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      Phenotypic characterization of kidney stone formers by endoscopic and histological quantification of intra-renal calcification

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          Interstitial Randall’s plaques and collecting duct plugs are distinct forms of renal calcification thought to provide sites for stone retention within the kidney. Here we assessed kidney stone precursor lesions in a random cohort of stone formers undergoing percutaneous nephrolithotomy. Each accessible papilla was endoscopically mapped following stone removal. The percent papillary surface area covered by plaque and plug were digitally measured using image analysis software. Stone composition was determined by micro-computed tomography and infrared analysis. A representative papillary tip was biopsied. Twenty-four hour urine collections were used to measure supersaturation and crystal growth inhibition. The vast majority (99%) of stone formers had Randall’s plaque on at least 1 papilla, while significant tubular plugging (over 1% of surface area) was present in about one-fifth of patients. Among calcium oxalate stone formers the amount of Randall’s plaque correlated with higher urinary citrate levels. Tubular plugging correlated positively with pH and brushite supersaturation but negatively with citrate excretion. Lower urinary crystal growth inhibition predicted the presence of tubular plugging but not plaque. Thus, tubular plugging may be more common than previously recognized among patients with all types of stones, including some with idiopathic calcium oxalate stones.

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          Most cited references 25

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           Lea Randall (1937)
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            EQUIL2: a BASIC computer program for the calculation of urinary saturation.

            A BASIC computer program for the calculation of urinary supersaturation with respect to the common kidney stone components is described. In vitro and in vivo tests show that the program described accurately calculates supersaturation. The application of this computer program to urolithiasis research is discussed.
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              Randall's plaque: pathogenesis and role in calcium oxalate nephrolithiasis.

               A Evan,  J Lingeman,  F Coe (2006)
              The purpose of these studies was to test the hypothesis that Randall's plaque develops in unique anatomical sites of the kidney and their formation is conditioned by specific stone-forming pathophysiologies. We performed intraoperative papillary biopsies from kidneys of idiopathic-calcium oxalate (CaOx), intestinal bypass for obesity, brushite (BR) and cystine stone formers (SF) during percutaneous nephrolithotomy. Tissues were examined by infrared analysis and light and electron microscopy. Our analysis revealed a distinct pattern of mineral deposition and papillary pathology for each type of SF. CaOx SF had interstitial apatite crystals beginning at thin loops of Henle. These deposits termed Randall's plaque are thought to serve as sites for stone attachment. No tubular injury was noted. Intestinal bypass patients possessed intraluminal apatite deposits in inner medullary collecting ducts (IMCD) with associated cell injury. BR SF showed the most severe form of cortical and medullary changes with sites of Randall's plaque, and yellowish intraluminal deposits of apatite in IMCD. Cystine SF had plugging of ducts of Bellini with cystine crystals and apatite deposits in IMCD and loops of Henle. Intratubular sites of crystalline deposits were always associated to adjacent regions of interstitial fibrosis. The metabolic, anatomic, and surgical pathologic findings in four distinct groups of SF clearly show that 'the histology of the renal papilla from a stone former, is particular to the clinical setting'. We believe our approach to studying stone disease will provide insights into the pathogenesis of stone formation for each type of SF that will lead to improved clinical treatment.

                Author and article information

                Kidney Int
                Kidney Int.
                Kidney international
                29 May 2013
                22 May 2013
                October 2013
                01 April 2014
                : 84
                : 4
                : 818-825
                [1 ]Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN
                [2 ]Department of Urology, Mayo Clinic, Rochester, MN
                [3 ]Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN
                [4 ]Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN
                [5 ]Department of Radiology, Mayo Clinic, Rochester, MN
                [6 ]Biomedical Imaging Resource Core, Mayo Clinic, Rochester, MN
                [7 ]Indiana University School of Medicine, Indianapolis, IN
                Author notes
                Correspondence: John C. Lieske, M.D., Mayo Clinic Division of Nephrology and Hypertension, 200 First Street SW, Rochester, MN 55905, Telephone: (507)284-2064; FAX: (507)266-9315, Lieske.John@ 123456mayo.edu
                Funded by: National Institute of Diabetes and Digestive and Kidney Diseases : NIDDK
                Award ID: P50 DK083007 || DK


                calcium oxalate, calcium phosphate, collecting duct, randall’s plaque, tubular plug


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