Table 1.

Summary of published pharmacological intervention trials evaluating effects on kidney function and injury.

Study	Population	Baseline Bicarbonate (mEq/L)	Total Sample Size	Intervention	Duration	Main Findings
UBI [64]	CKD stages 3–5	18–24	795	NaHCO3 to target bicarbonate 24–28 mEq/L	36 months	Lower risks of serum creatinine doubling, renal replacement therapy, and death
BiCARB [67]	Age > 60 eGFR < 30	<22	300	NaHCO3 up to 3000 mg/d	24 months	No significant effect on short physical performance battery after 12 months. Shorter 6-minute walking distance and reduction in handgrip strength in treatment group. More adverse events with treatment
Alkali Therapy in CKD [69]	CKD stage 3 or 4	20–26	149	NaHCO3 0.4 mEq/kg (ideal bodyweight/day)	24 months	No significant effects on bone mineral density, sit-to-stand time, other physical function assessments, and eGFR
BASE Pilot Trial [70]	CKD stage 3b or 4; or CKD stage 3a with ACR ≥ 50 mg/g	20–28	192	NaHCO3 0.5 or 0.8 mEq/kg (lean bodyweight/day)	28 weeks	No significant effects on blood pressure and weight Dose-dependent increase in sodium bicarbonate levels Dose-dependent increase in urinary ACR
VA–Bicarb Trial [68]	Diabetic CKD stages 2–4 with ACR > 30 mg/g	22–28	74	NaHCO3 0.5 mEq/kg lean bodyweight/day	6 months	No statistically significant effects on urinary markers of kidney injury
Veverimer (40-week extension study) [71]	eGFR 20–40 mL/min per 1.73 m2	12–20	196	Veverimer 6g/day then titrated to target bicarbonate level (22–29 mEq/L)	52 weeks	3% in veverimer vs. 10% in placebo; discontinued treatment Treatment with veverimer improved physical function. Fewer treated with veverimer died or progressed to ESKD.
VALOR–CKD Trial [62]	eGFR 20–40 mL/min per 1.73 m2	12–20	1480	Veverimer vs. placebo	Mean follow-up: 26.7 months	Higher-than-expected bicarbonate level in placebo group No statistically significant difference in kidney events
De brito-Ashurst et al. [63]	CKD stages 4–5	17–19	134	NaHCO3 titrate to ≥23 mEq/L vs. usual care	2 years	Lower CrCl decline (−1.88 vs. −5.93 mL/min) Lower relative risk of ESKD 0.13 (95% CI, 0.04–0.40)
Phisitkul et al. [37]	eGFR 20–60, Hypertension	<22	59	Sodium Citrate 1 mEq/kg/d vs. usual care	2 years	Lower eGFR decline (−3.6 vs. −8.7 mL/min/1.73 m2)
Mahajan et al. [65]	CKD stage 2, Hypertension, ACR ≥ 300	-	120	NaHCO3 0.5 mEq/kg/d vs. equimolar NaCl vs. placebo	5 years	Lower eGFR decline (−6.8 vs. −10.8 vs. −12.7 mL/min/1.73 m2)
Preserve-Transplant Study [66]	Kidney transplant recipient >1 year, eGFR 15–89	<22	242	NaHCO3 1.5–4.5 g/d vs. placebo	2 years	No difference in eGFR between the groups.