I put together this summary from a presentation I attended at the National Kidney Foundation Spring Clinical Meeting on 10 April 2025. For a summary of all the presentations I attended – check out the full list here.

Session Presenter: Stewart Lecker MD PhD

Objectives:

1. Kidneys role in body PH
2. Kidney Acid excretion
3. Role of diet and protein in acid base balances

How do kidneys deal with acid production?

Kidneys deal with acid production in a 2 step process. When the body is maintaining bicarbonate levels at 24mE/L, the kidney will filter 3500mEq of bicarb each day.

The kidney needs to suck back bicarbonate by harnessing NaKATPase in the filtrate (soon to be urine).  The proximal tubule reabsorbs about 80% of the bicarbonate along its length. Filtering bicarbonate, NaKATPase creates a gradient, which results in the product of CO2 and Water.

The kidney also contributes to ammoniagenesis by taking amino acids and forming ammonia. It then recycles the ammonia to help the body secrete additional hydrogen (acid). NKCC2 channels reabsorb the ammonia, allowing it to concentrate. Therefore:

• Net acid excretion = titratable acidity + NH4 + HCO3

The kidneys reabsorb one bicarbonate for every proton they secrete.  You can think of it as protons secretion and bicarb reabsorption.  These work together like two sides of one coin. 

But why does this all happen?

Why do we need to get rid of acids?

There are two types of acids:

1. Votatile acids: produced by oxidative metabolism of carbohydrates, fat and protein, excreted through lungs as CO2
2. Fixed acids – the kidney excretes these.  Produced by metabolism of certain amino acids, nucleic acids.

Only methionine and cystine create additional acids.  Other amino acids follow different catabolic pathways. 

The lungs excrete most acid produced from the digestion of food as CO₂, but the kidneys respond specifically to the consumption of certain amino acids.

The amount of acid that the kidneys excrete each day is 1mEq/kg/day.

In a study of women comparing three different diets.  The omnivore diet increased the acid excretion in the urine, which was higher than the lacto-ovo vegetarian and higher than the vegan diet, which was the lowest.  Why? Because animal based proteins contain more methionine compared to plant based foods. 

What three adaptations do the kidney makes to deal with the high acid load diets?

1. Clearance: A study found that when people consumed high red meat diets, their eGFR increased.  Likely because the kidney was working harder to get rid of the waste products (methionine).
2. Acid: Increased ammonia-genesis following an acid load from a high meat meal.  We can’t increase titratability in the body since that part is fixed, but we can produce more ammonia.
3. Potassium: Increasing the renal excretion of potassium also occurs because these diets contain high amounts of potassium.  Increased protein metabolism increases urea excretion, resulting in increased urea recycling increases flow through the distal nephron resulting in augmented potassium excretion.

What about plant-based diets?

If you produce an alkalosis by infusing bicarbonate or eating a high alkali diet your urine citrate increases. 

Citrate is fuel for the citric acid cycle in the mitochondria.  So in situations of alkalosis, the pH gradient is smaller, resulting in lower citrate utilization resulting in less citrate in the urine.  The opposite is true when the opposite conditions arise.

But why is high citrate in the urine good?  The kidney can use the citrate to increase potassium excretion as well.  This suggests that both ends of the spectrum for dietary acid load can increase potassium excretion.

What mal-adaptations are occurring?

We excrete our acid load to maintain balance, but in patients that have increased acid requirements for excretion, this occurs the augments of ammonia genesis which has trade offs including bone loss, muscle loss and low urine citrate.  Overtime acid stress can lead to loss of function nephrons, tubule interstitial injury and fibrosis, proinflammatory responses.

Questions from the audience:

Why does eGFR increase with increase protein load?

There are theories that certain amino acids can increase flow and turn on ammoniagenesis.  But beyond that the mechanism is not well elucidated.

Are all meats the same or do different meat types matter?

All meats are likely similar.

How could phosphorus absorption of different food sources (animal vs plant) impact this process?

Serum phosphates are very well regulated so it may not impact acid base physiology, unless serum phosphate levels are changing. 

No Acid, No Acidosis: Reconciling Epidemiology and Clinical Trial Data on Metabolic Acidosis

Presenter: Michal Melamed, MD, MHS

Objectives:

1. Describe the difference between observation associations of metabolic acidosis with outcomes and what clinical trails have shown
2. Understand current guidelines for treatment of acidosis

Question for the audience: What is clinically proven effect of sodium bicarbonate treatment? Does it:

• Slow CKD Progression?
• Decrease Hyperkalemia?
• Protect Bones?
• Protect Muscles?

The correct answer is: It decreases hyperkalemia.

What do we know about sodium bicarbonate treatment?

In a study, people living with stage 3 and 4 CKD were given sodium bicarbonate vs placebo.  They were able to show that over 24 months, serum potassium levels were lower and had almost 50% less hyperkalemia (K>5.0), compared to placebo.

As the kidney starts to fail, increased acid generation, bicarb remains normal and pH is normal.  As disease progresses CO2 falls and pH remains normal.  Current KDIGO guidelines used to recommend treatment at CO2 of 20mmol/L, but it is now at 18mmol/L.  But why did this change?

Rat models have shown that dietary acid load, gave sodium bicarbonate and less tubule interstitial disease and less complement activation. 

Epidemiology studies have shown that low sodium bicarbonate levels are associated with increased CKD disease progression.  But these are just associations.

In 2009, a study looked at sodium bicarb in people with CKD 4 and 5 vs usual care.  At 24 months there was reduced risk of starting dialysis.  But this study had some methodological concerns.

In the Goraya studies, researchers provided sodium bicarb, vs fruits and veg vs usual care (which is not a placebo).  They found that eGFR was better in sodium bicarb and fruits and veg vs usual care.

Summary of studies looking at bicarb and CKD progression:

• UBI – positive finding
• Bicarb – negative finding
• Alkali in CKD – not powered sufficiently
• Veterans – no change
• Base trial –  not powered to look at CKD progression
• Veverimer – not powered to look at CKD progression

However, it is important to consider that trials that aren’t placebo-controlled can make it harder to interpret the results.

What is veverimer?

Veverimer is a medication used to reduce metabolic acidosis without using sodium. In a placebo-controlled trial of this medication, researchers found no effect on CKD progression. Overall, they considered the study null

One potential reason for the null findings was the failure to achieve significant reductions of CO2 levels with veverimer.

In transplant patients, 240 patients got either sodium bicarb or placebo, but there was no change in eGFR, despite getting good separation in the CO2 levels.  Though one concern is was that researchers found that sodium bicarb increased ACR, which isn’t good.

Summary

• Animal data shows that metabolic acidosis can hasten Kidney damage
• Multiple observational studies show that low CO2 levels are associated with faster CKD progression
• One large study did not achieve separation
• So we cannot say that treating metabolic acidosis slows CKD progression

But why?

The potential concern is the diet.  The western diet is thought to be acidogenic and this is associated with increase osteoporosis.

Higher serum CO2 is associated with better BMD based on NHANES data.

K-citrate for 24 months (with normal eGFR) – had higher BMD than placebo.

If bone is one of the primary buffers for acid-base.  It is possible that low level acidosis associated with the Western Diet may be impacting bone health.

However no effects on BMD were observed with Alkali therapy in a CKD trial. 

Does Sodium Bicarb treatment increase systolic blood pressure?

There have been signals in a study that SBP will be higher with higher doses of Sodium Bicarb.  There are signals of increased edema and increased need for antihypertensive therapy. 

How dose sodium bicarb treatment in CKD impact bone health?

Summary:

Metabolic acidosis may contribute to osteoporosis and bone disease

Recommendation is to treat if CO2 is less than 18mmol/L

Treatment of metabolic acidosis can be dietary

Questions from the Audience

What about sodium citrate? Sodium citrate appears to be equivalent to sodium bicarbonate.

Is there a trial comparing veveremir to sodium bicarbonate? Unfortunately, no

My Key Take Aways:

I really enjoyed this talk and loved getting a thorough review of the physiology of metabolic acidosis in CKD and an update on the studies linking the treatment of acidosis with hard outcomes.

The key take aways for my practice are:

• Despite observational studies linking metabolic acidosis with CKD progression, the standard sodium bicarbonate therapy has failed to demonstrate slowing in clinical trials.
• Sodium bicarbonate has been found to be effective for lowering serum potassium
• The key contributors to dietary acid load are the amino acids methionine and cysteine, so for people looking to reduce their dietary acid load, limiting foods that contain these amino acids is likely important.