Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy

Abstract

In most patients with hypertensive nephropathy and low glomerular filtration rate (GFR), the kidney function progressively declines despite the adequate control of the hypertension with angiotensin-converting enzyme inhibition. Previously we found that 2 years of oral sodium citrate slowed GFR decline in patients whose estimated GFR (eGFR) was very low (mean 33 ml/min). This treatment also slowed GFR decline in an animal model of surgically reduced nephron mass. Here, we tested if daily oral sodium bicarbonate slowed GFR decline in patients with hypertensive nephropathy with reduced but relatively preserved eGFR (mean 75 ml/min) in a 5-year, prospective, randomized, placebo-controlled, and blinded interventional study. Patients matched for age, ethnicity, albuminuria, and eGFR received daily placebo or equimolar sodium chloride or bicarbonate while maintaining antihypertensive regimens (including angiotensin-converting enzyme inhibition) aiming for their recommended blood pressure targets. After 5 years, the rate of eGFR decline, estimated using plasma cystatin C, was slower and eGFR was higher in patients given sodium bicarbonate than in those given placebo or sodium chloride. Thus, our study shows that in hypertensive nephropathy, daily sodium bicarbonate is an effective kidney protective adjunct to blood pressure control along with angiotensin-converting enzyme inhibition.

Luminal Alkalinization Attenuates Proteinuria-Induced Oxidative Damage in Proximal Tubular Cells

“…44 -47 More recently, daily bicarbonate supplementation was reported to halt the progression of proteinuric human CKD without metabolic acidosis. 48 The underlying mechanism of these therapeutic effects could be explained by our present observation that luminal alkalinization suppresses intracellular ROS level in tubular cells. To firmly establish the therapeutic potential of luminal alkalinization, it would be necessary to examine whether other types of proteinuric tubular injury (e.g., diabetic nephropathy and chronic glomerulonephritis) are also attenuated by NaHCO 3 feeding.…”

Mechanisms and Treatment of CKD

“…it/remission/) and applied to all CKD patients with heavy proteinuria despite therapy. 75 This multimodal intervention strategy included lifestyle modifications such as sodium 93 and protein 30 intake restriction, smoking cessation, body weight loss, 94 optimal BP (target systolic/diastolic ,130/80 mmHg) and metabolic control (target hemoglobin A1C ,7.5%) in patients with diabetes, correction of metabolic acidosis 95 and hyperphosphatemia, 96 use of statins, 76,97,98 and dual RAS blockade with maximum tolerated doses of ACE inhibitors and ARBs, probably the mainstay of proteinuria management in this setting. 99 In a matched-cohort study, we compared the outcome of 56 CKD patients receiving the Remission Clinic approach because of persistent 24-hour proteinuria .3 g despite standard antihypertensive doses of an ACE inhibitor with that of 56 matched historical reference patients who had received ACE inhibitor therapy titrated to target BP.…”

Slowing Progression of Chronic Kidney Disease

“…21 The effects of sodium bicarbonate, sodium chloride, or placebo on the rate of eGFR decline in 120 subjects with macroalbuminuric hypertensive nephropathy demonstrated that after 5 years the rate of eGFR decline was slower in the bicarbonate group. 22 On the basis of this evidence, it is reasonable to maintain serum bicarbonate concentration 422 mmol/l in CKD patients. 2 …”