Professional Documents
Culture Documents
Nephrology
American Journal of
Donald E. Wesson e, f
a Departments of Internal Medicine, Texas A&M College of Medicine, Temple, TX, USA; b Departments of Internal
Medicine, Baylor Scott and White Health, Temple, TX, USA; c Statistical Savvy Consulting, Georgetown, TX, USA;
d Department of Surgery, Texas Tech University Health Sciences Center, Lubbock, TX, USA; e Department of Internal
Medicine, Texas A&M Health Sciences Center College of Medicine, Dallas, TX, USA; f Baylor Scott and White Health
Matching variables
Age, years 53.9 (4.8) 53.6 (5.3) 53.5 (5.2)
Gender
Female 20 (55.6) 20 (55.6) 20 (55.6)
Male 16 (44.4) 16 (44.4) 16 (44.4)
Ethnicity
White 5 (13.9) 8 (22.2) 6 (16.7)
African American 19 (52.8) 19 (52.8) 19 (52.8)
Hispanic 12 (33.3) 9 (25.0) 11 (30.5)
eGFR 39.5 (6.9) 39.6 (6.6) 39.4 (6.4)
Ualb 315 (73.1) 317 (71.6) 318 (71.2)
Outcome variables
PTCO2 22.9 (0.6) 23.1 (0.6) 22.9 (0.6) 0.619 1.000
BMI 28.2 (2.1) 28.3 (2.1) 28.8 (2.1) 0.434 1.000
SBP, mm Hg 158.6 (10.7) 165.8 (10.7) 163.3 (10.7) 0.017 0.374
LDL, mg/dL 151.9 (19.0) 157.2 (19.0) 161.8 (19.0) 0.102 1.000
HDL, mg/dL 50.6 (5.9) 51.5 (5.9) 50.9 (5.9) 0.820 1.000
Lp(a), mg/dL 81.8 (13.0) 81.9 (13.0) 84.3 (13.0) 0.438 1.000
Vitamin K1, mM 0.44 (0.20) 0.45 (0.24) 0.43 (0.18) 0.845 1.000
UNaV, mmol/8 h 74.9 (6.1) 74.3 (6.1) 73.9 (6.1) 0.779 1.000
UKV, mmol/8 h 33.5 (5.6) 33.1 (5.6) 34.0 (5.6) 0.791 1.000
Fruit intake, cups/day 0.98 (0.24) 0.95 (0.24) 0.99 (0.24) 0.787 1.000
The first variables are the variables the participants were matched by. No p value is provided since, by design, the groups are similar.
Numerical variables are reported as mean (SD) or n (%).
UC = group treated according to extant guidelines but without dietary acid reduction therapy; HCO3 = group given dietary acid re-
duction therapy with oral NaHCO3 to treat metabolic acidosis; F + V = group given dietary acid reduction therapy as base-producing
fruits and vegetables to treat metabolic acidosis.
Linear Mixed models were used to adjust for the clustering due to matching and to calculate the SDs.
SBP, systolic blood pressure; eGFR, estimated glomerular filtration rate; PTCO2, plasma total CO2 (nearly identical to plasma
[HCO3]); BMI, body mass index; LDL, low-density lipoprotein cholesterol; Lp(a), lipoprotein (a); HDL, high-density lipoprotein cho-
lesterol; UC, usual care; Ualb, urine albumin.
25
24
PTCO2, mM
23
22
F + V. The net change was significantly different from UC was not a significant factor in the net eGFR decrease at
in both HCO3 and F + V and was greater in F + V than 5 years.
HCO3. Table 2 shows that at 5 years, there was a greater Five-year UNaV was lower in F + V than UC but that
net increase in vitamin K1 compared to baseline in F + V for HCO3 was higher than UC as in Table 2. There was no
but not in HCO3 or UC, with the change in UC and HCO3 net UNaV change in UC, but F + V had a net decrease
being not different from zero. while HCO3 had a net UNaV increase. The change in
Table 2 shows a net decrease in SBP at 5 years for all UNaV for both F + V and HCO3 was significantly differ-
3 groups, but the net decrease was greater in F + V than ent from the change for UC. On the other hand, Table 2
HCO3 and UC. The net SBP decrease for HCO3 was not shows that 5-year UKV was higher in F + V than both
statistically different from UC. Furthermore, a greater HCO3 and UC, but UKV in HCO3 and UC were not dif-
percentage of F + V (mean 89%, 95% CI 73–97) achieved ferent from each other. There was no net UKV change in
the SBP goal of ≤130 mm Hg than HCO3 (17%, 95% CI HCO3 and UC, F + V had a net UKV increase, and the net
7–34) and UC (27%, 95% CI 13–46). Figure 3 shows the UKV change for F + V was greater than that for both
course of eGFR in the 3 groups. Although Table 2 shows HCO3 and UC. Table 2 also shows that patient-recorded
a net eGFR decrease at 5 years for all 3 groups, both F + 5-year F + V consumption was higher in the F + V group
V and HCO3 had a smaller net eGFR decrease than UC than both HCO3 and UC, but F + V consumption in
at 5 years. Furthermore, a greater percentage of F + V HCO3 and UC were not different from each other. There
(40%, 95% CI 42–76%) and HCO3 (34%, 95% CI 46.5– was no net F + V consumption change in HCO3 and UC,
80.3%) achieved the goal of maintaining eGFR ≥30 mL/ and the net F + V consumption change for F + V was
min/1.73 m2 than UC (6%, 95% CI 1–20%). To assess if greater than that for both HCO3 and UC.
BMI played a role in the eGFR decrease, we ran a model Table 3 shows the median change in medication dosage
with both BMI difference at 5 years and treatment group at 5-year follow-up and the distribution of number of pa-
including interaction between BMI and treatment tients within each of the 3 groups who at 5 years had a de-
group. Neither the interaction term nor the BMI differ- crease, no change, or an increase in the dose of the 7 top
ence was statistically significant (p values = 0.42 and prescribed medications for patients. The table shows that
0.84, respectively), indicating that the BMI difference there were significant differences among the 3 groups in
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F + V, fruits and vegetables; UC, usual care; PTCO2, plasma total CO2; BMI, body mass index; LDL, low-density lipoprotein; HDL,
high-density lipoprotein; SBP, systolic blood pressure; eGFR, estimated glomerular filtration rate; UNaV, urine excretion of sodium;
UKV, urine excretion of potassium.
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55
50
45
eGFR, mL/min/1.73 m2
40
35
30
25
20
the percentage of patients who had changes in doses of yields fewer CVD outcomes, F + V might be preferred
clonidine and atorvastatin, but the adjusted p value for initial therapy for CKD-related metabolic acidosis, de-
enalapril was not significant. For each of these drugs, spite it being more challenging than NaHCO3 to imple-
F + V had a greater number of patients who had had a de- ment, given its potential to concomitantly reduce the sub-
crease in dosage than HCO3 and UC. Descriptively, more stantial CVD risk in patients with CKD [2–4].
F + V patients had a decrease in dosage of diltiazem and We previously reported in interim analysis for these
hydrochlorthiazide. There was no difference in the num- same patients that both dietary H+ reduction interven-
ber of distribution of patients who had changes in drug tions better preserved eGFR than UC at 3 years [13]. The
doses among the 3 groups for furosemide and atenolol. current 5-year eGFR results for these same patients are
qualitatively the same, supporting that these interven-
tions provide long-term eGFR protection.
Discussion Management approaches that have successfully re-
duced CVD risk in non-CKD patients might require
The current study showed that dietary acid reduction modification in CKD to achieve similar success. Some re-
with either NaHCO3 or F + V yielded comparable im- ports suggest that traditional CVD risk factors such as
provement of metabolic acidosis in patients with CKD, increased serum lipids, including LDL-c, are less predic-
but F + V yielded better improvement in CVD risk indi- tive of CVD risk in CKD compared to non-CKD patients
cators including SBP, LDL, Lp(a), BMI, and serum vita- [44, 45]. Recent reports, however, support that increased
min K1 as secondary outcomes of these studies in which LDL-c is indeed predictive of major CVD events in pa-
the primary outcome was change in eGFR. These data tients with CKD and that its reduction is associated with
support the need for subsequent studies with larger sam- a reduced risk of CVD events [18]. Also, statins might be
ple size and longer follow-up to test if the better improve- less effective in lowering LDL-c as eGFR declines [46]
ment in CVD risk indicators with F + V translates into and/or might promote vascular calcification through in-
fewer adverse CVD outcomes than treatment with oral hibition of vitamin K synthesis [47], suggesting that this
NaHCO3. If such follow-up studies show that F + V com- standard CVD risk reduction intervention might be less
pared to NaHCO3 treatment of metabolic acidosis indeed effective, or possibly even detrimental, in patient with
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* No test was possible since 100% of the F + V group had a decrease making the matrix used in the calculation nonpositive definite.
◆ No test was possible since in the UC and the HCO group 100% of the participants had no change in dose.
3
UC, usual care; F + V, fruits and vegetables.
CKD. Furthermore, CAC is more common and more se- [5]. Large-scale studies with longer follow-up will better
vere in CKD [21] and has a stronger association with risk test this hypothesis.
of CVD and mortality in CKD patients [22]. Moreover, Although epidemiologic studies suggest that metabol-
F + V reduced LDL-c [17] and diets high in F + V are as- ic acidosis further increases the already increased CVD
sociated with reduced CAC [19, 20], additionally sup- risk in CKD [5], the present studies support that correc-
porting F + V as an effective adjunct to standard CVD risk tion of metabolic acidosis with F + V more comprehen-
reduction strategies to reduce the high CVD risk in CKD sively improved the examined CVD risk factors than cor-
patients [2] which metabolic acidosis increases further rection with NaHCO3. Among the examined CVD risk
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