Dr. Manoj Monga, MD, presented “How to Prevent the Formation of Kidney Stones” at the 26th Annual Perspectives in Urology: Point-Counterpoint, November 10, 2017 in Scottsdale, AZ

How to cite: Monga, Manoj “How to Prevent the Formation of Kidney Stones” November 10, 2017. Accessed Aug 2020. https://grandroundsinurology.com/prevent-formation-kidney-stones/

Summary:

Dr. Manoj Monga, MD, discusses the various dietary and medical approaches to prevent the formation of kidney stones and kidney stone recurrence.

How to Prevent the Formation of Kidney Stones

Transcript:

So next we’re going to be talking about dietary and pharmacological ways to try to decrease this chance of stone recurrence.  I think these are supposed to be interactive talks, there’s a big push to make your talks interactive and that’s really not something new.  When I was kid growing up in Ireland, in Canada, there was a show called Romper Room.  Did anybody watch Romper Room?  Yeah.  So do you remember the magic mirror at the end where they hold up a mirror and I see David and Ryan and Manoj.  It never got to Manoj, but the magic mirror, I’m going to hold that up now and I’m going to say I see Dr. Pepper, Diet Coke, Diet Coke, Diet Coke, two bottles of water, good for you.  We’ve got our work cut out for us I think with this talk.

So stones are common, one out of eight people have stones.  The chance of recurrence of a stone if you have a stone is about 50% at five years.  This is really a time where you can capture the patient.  They come in in pain, hopefully they’ve passed the stone or you get it out for them.  But now they really want to know what did I do wrong?  How do I prevent my next stone?

That’s cool.  You stare at this for 19 minutes a day, and you won’t form another stone.

The next slide we showed we did a study when I was in San Diego where we looked at twins.  And with identical twins if you take one parameter, plot it against the other twin, you can come up with a score called heritability which tells you how much of that characteristic is based on their genes. 

For almost everything in stone disease, whether you’re looking at calcium oxalate, uric acid, the heritability is high.  Over 80% if you look at calcium oxalate supersaturation, about 84% of it is related to the gene so that question, what did I do wrong, you picked the wrong parents, so back and pick other parents, you’ll do better next time around.  But this doesn’t mean that you can’t change that risk with diet and medications.  We reassure them that there are things that they can do.  Also pointing out pH, uric acid supersaturations, those are the two things that are less likely linked to genes.  So more likely you’ll be able to modulate the risk factor for someone with those two parameters and decrease their chance significantly of having recurrent stone.

All patients get these recommendations, and how many of you have heard Michael Moiat [phonetic] talk.  I’m sure many of you have.  At the beginning of his dietary talks he always says that whenever we are telling patients for stones for prostate cancer, the first thing is to make sure it’s good for your overall health.  Because cardiac is the main issue, sorry, David, and if you can increase the risk of something being good while minimizing or decreasing the risk of a cardiovascular event, you’re doing a good benefit for the patient.  So you’ll notice that all these things are relatively healthy.  Increased fluids, decrease sodium, increase citrates, and take adequate amount of calcium.  

Ten 10-oz glasses a day, one way to tell a patient, drink enough to make two liters of urine, that’s another way.  When you look at your urine can you see through it, is it pale?  A variety of ways to try to get the patient to this level here, ongoing stone studies currently looking at smart bottles.  Or apps.  Different ways to use technology to help improve patient compliance and hopefully have an impact on their stone risk.  Sodium restriction, 1,500 mg/day.  Dietary citrate can be concentrated lemons and limes, 4 ounces and we’ll talk about some other alternatives.  And then adequate amount of calcium, as you know calcium binds oxalate in the bowel, restricting calcium increases your risk because you lose that ability to prevent hyperoxaluria.  So two to three servings per day, 1,200 mg per day.

But what’s the evidence to support these recommendations?  We’ll start with fluids.  Five year study, patients were randomized to either treatment or placebo or no treatment.  The treatment arm was told drink enough so you make two liters of urine a day.  Marked decreased in stone recurrence, and for those 12% of patients who did reform a stone again, their time to recurrence was longer than in the group that did not receive those recommendations, so high level evidence supporting the use of fluids.

Fluids can come in many forms.  It can come in a glass, it can come in a bottle, but it can also come in the form of ice cream, soup, jello’s, a variety of ways so you’re not drowning the patient, to increase the fluid throughout their diet.  Now I pounced on a few people for their drinks.  Dark Colas are bad, clear Colas are good, so if you chose the Sprite, the Sprite Zero, you’re in good shape.  The more you drink, the less likely you are to form stones.  

This study they took people who are drinking a fair amount of sodas, 160 ccs a day and asked them to stop.  If they stopped and they were drinking dark colas, because dark colas have phosphoric acid.  The risk of stones went down. If they were drinking Sprite, 7-Up, ginger ale, those have citric acid, the risk of stones went up.  If you have a patient who really needs that soda, have them drink a diet soda and have them drink a soda that’s clear as opposed to dark because you can actually decrease the risk of stones due to the citric acid concentrations.

Citric acid is important.  A variety of different stages, supersaturation, nucleation, growth, and aggregation of stones, a variety of reasons why increasing dietary citrate is important.  

Four ounces of concentrated lemon juice was the first way it was studied, Stoler [phonetic] demonstrated that urinary citrates increase with no change in urinary oxalates.  

Citrates are found in a variety of places.  Fresh lemons and limes are the best source.  Concentrated lemons and limes are good, orange juice is good, lemonade isn’t so good because only about 5% to 10% of lemonade is actually lemon juice.  Sometimes patients say, make it easy for me.  Can you give me an easy diet; I don’t want to worry about four ounces or three ounces.  The easy thing is eat lots of fruits and vegetables.  If you add fruits and vegetables to the diet of a stone former, you increase potassium, magnesium, citrate, calcium, and con decrease the calcium oxalate that supersaturation by 52%.  In contrast if one takes, normal people, not stone formers, and ask them to eliminate those foods, their risk of stones increases dramatically.  So fruits and vegetables is the easy answer you’ll find not only for citrates, but a few other things in the talk as we go on.

Now all citrate is not the same.  Citric acid in the diet comes in two forms, citric acid, and potassium citrate.  Citric acid is rich in lemons and limes whereas melons and tomatoes are rich in potassium citrate so the error or personalized medicine doesn’t just apply to prostate cancer, it applies to dietary recommendations for stones.  

If you have a patient where the goal is to raise citrate, but their pH is already high, say they have RTA, distal renal tubular acidosis, their pH is already 6 or 7 but their citrate is low, for those patients, personalize their approach, recommend lemons and limes, but perhaps don’t recommend these.  In contrast if you have a more common patient, the patient with a low pH, and low citrate, maybe a calcium oxalate stone former or a uric acid stone former, those will be patients where you would focus on the melons, tomatoes.  And oranges have about a balanced amount of citrate acid and potassium citrate.

Don’t limit the calcium.  Limiting calcium increased the risk of symptomatic stones by causing an increase in the risk of hyperoxaluria.  

This just shows that the less dietary calcium you take in, the higher your chance of stones compared to those who take in more calcium.  One of the controversies is calcium supplements and unfortunately calcium supplements do slightly increase the risk.  Now it’s difficult to know whether it’s the supplement or the timing that you’re taking it.  So one of the things with the dietary calcium, we do is if patients can’t give up their strawberries, we tell them to put some cream on it.  If you can’t give up your broccoli or spinach, out some cheese on it.  Trying to balance the calcium and the oxalate intake to promote the binding in the bowel is important and perhaps you’re losing that if you’re just taking a calcium supplement in the morning.

Dietary calcium can come in a variety of forms.  You see that you really need about three to four servings a day to be able to reach this 1,200 mg target for the day.

Dietary salt administration is important because one teaspoon of salt will increase urinary calcium 23 mg, leads to higher rates of bone resorption.  It has a great effect if you have a lot dietary calcium intake.  

We eat about twice as much sodium as is recommended.  Over 3,000 mg a day of sodium increasing not only the risk of stones, but that important thing, cardiovascular disease.

Does limiting sodium impact stone disease?  And the answer is yes.  First looking at those who limited their sodium, what happened to their urinary sodium?  It went down significant compared to controls.  Does that make it change in the urinary calcium?  Again the answer is yes.  Limiting your sodium decreases the urinary calcium significantly. Indeed 62% of patients could normalize their urinary calcium just by limiting their sodium.  So the first line therapy for hypercalciuria is sodium restriction.

What’s the first line therapy for someone with hypercalciuria?  Sodium restriction.  Very good.

If that doesn’t work the second line therapy is fish oil.  Fish oil decreased PGE2, decreases renal calcium excretion and it improves renal reabsorption, decreases the risk of bone resorption.  

It can be found in a variety of foods, salmon, tuna, mackerel, a variety of nuts and oils.

But it’s more commonly used in the US and elsewhere as a supplement, 1,800 mg of EPA, the active ingredient decreases urinary calcium and improves urinary citrate.

The third line therapy is thiazides.  We use thiazides if dietary sodium restriction and fish oil isn’t adequate.  We repeat the 24-hour urine three months after they’ve done those two things.  At that point, we’ll introduce a thiazide.  Acts on the distant tubule, increases calcium reabsorption, increased bone mineral density.  

This will be just one of many studies showing three years follow-up, decrease in urine calcium.  And improvement in stone-free rates.

The AUA guidelines for medical therapy came out two years ago.  We did an AHRQ study prior to that to develop the database that was used to develop the guidelines.  So we looked only at studies that had a clinical outcome of stone recurrence, either radiographic or symptomatic.  You can see the numbers of studies are few, the numbers of patients are small, but a marked decrease, about 50% in the risk of stones by giving thiazides to people who have recurrent calcium stones.  Now these aren’t select patients, these aren’t patients with high urinary calcium, these are all comers.  None of these RCTs selected patients specifically based on their urinary calcium level.

Another issue is the bone health.  Bones and stones are related.  A Minnesota study demonstrated that the risk of vertebral fractures was higher in stone formers than you would expect.

Well, you say that’s okay, just give them calcium and vitamin D, you already told us that taking calcium is good.  Unfortunately, calcium and vitamin D, the common approach to patients with bone disease isn’t effective though these lines look different, the risk of hip fracture was the same statistically in those who received placebo compared to those who received calcium and vitamin D.  So the approaches that we’re using to treat bone disease are not effective, but they are effective at increasing the risk of stones.  

So what can we use to improve bone health, but also decrease the risk of stones.  We start with potassium citrate.  Potassium citrate improves the bone density in the microarchitecture in the lumbar spine, differences in bone marrow density at two years, and at the femoral neck.  

What if you add a thiazide?  Thiazides and potassium citrate in combination improved bone mineral density in the lumbar area, in the femoral neck and in the radial shaft.  Three and a half year follow-up.  Marked improvements in urinary calcium, and a marked decrease in stone formation.  So treat the bones and treat the stones with thiazides and citrates.

These are the variety of medications that are used. Insufficient data to say which works best, note that hydrochlorothiazide is a BID dosing to achieve the improvements in stone and bone health.  And it’s important to replenish the potassium and it’s best to use a citrate supplementation, that way you’re recruiting both with the thiazide and the potassium citrate.

Beyond that use, citrate has other important roles, alkaline therapy increasing the pH, decreases the supersaturation for calcium oxalate and calcium phosphate.  

Stone-free rate higher at three years, and potassium supplements are better than sodium based supplements.  We’ve talked already about increased sodium, increased hypercalciuria, increasing the risk of stones, which explains why a sodium based supplement is not as effective as a potassium based supplement.

Preminger’s three year data demonstrating marked decreases in stone formation.

Our AHRQ study, fewer studies, fewer patients, a wider range in terms of effect, but still an effect.  Again, unselected patients, not based on low citrate, all were current stone formers treated empirically.  

Which raises the question, should we be doing 24-hour urine collections?  Is that important to guide therapy or should everyone be getting a thiazide and a citrate.  That’s an area of controversy currently, we don’t really have good evidence to support the use for 24-hour urine collection.  Where I find 24-hour urine collections helpful first is to stratify therapy.  Half the patients who responded on diet alone so half of them won’t need medications.  And to improve compliance in terms of encouraging patients things are improving, continue to do what you’re doing, maybe do some find tweaking to decrease your risk further.

So what if the 24-hour urine shows a hyperoxaluria?  This is probably the hardest, these are foods that people enjoy, these are foods that are otherwise healthy.  So getting back to making recommendations that are good for your overall health, if it’s a diabetic, they need their nuts for protein, if they’re obese, maybe this is a good diet for them.  Overall, this is a healthy food to follow, and we don’t recommend limiting oxalates until the urinary oxalate is high.  Only about 30% of stone formers are going to have hyperoxaluria, the remainder of those stone formers can avoid limiting their oxalate.  The two foods to focus on are spinach and rhubarb.  You see that the amount of oxalate in those two foods is markedly higher than anything else.

University of Wisconsin has looked at where does the oxalate come from in our Western diet?  Spinach, nuts, and seeds and potatoes account for almost half of the dietary oxalate.  Tea, fruits, other leafy green vegetables account for less than 10% so if people say I like iced tea, I say drink more of it.  The more fluid you drink, the better.  The amount of oxalate that you can get out of tea is so low, maybe add some milk to your tea.  That way you’re balancing the calcium, the oxalate and decreasing your risk even further of hyperoxaluria.  

A nice little study to support that is this one looking at chocolate.  Who likes chocolate?  Good.  So if you like chocolate, milk chocolate, the milk binds the oxalate, decreases the amount of hyperoxaluria you see, compared to dark chocolate which obviously doesn’t have the calcium to offset the oxalate absorption.  So the first approach to hyperoxaluria is diet.  Limiting oxalate appropriately, but also making sure they’re taking in adequate amount of calcium.  It may be that they’re just not taking enough calcium, and by taking more calcium, they’ll be able to prevent oxalate absorption.

Second-line therapy in this situation is vitamin B6.  Vitamin B6 changes the conversion of glyoxylate to glycine, so you’re forming less oxalate in your metabolism.  It’s been shown to be that if you increase your vitamin B6, you can decrease your stone risk, and people who form stones and have hyperoxaluria typically have a B6 deficient diet.

Fruits and vegetable we come back to that theme, many fruits and vegetables are rich in vitamin B6.  If a patient has hyperoxaluria we usually start with a supplement, 50 mg a day, and gradually titrate up.  At this level here we start to ask patients about numbness or tingling, peripheral neuropath can be one of the side effects of higher doses of vitamin B6.  

Small number of patients, one year follow-up, 72% of our patients responded to vitamin B6 with lower oxalate levels and decreases in calcium oxalate supersaturation.  

Lastly uric acid stones.  When do you suspect it?  Radiolucent on KUB, Hounsfield units low, lower urine pH, about 60% of patients with stones and have gout will be uric acid stones, 40% of patients with gout will have a calcium based stone so don’t assume it’s a uric acid stone just because the patient has gout.  Here the goal is to not only prevent the stones, but also perhaps dissolve them.  

Uric acid just like oxalate comes from the diet as well as from your body’s metabolism.  

If you are on a high protein diet, Atkins diet or something similar to that, it increases the risk of stones, not only because of more uric acid, but also more urinary calcium, lower citrates, lower pHs, increased bone resorption, all of these things predisposing you to more stones.  

But the goal is not to decrease or eliminate your protein completely, but just to moderate the amount.  Our dieticians will either tell patients to think about a pack of cards, or look at the palm of their hands and so for each protein serving, the size of the protein whether it’s fish, steak, poultry, they’re all the same, it’s more portion size as opposed to what to eat, or what not to eat.

More important though than the protein is the pH.  Because of the solubility of uric acid, that’s why it’s effective to prevent and dissolve stones without alkalinization.  

Best depicted here, this dotted line would be the supersaturation for uric acid.  We see here that if your pH is 5, even one bite at that steak and you’re starting to form a stone.  Even a small amount of dietary uric acid intake will lead to supersaturation and stone formation with the pH of 5.  In contrast if you take your potassium citrate before you eat that sirloin or poultry, it doesn’t matter how big your portion size is, you’ll stay below that supersaturation rate.  So if you had asked which is more important, protein moderation or alkalization, the answer will be alkalization.

This is especially important today as we get bigger.  As the weight goes up, the pH goes down, so one of the risks factors for stones in the obese patient is a lower pH because of problems with ammoniagenesis.  

As you would expect then, in obese patients, 63% of them will have uric acid stones, compared to perhaps 20% in the general population.

It’s important of you look at the way they presented what’s changing in the 24-hour urine, more common to see stones in women, more common to see stones as people get older, and more common to see stones in the obese patient.

Hypocitraturia, increasing especially in the obese patient, and hyperoxaluria increasing especially in men.

Other things presented at the AUA this year in terms of obesity or the metabolic syndrome or both, the more severe your metabolic syndrome, the more number of traits that you have, the more severe your disease is, the more chances you’re going to have recurrent stones and the more chances you’re going to have multiple stones.

Dr. Assimos demonstrated that if you have a high BMI, you also have a higher risk of hyperoxaluria.  And that risk of hyperoxaluria correlates with your hemoglobin A1c.  So lose weight, keep your diabetes under control, many risk factors associated with stones whether they be low pH, high calcium, or high oxalate that are going to increase the risk of stones in those with those syndromes.

Lastly, we come to allopurinol or feboxisat.  The two xanthine oxidase inhibitors that prevent the conversion of xanthine to uric acid.  This would be the last tier so we rarely use these medications. We usually rely on diet and alkalinization alone.  We’ll start at 100 mg and titrate up to 300 mg.  This will be the patient who has persistent hyperuricosuria, or elevated uric acid supersaturations on 24-hour urines after alkalinization and dietary measures.

Now it’s important that the guidelines don’t talk much about uric acid stones because we don’t have data.  There are no RCTs looking at uric acid stones for allopurinol or alkalinization specifically as it relates to stone recurrence.  

You might ask how effective are these therapies.  I alluded to earlier half the time the abnormalities will normalize just with diet alone.  So as an advanced practice provider, this is really unique thing to do, to set up a stone prevention clinic.  I’d encourage all of you to think about that.  Dieticians can’t bill for stone disease, advanced practice providers can.  They can really facilitate the flow of your stone patient focusing on prevention using diet and medications.

For the half of the patients who don’t respond to diet alone, how do they do with medications?  About 70% to 80% response at one year to either a thiazide, a citrate, or a xanthine oxidase inhibitor.

So this is a recent data with the Urologic Diseases in America from Matlaga.  I really only want to point out that if this is all the medicine that we’re giving, this is all opioids.  So the upload epidemic is severe in stone disease.  These are younger patients, sorry, this is older patients, Medicare, this is private insurers.  We’re doing a worse job in the young patients, the one who could benefit most from prevention.  Almost the only medicines we’re giving them are opioids.  We need to do more on the preventive side.

Why do we need to do more?  Because one thing is it’s difficult.  Compliance overall is good with thiazides and nocturnal, but citrates, maybe the cost, maybe the side effects, for some reason we need better citrates to be able to be compliant.  It’s been shown that men, those in the Midwest, salaried, those are on multiple drugs used to taking chronic drugs are more likely to be compliant with stone prevention.  

But stone prevention is important for overall population health.  If you’re compliant, 30% chance of admissions for stone–decrease in admissions, 25% decrease in ED visits, and 13% decrease in surgery for stone disease with appropriate compliance with preventive measures.

Lastly, we talked about diet, we talked about medicines, exercises perhaps the missing link.  The NHANES data asks, have you ever had a stone?  Eight percent of people say yes.  The relative risk of having a stone is lower if you exercise for 10 minutes day, it’s lower if you exercise vigorously for 10 minutes a day, and it’s lower if you walk or bicycle to school, or work.  It’s higher if you work in a vigorous-intensity activity, so if one thinks about this, this might be the worker outside, the construction worker swinging a hammer.  Maybe they don’t have time to rehydrate.  Maybe their work conditions are predisposing them, or maybe it’s the type of activity.

These are activities that impact bone health.  Walking, running, if you look at astronaut studies and their risk for stones, you can decrease the risk of stones in astronauts if you put them on a treadmill, but you also simulate gravity by using a vacuum suction.  You don’t do it–you can’t do it in microgravity where they don’t have that force on the limbs and the spine to maintain bone health, so it may be that this vigorous intensity activity is more upper body and has less impact on bone health, and that’s why they have a higher risk of stones.

So lastly I’ll point out one study where compliance also related to the 24-hour urine test.  It’s hard to do. Patients don’t want to carry around the jug for a whole day.  They’ll typically do this on a Sunday when they’re at home.  It may not be reflective of their overall risk because their diet on a Sunday may not be the same as Monday through Friday.  

So we ask the question, could you simplify it?  Instead of collecting for 24-hours what about just collecting it from 7:00 p.m. to 7:00 a.m.?  In doing so, maybe it will be a better predictor of stone risk.  We know that urine is more concentrated at night than in the day, so maybe we would unveil more abnormalities than we currently see, but more importantly improve patient compliance, decrease the burden on the patient, and decrease the dependency on weekend collections.  

So we try to correlate a 12-hour versus 24-hour urine, and you see that essentially all of the parameters we look at correlate very well.

Supersaturations correlate tightly.  You’re able to detect almost all the patients who had an abnormality but more importantly identify additional ones who are missed by doing a 24-hour urine collection.  

We’re able to identify all the parameters, all the patients who had hyperoxaluira, hypercitraturia.

And in addition to some patients who were missed.

In summary, 12-hour night time 24-hour urine may be better.  Better patient compliance, better ability to detect abnormalities, and direct the best approach to stone prevention.