Alkali therapy of metabolic acidosis in patients with chronic kidney disease (CKD) with plasma total CO2 (TCO2) below 22 mmol/l per KDOQI guidelines appears to preserve estimated glomerular filtration rate (eGFR). Since angiotensin II mediates GFR decline in partial nephrectomy models of CKD and even mild metabolic acidosis increases kidney angiotensin II in animals, alkali treatment of CKD-related metabolic acidosis in patients with plasma TCO2 over 22 mmol/l might preserve GFR through reduced kidney angiotensin II. To test this, we randomized 108 patients with stage 3 CKD and plasma TCO2 22-24 mmol/l to Usual Care or interventions designed to reduce dietary acid by 50% using sodium bicarbonate or base-producing fruits and vegetables. All were treated to achieve a systolic blood pressure below 130 mm Hg with regimens including angiotensin converting enzyme inhibition and followed for 3 years. Plasma TCO2 decreased in Usual Care but increased with bicarbonate or fruits and vegetables. By contrast, urine excretion of angiotensinogen, an index of kidney angiotensin II, increased in Usual Care but decreased with bicarbonate or fruits and vegetables. Creatinine-calculated and cystatin C-calculated eGFR decreased in all groups, but loss was less at 3 years with bicarbonate or fruits and vegetables than Usual Care. Thus, dietary alkali treatment of metabolic acidosis in CKD that is less severe than that for which KDOQI recommends therapy reduces kidney angiotensin II activity and preserves eGFR.

SummaryBackground and objectives Current guidelines recommend Na + -based alkali for CKD with metabolic acidosis and plasma total CO 2 (PTCO 2 ) , 22 mM. Because diets in industrialized societies are typically acid-producing, we compared base-producing fruits and vegetables with oral NaHCO 3 (HCO 3 ) 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 PTCO 2 level , 22 mM, and were receiving angiotensin-converting enzyme inhibition were randomly assigned to 1 year of daily oral NaHCO 3 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 PTCO 2 was higher than baseline in the HCO 3 group (21.261.3 versus 19.561.5 mM; P,0.01) and the fruits and vegetables group (19.961.7 versus 19.361.9 mM; P,0.01), consistent with improved metabolic acidosis, and was higher in the HCO 3 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 NaHCO 3 in individuals with stage 4 CKD yielded eGFR that was not different, was associated with higher-than-baseline PTCO 2 , 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.

The neutralization of dietary acid with sodium bicarbonate decreases kidney injury and slows the decline of the glomerular filtration rate (GFR) in animals and patients with chronic kidney disease. The sodium intake, however, could be problematic in patients with reduced GFR. As alkali-induced dietary protein decreased kidney injury in animals, we compared the efficacy of alkali-inducing fruits and vegetables with oral sodium bicarbonate to diminish kidney injury in patients with hypertensive nephropathy at stage 1 or 2 estimated GFR. All patients were evaluated 30 days after no intervention; daily oral sodium bicarbonate; or fruits and vegetables in amounts calculated to reduce dietary acid by half. All patients had 6 months of antihypertensive control by angiotensin-converting enzyme inhibition before and during these studies, and otherwise ate ad lib. Indices of kidney injury were not changed in the stage 1 group. By contrast, each treatment of stage 2 patients decreased urinary albumin, N-acetyl β-D-glucosaminidase, and transforming growth factor β from the controls to a similar extent. Thus, a reduction in dietary acid decreased kidney injury in patients with moderately reduced eGFR due to hypertensive nephropathy and that with fruits and vegetables was comparable to sodium bicarbonate. Fruits and vegetables appear to be an effective kidney protective adjunct to blood pressure reduction and angiotensin-converting enzyme inhibition in hypertensive and possibly other nephropathies.

Background: Current guidelines recommend treatment of metabolic acidosis in chronic kidney disease (CKD) with sodium-based alkali. We tested the hypothesis that treatment with base-producing fruits and vegetables (F + V) better improves cardiovascular disease (CVD) risk indicators than oral sodium bicarbonate (NaHCO₃). Methods: We randomized 108 macroalbuminuric, matched, nondiabetic CKD patients with metabolic acidosis to F + V (n = 36) in amounts to reduce dietary acid by half, oral NaHCO₃ (HCO₃, n = 36) 0.3 mEq/kg bw/day, or to Usual Care (UC, n = 36) to assess the 5-year effect of these interventions on estimated glomerular filtration rate (eGFR) course as the primary analysis and on indicators of CVD risk as the secondary analysis. Results: Five-year plasma total CO₂ was higher in HCO₃ and F + V than UC but was not different between HCO₃ and F + V (difference p value < 0.01). Five-year net eGFR decrease was less in HCO₃ (mean –12.3, 95% CI –12.9 to –11.7 mL/min/1.73 m²) and F + V (–10.0, 95% CI –10.6 to –9.4 mL/min/1.73 m²) than UC (–18.8, 95% CI –19.5 to –18.2 mL/min/1.73 m²; p value < 0.01) but was not different between HCO₃ and F + V. Five-year systolic blood pressure was lower in F + V than UC and HCO₃ (p value < 0.01). Despite similar baseline values, F + V had lower low-density lipoprotein, Lp(a), and higher serum vitamin K1 (low serum K1 is associated with coronary artery calcification) than HCO₃ and UC at 5 years. Conclusion: Metabolic acidosis improvement and eGFR preservation were comparable in CKD patients treated with F + V or oral NaHCO₃ but F + V better improved CVD risk indicators, making it a potentially better treatment option for reducing CVD risk.