Intratubular crystallization of calcium oxalate in the presence of membrane vesicles: An in vitro study

J. M. Fasano, S. R. Khan

Research output: Contribution to journalArticle

Abstract

Background. Since urine spends only a few minutes in the renal tubules and has a low supersaturation with respect to calcium oxalate (CaOx), nucleation of CaOx crystals in the kidneys is most probably heterogeneous. We have proposed that membranes of cellular degradation products are the main substrate for crystal nucleation. The purpose of our study was to determine the site of membrane-mediated crystal nucleation within the renal tubules and the required lag time, factors that determine whether crystallization results in crystalluria or nephrolithiasis. Methods. Nucleation of CaOx was allowed to occur in five different artificial urine solutions with ionic concentrations simulating urine in proximal tubules (PTs), descending (DLH) and ascending (ALH) limbs of the loop of Henle, distal tubules (DTs), and collecting ducts (CDs). A constant composition crystallization system was used. Experiments were run for two hours with or without the renal tubular brush border membrane (BBM) vesicles. Results. The addition of BBM significantly reduced the nucleation lag time and increased the rate of crystallization. The average nucleation lag time decreased from 84.6 ± 43.4 minutes to 24.5 ± 19 minutes in PTs, from 143.6 ± 29 to 70.2 ± 53.4 minutes in DLH, from 17.6 ± 8.6 minutes to 0.625 ± 0.65 minutes in DTs and from 9.54 ± 3.03 minutes to 0.625 ± 0.65 minutes in CDs. There was no nucleation in the ALH solution without BBM for two hours. CaOx dihydrate (COD) was common in most solutions. Calcium phosphate (CaP) also nucleated in the DLH and CD solutions. Conclusions. In the absence of membrane vesicles, there was no crystallization in any of the solutions within the time urine spends in the renal tubules. As a result, homogeneous nucleation of crystals anywhere within the nephron appears unlikely. However, BBM-supported nucleation is possible in the DTs as well as CDs. A high crystallization rate in CDs would promote rapid crystal growth and aggregation, resulting in crystal retention within the kidneys and development of nephrolithiasis.

Original languageEnglish (US)
Pages (from-to)169-178
Number of pages10
JournalKidney International
Volume59
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Calcium Oxalate
Crystallization
Membranes
Microvilli
Kidney
Urine
Nephrolithiasis
Loop of Henle
Nephrons
In Vitro Techniques

Keywords

  • Biomineralization
  • Calcium phosphate
  • Matrix vesicles
  • Nephrolithiasis
  • Renal stones

ASJC Scopus subject areas

  • Nephrology

Cite this

Intratubular crystallization of calcium oxalate in the presence of membrane vesicles : An in vitro study. / Fasano, J. M.; Khan, S. R.

In: Kidney International, Vol. 59, No. 1, 2001, p. 169-178.

Research output: Contribution to journalArticle

@article{d1eaaefcc37446d588f20e607dc7d8d6,
title = "Intratubular crystallization of calcium oxalate in the presence of membrane vesicles: An in vitro study",
abstract = "Background. Since urine spends only a few minutes in the renal tubules and has a low supersaturation with respect to calcium oxalate (CaOx), nucleation of CaOx crystals in the kidneys is most probably heterogeneous. We have proposed that membranes of cellular degradation products are the main substrate for crystal nucleation. The purpose of our study was to determine the site of membrane-mediated crystal nucleation within the renal tubules and the required lag time, factors that determine whether crystallization results in crystalluria or nephrolithiasis. Methods. Nucleation of CaOx was allowed to occur in five different artificial urine solutions with ionic concentrations simulating urine in proximal tubules (PTs), descending (DLH) and ascending (ALH) limbs of the loop of Henle, distal tubules (DTs), and collecting ducts (CDs). A constant composition crystallization system was used. Experiments were run for two hours with or without the renal tubular brush border membrane (BBM) vesicles. Results. The addition of BBM significantly reduced the nucleation lag time and increased the rate of crystallization. The average nucleation lag time decreased from 84.6 ± 43.4 minutes to 24.5 ± 19 minutes in PTs, from 143.6 ± 29 to 70.2 ± 53.4 minutes in DLH, from 17.6 ± 8.6 minutes to 0.625 ± 0.65 minutes in DTs and from 9.54 ± 3.03 minutes to 0.625 ± 0.65 minutes in CDs. There was no nucleation in the ALH solution without BBM for two hours. CaOx dihydrate (COD) was common in most solutions. Calcium phosphate (CaP) also nucleated in the DLH and CD solutions. Conclusions. In the absence of membrane vesicles, there was no crystallization in any of the solutions within the time urine spends in the renal tubules. As a result, homogeneous nucleation of crystals anywhere within the nephron appears unlikely. However, BBM-supported nucleation is possible in the DTs as well as CDs. A high crystallization rate in CDs would promote rapid crystal growth and aggregation, resulting in crystal retention within the kidneys and development of nephrolithiasis.",
keywords = "Biomineralization, Calcium phosphate, Matrix vesicles, Nephrolithiasis, Renal stones",
author = "Fasano, {J. M.} and Khan, {S. R.}",
year = "2001",
doi = "10.1046/j.1523-1755.2001.00477.x",
language = "English (US)",
volume = "59",
pages = "169--178",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Intratubular crystallization of calcium oxalate in the presence of membrane vesicles

T2 - An in vitro study

AU - Fasano, J. M.

AU - Khan, S. R.

PY - 2001

Y1 - 2001

N2 - Background. Since urine spends only a few minutes in the renal tubules and has a low supersaturation with respect to calcium oxalate (CaOx), nucleation of CaOx crystals in the kidneys is most probably heterogeneous. We have proposed that membranes of cellular degradation products are the main substrate for crystal nucleation. The purpose of our study was to determine the site of membrane-mediated crystal nucleation within the renal tubules and the required lag time, factors that determine whether crystallization results in crystalluria or nephrolithiasis. Methods. Nucleation of CaOx was allowed to occur in five different artificial urine solutions with ionic concentrations simulating urine in proximal tubules (PTs), descending (DLH) and ascending (ALH) limbs of the loop of Henle, distal tubules (DTs), and collecting ducts (CDs). A constant composition crystallization system was used. Experiments were run for two hours with or without the renal tubular brush border membrane (BBM) vesicles. Results. The addition of BBM significantly reduced the nucleation lag time and increased the rate of crystallization. The average nucleation lag time decreased from 84.6 ± 43.4 minutes to 24.5 ± 19 minutes in PTs, from 143.6 ± 29 to 70.2 ± 53.4 minutes in DLH, from 17.6 ± 8.6 minutes to 0.625 ± 0.65 minutes in DTs and from 9.54 ± 3.03 minutes to 0.625 ± 0.65 minutes in CDs. There was no nucleation in the ALH solution without BBM for two hours. CaOx dihydrate (COD) was common in most solutions. Calcium phosphate (CaP) also nucleated in the DLH and CD solutions. Conclusions. In the absence of membrane vesicles, there was no crystallization in any of the solutions within the time urine spends in the renal tubules. As a result, homogeneous nucleation of crystals anywhere within the nephron appears unlikely. However, BBM-supported nucleation is possible in the DTs as well as CDs. A high crystallization rate in CDs would promote rapid crystal growth and aggregation, resulting in crystal retention within the kidneys and development of nephrolithiasis.

AB - Background. Since urine spends only a few minutes in the renal tubules and has a low supersaturation with respect to calcium oxalate (CaOx), nucleation of CaOx crystals in the kidneys is most probably heterogeneous. We have proposed that membranes of cellular degradation products are the main substrate for crystal nucleation. The purpose of our study was to determine the site of membrane-mediated crystal nucleation within the renal tubules and the required lag time, factors that determine whether crystallization results in crystalluria or nephrolithiasis. Methods. Nucleation of CaOx was allowed to occur in five different artificial urine solutions with ionic concentrations simulating urine in proximal tubules (PTs), descending (DLH) and ascending (ALH) limbs of the loop of Henle, distal tubules (DTs), and collecting ducts (CDs). A constant composition crystallization system was used. Experiments were run for two hours with or without the renal tubular brush border membrane (BBM) vesicles. Results. The addition of BBM significantly reduced the nucleation lag time and increased the rate of crystallization. The average nucleation lag time decreased from 84.6 ± 43.4 minutes to 24.5 ± 19 minutes in PTs, from 143.6 ± 29 to 70.2 ± 53.4 minutes in DLH, from 17.6 ± 8.6 minutes to 0.625 ± 0.65 minutes in DTs and from 9.54 ± 3.03 minutes to 0.625 ± 0.65 minutes in CDs. There was no nucleation in the ALH solution without BBM for two hours. CaOx dihydrate (COD) was common in most solutions. Calcium phosphate (CaP) also nucleated in the DLH and CD solutions. Conclusions. In the absence of membrane vesicles, there was no crystallization in any of the solutions within the time urine spends in the renal tubules. As a result, homogeneous nucleation of crystals anywhere within the nephron appears unlikely. However, BBM-supported nucleation is possible in the DTs as well as CDs. A high crystallization rate in CDs would promote rapid crystal growth and aggregation, resulting in crystal retention within the kidneys and development of nephrolithiasis.

KW - Biomineralization

KW - Calcium phosphate

KW - Matrix vesicles

KW - Nephrolithiasis

KW - Renal stones

UR - http://www.scopus.com/inward/record.url?scp=0035173432&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035173432&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.2001.00477.x

DO - 10.1046/j.1523-1755.2001.00477.x

M3 - Article

C2 - 11135069

AN - SCOPUS:0035173432

VL - 59

SP - 169

EP - 178

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 1

ER -