Queens of the Stone Age

I was very familiar with kidney stones long before I learned about them in medical school. My mother suffered from numerous kidney stones over the years, and I vividly recall her writhing on the bathroom floor and vomiting from the severe pain. Some say the pain from kidney stones—called renal colic—rivals or even surpasses that of childbirth.

Since the stone age

An association between kidney stones and renal colic has been known for over 2000 years (not quite since the stone age). Hippocrates, considered the founder of medicine, referred to kidney stones as “first disease of the kidneys” as early at 400 B.C. But what are these devilish little stones, and why must they hurt us so?

Kidney stones (also known as renal calculi) occur when certain minerals accumulate in the urine, begin to crystallize, and eventually form larger, solid stones. Among their functions, kidneys work to extract waste from the blood and excrete it into the urine. Stones form within the collecting system of the urinary tract—hollow structures connected to the kidneys that collect urine and direct it to your bladder—later to be tinkled into an appropriate place (this last part is for my toddler).

Kidney stones come in quite a few different flavors (not literally), but I will focus on the 3 most common types that account for 99% of all kidney stones.

1. Calcium: The vanilla of kidney stones (I went there). Accounting for about 80% of renal calculi, these are comprised of either calcium oxalate, calcium phosphate, or a mixture of these substances.
   1. Most calcium-containing stones are idiopathic, meaning they have no clear identifiable cause.
   2. Patients who have higher levels of calcium in their urine are (logically) at higher risk for stone formation, as are patients with the rare condition of primary oxaluria, in which increased urinary oxalate is present.
   3. Certain diuretics and anti-seizure medications are also known to increase the risk of calcium stones.
2. Struvite: Strawberry with bacteria sprinkles. These stones comprised of magnesium ammonium phosphate usually occur in the setting of urinary tract infection caused by specific types of bacteria—bacteria that produce an enzyme called urease. Urease breaks down urea (a major component of urine) to create ammonium, which in turn increases the pH of the urine and contributes to formation of struvite stones.
   1. Struvite stones can grow quite large to fill the branching collecting system of the kidney; we call these staghorn calculi due to their resemblance to the antlers of deer and other horned creatures (to me, they look like moose antlers).
3. Uric acid: Maple bacon ice cream. Uric acid is a normal byproduct of the breakdown of purine, a compound important in metabolism and the formation of DNA. Like calcium stones, most uric acid stones are idiopathic. However, a few conditions can increase risk for uric acid stone formation, the most important one being low urinary pH, i.e., acid urine! (Relax, acid urine does not actually “burn” anything.)
   1. Gout, an inflammatory arthritis, increases risk for uric acid stone formation. Gout results in deposition of monosodium urate—a substance related to uric acid.
   2. Diets high in meat also increase the risk for uric acid stones (the bacon connection). Meats are high in purine, which breaks down into uric acid.

Rock and roll all night and potty every day

If you’ve passed a kidney stone, you know it hurts. But how does a stone actually cause pain, and why is it so intense?

The relatively capacious collecting system near the kidney narrows as it approaches the thin, straw-like ureter (Fig. 1). When a stone moves out of the kidney, it can become lodged at one of several sites along the ureter and cause obstruction. The kidney does not like this—at all. Obstruction of the ureter causes urine to back up behind the stone, stretching the collecting system above that level. Nerve endings in the kidney and ureter detect this stretch, manifested as intense pain known as renal colic.

Kidney stones often get stuck at two specific spots: the ureteropelvic junction (UPJ) and the ureterovesical junction (UVJ). The UPJ—where the renal pelvis meets the ureter (Fig. 1)—is the first site of narrowing that a stone will encounter. Obstruction by a stone at this level will often manifest as pain in the upper back near the kidney. The UVJ—where the ureter meets the bladder—is another common site of obstruction, with pain from a stone here often felt in the testicle or labia. Many of the same nerves which sense pain from kidney stone obstruction are linked to nerves that supply the bowel, and this connection is thought to account for the pronounced nausea and vomiting associated with kidney stones.

While obstruction is painful in itself, rising pressures in the renal collecting system release chemicals called prostaglandins—whose effects ensure kidney stones are really, really painful. Prostaglandins induce increased peristalsis—muscle contractions in the wall of the ureter—in an attempt to push the stone through. To this end, they also increase blood flow to the kidneys and produce more urine. Finally (and also painfully), muscle contraction and spasm in the ureters eventually releases lactic acid, the chemical responsible for the “muscle burn” sensation during intense exercise.

Ouch.

Heeere, kidney kidney kidney (stones)

How and where do we find these painful little buggers? The vast majority of kidney stones contains calcium, which means they can be well seen with two imaging modalities: X-ray and CT.

On X-ray, calcium is the major reason bones appear bright. Our razor sharp logic tells us calcium-containing kidney stones should also be bright on X-ray (they are). Struvite stones are usually visible on X-ray as well, especially if they are large or have a calcium component. Uric acid stones, however, do not absorb enough X-rays to be visible on an X-ray image.

CT is the gold standard for evaluation of suspected kidney stones, and is much more sensitive for detection of small stones compared to X-ray. Over 99% of kidney stones—including calcium-containing, struvite, and uric acid stones—are visible on CT, and these stones appear bright (dense). It is sometimes possible to determine stone composition by measuring density on the CT image; uric acid stones reliably measure lower in Hounsfield Units compared to calcium stones. Stones that are dark (lucent) on CT are rare birds and can be difficult to see; examples are stones composed of certain medications and so-called matrix stone made of proteins or carbohydrates.

If kidney stones are strongly suspected, a CT scan is usually done without intravenous contrast; contrast is excreted through the kidneys and can obscure stones. CT can pinpoint the location of a stone and determine the degree to which it obstructs the collecting system. A stone can become lodged anywhere along the course of ureter, including the most common sites of obstruction: the UPJ and UVJ. When obstructed, the collecting system before the obstruction dilates (enlarges) and often becomes “angry-looking,” meaning fluid and inflammation develops around it.

As you would imagine, the larger the kidney stone you are trying to squeeze through your ureter (and eventually your urethra), the higher the unpleasantness factor. Radiologists always measure the size of a kidney stone to help estimate the chance it will pass on its own, i.e. without the intervention of a urologist. Over 80% of stones measuring less than 4mm will pass on their own; that number drops to 50% for stones 4-6mm, and 20% for stones more than 6mm.

Radiologists must be on the lookout for a couple important complications of kidney stones: collecting system rupture and pyelonephritis. In some cases, obstruction may increase pressure in the renal collecting system beyond the breaking point, and it will literally burst like a balloon, with urine leaking out around the kidney. Sometimes this will be need to be treated surgically, but it may also heal on its own with more conservative measures.

Pyelonephritis is infection of the kidney, and can occur with or without kidney stones. Simultaneous obstruction of the collecting system and infection is an emergency; if not treated quickly, infection can rapidly spread to the bloodstream and/or kidney function can be permanently damaged. Usually this is treated by percutaneous nephrostomy: placement of a small, thin tube through the skin surface into the collecting system to permit external drainage.

Which brings us to…

More notes on treatment

Kidney stones are usually managed by urologists—surgeons who specialize in the kidneys and renal collecting system—and the subtleties of treatment are admittedly beyond my area of expertise. In general, smaller stones are treated with fluid, pain medication, and time, in the hope they will pass on their own. Larger or persistent stones may need some help getting out, often accomplished with extracorporeal shock wave lithotripsy (ESWL), which I have always thought sounds like an experimental military weapon. ESWL uses sound waves to break up kidney stones into smaller pieces, increasing the chance they will pass. In some cases, urologists must reach directly into the renal collecting system (via the bladder) to extract stones.

Two specific additional treatments also bear mentioning. Struvite stones occur in the setting of bacterial infection, and thus the infection must be treated fully to prevent recurrence of stones. This includes complete removal of all stone fragments, as they can harbor bacteria and result in recurrent infection if left behind. Uric acid stones are the easiest to treat of all kidney stones. Because they form in acidic (low pH) urine, increasing the pH (alkalinizing) the urine causes them to simply dissolve.

In summary, kidney stones are common and not fun, and I hope you never get one. If you do, however, know that in most cases they are very treatable.

Comments? Questions? Please post them below.