Association of tubular solute clearances with the glomerular filtration rate and complications of chronic kidney disease: the Chronic Renal Insufficiency Cohort study. Issue 7 (17th November 2020)

• Record Type: Journal Article
• Authors: Chen, Yan; Zelnick, Leila R; Wang, Ke; Katz, Ronit; Hoofnagle, Andrew N; Becker, Jessica O; Hsu, Chi-Yuan; Go, Alan S; Feldman, Harold I; Mehta, Rupal C; Lash, James P; Waikar, Sushrut S; Hamm, L; Chen, Jing; Shafi, Tariq; Kestenbaum, Bryan R
• Is Part Of: Nephrology dialysis transplantation. Volume 36:Issue 7(2021)
• Page Start: 1271
• Page End: 1281
• Publication Date: 2020-11-17
• Subjects: CKD complications -- glomerular filtration rate -- proximal tubular secretion -- secretory solutes clearances; Nephrology -- Periodicals; Hemodialysis -- Periodicals; Kidneys -- Transplantation -- Periodicals; Hemodialysis; Kidneys -- Transplantation; Nephrology; Periodicals; 616.61
• DOI: 10.1093/ndt/gfaa057
• Languages: English
• ISSNs: 0931-0509

Abstract

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 125 I-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.