Urine testing to differentiate glomerular from tubulointerstitial diseases on kidney biopsy

Background: Differentiating between glomerular and tubulointerstitial diseases can guide selection of appropriate patients for kidney biopsy. The aim of this study is to identify urine tests that can differentiate between these histological diagnoses. Methods: In this sub-study of a prospectively en...

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Main Authors: Anna C. Tran, Hannah Melchinger, Jason Weinstein, Melissa Shaw, Candice Kent, Mark A. Perazella, F. Perry Wilson, Chirag R. Parikh, Dennis G. Moledina
Format: Article
Language:English
Published: Elsevier 2022-05-01
Series:Practical Laboratory Medicine
Online Access:http://www.sciencedirect.com/science/article/pii/S2352551722000105
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author Anna C. Tran
Hannah Melchinger
Jason Weinstein
Melissa Shaw
Candice Kent
Mark A. Perazella
F. Perry Wilson
Chirag R. Parikh
Dennis G. Moledina
author_facet Anna C. Tran
Hannah Melchinger
Jason Weinstein
Melissa Shaw
Candice Kent
Mark A. Perazella
F. Perry Wilson
Chirag R. Parikh
Dennis G. Moledina
author_sort Anna C. Tran
collection DOAJ
description Background: Differentiating between glomerular and tubulointerstitial diseases can guide selection of appropriate patients for kidney biopsy. The aim of this study is to identify urine tests that can differentiate between these histological diagnoses. Methods: In this sub-study of a prospectively enrolled cohort of participants with urine samples concurrent with their kidney biopsy, we tested the association of 24 features on urinalysis, urine sediment microscopy, and biomarkers of glomerular and tubular injury and inflammation with histological diagnosis of glomerular or tubulointerstitial disease. We selected a combination of features associated with glomerular disease using stepwise forward and backward regression, and LASSO algorithm after dividing the cohort into training (70%) and test (30%) sets. Results: Of 359 participants, 121 had glomerular, 89 had tubulointerstitial diseases, and 149 were classified as mixed. Compared to patients with tubulointerstitial diseases, those with glomerular diseases had more dipstick hematuria (3+ vs. 1+, P < 0.001) and urine albumin (1.25 vs. 0.09 mg/mg, P < 0.001). Patients with glomerular diseases had higher levels of tubular health biomarkers (Uromodulin, 1.22 vs. 0.92, P = 0.03). In a multivariable model, higher urine albumin, dipstick blood, and urine uromodulin were independently associated with higher odds of glomerular diseases (test set AUC, 0.81 (0.69, 0.93)). Conclusion: Urine tests, including urine albumin, dipstick blood, and urine uromodulin, were associated with the histological diagnosis of glomerular disease. These findings can help clinicians differentiate between glomerular and tubulointerstitial diseases and guide clinical decisions regarding a kidney biopsy.
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spelling doaj.art-47946c708d27483990c02b232ca9fd872022-12-22T00:11:31ZengElsevierPractical Laboratory Medicine2352-55172022-05-0130e00271Urine testing to differentiate glomerular from tubulointerstitial diseases on kidney biopsyAnna C. Tran0Hannah Melchinger1Jason Weinstein2Melissa Shaw3Candice Kent4Mark A. Perazella5F. Perry Wilson6Chirag R. Parikh7Dennis G. Moledina8Yale College, New Haven, CT, USASection of Nephrology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Clinical and Translational Research Accelerator, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USASection of Nephrology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Clinical and Translational Research Accelerator, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USASection of Nephrology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Clinical and Translational Research Accelerator, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USASection of Nephrology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Clinical and Translational Research Accelerator, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USASection of Nephrology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USASection of Nephrology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Clinical and Translational Research Accelerator, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USADivision of Nephrology, Department of Internal Medicine, Johns Hopkins Medicine, Baltimore, MD, USASection of Nephrology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Clinical and Translational Research Accelerator, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA; Corresponding author. Clinical and Translational Research Accelerator, 60 Temple St. Ste 6C, New Haven, CT, 06510, USA.Background: Differentiating between glomerular and tubulointerstitial diseases can guide selection of appropriate patients for kidney biopsy. The aim of this study is to identify urine tests that can differentiate between these histological diagnoses. Methods: In this sub-study of a prospectively enrolled cohort of participants with urine samples concurrent with their kidney biopsy, we tested the association of 24 features on urinalysis, urine sediment microscopy, and biomarkers of glomerular and tubular injury and inflammation with histological diagnosis of glomerular or tubulointerstitial disease. We selected a combination of features associated with glomerular disease using stepwise forward and backward regression, and LASSO algorithm after dividing the cohort into training (70%) and test (30%) sets. Results: Of 359 participants, 121 had glomerular, 89 had tubulointerstitial diseases, and 149 were classified as mixed. Compared to patients with tubulointerstitial diseases, those with glomerular diseases had more dipstick hematuria (3+ vs. 1+, P < 0.001) and urine albumin (1.25 vs. 0.09 mg/mg, P < 0.001). Patients with glomerular diseases had higher levels of tubular health biomarkers (Uromodulin, 1.22 vs. 0.92, P = 0.03). In a multivariable model, higher urine albumin, dipstick blood, and urine uromodulin were independently associated with higher odds of glomerular diseases (test set AUC, 0.81 (0.69, 0.93)). Conclusion: Urine tests, including urine albumin, dipstick blood, and urine uromodulin, were associated with the histological diagnosis of glomerular disease. These findings can help clinicians differentiate between glomerular and tubulointerstitial diseases and guide clinical decisions regarding a kidney biopsy.http://www.sciencedirect.com/science/article/pii/S2352551722000105
spellingShingle Anna C. Tran
Hannah Melchinger
Jason Weinstein
Melissa Shaw
Candice Kent
Mark A. Perazella
F. Perry Wilson
Chirag R. Parikh
Dennis G. Moledina
Urine testing to differentiate glomerular from tubulointerstitial diseases on kidney biopsy
Practical Laboratory Medicine
title Urine testing to differentiate glomerular from tubulointerstitial diseases on kidney biopsy
title_full Urine testing to differentiate glomerular from tubulointerstitial diseases on kidney biopsy
title_fullStr Urine testing to differentiate glomerular from tubulointerstitial diseases on kidney biopsy
title_full_unstemmed Urine testing to differentiate glomerular from tubulointerstitial diseases on kidney biopsy
title_short Urine testing to differentiate glomerular from tubulointerstitial diseases on kidney biopsy
title_sort urine testing to differentiate glomerular from tubulointerstitial diseases on kidney biopsy
url http://www.sciencedirect.com/science/article/pii/S2352551722000105
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