TY - JOUR
T1 - Higher net acid excretion is associated with a lower risk of kidney disease progression in patients with diabetes
AU - Chronic Renal Insufficiency Cohort Study Investigators
AU - Scialla, Julia J.
AU - Asplin, John
AU - Dobre, Mirela
AU - Chang, Alex R.
AU - Lash, James
AU - Hsu, Chi yuan
AU - Kallem, Radhakrishna R.
AU - Hamm, L. Lee
AU - Feldman, Harold I.
AU - Chen, Jing
AU - Appel, Lawrence J.
AU - Anderson, Cheryl A.M.
AU - Wolf, Myles
AU - Feldman, Harold I.
AU - Go, Alan S.
AU - He, Jiang
AU - Kusek, John W.
AU - Ojo, Akinlolu
AU - Rahman, Mahboob
AU - Townsend, Raymond R.
N1 - Publisher Copyright:
© 2016 International Society of Nephrology
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Higher diet-dependent nonvolatile acid load is associated with faster chronic kidney disease (CKD) progression, but most studies have used estimated acid load or measured only components of the gold standard, net acid excretion (NAE). Here we measured NAE as the sum of urine ammonium and titratable acidity in 24-hour urines from a random subset of 980 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. In multivariable models accounting for demographics, comorbidity and kidney function, higher NAE was significantly associated with lower serum bicarbonate (0.17 mEq/l lower serum bicarbonate per 10 mEq/day higher NAE), consistent with a larger acid load. Over a median of 6 years of follow-up, higher NAE was independently associated with a significantly lower risk of the composite of end-stage renal disease or halving of estimated glomerular filtration rate among diabetics (hazard ratio 0.88 per 10 mEq/day higher NAE), but not those without diabetes (hazard ratio 1.04 per 10 mEq/day higher NAE). For comparison, we estimated the nonvolatile acid load as net endogenous acid production using self-reported food frequency questionnaires from 2848 patients and dietary urine biomarkers from 3385 patients. Higher net endogenous acid production based on biomarkers (urea nitrogen and potassium) was modestly associated with faster CKD progression consistent with prior reports, but only among those without diabetes. Results from the food frequency questionnaires were not associated with CKD progression in any group. Thus, disparate results obtained from analyses of nonvolatile acid load directly measured as NAE and estimated from diet suggest a novel hypothesis that the risk of CKD progression related to low NAE or acid load may be due to diet-independent changes in acid production in diabetes.
AB - Higher diet-dependent nonvolatile acid load is associated with faster chronic kidney disease (CKD) progression, but most studies have used estimated acid load or measured only components of the gold standard, net acid excretion (NAE). Here we measured NAE as the sum of urine ammonium and titratable acidity in 24-hour urines from a random subset of 980 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. In multivariable models accounting for demographics, comorbidity and kidney function, higher NAE was significantly associated with lower serum bicarbonate (0.17 mEq/l lower serum bicarbonate per 10 mEq/day higher NAE), consistent with a larger acid load. Over a median of 6 years of follow-up, higher NAE was independently associated with a significantly lower risk of the composite of end-stage renal disease or halving of estimated glomerular filtration rate among diabetics (hazard ratio 0.88 per 10 mEq/day higher NAE), but not those without diabetes (hazard ratio 1.04 per 10 mEq/day higher NAE). For comparison, we estimated the nonvolatile acid load as net endogenous acid production using self-reported food frequency questionnaires from 2848 patients and dietary urine biomarkers from 3385 patients. Higher net endogenous acid production based on biomarkers (urea nitrogen and potassium) was modestly associated with faster CKD progression consistent with prior reports, but only among those without diabetes. Results from the food frequency questionnaires were not associated with CKD progression in any group. Thus, disparate results obtained from analyses of nonvolatile acid load directly measured as NAE and estimated from diet suggest a novel hypothesis that the risk of CKD progression related to low NAE or acid load may be due to diet-independent changes in acid production in diabetes.
KW - chronic kidney disease
KW - diabetic nephropathy
KW - nutrition
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U2 - 10.1016/j.kint.2016.09.012
DO - 10.1016/j.kint.2016.09.012
M3 - Article
C2 - 27914710
AN - SCOPUS:85006459161
SN - 0085-2538
VL - 91
SP - 204
EP - 215
JO - Kidney international
JF - Kidney international
IS - 1
ER -