Urinalysis findings and urinary kidney injury biomarker concentrations

Girish N. Nadkarni, Steven G. Coca, Allison Meisner, Shanti Patel, Kathleen F. Kerr, Uptal D. Patel, Jay L. Koyner, Amit X. Garg, Heather Thiessen Philbrook, Charles L. Edelstein, Michael Shlipak, Joe El-Khoury, Chirag Parikh, Jai Raman, Valluvan Jeevanandam, Shahab Akhter, Cary Passik, Judy Nagy, Madhav Swaminathan, Michael Chu & 17 others Martin Goldbach, Lin Ruo Guo, Neil McKenzie, Mary Lee Myers, Richard Novick, Mac Quantz, Michael Zappitelli, Ana Palijan, Michael Dewar, Umer Darr, Sabet Hashim, John Elefteriades, Arnar Geirsson, Susan Garwood, Isabel Butrymowicz, Harlan Krumholz, Stephanie Dixon

Research output: Contribution to journalArticle

Abstract

Introduction: Urinary biomarkers of kidney injury are presumed to reflect renal tubular damage. However, their concentrations may be influenced by other factors, such as hematuria or pyuria. We sought to examine what non-injury related urinalysis factors are associated with urinary biomarker levels. Methods: We examined 714 adults who underwent cardiac surgery in the TRIBE-AKI cohort that did not experience post-operative clinical AKI (patients with serum creatinine change of ≥ 20% were excluded). We examined the association between urinalysis findings and the pre- and first post-operative urinary concentrations of 4 urinary biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and liver fatty acid binding protein (L-FABP). Results: The presence of leukocyte esterase and nitrites on urinalysis was associated with increased urinary NGAL (R2 0.16, p < 0.001 and R2 0.07, p < 0.001, respectively) in pre-operative samples. Hematuria was associated with increased levels of all 4 biomarkers, with a much stronger association seen in post-operative samples (R2 between 0.02 and 0.21). Dipstick proteinuria concentrations correlated with levels of all 4 urinary biomarkers in pre-operative and post-operative samples (R2 between 0.113 and 0.194 in pre-operative and between 0.122 and 0.322 in post-operative samples). Adjusting the AUC of post-operative AKI for dipstick proteinuria lowered the AUC for all 4 biomarkers at the pre-operative time point and for 2 of the 4 biomarkers at the post-operative time point. Conclusions: Several factors available through urine dipstick testing are associated with increased urinary biomarker concentrations that are independent of clinical kidney injury. Future studies should explore the impact of these factors on the prognostic and diagnostic performance of these AKI biomarkers.

Original languageEnglish (US)
Article number218
JournalBMC Nephrology
Volume18
Issue number1
DOIs
StatePublished - Jul 6 2017

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Urinalysis
Biomarkers
Kidney
Wounds and Injuries
Hematuria
Operative Time
Proteinuria
Area Under Curve
Pyuria
Fatty Acid-Binding Proteins
Interleukin-18
Nitrites
Thoracic Surgery
Creatinine
Urine

Keywords

  • Acute kidney injury
  • Biomarkers
  • Urinalysis
  • Urine dipstick
  • Variability

ASJC Scopus subject areas

  • Nephrology

Cite this

Nadkarni, G. N., Coca, S. G., Meisner, A., Patel, S., Kerr, K. F., Patel, U. D., ... Dixon, S. (2017). Urinalysis findings and urinary kidney injury biomarker concentrations. BMC Nephrology, 18(1), [218]. https://doi.org/10.1186/s12882-017-0629-z

Urinalysis findings and urinary kidney injury biomarker concentrations. / Nadkarni, Girish N.; Coca, Steven G.; Meisner, Allison; Patel, Shanti; Kerr, Kathleen F.; Patel, Uptal D.; Koyner, Jay L.; Garg, Amit X.; Thiessen Philbrook, Heather; Edelstein, Charles L.; Shlipak, Michael; El-Khoury, Joe; Parikh, Chirag; Raman, Jai; Jeevanandam, Valluvan; Akhter, Shahab; Passik, Cary; Nagy, Judy; Swaminathan, Madhav; Chu, Michael; Goldbach, Martin; Guo, Lin Ruo; McKenzie, Neil; Myers, Mary Lee; Novick, Richard; Quantz, Mac; Zappitelli, Michael; Palijan, Ana; Dewar, Michael; Darr, Umer; Hashim, Sabet; Elefteriades, John; Geirsson, Arnar; Garwood, Susan; Butrymowicz, Isabel; Krumholz, Harlan; Dixon, Stephanie.

In: BMC Nephrology, Vol. 18, No. 1, 218, 06.07.2017.

Research output: Contribution to journalArticle

Nadkarni, GN, Coca, SG, Meisner, A, Patel, S, Kerr, KF, Patel, UD, Koyner, JL, Garg, AX, Thiessen Philbrook, H, Edelstein, CL, Shlipak, M, El-Khoury, J, Parikh, C, Raman, J, Jeevanandam, V, Akhter, S, Passik, C, Nagy, J, Swaminathan, M, Chu, M, Goldbach, M, Guo, LR, McKenzie, N, Myers, ML, Novick, R, Quantz, M, Zappitelli, M, Palijan, A, Dewar, M, Darr, U, Hashim, S, Elefteriades, J, Geirsson, A, Garwood, S, Butrymowicz, I, Krumholz, H & Dixon, S 2017, 'Urinalysis findings and urinary kidney injury biomarker concentrations', BMC Nephrology, vol. 18, no. 1, 218. https://doi.org/10.1186/s12882-017-0629-z
Nadkarni GN, Coca SG, Meisner A, Patel S, Kerr KF, Patel UD et al. Urinalysis findings and urinary kidney injury biomarker concentrations. BMC Nephrology. 2017 Jul 6;18(1). 218. https://doi.org/10.1186/s12882-017-0629-z
Nadkarni, Girish N. ; Coca, Steven G. ; Meisner, Allison ; Patel, Shanti ; Kerr, Kathleen F. ; Patel, Uptal D. ; Koyner, Jay L. ; Garg, Amit X. ; Thiessen Philbrook, Heather ; Edelstein, Charles L. ; Shlipak, Michael ; El-Khoury, Joe ; Parikh, Chirag ; Raman, Jai ; Jeevanandam, Valluvan ; Akhter, Shahab ; Passik, Cary ; Nagy, Judy ; Swaminathan, Madhav ; Chu, Michael ; Goldbach, Martin ; Guo, Lin Ruo ; McKenzie, Neil ; Myers, Mary Lee ; Novick, Richard ; Quantz, Mac ; Zappitelli, Michael ; Palijan, Ana ; Dewar, Michael ; Darr, Umer ; Hashim, Sabet ; Elefteriades, John ; Geirsson, Arnar ; Garwood, Susan ; Butrymowicz, Isabel ; Krumholz, Harlan ; Dixon, Stephanie. / Urinalysis findings and urinary kidney injury biomarker concentrations. In: BMC Nephrology. 2017 ; Vol. 18, No. 1.
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AU - Nadkarni, Girish N.

AU - Coca, Steven G.

AU - Meisner, Allison

AU - Patel, Shanti

AU - Kerr, Kathleen F.

AU - Patel, Uptal D.

AU - Koyner, Jay L.

AU - Garg, Amit X.

AU - Thiessen Philbrook, Heather

AU - Edelstein, Charles L.

AU - Shlipak, Michael

AU - El-Khoury, Joe

AU - Parikh, Chirag

AU - Raman, Jai

AU - Jeevanandam, Valluvan

AU - Akhter, Shahab

AU - Passik, Cary

AU - Nagy, Judy

AU - Swaminathan, Madhav

AU - Chu, Michael

AU - Goldbach, Martin

AU - Guo, Lin Ruo

AU - McKenzie, Neil

AU - Myers, Mary Lee

AU - Novick, Richard

AU - Quantz, Mac

AU - Zappitelli, Michael

AU - Palijan, Ana

AU - Dewar, Michael

AU - Darr, Umer

AU - Hashim, Sabet

AU - Elefteriades, John

AU - Geirsson, Arnar

AU - Garwood, Susan

AU - Butrymowicz, Isabel

AU - Krumholz, Harlan

AU - Dixon, Stephanie

PY - 2017/7/6

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N2 - Introduction: Urinary biomarkers of kidney injury are presumed to reflect renal tubular damage. However, their concentrations may be influenced by other factors, such as hematuria or pyuria. We sought to examine what non-injury related urinalysis factors are associated with urinary biomarker levels. Methods: We examined 714 adults who underwent cardiac surgery in the TRIBE-AKI cohort that did not experience post-operative clinical AKI (patients with serum creatinine change of ≥ 20% were excluded). We examined the association between urinalysis findings and the pre- and first post-operative urinary concentrations of 4 urinary biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and liver fatty acid binding protein (L-FABP). Results: The presence of leukocyte esterase and nitrites on urinalysis was associated with increased urinary NGAL (R2 0.16, p < 0.001 and R2 0.07, p < 0.001, respectively) in pre-operative samples. Hematuria was associated with increased levels of all 4 biomarkers, with a much stronger association seen in post-operative samples (R2 between 0.02 and 0.21). Dipstick proteinuria concentrations correlated with levels of all 4 urinary biomarkers in pre-operative and post-operative samples (R2 between 0.113 and 0.194 in pre-operative and between 0.122 and 0.322 in post-operative samples). Adjusting the AUC of post-operative AKI for dipstick proteinuria lowered the AUC for all 4 biomarkers at the pre-operative time point and for 2 of the 4 biomarkers at the post-operative time point. Conclusions: Several factors available through urine dipstick testing are associated with increased urinary biomarker concentrations that are independent of clinical kidney injury. Future studies should explore the impact of these factors on the prognostic and diagnostic performance of these AKI biomarkers.

AB - Introduction: Urinary biomarkers of kidney injury are presumed to reflect renal tubular damage. However, their concentrations may be influenced by other factors, such as hematuria or pyuria. We sought to examine what non-injury related urinalysis factors are associated with urinary biomarker levels. Methods: We examined 714 adults who underwent cardiac surgery in the TRIBE-AKI cohort that did not experience post-operative clinical AKI (patients with serum creatinine change of ≥ 20% were excluded). We examined the association between urinalysis findings and the pre- and first post-operative urinary concentrations of 4 urinary biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and liver fatty acid binding protein (L-FABP). Results: The presence of leukocyte esterase and nitrites on urinalysis was associated with increased urinary NGAL (R2 0.16, p < 0.001 and R2 0.07, p < 0.001, respectively) in pre-operative samples. Hematuria was associated with increased levels of all 4 biomarkers, with a much stronger association seen in post-operative samples (R2 between 0.02 and 0.21). Dipstick proteinuria concentrations correlated with levels of all 4 urinary biomarkers in pre-operative and post-operative samples (R2 between 0.113 and 0.194 in pre-operative and between 0.122 and 0.322 in post-operative samples). Adjusting the AUC of post-operative AKI for dipstick proteinuria lowered the AUC for all 4 biomarkers at the pre-operative time point and for 2 of the 4 biomarkers at the post-operative time point. Conclusions: Several factors available through urine dipstick testing are associated with increased urinary biomarker concentrations that are independent of clinical kidney injury. Future studies should explore the impact of these factors on the prognostic and diagnostic performance of these AKI biomarkers.

KW - Acute kidney injury

KW - Biomarkers

KW - Urinalysis

KW - Urine dipstick

KW - Variability

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