Safety and efficacy of sodium bicarbonate for treating metabolic acidosis in chronic kidney disease: A systematic review and meta-analysis

Table 1 Study characteristics

Ref.	Study design	Study sample	Intervention/control name		Sample size		Follow-up duration	Dosage of sodium bicarbonate
			Intervention	Control	Intervention	Control	Months
Mathur et al[28]	RCT	Mild to moderate CKD with serum creatinine < 5 mg/dL	Sodium bicarbonate	Placebo	20	20	3	1.2 mEq/kg
Ashurst et al[27]	RCT	Creatinine clearance 15 to 30 ml/min per 1.73 m2 and serum bicarbonate 16 to 20 mmol/L	Sodium bicarbonate	Standard care	67	67	24	600 mg
Goraya et al[26]	RCT	eGFR, 15-29 ml/min per 1.73 m2 and PTCO2 level < 22 mm	Sodium bicarbonate	Fruits and vegetables	35	36	12	1.0 mEq/kg
Abramowitz et al[35]	Clinical trial	eGFR 15-45 ml/min per 1.73 m2 and serum bicarbonate 20-24 mEq/L	Sodium bicarbonate	Placebo	20	20	3	1.0 mEq/kg
Goraya et al[25]	RCT	eGFR 30-59 ml/min and metabolic acidosis characterized by plasma TCO2 > 22 but < 24 mmol/L	Sodium bicarbonate	Standard care	36	36	36	0.3 mEq/kg
Jeong et al[36]	Clinical trial	eGFR < 15-30 mL/min per 1.73 m2 and CO2 less than 22 mEq/L	Sodium bicarbonate	Standard care	40	40	12	1000 mg
Bellasi et al[29]	RCT	CKD-3b-4 with DM2 and serum bicarbonate levels below 24 mEql/L	Sodium bicarbonate	Standard care	71	74	12	0.5 mmol/kg
Yan et al[30]	RCT	eGFR of 15-60 ml/min/1.73 m2, serum HCO3- level of 16-20 mmol/L	Sodium bicarbonate	Placebo	42	42	4.25	N/A
Kendrick et al[31]	RCT	eGFR 15-44 ml/min per 1.73 m2 with low serum bicarbonate levels (16-21 mEq/L)	Sodium bicarbonate	Control group	10	10	6	650 mg
Di Iorio et al[22]	RCT	CKD stage 3-5, serum bicarbonate > 18 and < 24 mmol/L	Sodium bicarbonate	Standard care	376	364	36	N/A
Aigner et al[24]	RCT	CKD stage 3-4 with serum HCO3- ≤ 21 mmol/L	Sodium bicarbonate	Rescue group	18	17	1	840 mg
Goraya et al[23]	RCT	eGFR 30-59 mL/min/1.73 m2 and plasma total CO2 > 22 mM but < 24 mM	Sodium bicarbonate	Standard care	36	36	60	0.3 mEq/kg
Raphael et al[17]	RCT	eGFR 20-44 or 45-59 ml/min per 1.73 m2 and serum bicarbonate 20-28 meq/L	Sodium bicarbonate	Placebo	HD: 90; LD: 90	52	2.25	0.8 mEq/kg
Kittiskulnam et al[28]	RCT	eGFR 15-59 mL/min/1.73 m2, serum bicarbonate level < 22 mEq/L	Sodium bicarbonate	LD sodium bicarbonate	21	21	4	300 mg
Melamed et al[19]	RCT	eGFR of 15-59 ml/min/1.73m2, and serum bicarbonate levels 20 to 26 mEq/L	Sodium bicarbonate	Placebo	74	75	24	0.4 mEq/kg
Dubey et al[33]	RCT	CKD stages 3 and 4 and serum bicarbonate levels < 22 mEq/dL	Sodium bicarbonate	Standard care	94	94	6	0.5 mEq/kg
Witham et al[20]	RCT	CKD stages 3 and 4, and serum bicarbonate levels < 22 mEq/dL	Sodium bicarbonate	Placebo	152	148	24	500 mg
Alva et al[21]	RCT	eGFR of 15-30 mL/min/1.73 m2 and serum bicarbonate 10-20 mm/L	Sodium bicarbonate	Standard care	33	34	9	600 mg
Gaggl et al[34]	RCT	eGFR between 60 and 15 mL/min per 1.73 m2 and a serum HCO3- of ≤ 21 mmol/L	Sodium bicarbonate	Rescue group	24	23	2	N/A
Bovée et al[16]	RCT	eGFR 15-30 ml/min/1.73m2 and plasma bicarbonate levels between 15.0 and 24.0 mmol/L	Sodium bicarbonate	Sodium chloride	15	15	1	1000 mg
Mohebbi et al[32]	RCT	eGFR between 15 mL/min per 1.73 m² and 89 mL/min per 1.73 m² and serum bicarbonate of 22 mmol/L or less	Sodium bicarbonate	Placebo	119	121	24	500 mg
Sorohan et al[15]	RCT	eGFR between 45 and 15 mL/min/1.73 m2 and serum bicarbonate between 10 and 22 mmol/L	Sodium bicarbonate	Sodium citrate	62	62	12	600 mg

RCT: Randomized controlled trial; eGFR: Estimated glomerular filtration rate; CKD: Chronic kidney disease; HD: High dose; LD: Low dose; N/A: Not applicable.

Table 2 Baseline patient characteristics, n (%)/mean ± SD

Ref.	Age (year)		Male		eGFR (mL/min)		Serum HCO3- (mmol/L)		Serum K+ (mmol/L)		Serum Na+ (mmol/L)
	Intervention	Control	Intervention	Control	Intervention	Control	Intervention	Control	Intervention	Control	Intervention	Control
Mathur et al[28]	37.5 ± 17	43.5 ± 10.5	12 (60)	13 (65)	-	-	19.49 ± 5.51	19.35 ± 3.74	-	-	-	-
Ashurst et al[27]	54.78 ± 2.56	54.77 ± 2.34	35 (52)	34 (51)	-	-	19.8 ± 2.2	19.9 ± 1.5	-	-	-	-
Goraya et al[26]	54.2 ± 5.3	53.9 ± 6.9	18 (51)	20 (56)	-	-	-	-	4.1 ± 0.2	4.1 ± 0.2	139.9 ± 1.2	139.8 ± 1.3
Abramowitz et al[35]	63.1 ± 10.8	-	8 (40)	-	32.9 ± 8.9	-	23.0 ± 2.4	-	4.6 ± 0.4	-	-	-
Goraya et al[25]	53.6 ± 5.3	53.9 ± 4.8	16 (44)	16 (44)	-	-	-	-	4.24 ± 0.12	4.29 ± 0.14	-	-
Jeong et al[36]	53.3 ± 13.5	55.8 ± 12.7	21 (52.5)	26 (57.5)	16.7 ± 6.1	17.7 ± 6.4			5.25 ± 0.71	5.44 ± 0.63	-	-
Bellasi et al[29]	64.9 ± 11.8	66.0 ± 12.9	47 (66)	36 (48)	-	-	21.2 ± 1.9	21.6 ± 2.0	-	-	-	-
Yan et al[30]	53.10 ± 6.11	53.10 ± 8.66	25 (59.5)	24 (57.1)	19.09 ± 2.26	18.43 ± 1.89	16.49 ± 1.22	16.14 ± 1.40	-	-	-	-
Kendrick et al[31]	59 ± 12	-	10 (50)	-	25 ± 8	24 ± 8	19.3 ± 2.9	19.7 ± 2.3	-	-	-	-
Di Iorio et al[22]	67.6 ± 15.1	68.1 ± 14.7	234 (62.2)	224 (61.5)	33.4 ± 12.4	36.9 ± 10.8	21.7 ± 2.6	21.4 ± 2.1	4.9 ± 0.5	4.9 ± 0.6	139 ± 2.9	139 ± 2.8
Aigner et al[24]	59.94 ± 12.46	53.12 ± 17.74	12 (66.7)	11 (52.9)	23.64 ± 5.87	27.45 ± 10.05	18.78 ± 1.59	19.28 ± 1.55	4.83 ± 0.47	4.94 ± 0.61	140 ± 3.03	139 ± 2.6
Goraya et al[23]	53.6 ± 5.3	53.9 ± 4.8	16 (44.4)	16 (44.4)	39.6 ± 6.6	39.5 ± 6.9	-	-	-	-	-	-
Raphael et al[17]	HD: 67 ± 11 LD: 66 ± 14	66 ± 11	HD: 61 (68) LD: 69 (60)	39 (75)	HD: 36 ± 10 LD: 37 ± 10	35 ± 9	HD: 24 ± 2 LD: 24 ± 2	24 ± 2	4.4 ± 0.4	4.5 ± 0.5	-	-
Kittiskulnam et al[28]	61.2 ± 9.8	61.2 ± 9.8	12 (57.1)	12 (57.1)	32.4 ± 14.1	-	21.0 ± 2.1	-	-	-	-	-
Melamed et al[19]	60.3 ± 14.1	61.6 ± 10.9	36 (49)	33 (44)	36.4 ± 11.4	36.2 ± 11.1	24.0 ± 2.2	24.1 ± 2.6	4.5 ± 0.5	4.6 ± 0.5	-	-
Dubey et al[33]	50.12 ± 11.6	50.30 ± 11.4	68 (72.3)	66 (70.2)	29.2 (27-31.3)	31.5 (29.3-33.8)	18.1 (17.7-18.6)	18.1 (17.6-18.6)	-	-	-	-
Witham et al[20]	73.9 ± 7.6	74.0 ± 6.6	110 (72.4)	104 (70.3)	19.7 ± 6.5	18.2 ± 6.4	20.6 ± 2.6	20.1 ± 2.5	4.9 ± 0.5	4.9 ± 0.5	-	-
Alva et al[21]	-	-	23 (69.7)	25 (73.53)	22.39 ± 4.08	21.21 ± 4.37	16.62 ± 3.05	16.84 ± 2.17	-	-	-	-
Gaggl et al[34]	58 ± 12.8	56 ± 16.5	15 (62)	14 (61)	25.33 ± 7.5	27 ± 9.7	18.8 ± 1.8	19.2 ± 1.5	-	-	-	-
Bovée et al[16]	61 ± 17	61 ± 14	11 (73)	14 (93)	21 ± 6	22 ± 3	20.8 ± 3.9	21.8 ± 2.9	5.1 ± 0.7	5.0 ± 0.6	-	-
Mohebbi et al[32]	55.7 ± 13.2	55.3 ± 13.8	82 (69)	85 (70)	48.2 ± 16.3	47.7 ± 15.8	21.3 ± 2.6	21.0 ± 2.7	-	-	-	-
Sorohan et al[15]	57.37 ± 10.25	57.95 ± 10.22	35 (56.5)	35 (56.5)	23.68 ± 9.05	24.93 ± 6.70	17.16 ± 1.62	17.53 ± 2.05	5.00 ± 0.34	4.88 ± 0.44	138.71 ± 1.41	138.44 ± 2.61