Ke Wang1,2, Leila R Zelnick1,2, Andrew N Hoofnagle2,3, Yan Chen2,4, Ian H de Boer1,2, Jonathan Himmelfarb1,2, Bryan Kestenbaum1,2. 1. Department of Medicine, Division of Nephrology, University of Washington, Seattle, WA, USA. 2. Kidney Research Institute, Seattle, WA, USA. 3. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA. 4. Department of Epidemiology, University of Washington, Seattle, WA, USA.
Abstract
BACKGROUND: Laboratory measures of glomerular function such as the glomerular filtration rate (GFR) contribute toward clinical evaluation of chronic kidney disease (CKD). However, diverse CKD etiologies have distinct pathological mechanisms that may differentially impact the kidney tubules. Little is known regarding how tubular function changes with varying kidney disease types. METHODS: We used targeted mass spectrometry to quantify paired serum and urine concentration of 11 solutes of proximal tubular secretion in 223 patients from an outpatient CKD cohort. We reviewed clinic notes to ascertain the primary CKD diagnosis and categorized these as vascular, diabetic, glomerular or tubulointerstitial. We used one-way analysis of variance to compare secretory solute clearance across diagnoses setting a false discovery threshold of ≤5% and used linear regression to compare differences after adjustments for estimated GFR, age, race, sex, body mass index and urine albumin excretion. RESULTS: After full adjustment, glomerular disease was associated with higher clearances of three tubular secretory solutes compared with vascular disease: 48% higher isovalerylglycine clearance [95% confidence interval (CI) 18-87%], 28% higher kynurenic acid clearance (95% CI 3-59%) and 33% higher tiglylglycine clearance (95% CI 7-67%). Diabetic kidney disease (DKD) was associated with 39% higher isovalerylglycine clearance compared with vascular disease (95% CI 13-72%). CONCLUSION: Glomerular disorders and DKD are associated with higher net clearances of several secretory solutes compared with vascular causes of kidney disease. These findings suggest that different underlying etiologies of CKD may differentially impact proximal tubular secretory pathways.
BACKGROUND: Laboratory measures of glomerular function such as the glomerular filtration rate (GFR) contribute toward clinical evaluation of chronic kidney disease (CKD). However, diverse CKD etiologies have distinct pathological mechanisms that may differentially impact the kidney tubules. Little is known regarding how tubular function changes with varying kidney disease types. METHODS: We used targeted mass spectrometry to quantify paired serum and urine concentration of 11 solutes of proximal tubular secretion in 223 patients from an outpatient CKD cohort. We reviewed clinic notes to ascertain the primary CKD diagnosis and categorized these as vascular, diabetic, glomerular or tubulointerstitial. We used one-way analysis of variance to compare secretory solute clearance across diagnoses setting a false discovery threshold of ≤5% and used linear regression to compare differences after adjustments for estimated GFR, age, race, sex, body mass index and urine albumin excretion. RESULTS: After full adjustment, glomerular disease was associated with higher clearances of three tubular secretory solutes compared with vascular disease: 48% higher isovalerylglycine clearance [95% confidence interval (CI) 18-87%], 28% higher kynurenic acid clearance (95% CI 3-59%) and 33% higher tiglylglycine clearance (95% CI 7-67%). Diabetic kidney disease (DKD) was associated with 39% higher isovalerylglycine clearance compared with vascular disease (95% CI 13-72%). CONCLUSION: Glomerular disorders and DKD are associated with higher net clearances of several secretory solutes compared with vascular causes of kidney disease. These findings suggest that different underlying etiologies of CKD may differentially impact proximal tubular secretory pathways.
Authors: Tammy L Sirich; Benjamin A Funk; Natalie S Plummer; Thomas H Hostetter; Timothy W Meyer Journal: J Am Soc Nephrol Date: 2013-11-14 Impact factor: 10.121
Authors: Joachim H Ix; Christina L Wassel; Lesley A Stevens; Gerald J Beck; Marc Froissart; Gerjan Navis; Roger Rodby; Vicente E Torres; Yaping Lucy Zhang; Tom Greene; Andrew S Levey Journal: Clin J Am Soc Nephrol Date: 2010-10-21 Impact factor: 8.237
Authors: Astrid M Suchy-Dicey; Thomas Laha; Andrew Hoofnagle; Rick Newitt; Tammy L Sirich; Timothy W Meyer; Ken E Thummel; N David Yanez; Jonathan Himmelfarb; Noel S Weiss; Bryan R Kestenbaum Journal: J Am Soc Nephrol Date: 2015-11-27 Impact factor: 10.121
Authors: Yan Chen; Leila R Zelnick; Andrew N Hoofnagle; Catherine K Yeung; Laura M Shireman; Brian Phillips; Calder C Brauchla; Ian de Boer; Linda Manahan; Susan R Heckbert; Jonathan Himmelfarb; Bryan R Kestenbaum Journal: J Am Soc Nephrol Date: 2020-11-25 Impact factor: 10.121
Authors: Pranav S Garimella; Ronit Katz; Sushrut S Waikar; Anand Srivastava; Insa Schmidt; Andrew Hoofnagle; Ragnar Palsson; Helmut G Rennke; Isaac E Stillman; Ke Wang; Bryan R Kestenbaum; Joachim H Ix Journal: Am J Kidney Dis Date: 2021-09-24 Impact factor: 11.072
Authors: Yan Chen; Leila R Zelnick; Matthew P Huber; Ke Wang; Nisha Bansal; Andrew N Hoofnagle; Rajan K Paranji; Susan R Heckbert; Noel S Weiss; Alan S Go; Chi-Yuan Hsu; Harold I Feldman; Sushrut S Waikar; Rupal C Mehta; Anand Srivastava; Stephen L Seliger; James P Lash; Anna C Porter; Dominic S Raj; Bryan R Kestenbaum Journal: Am J Kidney Dis Date: 2021-01-07 Impact factor: 11.072
Authors: Bayan Hassan Banimfreg; Hussam Alshraideh; Abdulrahim Shamayleh; Adnane Guella; Mohammad Harb Semreen; Mohammad Tahseen Al Bataineh; Nelson C Soares Journal: Biomolecules Date: 2022-07-08