Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes

Boris B. Betz, Sara J. Jenks, Andrew D. Cronshaw, Douglas J. Lamont, Carolynn Cairns, Jonathan R. Manning, Jane Goddard, David J. Webb, John J. Mullins, Jeremy Hughes, Stela Mclachlan, Mark W J Strachan, Jackie F. Price, Bryan R. Conway (Lead / Corresponding author)

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m2 (odds ratio 0.48; 95% confidence interval, 0.26-0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations.

Original languageEnglish
Pages (from-to)1125-1135
Number of pages11
JournalKidney International
Volume89
Issue number5
Early online date7 Mar 2016
DOIs
Publication statusPublished - May 2016

Fingerprint

Diabetic Nephropathies
Epidermal Growth Factor
Type 2 Diabetes Mellitus
Rodentia
Biomarkers
Kidney
Odds Ratio
Confidence Intervals
Creatinine
Peptides
Albuminuria
Glomerular Filtration Rate
Hyperglycemia
Proteins
Enzyme-Linked Immunosorbent Assay
Urine
Hypertension
Population

Keywords

  • diabetic nephropathy
  • epidermal growth factor
  • peptidomics

Cite this

Betz, Boris B. ; Jenks, Sara J. ; Cronshaw, Andrew D. ; Lamont, Douglas J. ; Cairns, Carolynn ; Manning, Jonathan R. ; Goddard, Jane ; Webb, David J. ; Mullins, John J. ; Hughes, Jeremy ; Mclachlan, Stela ; Strachan, Mark W J ; Price, Jackie F. ; Conway, Bryan R. / Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes. In: Kidney International. 2016 ; Vol. 89, No. 5. pp. 1125-1135.
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abstract = "Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m2 (odds ratio 0.48; 95{\%} confidence interval, 0.26-0.90), rapid (over 5{\%} per annum) decline in renal function (odds ratio 0.44; 95{\%} confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95{\%} confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations.",
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Betz, BB, Jenks, SJ, Cronshaw, AD, Lamont, DJ, Cairns, C, Manning, JR, Goddard, J, Webb, DJ, Mullins, JJ, Hughes, J, Mclachlan, S, Strachan, MWJ, Price, JF & Conway, BR 2016, 'Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes', Kidney International, vol. 89, no. 5, pp. 1125-1135. https://doi.org/10.1016/j.kint.2016.01.015

Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes. / Betz, Boris B.; Jenks, Sara J.; Cronshaw, Andrew D.; Lamont, Douglas J.; Cairns, Carolynn; Manning, Jonathan R.; Goddard, Jane; Webb, David J.; Mullins, John J.; Hughes, Jeremy; Mclachlan, Stela; Strachan, Mark W J; Price, Jackie F.; Conway, Bryan R. (Lead / Corresponding author).

In: Kidney International, Vol. 89, No. 5, 05.2016, p. 1125-1135.

Research output: Contribution to journalArticle

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T1 - Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes

AU - Betz, Boris B.

AU - Jenks, Sara J.

AU - Cronshaw, Andrew D.

AU - Lamont, Douglas J.

AU - Cairns, Carolynn

AU - Manning, Jonathan R.

AU - Goddard, Jane

AU - Webb, David J.

AU - Mullins, John J.

AU - Hughes, Jeremy

AU - Mclachlan, Stela

AU - Strachan, Mark W J

AU - Price, Jackie F.

AU - Conway, Bryan R.

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N2 - Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m2 (odds ratio 0.48; 95% confidence interval, 0.26-0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations.

AB - Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m2 (odds ratio 0.48; 95% confidence interval, 0.26-0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations.

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