Dietary Acid Reduction With Fruits and Vegetables or Bicarbonate Attenuates Kidney Injury in Patients With a Moderately Reduced Glomerular Filtration Rate Due to Hypertensive Nephropathy

Nimrit Goraya; Jan Simoni; Chanhee Jo; Donald E Wesson


Kidney Int. 2012;81(1):86-93. 

In This Article

Materials and Methods

This interventional study compared the effect of 30 days of reduced dietary acid with added daily oral NaHCO3 (HCO3) or added F+V on urine parameters of kidney injury in subjects with macroalbuminuric CKD (urine albumin-to-creatinine ratio >200 mg/g Cr) due to hypertensive nephropathy and stage 1 (>90 ml/min, CKD 1) or stage 2 (60–90 ml/min, CKD 2) eGFR by MDRD formula.[28] Primary outcome was the effect of these interventions on urine excretion of the following parameters of kidney injury: Ualb as a general marker of progressive kidney injury,[10] UNAG as a marker of kidney tubulo-interstitial injury[11] and because it reflected kidney injury induced by dietary acid in experimental model of CKD,[5,22] and transforming growth factor β (UTGFV) because it also reflected kidney injury induced by dietary acid in an experimental model of CKD[22] and because it might be a mediator of hypertensive nephropathy.[12] Secondary outcomes were the effects of these interventions on UET and Ualdo, two mediators of dietary acid-induced kidney injury and GFR decline in an animal model of CKD without metabolic acidosis.[7] We excluded subjects with metabolic acidosis (plasma TCO2 <24.5 mmol/l, the lower limit of normal for our laboratory).

The protocol is outlined in Figure 4. Three groups of CKD1 and CKD 2 were studied. (1) A total of 26 CKD 1 and 40 CKD 2 subjects received oral NaHCO3 at a concentration of 0.5 mEq/kg/day for 30 days (HCO3) as scored tablets containing 10 mEq NaHCO3 with sucrose. Each subject was prescribed tablets to the nearest one-half tablet by body weight in kg (for example, a 70 kg subject received 3.5 tablets daily); (2) A total of 26 CKD 1 and 40 CKD 2 subjects received an amount of F+V, free of charge to reduce their dietary acid by 50%, focusing primarily on F+V that are particularly base-inducing.[9] Fruits such as apples, apricots, oranges, peaches, pears, raisins, and strawberries were predominantly provided. Vegetables such as carrots, cauliflower, eggplant, lettuce, potatoes, spinach, tomatoes, and zucchini were predominantly provided. Subjects did not receive specific dietary instructions and were allowed to integrate the added F+V into their ad lib diets as they wished. Dietary acid was measured before and after interventions using 3-day diaries of food intake and a published formula.[9] The necessary amount of F+V was prescribed by a dietician and distributed from a community center food bank used by all F+V subjects. To assure that each F+V subject received sufficient F+V, we provided the described amount for each member of the household; (3) A total of 27 CKD 1 and 40 CKD 2 subjects had no intervention (Time Control). Otherwise, all subjects were allowed to eat ad lib. Other inclusion criteria were as follows: (1) non-malignant hypertension; (2) 60≥eGFR<90 ml/min for CKD 2, >90 ml/min for CKD 1; (3) ≥2 primary care physician visits in the preceding year, showing compliance with clinic visits; (4) age ≥18 years and able to give consent. Exclusion criteria were as follows: (1) primary kidney disease or findings consistent thereof such as ≥3 red blood cells per high-powered field of urine or urine cellular casts; (2) history of diabetes or fasting blood glucose ≥110 mg/dl; (3) history of malignances, chronic infections, pregnancy, or clinical evidence of cardiovascular disease; and (4) peripheral edema or diagnoses associated with edema such as heart/liver failure or nephrotic syndrome. The diagnosis of hypertensive nephropathy as the exclusive nephropathy cause was made clinically by excluding subjects with systemic diseases associated with nephropathy, nephrotic-range proteinuria, and urine abnormalities other than albuminuria. None had a kidney biopsy. Secondary causes of hypertension such as renal artery stenosis and hyperaldosteronism were excluded clinically. Kidney Doppler studies and plasma aldosterone-to-renin ratios were not carried out. Subjects were recruited as described.[4] All had had their Sys BP reduced toward a target of <130 mm Hg using a previously described protocol[25] with regimens including angiotensin-converting enzyme inhibitors as recommended for hypertensives with albuminuria.[29]

Figure 4.

Outline of the protocol to test the effect after 30 days on parameters of kidney injury of no intervention (Time Control), daily oral NaHCO3 at a concentration of 0.5 mEq/kg bw/day, or fruits+vegetables given in amounts designed to reduce dietary acid intake by 50%.

Eight-hour (0800 to 1600 h) urine NAE (8 h NAE) was measured and calculated from urine titratable acidity, ammonium (NH4+), and HCO3 ([NH4+]+[titratable acidity]−[HCO3]) as described earlier[4] at baseline and 30 days after the intervention. Sys BP and venous plasma acid–base parameters, ET-1, and aldosterone were measured at baseline and after the intervention. Urine excretion of albumin, NAG, TGF, ET-1, aldo, Na+, and K+ were each measured before and after intervention in a morning urine specimen and factored per gram of Cr.

Our IRB approved the protocol.

Analytical Methods

Plasma and urine Cr and urine albumin were measured using the Sigma Diagnostics Creatinine Kit (Procedure No. 555, Sigma Diagnostics, St Louis, MO).[30] The IRMA SL Series 2000 blood analysis system (Edison, NJ) measured venous plasma/blood pH and plasma CO2. Urine and plasma TCO2 were measured using ultrafluorometry.[31] Urine titratable acidity was measured by correction to the ambient plasma pH by NaOH addition, and NH4+ by the Formalin titrametric (to ambient plasma pH) method.[32] Plasma ET and urinary ET were measured with an RIA kit (Peninsula Laboratories, Belmont, CA) after extraction using Bound Elut C18 columns (Varian, Harbor City, CA).[13] Plasma and urine aldosterone were measured after extraction with Bound Elut C18 columns (Varian) using a radioimmunoassay kit (Diagnostic Products Corporation, Los Angeles, CA) as performed previously.[7] Urine ET and aldosterone excretion were expressed per gram Cr of a spot AM specimen.

Statistical Methods

Patient characteristics at the time of study enrollment were tabulated by percentages or described by mean and standard deviation. We first compared the baseline characteristics among the six subject groups with the χ 2-test or the one-way analysis of variance, as appropriate. The primary outcomes were Ualb, UNAG, and UTGF in response to 30 days of oral F+V or NaHCO3. Secondary outcomes included plasma ET, plasma aldo, Ualdo, urine 8 h NAE, and venous TCO2. The changes from pre to post for each group were described by mean and s.d., and they were considered with a one-sample t-test. The differences among the three groups within CKD cohort were considered with one-way analysis of variance followed by post-hoc Tukey's test. In addition, outcomes were compared between a group in CKD 1 and a corresponding CKD 2 group with a two-sample t-test. A P-value of less than 0.05 indicates a statistical significance. SAS version 9.2 (SAS Institute, Cary, NC) was used for the statistical analysis and graphs were created using R 2.12.1 (R Core Development Team, 2010).


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: