We have already shown you that drinking just some sugar water will raise your urine calcium and at the same time lower your urine volume. The net effect will raise kidney stone risk by saturating stone forming salts. We obviously did not do a good enough job. It isn’t that people don’t believe us, it’s just not on anyone’s mind most of the time. The Allegory of Gluttony and Lust (Hieronymus Bosch, 1460 – 1516), oil on panel, hangs in the Yale University Art Gallery, New Haven CT. It seems to capture a bit of the evils of sugar excess. 

In the last several years, Megan Prochaska, a brilliant young investigator and colleague at University of Chicago, did a really lovely study. In this study, she gave six women simply glucose dissolved in water and nothing else. As expected, the urine calcium went up. We already showed you something just like that, done over 60 years ago. The difference is that this time Megan figured out exactly what the kidney is doing to liberate all that calcium.

Basically, there is no way around it, there is no way to prevent it, it is simply built into the mineral system that a glucose load will raise the urine calcium for a couple of hours. Maybe this time, because she did such a nice study, there’ll be more attention paid to the risks of sugar for stone formers.

We already know why the urine volume goes down when you take in glucose. The brain is constantly sensing the osmotic force of the blood, much of which is from sodium but not a trivial amount also from molecules like glucose. When the blood glucose goes up, the brain releases vasopressin and the kidneys retain water. That effect is very rapid and lasts as long as the sugar is elevated.

EFFECTS OF GLUCOSE

 Thick Ascending Limb

Let’s talk about how to read the graph. Look at the upper left figure. Along the bottom are six different urine collections, following a group of baseline collections labelled as ‘0’. Along the left side is the blood glucose concentration. Each of the periods is 30 minutes.

As you might expect, blood glucose level goes up within 30 minutes of drinking the glucose and water, it reaches a peak at about one hour (period 2) and then begins to fall. In the upper middle panel you can see the urine calcium begins to rise and reaches a peak around the third period, stays up and then comes back down. Remember, there’s no calcium in the drink, just sugar. You don’t have to work too hard to imagine where that calcium is coming from. Hint, from bone.

Now, look just below, in the lower middle panel. That shows the urine magnesium. It goes up just like the calcium, maybe even a little more vigorously. Why do we care about the magnesium? Because magnesium is good marker for the behavior of a segment of the kidney called the thick ascending limb. It is that place in the kidney where calcium and magnesium are most completely coordinated. So the fact that both went up at the same time makes clear that this segment of the kidney is responding to the glucose.

There is just a little more detail that we need to talk about. We are not showing you just how much calcium or magnesium there is in the urine, we are showing you the fraction of the calcium and magnesium that are filtered out of the blood by the kidney and that appear in the urine. So we are looking at the actual behavior of the kidney cells that take back into the blood what has been filtered. Glucose in water reduces the rate at which the cells of the thick ascending limb take calcium and magnesium back out of the filtered fluid into the blood. We are looking at the details of how the kidney cells function.

The Cell Surface Calcium Receptor

How could the thick ascending limb know that the blood glucose has risen?

It can tell because like many cells in the body it expresses on its surface the so-called calcium receptor. This receptor, which does indeed sense the level of blood calcium, also responds to a number of nutrients like, for example, amino acids. It also can respond to blood glucose. When blood glucose goes up, the receptor can signal the cells, and the signal is just like when the calcium goes up.

In fact, when the blood calcium does go up, it is a good thing to have the thick ascending limb liberate calcium in the urine. It is one of the ways that the blood calcium can be kept constant even though we eat it or drink it in our milk. Here, however, the signal is false. It is not calcium, simply glucose, but the cells cannot tell the difference. They liberate calcium into the urine as if the subjects had eaten calcium. Essentially, they lose bone calcium for no good reason. And, of course, urine stone risk goes up.

There are two more panels on the large graph, and I’m not going to say anything about them here. The urine becomes very acidic when you take in the glucose and of course the serum insulin goes up. Both are very interesting, but they are off target from what we want to talk about here. Those of you who are really interested in the matter can look at the paper.

CAN WE NEVER EAT SUGAR?

Before we leave here, let’s put this in a little different way. Just eating a big cookie, or a candy bar, signals the kidney as if you had taken in calcium. The so-called calcium receptor can respond to the rise of blood glucose from your candy bar, and the cells of the thick ascending limb liberate excess calcium into the urine and raise your stone risk for an hour or two.

ust because it’s only an hour or two don’t think it is trivial. Remember, at the same time, vasopressin will lower your urine volume, just when the urine calcium is going up. It is a perfect recipe for making stone crystals.

Let’s keep the message straight. We do not mean that you can’t have any sugar. We mean that if you eat enough sugar rapidly enough so your blood glucose goes up, as it does here, urine calcium will go up and stone risk as well. The effect is from the rising blood sugar. Glycemic load is all about the amount of blood sugar increase from a serving of a particular food. So if you just do what is recommended, and try to avoid high glycemic load foods, what we show here is not likely to happen to you.

PARATHYROID HORMONE AND TRPV5

Now, look at the upper right panel of the first picture we showed you (look back). It shows the blood level of parathyroid hormone. See how it falls in periods 1 and 2. The reason: of all cells in the body, the parathyroid cells most need to sense the blood calcium because they regulate the blood calcium. So they have the same cell calcium receptor as the thick ascending limb, probably even more sensitive. And, just as responsive to glucose. So the same signal that causes the thick ascending limb to give up calcium also lowers the blood parathyroid hormone.

The parathyroid hormone effects calcium reabsorption in a different part of the kidney altogether, the distal convoluted tubule. In that part of the kidney, calcium in the tubule fluid can enter the cells through a channel called TRP V5 (TRPV5 stands for Transient Receptor Potential Vanilloid member 5.) The amount of that channel in the membrane of the cells is controlled by the parathyroid hormone. When that hormone goes down so will the channel.

Is that true here? Indeed it is. Look at the box plots in the little figure. The upper left box plot shows the values for the channel before and during the glucose load. You can see clearly the number of channels goes way down.

Why does that matter? If the calcium cannot enter into the cells of the distal convoluted tubules, those tubules cannot move the calcium back into the blood. Put another way, the fall of parathyroid hormone lowers the number of channels in the membranes of the distal convoluted tubule, and that segment of the kidney can no longer reabsorb back into blood the usual fraction of the calcium that has been filtered by the kidney. The result will be that more of the filtered calcium appears in the urine.

For those of you who care how this was done, the measurement was made in tiny membrane vesicles that kidney cells are forever shedding into the urine. One can harvest these vesicles, and determine the concentration, or density, of the channel, in the membranes of the cells.

We measured three other channels as well. The one in the upper right panel has to do with the proximal tubule, the one in the lower left panel with the thick ascending limb, and the one on the lower right with the collecting duct. None of them changed, and none of them are known to be tightly regulated by parathyroid hormone.

LET’S SUM EVERYTHING UP.

When we take in a load of sugar, blood glucose will rise. The amount of the rise will depend on the glycemic load of what we ate and, although we have not mentioned this before, on whether or not and to what extent we have insulin resistance. The rise of blood sugar will affect the thick ascending limb through its calcium receptor, and the distal convoluted tubule through a reduction of serum parathyroid hormone so that both parts of the kidney liberate more calcium in the urine. Taken together, these two effects seem to be the reason for the calcium loss.

What can we do about this?

The best course is just to follow nutrition guidelines and stay away from high glycemic loads. By now, we imagine everybody is familiar with this idea. Here is an excellent list.

We think every stone farmer should be attentive to this problem. Periods of high crystallization risk can matter. We have shown throughout the site how nucleation of brushite can be rapid, and how brushite can foster calcium oxalate and hydroxyapatite crystallization and give rise to kidney stones. Sugar loads are pretty easy to avoid. They are not in general healthy either,.

Although by now I think everyone knows we should avoid extra sugar to prevent obesity, diabetes, and all the complications that ensue, here we are showing you the details of why a sugar load will raise your stone risk and there is nothing you can do about it except lower the amount of sugar you eat. We hope it works. We hope that having in mind the details of the way that candy bar can raise your stone risk will, maybe, help change your habits.

A Comment from Dr Prochaska

Investigations into the “the sugar story” date back to the work of an exceptional scientist named Lack Lemann. Recently, I picked this story back up because while we know that sugar intake increases kidney stone risk, we have not fully understood why. Our study provided new insight into why an acute sugar load increases urine calcium levels in the short term. We still have more work to do to understand the longer-term intake effects on stone risk and bone disease, but it is clear that sugar loads can contribute to kidney stone formation.