Acid retention in chronic kidney disease is inversely related to GFR

Abstract

Greater H retention in animal models of chronic kidney disease (CKD) mediates faster glomerular filtration rate (GFR) decline and dietary H reduction slows eGFR decline in CKD patients with reduced eGFR and H retention due to the high acid (H) diets of developed societies. We examined if H retention in CKD is inversely associated with estimated GFR (eGFR) using cross-sectional and longitudinal analysis of individuals with CKD stage 1 (>90 ml·min·1.73 m), CKD stage 2 (60-89 ml/min per 1.73 m), and CKD stage 3 (30-59 ml·min·1.73 m) eGFR. H retention was assessed using the difference between observed and expected plasma total CO 2 h after 0.5 meq/kg body wt oral NaHCO. H retention was higher in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P < 0.02) at baseline and 5 yr, and was higher in CKD 2 vs. CKD 1 ( P < 0.01) at 10 yr. All groups had lower eGFR at subsequent time points ( P < 0.01) but H retention was not different among the three time points for CKD 1. By contrast, eGFR decrease was associated with higher H retention in CKD 2 at 5 yr ( P = 0.04) and 10 yr ( P < 0.01) and with higher H retention in CKD 3 at 5 yr ( P < 0.01). Yearly eGFR decline rate was faster in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P < 0.01). The data show that H retention is inversely associated with eGFR, with faster eGFR decline, and support the need for greater dietary H reduction therapy for CKD individuals with lower eGFR.

Dietary Influence on Body Fluid Acid-Base and Volume Balance: The Deleterious “Norm” Furthers and Cloaks Subclinical Pathophysiology

“…The retained acids seem largely buffered by the bones. The underlying mechanisms of kidney and bone injury induced by acid-retention can be multiple, including NH 3 /NH 4 + genesis, inflammation and activation of complement and RAAS [ 26 , 27 , 28 ]. Similar correlations of acid retention without overt acidosis has also been observed in patients with reduced kidney function [ 27 ].…”

Urinary citrate: helpful to predict acid retention in CKD patients?

“…1 The main reason is the impaired ability to maintain a normal acid balance that occurs early during the course of chronic kidney disease because the capacity of the kidney to excrete the daily acid load progressively declines, mainly because of a decrease in urinary ammonia excretion. 2,3 Of note, acid imbalance occurs earlier than the decrease in plasma total CO 2 concentration and therefore is present in CKD patients with normal plasma acid-base parameters. 3 Finally, acid imbalance is an independent risk factor for the faster rate of CKD progression and end-stage renal disease (reviewed in Goraya and Wesson 4 ); however, this risk is not linked to the lower total CO 2 concentration but to lower urinary ammonia excretion.…”

“…John R. Asplin 1 and David S. Goldfarb 2,3 The most important variable leading to uric acid stones is low urine pH. Major causal conditions associated with low urine pH are metabolic syndrome and diabetes.…”

Kidney Response to the Spectrum of Diet-Induced Acid Stress

“…Patients with normal GFR given an increment in dietary H + have cumulative urine H + excretion less than the cumulative increment in dietary H + , consistent with H + retention [ 1 ]. Other studies support the presence of H + retention in CKD patients with reduced estimated glomerular filtration rate (eGFR) [ 23 , 24 , 25 , 26 ], even in the absence of metabolic acidosis [ 23 , 25 , 26 ], which is greater in magnitude in those with lower eGFR [ 26 ]. On the other hand, CKD patients with reduced GFR can have greater increases in [H + ] and greater decreases in [HCO 3 ] in response to the same increment in dietary H + , even developing metabolic acidosis at levels of dietary H + that do not cause metabolic acidosis in patients with higher GFR [ 27 ].…”