Utility of endogenous creatinine clearance as a measure of renal function in mice

Stephen R. Dunn, Zhonghua Qi, Erwin P. Bottinger, Matthew D. Breyer, Kumar Sharma

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Background. The use of endogenous plasma creatinine levels and creatinine clearance as a tool to evaluate renal function in mice has come under scrutiny as prior studies have reported that the Jaffé alkaline picrate method grossly overestimates true plasma creatinine in mice. As members of the NIDDK Animal Models of Diabetic Complications Consortium (AMDCC), we evaluated the performance and feasibility of an alternative high-performance liquid chromatography (HPLC)-based method for standard determination of plasma creatinine and creatinine clearance in mice. Our purpose was to develop a simple method that provides a reliable, reproducible, and sensitive assay for small volumes (<25 μL) of mouse plasma and sera. Methods. We compared creatinine clearance measured by HPLC with the Jaffé method and HPLC creatinine clearance with inulin clearance [fluoroscein isothiocyanate (FITC) inulin in an osmotic pump implanted in mouse] in C57BL/6J mice. Different groups of mice underwent either one of two protocols. Protocol A included dietary intervention with normal, low salt plus enalapril, or high salt. Protocol B induced diabetes using streptozotocin. Results. First, mean plasma creatinine levels were significantly lower (P < 0.0001) by HPLC (0.128 ± 0.026 mg/dL) vs. Jaffé (0.4 ± 0.12 mg/dL) for mice on a normal diet. Urine creatinine concentrations measured by HPLC were 10% lower than by Jaffé (P < 0.01). Second, mean creatinine clearance by HPLC for mice on a normal diet was 255 ± 68 μL/min. Mice on low salt diet plus enalapril had reduced creatinine clearance (72.8 ± 24.2 μL/min) while mice on high salt diet had an elevated creatinine clearance (355 ± 105 μL/min). Third, diabetic mice (19 to 24 weeks of diabetes) exhibited hyperfiltration as creatinine clearance was 524 ± 214 μL/min whereas nondiabetic age/gender-matched mice showed a mean creatinine clearance of 206 ± 41 μL/min. Finally, significant correlation was demonstrated for creatinine clearance by HPLC vs. inulin clearance (R = 0.643; P < 0.001). Conclusion. HPLC is highly accurate, much more sensitive and specific than the Jaffé method for plasma creatinine measurements in mice. Creatinine clearance in mice measured by HPLC reflects changes in renal function induced by diet and diabetes.

Original languageEnglish (US)
Pages (from-to)1959-1967
Number of pages9
JournalKidney International
Volume65
Issue number5
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

Fingerprint

Creatinine
Kidney
High Pressure Liquid Chromatography
Inulin
Diet
Enalapril
Salts
National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)
Sodium-Restricted Diet
Experimental Diabetes Mellitus
Diabetes Complications
Inbred C57BL Mouse
Animal Models
Urine

Keywords

  • C57BL/6J mice
  • Creatinine
  • Diabetes
  • Glomerular filtration rate (GFR)
  • High performance liquid chromatography (HPLC)
  • Inulin
  • Sodium diet

ASJC Scopus subject areas

  • Nephrology

Cite this

Utility of endogenous creatinine clearance as a measure of renal function in mice. / Dunn, Stephen R.; Qi, Zhonghua; Bottinger, Erwin P.; Breyer, Matthew D.; Sharma, Kumar.

In: Kidney International, Vol. 65, No. 5, 01.01.2004, p. 1959-1967.

Research output: Contribution to journalArticle

Dunn, Stephen R. ; Qi, Zhonghua ; Bottinger, Erwin P. ; Breyer, Matthew D. ; Sharma, Kumar. / Utility of endogenous creatinine clearance as a measure of renal function in mice. In: Kidney International. 2004 ; Vol. 65, No. 5. pp. 1959-1967.
@article{2d341bdc080640a48b4528a8b2ca04b6,
title = "Utility of endogenous creatinine clearance as a measure of renal function in mice",
abstract = "Background. The use of endogenous plasma creatinine levels and creatinine clearance as a tool to evaluate renal function in mice has come under scrutiny as prior studies have reported that the Jaff{\'e} alkaline picrate method grossly overestimates true plasma creatinine in mice. As members of the NIDDK Animal Models of Diabetic Complications Consortium (AMDCC), we evaluated the performance and feasibility of an alternative high-performance liquid chromatography (HPLC)-based method for standard determination of plasma creatinine and creatinine clearance in mice. Our purpose was to develop a simple method that provides a reliable, reproducible, and sensitive assay for small volumes (<25 μL) of mouse plasma and sera. Methods. We compared creatinine clearance measured by HPLC with the Jaff{\'e} method and HPLC creatinine clearance with inulin clearance [fluoroscein isothiocyanate (FITC) inulin in an osmotic pump implanted in mouse] in C57BL/6J mice. Different groups of mice underwent either one of two protocols. Protocol A included dietary intervention with normal, low salt plus enalapril, or high salt. Protocol B induced diabetes using streptozotocin. Results. First, mean plasma creatinine levels were significantly lower (P < 0.0001) by HPLC (0.128 ± 0.026 mg/dL) vs. Jaff{\'e} (0.4 ± 0.12 mg/dL) for mice on a normal diet. Urine creatinine concentrations measured by HPLC were 10{\%} lower than by Jaff{\'e} (P < 0.01). Second, mean creatinine clearance by HPLC for mice on a normal diet was 255 ± 68 μL/min. Mice on low salt diet plus enalapril had reduced creatinine clearance (72.8 ± 24.2 μL/min) while mice on high salt diet had an elevated creatinine clearance (355 ± 105 μL/min). Third, diabetic mice (19 to 24 weeks of diabetes) exhibited hyperfiltration as creatinine clearance was 524 ± 214 μL/min whereas nondiabetic age/gender-matched mice showed a mean creatinine clearance of 206 ± 41 μL/min. Finally, significant correlation was demonstrated for creatinine clearance by HPLC vs. inulin clearance (R = 0.643; P < 0.001). Conclusion. HPLC is highly accurate, much more sensitive and specific than the Jaff{\'e} method for plasma creatinine measurements in mice. Creatinine clearance in mice measured by HPLC reflects changes in renal function induced by diet and diabetes.",
keywords = "C57BL/6J mice, Creatinine, Diabetes, Glomerular filtration rate (GFR), High performance liquid chromatography (HPLC), Inulin, Sodium diet",
author = "Dunn, {Stephen R.} and Zhonghua Qi and Bottinger, {Erwin P.} and Breyer, {Matthew D.} and Kumar Sharma",
year = "2004",
month = "1",
day = "1",
doi = "10.1111/j.1523-1755.2004.00600.x",
language = "English (US)",
volume = "65",
pages = "1959--1967",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Utility of endogenous creatinine clearance as a measure of renal function in mice

AU - Dunn, Stephen R.

AU - Qi, Zhonghua

AU - Bottinger, Erwin P.

AU - Breyer, Matthew D.

AU - Sharma, Kumar

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Background. The use of endogenous plasma creatinine levels and creatinine clearance as a tool to evaluate renal function in mice has come under scrutiny as prior studies have reported that the Jaffé alkaline picrate method grossly overestimates true plasma creatinine in mice. As members of the NIDDK Animal Models of Diabetic Complications Consortium (AMDCC), we evaluated the performance and feasibility of an alternative high-performance liquid chromatography (HPLC)-based method for standard determination of plasma creatinine and creatinine clearance in mice. Our purpose was to develop a simple method that provides a reliable, reproducible, and sensitive assay for small volumes (<25 μL) of mouse plasma and sera. Methods. We compared creatinine clearance measured by HPLC with the Jaffé method and HPLC creatinine clearance with inulin clearance [fluoroscein isothiocyanate (FITC) inulin in an osmotic pump implanted in mouse] in C57BL/6J mice. Different groups of mice underwent either one of two protocols. Protocol A included dietary intervention with normal, low salt plus enalapril, or high salt. Protocol B induced diabetes using streptozotocin. Results. First, mean plasma creatinine levels were significantly lower (P < 0.0001) by HPLC (0.128 ± 0.026 mg/dL) vs. Jaffé (0.4 ± 0.12 mg/dL) for mice on a normal diet. Urine creatinine concentrations measured by HPLC were 10% lower than by Jaffé (P < 0.01). Second, mean creatinine clearance by HPLC for mice on a normal diet was 255 ± 68 μL/min. Mice on low salt diet plus enalapril had reduced creatinine clearance (72.8 ± 24.2 μL/min) while mice on high salt diet had an elevated creatinine clearance (355 ± 105 μL/min). Third, diabetic mice (19 to 24 weeks of diabetes) exhibited hyperfiltration as creatinine clearance was 524 ± 214 μL/min whereas nondiabetic age/gender-matched mice showed a mean creatinine clearance of 206 ± 41 μL/min. Finally, significant correlation was demonstrated for creatinine clearance by HPLC vs. inulin clearance (R = 0.643; P < 0.001). Conclusion. HPLC is highly accurate, much more sensitive and specific than the Jaffé method for plasma creatinine measurements in mice. Creatinine clearance in mice measured by HPLC reflects changes in renal function induced by diet and diabetes.

AB - Background. The use of endogenous plasma creatinine levels and creatinine clearance as a tool to evaluate renal function in mice has come under scrutiny as prior studies have reported that the Jaffé alkaline picrate method grossly overestimates true plasma creatinine in mice. As members of the NIDDK Animal Models of Diabetic Complications Consortium (AMDCC), we evaluated the performance and feasibility of an alternative high-performance liquid chromatography (HPLC)-based method for standard determination of plasma creatinine and creatinine clearance in mice. Our purpose was to develop a simple method that provides a reliable, reproducible, and sensitive assay for small volumes (<25 μL) of mouse plasma and sera. Methods. We compared creatinine clearance measured by HPLC with the Jaffé method and HPLC creatinine clearance with inulin clearance [fluoroscein isothiocyanate (FITC) inulin in an osmotic pump implanted in mouse] in C57BL/6J mice. Different groups of mice underwent either one of two protocols. Protocol A included dietary intervention with normal, low salt plus enalapril, or high salt. Protocol B induced diabetes using streptozotocin. Results. First, mean plasma creatinine levels were significantly lower (P < 0.0001) by HPLC (0.128 ± 0.026 mg/dL) vs. Jaffé (0.4 ± 0.12 mg/dL) for mice on a normal diet. Urine creatinine concentrations measured by HPLC were 10% lower than by Jaffé (P < 0.01). Second, mean creatinine clearance by HPLC for mice on a normal diet was 255 ± 68 μL/min. Mice on low salt diet plus enalapril had reduced creatinine clearance (72.8 ± 24.2 μL/min) while mice on high salt diet had an elevated creatinine clearance (355 ± 105 μL/min). Third, diabetic mice (19 to 24 weeks of diabetes) exhibited hyperfiltration as creatinine clearance was 524 ± 214 μL/min whereas nondiabetic age/gender-matched mice showed a mean creatinine clearance of 206 ± 41 μL/min. Finally, significant correlation was demonstrated for creatinine clearance by HPLC vs. inulin clearance (R = 0.643; P < 0.001). Conclusion. HPLC is highly accurate, much more sensitive and specific than the Jaffé method for plasma creatinine measurements in mice. Creatinine clearance in mice measured by HPLC reflects changes in renal function induced by diet and diabetes.

KW - C57BL/6J mice

KW - Creatinine

KW - Diabetes

KW - Glomerular filtration rate (GFR)

KW - High performance liquid chromatography (HPLC)

KW - Inulin

KW - Sodium diet

UR - http://www.scopus.com/inward/record.url?scp=2342570276&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2342570276&partnerID=8YFLogxK

U2 - 10.1111/j.1523-1755.2004.00600.x

DO - 10.1111/j.1523-1755.2004.00600.x

M3 - Article

C2 - 15086941

AN - SCOPUS:2342570276

VL - 65

SP - 1959

EP - 1967

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 5

ER -