Daily Oral Sodium Bicarbonate Preserves Glomerular Filtration Rate by Slowing its Decline in Early Hypertensive Nephropathy

Ashutosh Mahajan; Jan Simoni; Simon J. Sheather; Kristine R. Broglio; M.H. Rajab; Donald E. Wesson

Disclosures

Kidney Int. 2010;78(3):303-309. 

In This Article

Abstract and Introduction

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.

Introduction

Hypertensive nephropathy is the second leading cause of complete kidney failure in the United States of America,[1] and most with low glomerular filtration rate (GFR) due to hypertensive nephropathy have progressive GFR decline despite blood pressure reduction with regimens including renin–angiotensin system inhibition.[2] Low GFR can be associated with metabolic acidosis[3] and treatment with oral NaHCO3 slows the decline rate of creatinine (cr) clearance in subjects with very low cr clearance of various etiologies,[4] and with Na+ citrate slows the decline rate of estimated GFR (eGFR) in those with very low eGFR due to hypertensive nephropathy.[5] These data support that metabolic acidosis contributes to GFR decline in subjects with very low GFR. Nevertheless, progressive GFR decline occurs even among hypertensive nephropathy subjects with comparatively preserved, chronic kidney disease (CKD) stage 2 eGFR (60–90 ml/min).[2] The latter subjects are less likely to have metabolic acidosis by serum acid–base parameters,[3] so it is less clear that metabolic acidosis contributed to GFR decline.

Progressive GFR decline in animals with low GFR due to reduced nephron mass was slowed by oral alkali, despite serum acid–base parameters not different from those with intact nephron mass.[6] Similarly, acid-inducing diets led to endothelin (ET)-mediated GFR decline and oral alkali slowed GFR decline, better preserved GFR, and lowered kidney ET production in animals with reduced nephron mass.[6,7] Dietary acid-induced kidney injury in animals with intact nephron mass[8] and with reduced nephron mass[7] is mediated by tubulointerstitial injury through ET receptors.[7,8] Tubulointerstitial injury is a component of hypertensive nephropathy[9] and its increased severity might predict increased risk for nephropathy progression.[10] We tested the hypothesis that chronic oral NaHCO3 (1) slows GFR decline rate, (2) ameliorates urine ET-1 excretion, a surrogate of kidney ET production, and (3) ameliorates urine excretion of N-acetyl-β-D-glucosaminidase (NAG), a marker of kidney tubulointerstitial injury.

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