stones, whereas uric acid was positive in 4.06%.
Conclusion: The occurrence of renal stones according to epidemiological factors such as age and sex in our study are similar to those reported in studies from developed countries. The data on urinary stones indicate that 98% were located in the upper urinary tract. Oxalate stones represent the main form of urolithiasis, affecting males more than females. The most important cause studied for renal stone formation is metabolic disturbances, but the genetic factors associated with the occurrence and recurrence of stone and mineral homeostasis of ions in kidney of stone formers should be further evaluated.
... This feature, along with a compact radiating and concentric internal structure, allow classifying them as subtype Ia (Figure 2a), a category of kidney stones with peculiar minerogenetic mechanisms. In particular, umbilication (also known as papillary imprint) consists in a small depression (Figure 3a,b) representative of the contact with the renal papilla, by means of a calcium phosphate deposit known as Randall's plaque [43][44][45][46][47]. Formation of type I calculi is generally related to dietary habits as, for example, an excessive intake of oxalate-rich foods, low water intake, and low diuresis. ...
The present investigation exposes the main results raised from an active collaboration started in 2018 with the San Pio Hospital (Benevento, Southern Italy), aiming at a detailed mineralogical investigation of urinary stones of patients from the Campania region. Forty-nine uroliths (both bladder and kidney stones) have been surgically collected from patients admitted between 2018 and 2020 at the Department of Urology of the San Pio Hospital and characterized for clinical purposes and environmental biomonitoring from a mineralogical point of view. Possible causes and environmental implications were inferred according to the morpho-constitutional classification of the uroliths carried out by means of a conventional analytical approach. The mineralogical frequency distribution of uroliths from the Campanian region can be discussed as a function of dietary, socio-demographic, and environmental risk factors. Whewellite [CaC2O4·H2O] and weddellite [CaC2O4·(2+x)H2O], along with anhydrous calcium oxalate, represent the main mineralogical phases forming the biominerals examined here. Worth to note is that the percentage of oxalates in the Campanian region (ca. 51%) is quite comparable to those of other Mediterranean areas. Frequent uricite [C5H4N4O3] (ca. 33%), mainly observed in bladder stones of older male patients, could be related to an incorrect lifestyle and dietary habits. Occurrence of lower percentages of phosphate (i.e., brushite [CaHPO4·2(H2O)] and carbonated apatite [Ca10(PO4CO3)6(OH)8]) and mixed stones (such as, for example, a mixture of ammonium urate [NH4C5H3N4O3] and calcium oxalates) indicates specific etiopathogenetic mechanisms, suggesting proper therapeutical approaches.
... Crystallites in urine (homogeneous nucleation) are agglomerated at the surface of RP which serves as a nucleus (heterogenous nucleation). 16 A third family can be related to physiological calcifications (otoliths, tooth, 17 bone) which becomes pathological with diseases (bone and osteoporosis 18,19 ). ...
... However, Letavernier and colleagues have made observations that strongly suggest that the RP stone former has a distinctive clinical phenotype. 7,8 They distinguished calcium oxalate stones on RP by the presence of a plaque residue. Using that along with sex and age, they discovered important population-level distinctions between RP and non-RP stone formers over time and in men and women of different ages. ...
... Using that along with sex and age, they discovered important population-level distinctions between RP and non-RP stone formers over time and in men and women of different ages. 7 The present work, which uses the same stone distinction to mark patients as producing RP stones or not, allows us to make new observations at the patient level concerning these two types of stone formers. ...
... The best understood mechanism of renal stone formation is that of RP. 7 With RP, the calcified tissue at the tip of the renal papilla shows overgrowth by stone minerals from the urine, 20 and the stone remains attached to the renal tissue while it is small. It has been known for some time that this type of stone can be released spontaneously from the kidney and that the passed stone can often carry with it some calcified papillary tissue as evidence of its previous attachment within the renal space. ...
Introduction About 1-in-11 Americans will experience a kidney stone, but underlying causes remain obscure. The objective of the present study was to separate idiopathic calcium oxalate stone formers by whether or not they showed positive evidence of forming a stone on Randall's plaque (RP). Materials and Methods In patients undergoing either percutaneous or ureteroscopic procedures for kidney stone removal, all stone material was extracted, and analyzed using micro computed tomographic imaging (micro CT), in order to identify those attached to RP. 24-hour urines were collected weeks after the stone removal procedure and off of medications that would affect urine composition. Endoscopic video was analyzed for papillary pathology (RP, pitting, plugging, dilated ducts, loss of papillary shape) by an observer blinded to the data on stone type. Percent papillary area occupied by RP and ductal plugging was quantified using image analytic software. Results Patients having even 1 stone on RP (N=36) did not differ from Non-RP patients (N=37) in age, sex, BMI, or other clinical characteristics. Compared to the Non-RP group, RP stone formers had more numerous but smaller stones, more abundant papillary RP, and fewer ductal plugs, both by quantitative measurement of surface area (on average, 3 times more plaque area, but only 41% as much plug area as Non-RP) and by semi-quantitative visual grading. Serum and blood values did not differ between RP and Non-RP stone formers by any measure. Conclusions Growth of many small stones on plaque seems the pathogenetic scheme for the RP stone forming phenotype, whereas the Non-RP phenotype stone pathogenesis pathway is less obvious. Higher papillary plugging in Non-RP suggests that plugs play a role in stone formation, and that these patients have a greater degree of papillary damage. Underlying mechanisms that create these distinctive phenotypes are presently unknown.
... The observation of urinary stones by means of a stereomicroscope represents a first fundamental approach in their characterization, providing important information in terms of etiological or pathophysiological conditions . This examination is based on a morphological evaluation of the aggregates, taking into account color, shape, aspect of the surface and the section, presence of umbilication (papillary imprint) and Randall's Plaque (Abrol & Kekre, 2014;Ç iftçioglu et al., 2008;Letavernier et al., 2016). Figure 1 reports selected micrographs of the examined bladder stones. ...
... The observation of urinary stones by means of a stereomicroscope represents a first fundamental approach in their characterization, providing important information in terms of etiological or pathophysiological conditions . This examination is based on a morphological evaluation of the aggregates, taking into account color, shape, aspect of the surface and the section, presence of umbilication (papillary imprint) and Randall's Plaque (Abrol & Kekre, 2014;Ç iftçioglu et al., 2008;Letavernier et al., 2016). Figure 1 reports selected micrographs of the examined bladder stones. ...
This paper represents the first result of an active collaboration between the University of Sannio and the San Pio Hospital (Benevento, Italy), started in the 2018, that aims to a detailed mineralogical investigation of urinary stones of patients from Campania region. Herein, selected human bladder stones have been deeply characterized for clinical purposes and environmental biomonitoring, focusing on the importance to evaluate the concentration and distribution of undesired trace elements by means of microscopic techniques in the place of conventional wet chemical analyses. A rare bladder stones with a sea-urchin appearance, known as jackstone calculus, were also investigated (along with bladder stones made of uric acid and brushite) by means a comprehensive analytical approach, including Synchrotron X-ray Diffraction and Simultaneous Thermal Analyses. Main clinical assumptions were inferred according to the morpho-constitutional classification of bladder stones and information about patient’s medical history and lifestyle. In most of the analyzed uroliths, undesired trace elements such as copper, cadmium, lead, chromium, mercury and arsenic have been detected and generally attributable to environmental pollution or contaminated food. Simultaneous occurrence of selenium and mercury should denote a methylmercury detoxification process, probably leading to the formation of a very rare HgSe compound known as tiemannite.
... 4,5 Kidney stones show a great chemical diversity 6,7 but the most common composition corresponds to calcium oxalate monohydrate, found in patients without any systemic disorder (so-called idiopathic stones). In many cases, [8][9][10] these stones originate from mineral deposits at the tip of renal papillae known as Randall's plaques (RPs). [11][12][13] Interestingly, they are not only detected as an anchored site for stone formation in renal-stoneforming patients but also in incipient forms in more than two thirds of people without kidney stone. ...
... RPs are mainly composed of nanocrystalline carbonated hydroxyapatite and amorphous carbonated calcium phosphate but other chemical compounds, such as whitlockite, brushite or monosodium urate were also detected. 9 Moreover, FTIR data show clearly that, in large RPs, apatite presents variable levels of carbonation. 15 These observations support the idea that several mechanisms may be involved in the pathogenesis of RPs. ...
Idiopathic kidney stones originate mainly from calcium phosphate deposits at the tip of renal papillae, known as Randall’s plaques (RPs), also detected in most human kidneys without stones. However, little is known about the mechanisms involved in RP formation. The localization and characterization of such nano-sized objects in the kidney remains a real challenge making their study arduous. This study provides a nanoscale analysis of the chemical composition and morphology of incipient RPs, characterizing in particular the interface between the mineral and the surrounding organic compounds. Relying on data gathered from a calculi collection, the morphology and chemical composition of incipient calcifications in renal tissue was determined using spatially resolved electron energy-loss spectroscopy (EELS). We detected micro-calcifications and individual nano-calcifications found at some distance from the larger ones. Strikingly, concerning the smaller ones, we show that two types of nano-calcifications coexist: calcified organic vesicles and nanometric mineral granules mainly composed of calcium phosphate with carbonate in their core. Interestingly, some of these nano-calcifications present similarities with those reported in physiological bone or pathological cardiovascular biominerals, suggesting possible common formation mechanisms. However the high diversity of these nano-calcifications suggests that several mechanisms may be involved (nucleation on a carbonate core or on organic compounds). In addition, incipient RPs also appear to present specific features at larger scales revealing secondary calcified structures embedded in a fibrillar organic material. Our study proves that analogies exist between physiological and pathological biominerals and provides information to understand the physico-chemical processes involved in pathological calcification formation.
... Randall's plaque was found in stone formers in 57%-99% of patients when reno-ureterocopy was performed. The prevalence seems lower in France than in North American studies [45][46][47][48][49]. Although Randall's plaques seem to be very frequent, common papillary calcifications are usually too small to be evidenced by CT-scan (unlike PXE patients). ...
Pseudoxanthoma elasticum is a rare disease mainly due to ABCC6 gene mutations and characterized by ectopic biomineralization and fragmentation of elastic fibers resulting in skin, cardiovascular and retinal calcifications. It has been recently described that pyrophosphate (a calcification inhibitor) deficiency could be the main cause of ectopic calcifications in this disease and in other genetic disorders associated to mutations of ENPP1 or CD73. Patients affected by Pseudoxanthoma Elasticum seem also prone to develop kidney stones originating from papillary calcifications named Randall’s plaque, and to a lesser extent may be affected by nephrocalcinosis. In this narrative review, we summarize some recent discoveries relative to the pathophysiology of this mendelian disease responsible for both cardiovascular and renal papillary calcifications, and we discuss the potential implications of pyrophosphate deficiency as a promoter of vascular calcifications in kidney stone formers and in patients affected by chronic kidney disease.
... Crystallites in urine (homogeneous nucleation) are agglomerated at the surface of RP which serves as a nucleus (heterogenous nucleation). 16 A third family can be related to physiological calcifications (otoliths, tooth, 17 bone) which becomes pathological with diseases (bone and osteoporosis 18,19 ). ...
Research on pathological calcifications constitutes an exciting topic at the interface between physics, chemistry and medicine. The relationship between their physicochemical characteristics and the pathology responsible for their formation offers a unique opportunity to perform a significant medical diagnosis, to assess the interaction between drugs and these biological entities as well as to develop new drugs. Regarding synchrotron radiation, the emergence of microbeam allows the clinician to perform an early diagnosis. Indeed, we will start this review with a clinical case where Fourier transform infrared spectroscopy using synchrotron radiation as a probe allowed the clinician to save the kidney function of a patient. Following this example, we will see that investigations on pathological calcifications constitute an elegant way to gather major information on different public health problems such type 2 diabetes as well as on rare diseases. To attain this goal, this mini-review dedicated to structural and chemical investigations and based on selected and recent data collected through techniques using third generation synchrotron radiation as a probe is proposed to the reader.
