Yan Chen1,2, Leila R Zelnick2,3, Ke Wang2,3, Ronit Katz2,3, Andrew N Hoofnagle2,4, Jessica O Becker4, Chi-Yuan Hsu5, Alan S Go6, Harold I Feldman7,8, Rupal C Mehta9, James P Lash10, Sushrut S Waikar11, L Hamm12, Jing Chen12, Tariq Shafi13, Bryan R Kestenbaum2,3. 1. Department of Epidemiology, University of Washington, Seattle, WA, USA. 2. Kidney Research Institute, Seattle, WA, USA. 3. Department of Medicine, Division of Nephrology, University of Washington, Seattle, WA, USA. 4. Department of Laboratory Medicine, University of Washington, Seattle, WA, USA. 5. Department of Medicine, Division of Nephrology, University of California San Francisco, San Francisco, CA, USA. 6. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA. 7. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Philadelphia, PA, USA. 8. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia, PA, USA. 9. Department of Medicine, Division of Nephrology and Hypertension, Jesse Brown Veterans Administration Medical Center & Northwestern University, Chicago, IL, USA. 10. Department of Medicine, Division of Nephrology, University of Illinois at Chicago, Chicago, IL, USA. 11. Renal Division, Brigham and Women's Hospital, Boston, MA, USA. 12. Division of Nephrology and Hypertension, Tulane University Department of Medicine, New Orleans, LA, USA. 13. Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, MS, USA.
Abstract
BACKGROUND: The secretion of organic solutes by the proximal tubules is an essential intrinsic kidney function. The degree to which secretory solute clearance corresponds with the glomerular filtration rate (GFR) and potential metabolic implications of net secretory clearance are largely unknown. METHODS: We evaluated 1240 participants with chronic kidney disease (CKD) from the multicenter Chronic Renal Insufficiency Cohort (CRIC) Study. We used targeted mass-spectrometry to quantify candidate secretory solutes in paired 24-h urine and plasma samples. CRIC study personnel measured GFR using 125I-iothalamate clearance (iGFR). We used correlation and linear regression to determine cross-sectional associations of secretory clearances with iGFR and common metabolic complications of CKD. RESULTS: Correlations between iGFR and secretory solute clearances ranged from ρ = +0.30 for hippurate to ρ = +0.58 for kynurenic acid. Lower net clearances of most secretory solutes were associated with higher serum concentrations of parathyroid hormone (PTH), triglycerides and uric acid. Each 50% lower kynurenic acid clearance was associated with a 21% higher serum PTH concentration [95% confidence interval (CI) 15-26%] and a 10% higher serum triglyceride concentration (95% CI 5-16%) after adjustment for iGFR, albuminuria and other potential confounders. Secretory solute clearances were not associated with statistically or clinically meaningful differences in serum calcium, phosphate, hemoglobin or bicarbonate concentrations. CONCLUSIONS: Tubular secretory clearances are modestly correlated with measured GFR among adult patients with CKD. Lower net secretory clearances are associated with selected metabolic complications independent of GFR and albuminuria, suggesting potential clinical and biological relevance.
BACKGROUND: The secretion of organic solutes by the proximal tubules is an essential intrinsic kidney function. The degree to which secretory solute clearance corresponds with the glomerular filtration rate (GFR) and potential metabolic implications of net secretory clearance are largely unknown. METHODS: We evaluated 1240 participants with chronic kidney disease (CKD) from the multicenter Chronic Renal Insufficiency Cohort (CRIC) Study. We used targeted mass-spectrometry to quantify candidate secretory solutes in paired 24-h urine and plasma samples. CRIC study personnel measured GFR using 125I-iothalamate clearance (iGFR). We used correlation and linear regression to determine cross-sectional associations of secretory clearances with iGFR and common metabolic complications of CKD. RESULTS: Correlations between iGFR and secretory solute clearances ranged from ρ = +0.30 for hippurate to ρ = +0.58 for kynurenic acid. Lower net clearances of most secretory solutes were associated with higher serum concentrations of parathyroid hormone (PTH), triglycerides and uric acid. Each 50% lower kynurenic acid clearance was associated with a 21% higher serum PTH concentration [95% confidence interval (CI) 15-26%] and a 10% higher serum triglyceride concentration (95% CI 5-16%) after adjustment for iGFR, albuminuria and other potential confounders. Secretory solute clearances were not associated with statistically or clinically meaningful differences in serum calcium, phosphate, hemoglobin or bicarbonate concentrations. CONCLUSIONS: Tubular secretory clearances are modestly correlated with measured GFR among adult patients with CKD. Lower net secretory clearances are associated with selected metabolic complications independent of GFR and albuminuria, suggesting potential clinical and biological relevance.
Authors: Adriana J van Ballegooijen; Eugene P Rhee; Sammy Elmariah; Ian H de Boer; Bryan Kestenbaum Journal: J Am Soc Nephrol Date: 2015-06-05 Impact factor: 10.121
Authors: Megan Rossi; Katrina L Campbell; David W Johnson; Tony Stanton; David A Vesey; Jeff S Coombes; Kassia S Weston; Carmel M Hawley; Brett C McWhinney; Jacobus P J Ungerer; Nicole Isbel Journal: Arch Med Res Date: 2014-04-18 Impact factor: 2.235
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: Marc A Pfeffer; Emmanuel A Burdmann; Chao-Yin Chen; Mark E Cooper; Dick de Zeeuw; Kai-Uwe Eckardt; Jan M Feyzi; Peter Ivanovich; Reshma Kewalramani; Andrew S Levey; Eldrin F Lewis; Janet B McGill; John J V McMurray; Patrick Parfrey; Hans-Henrik Parving; Giuseppe Remuzzi; Ajay K Singh; Scott D Solomon; Robert Toto Journal: N Engl J Med Date: 2009-10-30 Impact factor: 91.245
Authors: James P Lash; Alan S Go; Lawrence J Appel; Jiang He; Akinlolu Ojo; Mahboob Rahman; Raymond R Townsend; Dawei Xie; Denise Cifelli; Janet Cohan; Jeffrey C Fink; Michael J Fischer; Crystal Gadegbeku; L Lee Hamm; John W Kusek; J Richard Landis; Andrew Narva; Nancy Robinson; Valerie Teal; Harold I Feldman Journal: Clin J Am Soc Nephrol Date: 2009-06-18 Impact factor: 8.237
Authors: Henricus A M Mutsaers; Lambertus P van den Heuvel; Lauke H J Ringens; Anita C A Dankers; Frans G M Russel; Jack F M Wetzels; Joost G Hoenderop; Rosalinde Masereeuw Journal: PLoS One Date: 2011-04-04 Impact factor: 3.240