Table 2.

Relationship between metabolic acidosis and kidney disease progression.

Type of study	Patients number	Main finding	Limitations	Reference
Retrospective	5,422	Weak association between low serum bicarbonate and progression of kidney disease	Only 9% of the participants have estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at baseline The estimation of progression of kidney disease is very limited	Shah et al., 2009 [67]
Retrospective	1,094	Higher serum bicarbonate is associated with reduced hazard of kidney disease progression	It is a secondary analysis Limited external validity	Raphael et al., 2011 [68]
Prospective, multicenter cohort	3,939	The risk of disease progression is 3% lower per 1 mM increase in serum bicarbonate level	Hazard ratio 0.97, 95% confidence interval 0.94–0.99	Dobre et al., 2013 [51]
Retrospective	113	Lower bicarbonate level is associated with high risk of kidney disease progression	At baseline, patients in the low-bicarbonate group have strikingly more impaired kidney function compared to patients in the high-bicarbonate group Small sample size High number of censored observations	Kanda et al., 2013 [70]
Retrospective	1,073	There is no significant association between lower bicarbonate level and incident eGFR <60 mL/min/1.73 m2	Serum bicarbonate level was calculated from the Henderson-Hasselbalch equation	Goldenstein et al., 2014 [71]
Retrospective	5,810	Serum bicarbonate categories are not associated with adjusted risk of incident eGFR <60 mL/min/1.73 m2	Total serum carbon dioxide was measured at baseline in serum samples long-term stored	Driver et al., 2014 [72]
Retrospective	632	No clear association between higher quartiles of net endogenous acid production (NEAP) and faster decline in GFR over follow-up	Higher quartiles of NEAP are associated with a faster decline in GFR, but there is no association in time-to-event analyses	Scialla et al., 2012 [69]