Preconditioning of the distal tubular epithelium of the human kidney precedes nephrocalcinosis

Verhulst, Anja; Asselman, Marino; Naeyer, S. De; Vervaet, Benjamin A.; Mengel, M.; Gwinner, Wilfried; D’Haese, Patrick C.; Verkoelen, Carl F.; Broe, Marc E. De

doi:10.1111/j.1523-1755.2005.00584.x

Cited by 59 publications

(69 citation statements)

References 35 publications

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“…Studies in our laboratory demonstrated that HAS2 mRNA and the production of high molecular weight HA are upregulated in subconfluent (developing) cultures and downregulated in confluent (mature) cultures (126). As mentioned previously, HA is expressed by renal tubular cells in human fetal kidneys but not in adult kidneys (3).…”

Section: Hamentioning

confidence: 84%

“…We define nephrocalcinosis as the retention of crystals in the renal tubules. Nephrocalcinosis occurs when the epithelial cells that line the renal tubules become susceptible to crystal attachment (3). Although the clinical consequence of nephrocalcinosis is not entirely clear, it may lead to abnormal renal tubular cell function, inflammation, and renal tissue damage.…”

Section: Renal Stone Diseasementioning

confidence: 99%

“…Once inside the cell, crystals slowly dissolved in lysosomes (73). A role for crystal uptake in renal stone disease is questionable, however, because intracellular crystals seldom are observed in the kidney (3,74), and in cell culture, crystals are taken up by proximal tubular cells but not by cells that are derived from segments where crystals are expected to be formed (e.g., the distal tubule, collecting ducts) (75,76). COM and hydroxyapatite crystals adhered to negatively charged cell surface molecules by a process that could be inhibited by GAG, polyglutamic acid, polyaspartic acid, nephrocalcin, uropontin, and citrate but not by THP (77,78).…”

Section: Crystal-cell Interactionsmentioning

confidence: 99%

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Crystal Retention in Renal Stone Disease

Verkoelen¹

2006

Journal of the American Society of Nephrology

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The mechanisms that are involved in renal stone disease are not entirely clear. In this article, the various concepts that have been proposed during the past century are reviewed briefly and integrated into current insights. Much attention is dedicated to hyaluronan (HA), an extremely large glycosaminoglycan that may play a central role in renal stone disease. The precipitation of poorly soluble calcium salts (crystal formation) in the kidney is the inevitable consequence of producing concentrated urine. HA is a major constituent of the extracellular matrix in the renal medullary interstitium and the pericellular matrix of mitogen/stress-activated renal tubular cells. HA is an excellent crystal-binding molecule because of its size, negative ionic charge, and ability to form hydrated gel-like matrices. Crystal binding to HA leads to crystal retention in the renal tubules (nephrocalcinosis) and to the formation of calcified plaques in the renal interstitium (Randall's plaques). It remains to be determined whether one or both forms of renal crystal retention are involved in the development of kidney stones (nephrolithiasis).

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Section: Hamentioning

confidence: 84%

Section: Renal Stone Diseasementioning

confidence: 99%

Section: Crystal-cell Interactionsmentioning

confidence: 99%

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Crystal Retention in Renal Stone Disease

Verkoelen¹

2006

Journal of the American Society of Nephrology

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“…However, levels do not differ from those of term infants; therefore, interpretation of these lower values in the aetiology of NC is still under debate, and additional studies are warranted. On the other hand, expression of crystal-binding molecules (hyaluronan and osteopontin) at the luminal surface of the distal tubular cells in preterm neonates precedes crystal retention at the distal nephron epithelium, the first step to NC [67]. Nephrocalcin and Tamm-Horsfall protein have not been studied in preterm neonates.…”

Section: Factors Inhibiting Nephrocalcinosismentioning

confidence: 99%

Nephrocalcinosis in preterm neonates

2010

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The prevalence of nephrocalcinosis (NC) in preterm neonates in recent reports is 7-41%. The wide range in prevalence is a consequence of different study populations and ultrasound equipment and criteria, in addition to a moderate interobserver variation. NC in preterm neonates has a multifactorial aetiology, consisting of low gestational age and birth weight, often in combination with severe respiratory disease, and occurs as a result of an imbalance between stone-promoting and stoneinhibiting factors. A limited number of histological studies suggest that calcium oxalate crystals play an important role in NC in premature neonates. In 85% of children resolution of NC occurs in the first years of life. Prematurity, per se, is associated with high blood pressure, relatively small kidneys, and (distal) tubular dysfunction. In addition, NC in preterm neonates can have long-term sequelae for glomerular and tubular function. Long-term follow-up of blood pressure and renal function of prematurely born children, especially with neonatal NC, is recommended. Prevention of NC with (low) oral doses of citrate has not resulted in a significant decrease in the prevalence of NC; a higher citrate dosage deserves further study. Future research pertaining to prevention of NC in preterm neonates is crucial.

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“…Hyaluronan expression on apical membranes of tubule epithelial cells has been associated with crystal adhesion (Asselman et al, 2003Verhulst et al, 2005). Therefore, we would expect to find hyaluronan expression in bypass patients, whose tubules contain crystals.…”

mentioning

confidence: 99%

Renal Intratubular Crystals and Hyaluronan Staining Occur in Stone Formers with Bypass Surgery but not with Idiopathic Calcium Oxalate Stones

Evan

Coe

Gillen

et al. 2008

The Anatomical Record

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Whether idiopathic calcium oxalate (CaOx) stone formers form inner medullary collecting duct (IMCD) crystal deposits bears on pathogenetic mechanisms of stone formation. In prior work, using light and transmission electron microscopy, we have found no IMCD crystal deposits. Here, we searched serial sections of papillary biopsies from a prior study of 15 idiopathic calcium oxalate stone formers, 4 intestinal bypass patients with CaOx stones, and 4 non-stone-forming subjects, and biopsies from an additional hitherto unreported 15 idiopathic calcium oxalate stone formers and 1 bypass patient using polarized light oil immersion optics, for deposits overlooked in our original study. We found no IMCD deposits in any of 1,500 serial sections from the 30 idiopathic calcium oxalate stone formers, nor in 87 additional sections from a frozen idiopathic calcium oxalate stone former biopsy sample processed without exposure to aqueous solutions. Among 4 of the 5 bypass patients but in none of the 30 idiopathic calcium oxalate stone formers or 4 normal stone formers, we found tiny birefringent thin crystalline overlays on scattered IMCD cell membranes. We also found IMCD lumen deposits in two bypass patients that contained mixed birefringent and nonbirefringent crystals, presumably CaOx and apatite. In the bypass patients, we observed focal apical IMCD cell hyaluronan staining, which was absent in idiopathic calcium oxalate stone formers. The absence of any IMCD deposits in 1,500 serial sections of biopsies from 30 idiopathic calcium oxalate stone formers allows us to place the upper limit on the probability of their occurrence at approximately 0.002 and place the lower limit of their size at the resolution of the optics (<0.2 m). The tiny deposits in bypass patients may be the initial crystal lesion.

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Preconditioning of the distal tubular epithelium of the human kidney precedes nephrocalcinosis

Cited by 59 publications

References 35 publications

Crystal Retention in Renal Stone Disease

Crystal Retention in Renal Stone Disease

Nephrocalcinosis in preterm neonates

Renal Intratubular Crystals and Hyaluronan Staining Occur in Stone Formers with Bypass Surgery but not with Idiopathic Calcium Oxalate Stones

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