Table 1.

Cohort studies of participants with non-dialysis chronic kidney disease and their acid-base status

Cohort	Time period, study design, country of origin	n	Study population	Determination of GFR	Acid-base measurement	Summary of findings on acid-base status
NephroTest8	1/2000–12/2006; prospective hospital-based; France	1,038	CKD stage 2–5 -mean age was 59 years -31% were women -6% were black	mGFR: measured by 51Cr-EDTA renal clearance; eGFR: estimated using 2 equations from the Modification -mean mGFR was 37±17 ml/min per 1.73m2	Venous total CO2 measured using electrode -acidosis defined as bicarbonate <22mEq/L or on bicarbonate therapy	-Overall prevalence of acidosis was 15%. -22% of participants with acidosis were on bicarbonate therapy. -The mGFR threshold for detecting acidosis with 90% sensitivity was 40 ml/min per 1.73m2.
Chronic Renal Insufficiency Cohort11,12,23	6/2003–12/2008 (enrollment); multicenter,observation al study; USA	3,939	eGFR 20–70 ml/min per 1.73m2 -mean age was 58 years -45.2% were women -41.8% were African American -48.5% had diabetes	GFR was assessed by a CRIC internal GFR estimating equation validated against iothalamate 125 clearance testing that uses serum Cr, cystatin C, age, sex and race -mean eGFR was 43±14 ml/min per 1.73m2	Serum bicarbonate measured using an enzymatic procedure with phosphoenolypyruvate carboxylase on the Ortho Vitros platform at the University of Pennsylvania Core Laboratory -low bicarbonate defined as bicarbonate <22mEq/L	-Median serum bicarbonate level was 24 (IQR 22–26) mEq/L. -Overall prevalence of low bicarbonate was 17.3%: 7% for CKD stage 2, 13% for stage 3 and 37% for stage 4.
African American Study of Kidney Disease and Hypertension13,14,28	2/1995–9/2001; multicenter, 3×2 factorial, randomized, controlled trial of intensive vs. standard blood pressure control; USA	1,094	GFR 20–65 ml/min per 1.73m2 -mean age was 54 years -~40% were women	GFR was assessed by renal clearance of iodine I125 iothalamate clearance -mean GFR was 46 ml/min per 1.73m2	Serum bicarbonate was measured using either the kinetic ultraviolet method or a CO2 electrode	-Mean serum bicarbonate was 25.1 mEq/L -4.3% had bicarbonate <20 mEq/L, 35.5% had bicarbonate between 20–24.9 mEq/L, and 5.5% had bicarbonate ≥30mEq/L
Health, Aging and Body Composition Study5	From 1997; prospective study of community elders; USA	2,287	Well-functioning adults aged 70–79 years -mean age was 76 years -51% were women -38% were black	GFR was estimated using creatinine and cystatin C and CKD-EPI Collaboration creatinine-cystatin C equation49 -mean GFR was 82.1 ml/min per 1.73m2	Arterialized venous blood gas was obtained and measured at the point of care. Bicarbonate was calculated using the Henderson-Hasselbalch equation	-mean AVpH was 7.41 -mean bicarbonate was 25.1 mEq/L -11% had bicarbonate <23 mEq/L and 10% had bicarbonate ≥28 mEq/L. -association of bicarbonate and mortality was U-shaped with the lowest mortality at bicarbonate of 26mEq/L
National Health and Nutrition Examination Survey15	1999–2004; nationally representative survey, USA	9,781	Noninstitutionalized civilian -mean age was 46 years	GFR was calculated using CKD-EPI Equation	Bicarbonate was measured in 2 labs by the phosphoenolpyruvate carboxylase method from 1999–2001 and with a pH-sensitive electrode from 2002–2004; bicarbonate levels in 1999–2002 was adjusted by adding 1.105 mEq/L -acidosis was defined as bicarbonate <23 mEq/L	-mean bicarbonate was 24.9 mEq/L -Mean estimated NEAP was 57.4 mEq/d -Greater dietary acid load is associated with lower bicarbonate.
Bronx, New York16	1/2001–12/2003 (baseline); retrospective cohort; USA	5,422	eGFR≥15 ml/min per 1.73m2 -mean age was 52 years -69% were women -25% were African American -31% were Hispanic -21% had diabetes	eGFR was calculated using the 4-variable Modification of Diet in Renal Disease Study equation -9% with eGFR <60 ml/min per 1.73m2	Serum bicarbonate measured using an enzymatic procedure with phosphoenolypyruvate carboxylase at Montefiore Medical Center -low bicarbonate was defined as ≤22mEq/L	-Prevalence of low bicarbonate was 20.7% for all, 20%, 21%, 48% for eGFR ≥60, 30–59 and 15–29 ml/min per 1.73m2, respectively -mean bicarbonate was 23±4.3, 24.8±2.9 mEq/L for eGFR 15–29, ≥60 ml/min per 1.73m2, respectively
Chronic Kidney Disease in Children21,22	1/2005–8/2009*; observation al study; USA and Canada	586*	eGFR 30–90 ml/min per 1.73m2 -median age was 11 years -38% were female -23% were black -23% had glomerular disease	GFR was determined by directly measured plasma iohexol disappearance curve50 -median GFR was 44 ml/min per 1.73m2	Bicarbonate was measured locally using enzymatic method	-29% were on alkali therapy -median bicarbonate was 22 mEq/L -median bicarbonate was 24, 22, 21 mEq/L among those with GFR GFR≥50, ≥30 to <50, and <30 ml/min per 1.73m2, respectively

Abbreviation: USA, United States of America; GFR, glomerular filtration rate; mGFR, measured GFR; eGFR, estimated GFR; CRIC, Chronic Renal Insufficiency Cohort; Cr, creatinine; IQR, interquartile range; AVpH, arteriovenous pH; NEAP, net endogenous acid production, CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration

^*studied by Furth et al²²