부산대학교 도서관

Introduction: Like metabolic acidosis, earlier stages of acid (H[sup.+]) stress, including an ongoing H[sup.+] challenge in the form of dietary H[sup.+], without or with steady-state H[sup.+] accumulation but with normal plasma total CO[sub.2] (PTCO[sub.2]) (the latter state known as eubicarbonatemic acidosis), are associated with augmented progression of chronic kidney disease (CKD), but diagnosis of this covert H[sup.+] stress is clinically problematic. Prior published studies to identify clinically practical biomarkers of covert H[sup.+] stress did not include assessments of either dietary H[sup.+] or H[sup.+] retention. Methods: We tested plasma pH (PpH), 8-h urine excretion of citrate (UcitV) or ammonium (UNH[sub.4][sup.+]V) as biomarkers of dietary H[sup.+] assessed as potential renal acid load (PRAL), and of steady-state H[sup.+] retention by comparing observed to expected PTCO[sub.2] increase 2 h after an oral NaHCO[sub.3] bolus. We recruited 313 non-diabetic participants with PTCO[sub.2] [GreaterEqual] 22 mM to exclude participants with metabolic acidosis and with eGFR (mean [SD], mL/min/1.73 m[sup.2]) stages G1 (n = 62, 99.2 [7.3]), G2 (n = 167, 73.8 [6.3]), and G3 (n = 84, 39.9 [6.7]). We performed linear regressions (LR) between H[sup.+] retention or PRAL (dependent variables) and PpH, UcitV, or UNH[sub.4][sup.+]V (independent variables) after adjusting for eGFR. Results: Steady-state H[sup.+] retention (mean [SD], mmol) increased with stage (G1 = 3.8 [12.5], G2 = 18.2 [12.4], and G3 = 25.6 [9.0]). PpH was not significantly associated with PRAL in any group, and its association with H[sup.+] retention was significant only for G3 (p < 0.01). UcitV association with PRAL was significant only for G1 (p < 0.01) but not for G2 (p = 0.65) or G3 (p = 0.11). UcitV association with H[sup.+] retention was negative for both G2 (p < 0.01) and G3 (p < 0.01) but was not significant for G1 (p = 0.50). Adding UNH[sub.4][sup.+]V to UcitV as a regressor for H[sup.+] retention increased r[sup.2] only marginally for G2 (0.61-0.63) and G3 (0.75-0.79). UNH[sub.4][sup.+]V association with PRAL was positive (p < 0.01) for G1 and G2 but was not significant for G3 (p = 0.46). UNH[sub.4][sup.+]V association with H[sup.+] retention was significant for both G2 (p < 0.04) and G3 (p < 0.01) but diverged directionally, being positive for G2 but negative for G3. Discussion: Among patients with CKD at risk for covert H[sup.+] stress, lower UcitV better identified eubicarbonatemic acidosis than UNH[sub.4][sup.+]V because the UNH[sub.4][sup.+]V versus H[sup.+] retention relationship diverged between G2 and G3. Neither test identified eubicarbonatemic acidosis with certainty, indicating need for further work to establish a clinically useful test. On the other hand, UNH[sub.4][sup.+]V had better utility identifying increased dietary H[sup.+] assessed as PRAL in G1 and G2. Keywords: Acidosis, Ammonium, Bicarbonate, Chronic kidney disease, Citrate, Glomerular filtration rate
Author(s): Nimrit Goraya [a,b]; Nicolaos E. Madias [c]; Abdullah Mamun [d]; Jan Simoni [e]; Donald E. Wesson [f] Introduction Ongoing acid (H[sup.+] ) challenges in the form of high H[sup.+] [...]