A comparison of treating metabolic acidosis in CKD stage 4 hypertensive kidney disease with fruits and vegetables or sodium bicarbonate

Abstract

Background and objectives: Current guidelines recommend Na(+)-based alkali for CKD with metabolic acidosis and plasma total CO2 (PTCO2) < 22 mM. Because diets in industrialized societies are typically acid-producing, we compared base-producing fruits and vegetables with oral NaHCO3 (HCO3) regarding the primary outcome of follow-up estimated GFR (eGFR) and secondary outcomes of improved metabolic acidosis and reduced urine indices of kidney injury.

Design, setting, participants, & measurements: Individuals with stage 4 (eGFR, 15-29 ml/min per 1.73 m(2)) CKD due to hypertensive nephropathy, had a PTCO2 level < 22 mM, and were receiving angiotensin-converting enzyme inhibition were randomly assigned to 1 year of daily oral NaHCO3 at 1.0 mEq/kg per day (n=35) or fruits and vegetables dosed to reduce dietary acid by half (n=36).

Results: Plasma cystatin C-calculated eGFR did not differ at baseline and 1 year between groups. One-year PTCO2 was higher than baseline in the HCO3 group (21.2±1.3 versus 19.5±1.5 mM; P<0.01) and the fruits and vegetables group (19.9±1.7 versus 19.3±1.9 mM; P<0.01), consistent with improved metabolic acidosis, and was higher in the HCO3 than the fruits and vegetable group (P<0.001). One-year urine indices of kidney injury were lower than baseline in both groups. Plasma [K(+)] did not increase in either group.

Conclusions: One year of fruits and vegetables or NaHCO3 in individuals with stage 4 CKD yielded eGFR that was not different, was associated with higher-than-baseline PTCO2, and was associated with lower-than-baseline urine indices of kidney injury. The data indicate that fruits and vegetables improve metabolic acidosis and reduce kidney injury in stage 4 CKD without producing hyperkalemia.

Figure 1.

Cascade of the selection process for study patients. F+V, fruits and vegetables. “Not treated” patients were not considered in the reported analysis.

Figure 2.

Box plots of plasma total CO₂ (TCO₂) (left) and 8-hour urine net acid excretion (8h NAE) (right) in patients with CKD stage 4 at baseline and 1-year follow-up. HCO₃ recipients were given oral NaHCO₃ at 1.0 mEq/kg lean body weight per day; the fruit and vegetable recipients were given fruits and vegetables in amounts designed to reduce potential renal acid load by half. The bottom and top of the boxes span the 25th and 75th percentile of data points. The dark bar within the box indicates the 50th percentile or median. The whiskers indicate 1.5 times the interquartile range from the lower and upper quartiles. F+V, fruits and vegetables; F/U, follow-up. *P<0.05 versus respective baseline; ⁺P<0.05 versus respective HCO₃ group.

Figure 3.

Box plots of 8-hour urine excretion of cystatin C (8h Cys Ex) (left) and of creatinine (8h Cr Ex) (right) at baseline and 1-year follow-up. The bottom and top of the boxes span the 25th and 75th percentile of data points. The dark bar within the box indicates the 50th percentile or median. The whiskers indicate 1.5 times the interquartile range from the lower and upper quartiles. F+V, fruits and vegetables; F/U, follow-up. *P<0.05 versus respective baseline.

Figure 4.

Box plots of plasma cystatin C–estimated GFR (cysGFR) (left) and of plasma creatinine–estimated GFR (crGFR) (right) at baseline and 1-year follow-up. The bottom and top of the boxes span the 25th and 75th percentile of data points. The dark bar within the box indicates the 50th percentile or median. The whiskers indicate 1.5 times the interquartile range from the lower and upper quartiles. F+V, fruits and vegetables; F/U, follow-up. *P<0.05 versus respective baseline.

Figure 5.

Box plots of the 8-hour urine excretion of indices of kidney injury. Urine albumin (8h urine albumin) is in the left panel, urine N-acetyl β-d-glucosaminidase (8h UNAG) is in the middle panel, and urine TGF-β (8h UTGF) is in the right panel. The bottom and top of the boxes span the 25th and 75th percentile of data points. The dark bar within the box indicates the 50th percentile or median. The whiskers indicate 1.5 times the interquartile range from the lower and upper quartiles. F+V, fruits and vegetables; F/U, follow-up. *P<0.05 versus baseline; ⁺P<0.05 versus HCO₃.

Figure 6.

Box plots of 8-hour urine aldosterone excretion (8h aldo) (left) and ratio of active (tetrahydrocortisol [THF]) to inactive (tetrahydrocortisone [THE]) urine cortisol metabolites (right) in CKD stage 4 at baseline and 1 year. The THF/THE ratio indirectly assesses 11β-hydroxysteroid dehydrogenase enzyme activity that converts glucocorticoids to inactive metabolites. Higher ratios indicate lower activity. The bottom and top of the boxes span the 25th and 75th percentile of data points. The dark bar within the box indicates the 50th percentile or median. The whiskers indicate 1.5 times the interquartile range from the lower and upper quartiles. F+V, fruits and vegetables; F/U, follow-up. *P<0.05 versus respective baseline; ⁺P<0.05 versus HCO₃.