Pathophysiology of Diet-Induced Acid Stress.

Diets can influence the body's acid-base status because specific food components yield acids, bases, or neither when metabolized. Animal-sourced foods yield acids and plant-sourced food, particularly fruits and vegetables, generally yield bases when metabolized. Modern diets proportionately contain more animal-sourced than plant-sourced foods, are, thereby, generally net acid-producing, and so constitute an ongoing acid challenge. Acid accumulation severe enough to reduce serum bicarbonate concentration, i.e., manifesting as chronic metabolic acidosis, the most extreme end of the continuum of "acid stress", harms bones and muscles and appears to enhance the progression of chronic kidney disease (CKD). Progressive acid accumulation that does not achieve the threshold amount necessary to cause chronic metabolic acidosis also appears to have deleterious effects. Specifically, identifiable acid retention without reduced serum bicarbonate concentration, which, in this review, we will call "covert acidosis", appears to cause kidney injury and exacerbate CKD progression. Furthermore, the chronic engagement of mechanisms to mitigate the ongoing acid challenge of modern diets also appears to threaten health, including kidney health. This review describes the full continuum of "acid stress" to which modern diets contribute and the mechanisms by which acid stress challenges health. Ongoing research will develop clinically useful tools to identify stages of acid stress earlier than metabolic acidosis and determine if dietary acid reduction lowers or eliminates the threats to health that these diets appear to cause.

Management of Metabolic Acidosis in Chronic Kidney Disease: Past, Present, and Future Direction.

Chronic kidney disease (CKD) is a major global epidemic associated with increased morbidity and mortality. Despite the effectiveness of kidney protection strategies of hypertension, diabetes, and lipid control and use of newer hypoglycemic agents and anti-angiotensin II drugs, the nephropathy in CKD continues unabated toward irreversible kidney failure. Thus, interventions targeting modifiable risk factors in CKD such as metabolic acidosis (MA) are needed. Acid reduction with sodium-based alkali has been shown to be an effective kidney-protection strategy for patients with CKD and reduced glomerular filtration rate (GFR). Small-scale studies reveal diets emphasizing ingestion of plant-sourced over animal-sourced protein reduce dietary acid, improve MA, and slow further nephropathy progression in patients with CKD and reduced GFR. Additionally, veverimer, an investigational, nonabsorbed polymer that binds and removes gastrointestinal hydrochloric acid, is being developed as a novel treatment for MA. As further studies define how to best use these interventions for kidney protection, clinicians must become aware of their potential utility in the management of patients with CKD. The aim of the present review is to explore the various intervention strategies that increase or normalize serum [HCO3-] in patients with CKD-associated MA or low normal serum [HCO3-] that may further slow progression of CKD.

Biomarkers of Covert Acid Stress in Patients with Chronic Kidney Disease: A Cross-Sectional Study.

INTRODUCTION: Like metabolic acidosis, earlier stages of acid (H+) stress, including an ongoing H+ challenge in the form of dietary H+, without or with steady-state H+ accumulation but with normal plasma total CO2 (PTCO2) (the latter state known as eubicarbonatemic acidosis), are associated with augmented progression of chronic kidney disease (CKD), but diagnosis of this covert H+ stress is clinically problematic. Prior published studies to identify clinically practical biomarkers of covert H+ stress did not include assessments of either dietary H+ or H+ retention. METHODS: We tested plasma pH (PpH), 8-h urine excretion of citrate (UcitV) or ammonium (UNH4+V) as biomarkers of dietary H+ assessed as potential renal acid load (PRAL), and of steady-state H+ retention by comparing observed to expected PTCO2 increase 2 h after an oral NaHCO3 bolus. We recruited 313 non-diabetic participants with PTCO2 ≥ 22 mM to exclude participants with metabolic acidosis and with eGFR (mean [SD], mL/min/1.73 m2) stages G1 (n = 62, 99.2 [7.3]), G2 (n = 167, 73.8 [6.3]), and G3 (n = 84, 39.9 [6.7]). We performed linear regressions (LR) between H+ retention or PRAL (dependent variables) and PpH, UcitV, or UNH4+V (independent variables) after adjusting for eGFR. RESULTS: Steady-state H+ retention (mean [SD], mmol) increased with stage (G1 = 3.8 [12.5], G2 = 18.2 [12.4], and G3 = 25.6 [9.0]). PpH was not significantly associated with PRAL in any group, and its association with H+ retention was significant only for G3 (p < 0.01). UcitV association with PRAL was significant only for G1 (p < 0.01) but not for G2 (p = 0.65) or G3 (p = 0.11). UcitV association with H+ retention was negative for both G2 (p < 0.01) and G3 (p < 0.01) but was not significant for G1 (p = 0.50). Adding UNH4+V to UcitV as a regressor for H+ retention increased r2 only marginally for G2 (0.61-0.63) and G3 (0.75-0.79). UNH4+V association with PRAL was positive (p < 0.01) for G1 and G2 but was not significant for G3 (p = 0.46). UNH4+V association with H+ retention was significant for both G2 (p < 0.04) and G3 (p < 0.01) but diverged directionally, being positive for G2 but negative for G3. DISCUSSION: Among patients with CKD at risk for covert H+ stress, lower UcitV better identified eubicarbonatemic acidosis than UNH4+V because the UNH4+V versus H+ retention relationship diverged between G2 and G3. Neither test identified eubicarbonatemic acidosis with certainty, indicating need for further work to establish a clinically useful test. On the other hand, UNH4+V had better utility identifying increased dietary H+ assessed as PRAL in G1 and G2.

Page Kidney From a Subcapsular Urinoma Following Contralateral Radical Nephrectomy.

Page kidney is a rare cause of hypertension and kidney injury; it results from extrinsic compression of the kidney due to fluid accumulation in the subcapsular space. Hypertensive crisis may be the only presenting clinical sign in patients with Page kidney. Urinomas are a very rare cause of Page kidney with very few cases reported in the literature. Urinoma should be suspected in patients presenting in hypertensive crisis who have a history of recent abdominal trauma, genitourinary malignancy, and renal instrumentation. Patients diagnosed with Page kidney from a urinoma should be managed with the least invasive means possible.

Treatment of Chronic Kidney Disease-Related Metabolic Acidosis With Fruits and Vegetables Compared to NaHCO3 Yields More and Better Overall Health Outcomes and at Comparable Five-Year Cost.

OBJECTIVES: Current guidelines recommend treatment of metabolic acidosis in chronic kidney disease (CKD) with Na+-based alkali but base-producing fruits and vegetables (F + V) might yield more and better health outcomes, making the intervention cost-effective. DESIGN AND METHODS: In this post hoc analysis of a clinical trial we randomized 108 macroalbuminuric, nondiabetic CKD stage 3 participants with metabolic acidosis to receive F + V (n = 36) calculated to reduce dietary acid by half, oral NaHCO3 (HCO3-, n = 36) 0.3 mEq/kg body weight/day, or Usual Care (UC, n = 36) assessed annually for 5 years. We calculated a mean overall health score for the groups as follows: 1 for improved, 0 for no change, and -1 for worsened at 5 years for plasma total CO2, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, change in medication dose (reduction = 1, increased = -1, no change = 0), and 1 for met goal and 0 for not meeting goal for estimated glomerular filtration rate (>30 mL/min/1.73 m2) and systolic blood pressure (<130 mm Hg). We also assessed the number of participants with cardiovascular disease events (myocardial infarctions + strokes) and group medication and hospitalization costs. RESULTS: Net plasma total CO2 increase at 5 years was no different between HCO3- and F + V. Average health scores at 5 years differed among groups (P < .01) with F + V (7.4 [mean] ± 1.6 [standard deviation]) being descriptively larger than HCO3- and UC (2.9 ± 1.6 and 1.2 ± 1.6, respectively). The number of participants suffering cardiovascular disease events differed among groups (P = .009) with none (0) in F + V, 6 in UC, and 2 in HCO3-. Total 5-year household cost per beneficial health outcome differed among groups (P = .005) with UC being highest and that for HCO3- and F + V being comparable. CONCLUSIONS: Metabolic acidosis improved comparably with F + V or standard oral NaHCO3, but F + V yielded ancillary beneficial health outcomes, fewer participants with adverse cardiovascular events, and per-household cost that was comparable to NaHCO3.

Novel dietary and pharmacologic approaches for acid-base modulation to preserve kidney function and manage uremia.

PURPOSE OF REVIEW: We review mechanisms for chronic kidney disease (CKD) progression that might be addressed with nonpharmacologic and novel pharmacologic interventions as strategies by which to slow or even prevent CKD progression. RECENT FINDINGS: Evolving data support the contribution of the broad spectrum of disorders of acid (H) accumulation, which we refer to as 'H stress', to CKD progression. Recent studies support that amelioration of H stress, including spectra of H accumulation that are insufficient to cause metabolic acidosis, is kidney-protective. In addition, gut-derived toxins appear to contribute to CKD progression and to the well described increased cardiovascular disease (CVD) risk in patients with CKD. Dietary and novel pharmacologic interventions hold promise as strategies to slow CKD progression through reducing levels of these gut-derived toxins. In addition, oxidative stress appears to mediate CKD progression and contributing factors like diet and cigarette smoking can exacerbate oxidative stress. Dietary changes and smoking cessation hold promise to favorably affect CKD progression by reducing kidney oxidative stress. SUMMARY: The urgent need to add to the traditional armamentarium of blood pressure control and antiangiotensin II pharmacologic therapy for kidney protection has led to investigations into additional kidney-protective strategies. Acid stress, a disordered gut microbiome, and oxidative stress each appear to contribute to CKD progression and can be potentially addressed by nonpharmacologic and novel pharmacologic interventions.

Urine citrate excretion identifies changes in acid retention as eGFR declines in patients with chronic kidney disease.

Previous studies have shown that acid (H+) retention in patients with chronic kidney disease (CKD) but without metabolic acidosis increases as the estimated glomerular filtration rate (eGFR) decreases over time. The present study examined whether changes in urine excretion of the pH-sensitive metabolite citrate predicted changes in H+ retention over time in similar patients with CKD that were followed for 10 yr. We randomized 120 CKD2 nondiabetic, hypertension-associated nephropathy patients with plasma total CO2 of >24 mM to receive 0.5 meq·kg body wt-1·day-1 NaHCO3 ([Formula: see text]; n = 40), 0.5 meq·kg body wt-1·day-1 NaCl (NaCl; n = 40), or usual care (UC; n = 40). We assessed eGFR (CKD-EPI) and H+ retention by comparing the observed with expected plasma total CO2 increase 2 h after an oral NaHCO3 bolus (0.5 meq/kg body wt). Although 10 yr versus baseline eGFR was lower for each group, 10-yr eGFR was higher (P < 0.01) in [Formula: see text] (59.6 ± 4.8 ml·min-1·1.73 m-2) than NaCl and UC (52.1 ± 5.9 and 52.3 ± 4.1 ml·min-1·1.73 m-2, respectively) groups. Less eGFR preservation was associated with higher 10-yr versus baseline H+ retention in the NaCl group (26.5 ± 13.1 vs. 18.2 ± 15.3 mmol, P < 0.01) and UC group (24.8 ± 11.3 vs. 17.7 ± 10.9 mmol, P < 0.01) and with lower 10-yr versus baseline 8-h urine citrate excretion (UcitrateV) for the NaCl group (162 ± 47 vs. 196 ± 52 mg, respectively, P < 0.01) and UC group (153 ± 41 vs. 186 ± 42 mg, respectively, P < 0.01). Conversely, better eGFR preservation in the [Formula: see text] group was associated with no differences in 10-yr versus baseline H+ retention (14.2 ±13.5 vs. 16.1 ± 15.1 mmol, P = 1.00) or UcitrateV (212 ± 45 vs. 203 ± 49 mg, respectively, P = 0.74). An overall generalized linear model for repeated measures showed that UcitrateV predicted H+ retention (P < 0.01). Less eGFR preservation in patients with CKD2 without metabolic acidosis was associated with increased H+ retention that was predicted by decreased UcitrateV.

Fruit and Vegetable Treatment of Chronic Kidney Disease-Related Metabolic Acidosis Reduces Cardiovascular Risk Better than Sodium Bicarbonate.

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.

Urine citrate excretion as a marker of acid retention in patients with chronic kidney disease without overt metabolic acidosis.

Acid (H+) retention appears to contribute to progressive decline in glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD), including some patients without metabolic acidosis. Identification of patients with H+ retention but without metabolic acidosis could facilitate targeted alkali therapy; however, current methods to assess H+ retention are invasive and have little clinical utility. We tested the hypothesis that urine excretion of the pH-sensitive metabolite citrate can identify H+ retention in patients with reduced GFR but without overt metabolic acidosis. H+ retention was assessed based on the difference between observed and expected plasma total CO2 after an oral sodium bicarbonate load. The association between H+ retention and urine citrate excretion was evaluated in albuminuric CKD patients with eGFR 60-89 ml/min/1.73m2 (CKD 2, n=40) or >90 ml/min/1.73m2 (CKD 1, n = 26) before and after 30 days of base-producing fruits and vegetables. Baseline H+ retention was higher in CKD 2, while baseline urine citrate excretion was lower in CKD 2 compared to CKD 1. Base-producing fruits and vegetables decreased H+ retention in CKD 2 and increased urine citrate excretion in both groups. Thus, H+ retention is associated with lower urine citrate excretion, and reduction of H+ retention with a base-producing diet is associated with increased urine citrate excretion. These results support further exploration of the utility of urine citrate excretion to identify H+ retention in CKD patients with reduced eGFR but without metabolic acidosis, to determine their candidacy for kidney protection with dietary H+ reduction or alkali therapy.

Clinical evidence that treatment of metabolic acidosis slows the progression of chronic kidney disease.

PURPOSE OF REVIEW: We review the growing clinical evidence that metabolic acidosis mediates chronic kidney disease (CKD) progression and that treatment to increase the associated low serum bicarbonate (HCO3) in CKD is disease-modifying. RECENT FINDINGS: Seven prospective studies of patients with wide ranges of estimated glomerular filtration rates (eGFRs) and serum HCO3 examined the effect on CKD of increasing serum HCO3 using dietary acid reduction with either oral alkali (sodium bicarbonate or sodium citrate), a vegetarian diet very low in acid-producing protein (0.3 g/kg/day) supplemented with ketoanalogues or added base-producing fruits and vegetables. Clinical outcomes included slower kidney function decline (using eGFR measurements) and fewer patients progressing to end-stage kidney disease. Post hoc analyses demonstrated that: treatment of metabolic acidosis for 2 years decreased the number of patients with at least a 40% eGFR decline, a validated surrogate for progression to end-stage kidney disease and across four studies, treatment to increase serum HCO3 by 4-6.8 mEq/l in acidotic patients with CKD was associated with a ∼4 ml/min/1.73 m reduction in the rate of eGFR decline over 6-24 months compared with controls. SUMMARY: Metabolic acidosis appears to enhance CKD progression and its treatment should be studied further as a potential disease-modifying intervention.

Kidney Response to the Spectrum of Diet-Induced Acid Stress.

Chronic ingestion of the acid (H⁺)-producing diets that are typical of developed societies appears to pose a long-term threat to kidney health. Mechanisms employed by kidneys to excrete this high dietary H⁺ load appear to cause long-term kidney injury when deployed over many years. In addition, cumulative urine H⁺ excretion is less than the cumulative increment in dietary H⁺, consistent with H⁺ retention. This H⁺ retention associated with the described high dietary H⁺ worsens as the glomerular filtration rate (GFR) declines which further exacerbates kidney injury. Modest H⁺ retention does not measurably change plasma acid⁻base parameters but, nevertheless, causes kidney injury and might contribute to progressive nephropathy. Current clinical methods do not detect H⁺ retention in its early stages but the condition manifests as metabolic acidosis as it worsens, with progressive decline of the glomerular filtration rate. We discuss this spectrum of H⁺ injury, which we characterize as “H⁺ stress”, and the emerging evidence that high dietary H⁺ constitutes a threat to long-term kidney health.

Acid retention in chronic kidney disease is inversely related to GFR.

Greater H+ retention in animal models of chronic kidney disease (CKD) mediates faster glomerular filtration rate (GFR) decline and dietary H+ reduction slows eGFR decline in CKD patients with reduced eGFR and H+ retention due to the high acid (H+) diets of developed societies. We examined if H+ retention in CKD is inversely associated with estimated GFR (eGFR) using cross-sectional and longitudinal analysis of individuals with CKD stage 1 (>90 ml·min- 1·1.73 m-2), CKD stage 2 (60-89 ml/min per 1.73 m2), and CKD stage 3 (30-59 ml·min- 1·1.73 m-2) eGFR. H+ retention was assessed using the difference between observed and expected plasma total CO2 2 h after 0.5 meq/kg body wt oral NaHCO3. H+ retention was higher in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P < 0.02) at baseline and 5 yr, and was higher in CKD 2 vs. CKD 1 ( P < 0.01) at 10 yr. All groups had lower eGFR at subsequent time points ( P < 0.01) but H+ retention was not different among the three time points for CKD 1. By contrast, eGFR decrease was associated with higher H+ retention in CKD 2 at 5 yr ( P = 0.04) and 10 yr ( P < 0.01) and with higher H+ retention in CKD 3 at 5 yr ( P < 0.01). Yearly eGFR decline rate was faster in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P < 0.01). The data show that H+ retention is inversely associated with eGFR, with faster eGFR decline, and support the need for greater dietary H+ reduction therapy for CKD individuals with lower eGFR.

Management of the Metabolic Acidosis of Chronic Kidney Disease.

Subjects with CKD and reduced glomerular filtration rate are at risk for chronic metabolic acidosis, and CKD is its most common cause. Untreated metabolic acidosis, even in its mildest forms, is associated with increased mortality and morbidity and should therefore be treated. If reduced glomerular filtration rate or the tubule abnormality causing chronic metabolic acidosis cannot be corrected, it is typically treated with dietary acid (H+) reduction using Na+-based alkali, usually NaHCO3. Dietary H+ reduction can also be accomplished with the addition of base-producing foods such as fruits and vegetables and limiting intake of H+-producing foods like animal-sourced protein. The optimal dose of Na+-based alkali that prevents the untoward effects of metabolic acidosis while minimizing adverse effects and the appropriate combination of this traditional therapy with dietary strategies remain to be determined by ongoing studies. Recent emerging evidence supports a phenomenon of H+ retention, which precedes the development of metabolic acidosis by plasma acid-base parameters, but further studies will be needed to determine how best to identify patients with this phenomenon and whether they too should be treated with dietary H+ reduction.

Dietary interventions to improve outcomes in chronic kidney disease.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is a major epidemic which has global outcomes with increased morbidity and mortality. Given the global implications of CKD, interventions that target modifiable risk factors for CKD are needed. Despite the effectiveness of kidney protection strategies such as hypertension and lipid control as well as the use of antiangiotensin II drugs, the nephropathy in many patients with CKD and reduced glomerular filtration rate (GFR) nevertheless continues to progress toward complete kidney failure. More concerning, CKD-related deaths and in years of life lost due to CKD continue to increase. In this article, we will explore the dietary interventions that recent small-scale studies support slowing the progression of CKD. RECENT FINDINGS: Dietary acid reduction with Na-based alkali has been shown to be an effective kidney protection strategy for CKD patients with reduced GFR. In addition, recent analyses support diet as the largest CKD-related death and disability risk factor. Small-scale studies show that diets which emphasize ingestion of plant-sourced protein more than animal-sourced protein reduce dietary acid, improve metabolic acidosis, and slow further nephropathy progression in patients with CKD and reduced GFR. SUMMARY: Dietary interventions are underused as kidney protection strategies. As further studies better define how to best use these dietary interventions for kidney protection, clinicians must become aware of their potential utility in the management of CKD patients.

Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate.

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.

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

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.