This may be the most important article – to me – I have written thus far.

It is a plea and argument that stone patients need more from us than prevention of stones, because often enough they harbor significant diseases that associate with stone forming and require their own treatments. We need to treat the patients, not just their stones.

The magnificent Garden of Earthly Delights (Hieronymus Bosch, 1450 – 1516) hangs in the Prado. I chose it here as it contains the whole world, which is to say that every patient is that self same.

Stone Formers Have Other Disease Risks

When you look at the data, kidney stones belong to a manifold of diseases that run together: Bone disease, kidney disease, hypertension, and stones themselves. This is to say that forming stones identifies someone as having a pattern of increased risk, modest risk, certainly, but well worth considering.

Renal and Cardiovascular Risk

For example, in Olmsted County about 1.2% of people eventually came to need dialysis or transplantation, but rates were 2.4% for those with stones. In other words low risk is amplified a bit. On the other hand, over 18 years, about 18% of people developed stage 3 chronic kidney disease (CKD) vs. 25% of stone formers. You might say modest CKD poses little threat to life, but in reality this kind of disease associates with higher rates of cardiovascular disease such as heart attack and stroke.

The same for hypertension. Having even one stone raises risk by about 1.5 times the rate for non stone formers.

While it is tempting to string these together in presumed causal linkages – e.g. stones damage kidneys, which leads to kidney disease and hypertension, etc – one may be better off to accept the simple fact of their association and act accordingly. Science will ultimately sort out what causes what.

Bone Risk

Likewise for bone disease. Whereas vertebral fracture in later life affected about 5% of people in Olmsted County, rates were over 20% in stone formers. I believe idiopathic hypercalciuria and low calcium diet massively contribute to this bone problem, but I am limited to my time and the future may show us more.

So What?

It is a matter of long term risk assessment and reduction. Stones tend to peak at younger ages, CKD, hypertension, and fractures come later in life. Both reduce life’s quality, and even longevity. If the final risk and type of damage is modest, risk mitigation seems equally so. Just a proper diet and – when needed – thiazide and potassium citrate should do wonders for stone reduction and improvement of health in later years. That self same diet acts against obesity, insulin resistance, diabetes, and osteoporosis. That is why the stone diet so much resembles the diet recommended for all Americans.

Systemic Diseases Can Cause Stones

One reason for all these associations may be that stones can arise from established systemic diseases that themselves affect kidneys, or bones, or blood pressure. For example, uric acid stones form because urine is too acidic. But that acid urine often comes from obesity, diabetes, or bowel or kidney disease, or insulin resistance, or metabolic syndrome. That will tend to associate stone forming with hypertension and bone and kidney disease when one looks at population studies. Likewise, cystinuria is an inherited disorder of kidney function, and chronic kidney disease is a common outcome. Renal tubular acidosis and Dent’s disease are other examples. Primary hyperparathyroidism is perhaps the clearest possible instance. It causes calcium stones and bone disease, and high serum calcium can damage kidneys and raise blood pressure.

In each case, disease causes stones and stones can add more injury on top of diseases that have preceded them. No one needs be surprised that hypertension, bone disease, and kidney disease accompany stones under such circumstances.

Idiopathic Calcium Stones Have Added Risks, Too

By contrast, common idiopathic calcium stones seem to arise from a complex interaction between genetics and our particularly bad modern diet so rich in salt and sugar and protein, and low in calcium and veggies. Such an interaction would fit with the familial nature of stones and the success of diet changes in reducing new stone formation. As an added pathway of injury, calcium deposits in the kidneys could raise blood pressure and cause kidney disease, and disorders like idiopathic hypercalciuria promote bone disease. 

This scenario posits that increased vulnerability to the bad effects of our modern diet may cause stones, bone disease, raise blood pressure, and by a multitude of pathways lead to kidney disease. In other words having stones is the mark of multiple vulnerabilities to a diet too rich in salt, sugar and protein, and low in potassium. Even though the linkages may be deeper and less apparent than this, stones become an all too obvious sign of what may be a manifold of disorders each of which deserves attention.

Preventing Stones Is Not Enough

Given this reasoning and the facts that have lead to it, proper care of stone patients cannot be stone prevention alone.

Of course we want to prevent stones. They are dangerous, painful, and utterly disruptive to a normal life. But beyond the stones, we want to treat or prevent the diseases they travel with. Because stones single out people with multiple disease risks, we need to treat the whole patient, not just prevent kidney stones.

Evaluate Every Patient

Systemic Causes Can be Hard to Diagnose

When they know about them, physicians are apt to treat systemic diseases effectively. But they may not know for some time.

Consider primary hyperparathyroidism. Mild increase of serum calcium can be lost in the noise and confusion of blood samples not always drawn fasting, not always drawn well, and not always run by highly precise labs. Vitamin D deficiency and even modest reduction of kidney function can mask primary hyperparathyroidism.

Intestinal  malabsorption may have few symptoms yet produce hyperoxaluria. Primary hyperoxaluria itself is not evident unless a 24 hour urine has been obtained. If stones are lost, or not analysed, uric acid stones and even cystinuria can be missed – for a while.

The rare genetic diseases – Dent’s disease, renal tubular acidosis as examples, can be colorful and odd looking but mainly we diagnose them from coordinated serum and urine laboratory measurements. The not uncommon and unfortunate tendency to restrict 24 hour urine testing to recurrent stone formers can much delay diagnosis.

Uric acid stone formers are rarely ‘idiopathic’ in that the low urine pH they require is not a normal finding. I already listed the panoply of underlying disorders one usually encounters. Almost never do they lack systemic problems, so almost never is it enough to just prevent more stones.

Likewise for struvite stones that bacteria produce. These infected foreign bodies need special surgical care. Often, struvite forms over calcium stones of idiopathic etiology, so two problems need attention.

Evaluate All First Time Stone Formers

Detect Systemic Diseases

Consequently, no stone former should be let go without a proper evaluation. You simply cannot diagnose systemic diseases without fasting blood and 24 hour urine testing combined with considerable clinical acuity. Of course stone analysis is paramount. How else to discover uric acid or cystine, or dreaded struvite – from infection. Explicitly, even first time stone formers cannot be left untested and told to drink more. That approach that invites mistake.

Improve Treatment Outcomes

Idiopathic calcium stone formers are diagnosed by exclusion. That means no one can be so classified without serum and 24 hour urine studies and stone analysis. Once identified, they are best off with immediate multimodality treatment. The more stones formed, the less effective our treatments. Just high fluids ignores the need for changes in diet calcium and sodium to protect against bone mineral loss, reduction of refined sugar as a hedge against insulin resistance and metabolic syndrome, as examples. It ignores the need to manage against bone and kidney disease, and high blood pressure.

Promote Healthy Diet

How can I best say this? Every first time stone former deserves serum and 24 hour urine testing. Period. Why wait? To neglect systemic disease is sinful. If idiopathic, stone prevention begins simply with a healthy diet that otherwise might have been put off for convenience’s sake, but followed from necessity contributes to a healthier life not only for the patient but the family as well.

Said perhaps more aptly, stone prevention based on a proper diet and medications when needed reduces risk of later life fractures, as well as high blood pressure, chronic kidney disease, and their associated increased risk of cardiovascular diseases such as heart attack and stroke.

Canary in the Mineshaft

Put another way, most patients will have idiopathic calcium stones.They are lucky in having no overt systemic diseases. But just because their idiopathic calcium stones bring patients to physicians for care, the stones cannot be all we attend to.

Bone Disease

‘Every stone clinic is a bone clinic‘ – Professor David Bushinsky.

Find It

Stone formers fracture more commonly than others do. I think idiopathic hypercalciuria and low calcium diets are a main reason why. But whatever the real reasons turns out to be, we want to lower that risk.

Given established idiopathic hypercalciuria, a bone mineral density (BMD) scan seems reasonable, and insurance carriers may pay for it. Multiple studies document reduced bone mineral density in IH. We do not have enough clinical data to advise a bone scan for other idiopathic stone formers, yet. Even so, I favor scans given a history of low calcium diet or of family fracturing. Obviously, we need more data about bone disease in non hypercalciuric calcium stone formers.

Treat It

We obtain a scan and estimate fracture risk. What then?

If fracture risk is modest, high calcium, low sodium diet should be reasonable. You might say it is also proper for IH as a way to prevent stones, and I agree. So in treating the one we help treat the other. Likewise for thiazide: proper to lower urine calcium and reduce new stones, known to improve bone mineral balance and reduce fractures.

I hear you saying, ‘so why measure BMD?’

Sometimes, we will find advanced bone disease at the beginning, and treat it with bone specific medications. If BMD is only modestly reduced we know we need to repeat the scan after some period of diet treatment. Should all be well – stable or improved BMD – we have done well. But if not, further treatment can be offered, such as bone specific medication appropriate to fracture risk.

What we gain is precious time, a baseline to work against, and a bone oriented follow up we might have otherwise not performed.

Hypertension

You might say, every primary care physician looks for hypertension, finds it, and treats it. But that cannot be. The fraction of people with high blood pressure under control from treatment has been estimated at only about 50%. 

Because stone formers are at higher risk than normal, we need to be sure about blood pressure. To me, this means not only making a measurement at clinical visits but also looking at what others have found. If values seem suspicious, the cost of home blood pressures is virtually negligible compared to the benefits of early recognition.

Once again, treatment of stones usually involves low sodium intake, high potassium from fruits and veggies, thiazide, and reduction of sugar intake – which will tend toward weight loss and improvement in insulin sensitivity. All of these measures can lower blood pressure and may suffice.

If it does not, we can augment medical treatment ourselves or work with primary care physicians to have it done if pressures remain above ideal despite the kidney stone diet and thiazide. Because we know risk of kidney disease is increased, we may be more vigilant than others.

Kidney Disease

It Happens

I am surprised kidneys fare as well as they do given repeated obstruction from stones, infections, and procedures like shock wave lithotripsy and percutaneous nephrolithotomy. All of these offer possibilities for kidney tissue injury and inflammation. Virtually all stone forming kidneys harbor calcium deposits. Tissue cannot but recognize them and react.

Years of work have established that resilience has its limits. Stone formers do progress to chronic kidney disease and even serious kidney failure at higher rates than normal.

We Can Help

One cannot reduce this complex matter to a few clinical nostrums. Say instead we have the responsibility for wary observance and care to mitigate. I mean by this attention to even slight reductions of eGFR and to stone related events that can damage kidneys. Obvious examples of the latter: contrast agents; dehydration from vomiting when NSAIDS are being used for stone pain; multiple shock wave procedures; painless and therefore missed stone obstruction.

Our basic stone prevention diet – low sodium, moderate protein – helps protect kidneys, as does attention to blood pressure. Likewise for reduced sugar intake that helps stave off obesity, insulin resistance, and diabetes. But stones themselves and the procedures to visualize or remove them can deceive us. The very urgency of a stone attack may divert attention from the need to protect against kidney injury, however inadvertent.

My Message to Patients

Stones are bad enough, but they may signal risk for as bad or worse. Shun monotherapies like ‘lots of water’; low oxalate diet as panacea; lemon juice; or nostrums found on the web. They are often ineffective and do not speak to all that may be wrong.

Demand blood and 24 hour urine testing after even one stone.

Ask about bone disease, blood pressure, kidney function.

Learn and follow the kidney stone diet. It has a good scientific base and matches what all US people are advised to eat anyway. The diet, supplemented with thiazide or potassium citrate when needed, helps protect against bone and kidney disease, and hypertension, as well as more stones.

Offered procedures, ask about kidney protection, risks to kidney function. Know what your kidney function is, and always ask about changes in it, if any.

Know your blood pressure and see it is kept in proper limits.

If your bone mineral density has been low, be sure it is re-measured at intervals, and that you get treatment, if needed, to stabilize it.

My Message to My Fellow Physicians

Stones can be the first sign of systemic diseases. Find them early.

Shun single modality remedies. Because they do not protect against bone or kidney disease, or against hypertension, they are wrong at their core: too narrow for a population at higher than normal risk. Especially first time stone formers, so numerous as they are, deserve a proper initial evaluation for systemic diseases, bone disease, hypertension, and kidney disease.

At minimum, every stone patients should follow the ideal US diet – which is indeed the ideal kidney stone diet. What possible reason can we adduce for acting otherwise?

The hypertension, bone disease, and kidney disease in our stone formers are our responsibility simply because we have ongoing treatment relationships centered around stones. Stone prevention modalities can benefit bone, blood pressure, and, consequently, kidneys. Stone passage and surgical interventions pose risks of kidney injury.

My Message to My Fellow Clinical Investigators

We lack important data concerning bone disease, hypertension, and kidney disease in idiopathic calcium stone formers. These are compelling problems. It is not for me to say what we need, it is for you to think about what we need to practice better, and help as best you can.

My Message to NIH – NIDDK

Shun and discourage thoughtless management of idiopathic stones as if stones were THE problem. Stones are part of a larger problem.

Lots of water, or lemon juice, magic enzymes and bacteria, or obsession over diet oxalate may reduce stone recurrence for a time. But such monovalent remedies are no service to patients who might have more benefitted from a better diet they do not understand and embrace because of distraction and false security.

The ideal stone diet follows the ideal national diet shaped by your peers in government service. We need funds to foster that diet in stone prevention because it also acts against bone disease, hypertension, obesity, and diabetes, crucial issues to stone patients at risk for fractures, hypertension, and kidney disease.

We need research that helps physicians detect and manage bone disease, hypertension, and kidney disease in stone formers in ways that are austere, efficient, comprehensive, and effective. That would be a dignified and thoughtful use of public funds.