Kidney stone disease

Abstract

About 5% of American women and 12% of men will develop a kidney stone at some time in their life, and prevalence has been rising in both sexes. Approximately 80% of stones are composed of calcium oxalate (CaOx) and calcium phosphate (CaP); 10% of struvite (magnesium ammonium phosphate produced during infection with bacteria that possess the enzyme urease), 9% of uric acid (UA); and the remaining 1% are composed of cystine or ammonium acid urate or are diagnosed as drug-related stones. Stones ultimately arise because of an unwanted phase change of these substances from liquid to solid state. Here we focus on the mechanisms of pathogenesis involved in CaOx, CaP, UA, and cystine stone formation, including recent developments in our understanding of related changes in human kidney tissue and of underlying genetic causes, in addition to current therapeutics.

Figure 1

Initial sites of crystal deposition and localization of osteopontin. The initial sites of calcium deposits in the deep papillary tissue of an idiopathic CaOx SF are shown in light (A) and transmission electron microscopic (TEM) images (B–D). In A, Yasue-stained (the Yasue stain detects calcium) biopsy tissue reveals sites of crystal deposits (arrows) within the BM of thin Henle loops and not in nearby inner medullary CDs. By TEM (B and C), the crystal deposits appear as single spheres with a multi-laminated (6–7 layers) internal morphology consisting of a central light region of crystalline material surrounded by a dark layer of matrix material (arrows). Note that the cells lining this Henle loop appear morphologically normal. Osteopontin (D) localizes on either side of the apatite layers, sometimes forming with a clear “tram track”–like appearance (arrows). Magnification: ×1,800 (A); ×20,000 (B); ×35,000 (C); ×37,000 (D). A and B reprinted from ref. . C and D reprinted with permission from Kidney International (21).

Figure 2

Accumulation of interstitial crystal deposits as seen in light and TEM images in a papillary biopsy from an idiopathic CaOx SF. (A) Light microscopy reveals extensive accumulation of crystalline deposits (green arrow) shown around the Henle loops and nearby vascular bundles and inner medullary CDs. This progressive accumulation of crystalline material in the interstitium results in the formation of incomplete to complete cuffs of plaque. (B) TEM reveals a normal thin Henle loop surrounded by a complete cuff of interstitial plaque. (C) TEM shows a site of plaque located in the interstitial space, away from a tubular wall. Note that single crystal deposits appear embedded in a sea of matrix. Magnification: ×1,500 (A); ×13,000 (B); ×13,000 (C). A reprinted from ref. . B reprinted with permission from Urological Research (123). C reprinted with permission from Kidney International (21).

Figure 3

Endoscopic and histological images from a SF following small bowel bypass. The papillary surface (A) shows small, round nodular structures (arrowheads) near the openings of the Bellini ducts; distinct sites of Randall plaque material are not found. (B) Biopsy through a region that contained nodules reveals crystal deposition in the lumens of a few CDs as far down as the Bellini ducts (indicate by the asterisk). Note dilated CDs (arrows) with cast material in regions of fibrosis around crystal deposit–filled CDs. (C) A single CD is shown to be completely filled with crystals with injured lining cells. Magnification: ×100 (B); ×550 (C). Reprinted with permission from ref. .

Figure 4

Endoscopic and histological images from a brushite SF. (A) Papilla from a brushite SF that was video recorded at the time of stone removal shows depressions (arrows) near the papillary tip and flattening, a phenomenon not seen in CaOx SFs. Like CaOx SFs, the papilla possessed sites of Randall plaque (arrowheads), though lesser in number. In addition, papillae possess sites of a yellowish crystalline deposit at the openings of Bellini ducts (indicated by the asterisk). These ducts were occasionally enlarged and filled with a crystalline material that protruded from the duct (inset, arrow) that might serve as a site for stone attachment. (B) Deposits in the lumens of an individual inner medullary CD (arrow) and in an occasional nearby Henle loop are shown. The crystal deposits greatly expanded the lumen of these tubules, and cell injury to the degree of complete cell necrosis was found. A cuff of interstitial inflammation and fibrosis accompanied sites of intraluminal disposition. (C and D) A cortical sample from a normal human kidney (C) compared with that of a brushite SF (D) that reveals advanced glomerulosclerosis (arrows), moderate tubular atrophy, and interstitial fibrosis — changes not seen in CaOx SFs. Magnification: ×1,400 (B); ×1,000 (C and D). A and B reprinted with permission from Kidney International (92). C and D reprinted with permission from Urological Research (123).