Metabolic Acidosis of CKD, Clinical Importance and Management
Presented by: Jessica Kendrick MD, MPH, Associate Professor of Medicine. University of Colorado, Denver
Who may benefit from taking Bicarbi or Bicarbi Double Strength (enteric coated sodium bicarbonate 650 or 1300 mg)
- Patients with uncontrolled Metabolic Acidosis (MA) on uncoated sodium bicarbonate.
- Those intolerant of the GI side effects found with uncoated sodium bicarbonate.
- People intolerant of the salty taste of uncoated sodium bicarbonate.
- Patients with uncontrolled MA on high pill counts may benefit from Bicarbi Double Strength.
Clinical Data Supporting Conservative Bicarbonate Management
Di lorio et al. J of Nephrology (2019) 32:989-1001
Treatment of metabolic acidosis with sodium bicarbonate delays progression of chronic kidney disease: The UBI study
Randomized controlled open label trial to determine the effect in 795 patients with CKD 3-5 of treatment of metabolic acidosis with sodium bicarbonate on creatinine doubling (primary endpoint), all-cause mortality, and time to renal replacement therapy versus standard of care over a 36 month period.
- Pretreatment eGFR 35.1
- Pretreatment serum bicarbonate 21.5 mmol/l
- On treatment serum bicarb for treatment group 25.7 mmol/l
Patients treated with sodium bicarbonate had a 57% lower hazard ratio of all cause mortality during the follow up period.
Patients treated with sodium bicarbonate had a 64% lower hazard ratio of a doubling of serum creatinine during the follow up period.
Patients treated with sodium bicarbonate had a 50% lower hazard ratio of initiating dialysis during the follow up period.
Note: Pre-treatment blood pressure in patients randomized to sodium bicarbonate: 129/73. On treatment BP for patients receiving sodium bicarbonate: 127/74.
Bicarbonate Supplementation slows progression of CKD and
improves nutritional status.
de Brito-Asurst et al. JASN 2009; 20:2075-2084Methods
- 134 patients with a mean CrCl of 20 ml/min
- Pre-treatment TCO2 of 19.9 meq/L
- Randomized to 2 groups
- Treatment with sodium bicarbonate
- Sodium Bicarbonate arm treated to TCO2 of at least 23 meq/L
- Change in CrCl at 2 years showed a 3 fold difference
- -1.88 ml/min for Bicarbonate group
- -5.93 ml.min for Control group
- Rapid decline in CrCl defined as -3 ml/min/yr
- 9% vs 45% (bicarb treatment vs. control)
- Percentage of patients reaching ESRD in 2 yrs
- 6.5% vs. 33% (bicarb treatment vs. control)
In a cohort of CKD 4 patients, raising TCO2 (serum bicarbonate) by just 3.1+ points slowed the decline in CrCl by 3 fold. This is seen in a patient set with a mean CrCl of 20 ml/min. This data shows the benefit to the patient with the potential to add years before reaching ESRD versus maintaining a sub-optimal TCO2.
Amelioration of metabolic acidosis in patients with low GFR
reduced kidney endothelin production and kidney injury and better preserved GFR.
Phisikul S. et al. KI 2010; 77:617-623Methods
- 59 patients with hypertensive nephropathy and a serum bicarbonate <22meq/L
- Mean eGFR of 33
- Well controlled BP with ACEi
- 30 patients took bicarbonate therapy
- 29 patients no bicarbonate intervention
- By 2 years of intervention the yearly eGFR change by group was:
- -1.60/year in bicarbonate therapy group
- -3.79/year in no bicarbonate intervention group
- Urinary endothelin-1 and marker of tubulointerstitial injury were lower in the bicarbonate therapy group.
In a cohort of CKD 3 patients with hypertensive nephropathy, treating with bicarbonate slowed the decline in GFR by more that 2 fold versus not bicarbonate intervention.Sodium Bicarbonate and Blood Pressure.
Clinical trial data shows that patients randomized to treat MA with sodium bicarbonate have virtually the same systolic and diastolic pressures as patients randomized to placebo.
Other published studies examining the impact of metabolic acidosis on the progression of CKD
- 1781 patients primarily with Non-Diabetic Renal Disease.
- Mean eGFR of 39
- Outcome Measurement: Risk of kidney failure defined as need for dialysis or transplantation
- Results: Lower serum bicarbonate was associated with an increased risk of kidney failure.
- Montefiore Medical Center Cohort
- 5422 patients from a single outpatient clinic wiht a median follow-up of 3.4 years
- Outcome Measurement: Decrease in eGFR by >50% of baseline or reaching an eGFR <15
- Results: Serum Bicarbonate <22meq/L was associated with a 2 fold increase of reaching the outcomes measurement endpoints.
- Chronic Renal Insufficiency Study (CRIC)
- 3586 Patients with Stage 2-4 CKD (mean eGFR 44.8) followed for 6 years.
- Outcomes Measurement: 50% reduction in eGFR or reaching ESRD.
- Results: Serum bicarbonate <22 meq/L was associated with a 2 fold increased risk of reaching the outcomes measurement endpoints.
- Veterans with CKD Study
- 1240 male veterans with stage 3-4 CKD and a mean eGFR of 37
- Outcomes Measurement: Reaching ESRD and all-cause mortality.
- Results: A serum bicarbonate ,22meq/L was associated with both a greater risk of ESRD and increased all-cause mortality.
- Clinical Outcomes in Kidney Transplant Study
- Multicenter retrospective cohort study of 2318 adult kidney transplant recipients.
- Outcomes Measurement: Prevalence of metabolic acidosis defined as serum bicarbonate <22 meq/L, decline in eGFR and graft loss.
- Results: 28.5 % of patients with an eGFR <60 had a serum Bicarbonate < 22meq/L at 1 month. 70% of patients with an eGFR <30 had a serum bicarbonate <22 meq/L at 36 months.
- Significant association between metabolic acidosis and graft loss.
8 Variable Kidney Failure Risk Indicator
As you know the progression of kidney disease is dependent on multiple factors. A kidney failure risk equation was developed by using meta-analysis of data from patients with CKD stages 3-5 referred to nephrologists in Canada, which has now been validated in more than 700,000 individuals spanning 30 + countries worldwide.
An estimator was developed using the equation. The estimator takes into account the 8 individual variables of gender, age, eGFR, UACR, serum calcium, serum phosphorus, serum bicarbonate (Total CO2) and serum albumin.
Users may be impressed by the calculated benefit of improved serum bicarbonate. Achieving optimal serum bicarbonate levels with Bicarbi may be a low cost, well tolerated manner in which to slow the progression of kidney function decline.
Nephcentric has had no influence in the development of the equation, nor does nephcentric make any claims on the accuracy of the estimator.
If you would like to access kidney failure risk estimator based off of the 8 variable equation or if you would like to access the clinical data from which the estimator was derived, please click the appropriate button below.
Click here for the supporting clinical data
Click here to access the estimator
Starting or converting patients to Bicarbi.
Clinical experience with Bicarbi indicates increased efficacy as compared to uncoated sodium bicarbonate tablets with a dramatically improved GI side effect profile. Based upon reports from clinicians, it generally appears that Bicarbi has 1.3 to 1.4 times the potency of raw uncoated sodium bicarbonate mg per mg. This said we frequently receive reports of Bicarbi having efficacy 2 times that of raw sodium bicarbonate. When switching a patient you may try 2 Bicarbi capsules for every 3 650 mg sodium bicarbonate tablets. For patients who are being newly started, a dose of 2 capsules per day is suggested, which can be adjusted as needed to achieve a serum bicarbonate of 23-29 mEq/l or as desired.
Patient and HCP feedback on Bicarbi
We solicit feedback from patients and HCPs about their experience with Bicarbi. We also track refill rates. Nationally, adherence rates for PO medications range between 37-72% depending on disease state, cost of therapy, and side effects. Our data indicate that the refill rates for bicarbi are above 80%. Patients taking Bicarbi tell us "It's like taking bicarb, but without the bloat and burp". Published Clinical data indicate the most common reason for intolerance or non-adherance to alkali therapy with sodium bicarbonate is due to GI side effects like bloating. (See Clinical References).
Dispense Bicarbi from your clinic
If you are interested in purchasing Bicarbi wholesale so it can be dispensed to patients from your clinic, please contact us at firstname.lastname@example.org