Why Do Kidney Stones Cause Pain?

P6140312Agonizing, intolerable, miserable, excruciating, stabbed with a knife, worse than childbirth.

As a urologist specializing in the treatment of patients with kidney stones I have learned a new lexicon exclusive to stone formers describing bouts of renal colic.

Pain, the hallmark symptom of stone disease, accounts for over one million emergency room visits by such patients in the United States each year.

Over the past several decades considerable progress has been made gaining insight into the physiology of renal colic and optimizing methods to treat it. However, despite improved scientific explanations we as clinicians still lack a perfect understanding of why it occurs.

PAIN FROM STONE PASSAGE

Patients have been suffering from renal colic secondary to stone disease for over two thousand years. As a matter of fact, it is remarkable how little has changed in its clinical presentation over this time period. In 400 B.C. Hippocrates referred to it as first disease of the kidneys. He was one of the initial observers to comprehend the association between urinary obstruction and pain, writing:

An acute pain is felt in the kidney, the loins, the flank and the testis of the affected side; the patient passes urine frequently; gradually the urine is suppressed. With the urine, sand is passed; as the sand passes along the urethra, it causes severe pain which is relieved when it is expelled; then the same sufferings begin again.

We have since come to appreciate the complex physiologic basis for this relationship at a much deeper level.

How Pain Begins

renal-stonesThe first step in this process is acute obstruction, most commonly from a stone. But in stone formers masses of crystals can create obstruction, as can blood clots if bleeding is particularly brisk.

Urine from the kidney can no longer pass to the bladder and as a result builds up and stretches the proximal – closest to the kidney – ureter and renal collecting system. This stretch activates nociceptive nerve fibers – fibers which sense injury – within an entire neuronal network located submucosally in the renal pelvis, calyces, capsule and ureter.

Figure 1 (left) – Example of obstructing proximal ureteral stone with dilation and stretch of the collecting system above the level of obstruction.

These fibers then transmit afferent signals to the T11 – L1 spinal cord which the body interprets as pain at the corresponding level of neuronal activation. As the stone migrates from the kidney down the ureter and towards the bladder, pain usually shifts downward as well. It is commonly sensed as high as the upper flank when the stone is lodged in the proximal ureter and as low as the labia/testicle when down near the uretero-vesical junction at the entry to the bladder.

Patients passing stones may experience other symptoms in addition to pain.  Many of the nerves involved in the process of obstruction are intimately linked to innervation of adjacent organs, for example the gastrointestinal tract. Cross activation of these associated nerve fibers has been proposed as an explanation for the nausea and vomiting which so often occurs in the setting of an acute episode of renal colic.

In rare instances patients may even have alternative symptoms without any pain at all. In some cases, particularly when the stone is at the uretero-vesical junction, urinary symptoms predominate and the only appreciable symptoms are urinary frequency, urgency and discomfort while voiding. These symptoms mimic urinary infection and often result in temporary mis-treatment with antibiotics until the correct diagnosis is made.

What Happens Later

Increasing renal pelvis pressure from persistent obstruction causes a release of prostaglandin E2. This chemical mediator of injury response produces a perfect storm.

It causes ureteral hyperperistalsis (increased intensity of the waves of coordinated ureteral contractions which normally drive urine down to the bladder) and eventually even ureteral spasm. It also leads to dilation of the afferent arterioles – those tiny resistance vessels which control the flow of blood into the capillaries of the kidneys.

The arteriolar dilation increases blood flow to the kidney and promotes a temporary diuresis just as ureteral smooth muscle hyperperistalsis and ultimately spasm tighten the ureter around the stone and worsen obstruction. Spasm leads to lactic acid build up, as occurs when any muscle is over-exercised, and sets off an inflammatory cascade that itself can worsen pain.

With time, blood flow to the affected kidney falls, even though the arterioles which let blood into the renal capillaries remain dilated. It falls because the efferent arterioles, which let blood out of the capillaries where filtration occurs, begin to constrict and raise filtration by the renal glomerulae. The increased filtration maintains and can even raise pressures.

glomerulus copy

Figure 2 – Diagram of blood flow to the nephron.  Blood enters through the afferent arteriole and is then filtered within the glomerulus, producing urine in the process. Blood exits through the efferent arteriole. Both the afferent and efferent arteriole are able to dilate and constrict in order to regulate pressure and ultimately filtration via urine production.

In many ways, this complex system is analogous to the soaker hoses many people use to water their lawns. The afferent arterioles are the faucet the hose is connected to and the efferent arterioles are the opening at the end of the hose which can be closed or left open into a sprinkler.

Filtration is the many tiny flows of water all along the hose which keep the grass growing.

When working appropriately, the faucet and the end are both open and water (urine) is produced at a slow, constant rate (Figure 4 – left). With an obstructing stone the faucet – so to speak – is opened more and the end clamped more so more fluid – water – is filtered out along the length of the hose at high pressure (Figure 4 – right). In the kidney this filtration is into the nephrons and raises pressure. When the clamp is tightened, the total amount of flow through the hose can fall just as the amount of water filtered out along the hose rises.

Figure 4 – Soaker Hose Analogy to Renal Blood Flow and Filtration. On the left, there is little pressure in the system and water (urine) seeps out slowly from along its length.  On the right, the inflow is much higher than the outflow and water (urine) shoots out from along the hose at exceedingly high pressure.

Screen Shot 2015-05-30 at 2.43.57 PM

Three Phases of Pain in more Detail

The Physiology

No discussion regarding ureteral obstruction would be complete without the work of E. Darracott Vaughan, who characterized the physiology of urinary obstruction in the 1970’s.

Assuming two functional kidneys, the physiologic effects of acute unilatScreen Shot 2015-05-21 at 11.04.09 PMeral ureteral obstruction can be marked by three distinct phases.

In phase one, the effects of the inflammatory cascade described above cause a progressive rise in renal blood flow and renal pelvis and ureteral pressure. This phase lasts for approximately one to one and a half hours. This is the portion where the afferent arteriole – the faucet – is maximally opened.

Phase two is marked by efferent arteriolar vasoconstriction which causes a decrease in overall renal blood flow but an increase in ureteral pressure for up to five hours. The faucet is opened and the end clamp is tightened.

Phase three is marked by a further decrease in renal blood flow to the affected kidney and ultimately decreased ureteral pressure. The end clamp is progressively tightened so blood flow to the kidney is reduced enough that filtration and urine production begin to fall, and pressure with it.

Measurements of ureteral pressure (red) and renal blood flow (blue) after onset of acute unilateral ureteral obstruction. (Courtesy Campbell-Walsh Urology, Tenth Edition, Elsevier Inc.)

The fall in blood flow is not injurious during an acute attack, but over time it can be. This means that relief of an obstructing stone is an important matter. Commonly stones pass of themselves. But stone attacks need medical attention because if the stone continues to obstruct it must be removed.

The Symptoms

It is easy to conjecture how these three distinct phases correlate clinically to the symptoms experienced during an acute episode of colic.

The onset of pain classically correlates to phase one and the inciting obstructive event. It is at this point that the patient commonly seeks care in the emergency room or physician’s office.

The pain classically persists at a severe level for several hours (phase two) but ultimately subsides, at least partially (phase three).

In many instances pain comes in waves, potentially a sign of intermittent obstruction activating the above pathway each time urinary flow is obstructed. This occurs through a combination of the stone moving and the tensions of the ureter with increases or decreases of muscle spasm.

THE CONUNDRUM – Pain Without Obstruction

Opinions of Urologists in General

Though the physiologic basis of pain in the setting of obstruction is clear, it does not provide an explanation for one of the most commonly encountered conundrums in stone disease – the symptomatic non-obstructing stone. These can be actual free stones that have not passed, stones attached to plaque, or actual plugs in the kidney tubules that are massed together enough to show up on a CT scan as ‘stones’ though actually tissue calcifications.

There is perhaps as much variation in clinical opinion in such instances as any other clinical scenario in the field.

If one were to ask a group of urologists whether they believed that small nonobstructing stones could cause renal colic, opinions would range from absolute certainty to complete dismissal of the concept altogether.

What Happens to Patients

As a result, there is no standard of care regarding how to optimally manage such patients. In all cases it is first imperative to rule out other potential sources of pain; however, such workups often end with the same result – a patient with bothersome flank pain and evidence of one or more nonobstructing stones on imaging.

Lacking a physiologic explanation to explain their symptoms, patients with pain and non obstructing stones are often sent for detailed workups, secondary and tertiary consultations and referral to pain specialists and even psychiatrists. However, in an age where flexible ureteroscopy can be performed quite safely and on an outpatient basis one must wonder whether such patients are being treated appropriately.

A Specific Example

As an example, I recently met a patient who had been referred from several hours away seeking a fourth opinion regarding her chronic flank pain. For months she had suffered from a severe ache in her left flank that had limited her ability to work and live her normal life.

She had attributed the pain to a 7 mm lower pole nonobstructing renal stone on that side which was discovered on a CTScreen Shot 2015-05-21 at 2.32.24 PM scan during her initial presentation to an outside emergency room (Figure 3). However, none of the physicians she had seen agreed with her self diagnosis.

Figure 3 – CT image of left lower pole nonobstructing stone (red arrow).  There is no evidence of obstruction or inflammation around the kidney.

In the ER she was given narcotic pain medication and sent home to follow-up with a urologist.

The first urologist she saw told her that while the stone was visible, its location within the kidney meant that it could not possibly be causing her pain. He refilled her prescription for pain medication and sent her to see a pain specialist.

The pain specialist tried physical therapy for what he thought may be a musculoskeletal source but ultimately this did not prove effective and she was given more pain medication.

She later sought care from a second urologist who also told her that the stone could not possibly be causing her pain in the absence of obstruction. This time however she was accused of having an agenda and seeking care specifically to get pain medication. Similar visits to a variety of emergency rooms elicited more CT scans as well as accusations of seeking pain medications. Each CT result was the same though, all demonstrating a 7 mm non obstructing left lower pole stone.

On one instance a treating practitioner even admonished her, saying that nonobstructing stones don’t cause pain and he should know since he too had been diagnosed with such stones incidentally on a CT scan.

Ultimately she made her way to the clinic for consultation at which point she was offered a ureteroscopy and stone removal. The procedure went well and she was discharged with a stent for one week. She was last seen back 5 weeks after the procedure and reported complete resolution of her pain. She was no longer taking any pain medication whatsoever and there was no evidence of any stone or hydronephrosis on follow-up imaging.

What is Known to Date

Such patients are frequently encountered. Despite a lack of physiologic explanation as to why these non-obstructing stones may cause pain, there is emerging evidence that they do and therefore that removal can cure it.

In 2006 Taub et al. described outcomes of twenty such patients who had chronic flank pain as well as radiographically evident calcifications within their papillae without obvious collecting system stones. Ureteroscopy with laser papillotomy to unroof and remove all evident stone was performed on twenty seven kidneys. Pain improvement was seen in 85% of cases with a durable improvement for greater than one year in nearly 60% of cases.

This study was then repeated on a multi-institutional level with 65 patients undergoing similar procedures over a ten year period. Overall there were 176 procedures performed in this cohort with patients reporting less pain after the procedure 85% of the time. The mean duration of response was 26 months with 60% of patients having sustainable improvements in their pain levels for over one year.

Finally, this clinical scenario is seen commonly enough that it garnered its own nickname at Massachusetts General Hospital where it has been described as “small stone syndrome”In a retrospective review of patients treated there with ureteroscopic removal of small nonobstructing stones (<4mm) for reasons related to chronic pain, 11/13 patients reported being pain free after the procedure with the other two noting a partial response.

What I think

We still do not completely understand the physiologic explanation for pain in these patients. However, much like Hippocrates over two thousand years ago, clinical observation often precedes scientific understanding. In this regard it is unfair to dismiss the notion that small non obstructing stones can elicit legitimate renal colic.

Physiologic breakthroughs in the understanding of pain signaling and inflammation are currently happening at a rapid rate and it is likely that in time we may be able to better decipher which non-obstructing stones are truly responsible for symptoms. However, until then, such scenarios will continue to be a commonly encountered clinical complexity for urologists.

For the time being I would still advocate consideration of alternative causes of pain in such situations including urinary infection, obstruction and malignancy. A careful history is critical to rule out non-urologic sources such as pathology within the musculoskeletal, pulmonary, gynecologic and gastrointestinal systems. Another important element of the history is whether the patient has previously passed a stone and if the current symptoms are similar to that experience.

Once other explanations have been ruled out, offering stone removal is entirely reasonable. This not only has the potential to improve pain but may also decrease the risk of future stone growth or spontaneous passage at a later date. In such instances, I prefer flexible ureteroscopy with stone removal to shock wave lithotripsy. First, ureteroscopy maximizes the likelihood that all stones can be identified and removed which is especially important in the event that pain persists after the procedure. Second, with ureteroscopy one can inspect the inside of the kidney in high definition which has the potential to offer information not readily available on x-rays and CT scans such as embedded stones, tissue calcifications, and other pathology (Figure 4).

Figure2 copy

Figure 4 – High definition images obtained during renal endoscopy demonstrating tubular plugging (stones embedded in the kidney) (Courtesy: AE Evan, IMCD and BD plugs: Do they have a role in stone formation). 

Finally, it is critical to establish realistic expectations before surgery in regards to pain control. Our understanding of this concept is in evolution and the published literature suggesting a treatment response is limited to relatively few patients. However, as science and history have shown us, just because we don’t fully understand the connection doesn’t mean it doesn’t exist.

More You Might Like

What Kidney Stones Are

Types of Kidney Stones

Do We Need to Analyse All Those Stones?

How Kidney Stones Form

When Crystals Plug The Kidneys

Medullary Sponge Kidneys

 

 

 

 

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Andrea Galloway
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Andrea Galloway

I am a 36 yr old women that has SLE Lupus. I have had kidney and bladder infections off & on for long time. I also have compact fractures in everyone of my vertebrates. So I know pain. But September,9 I started hurting extremely bad in my lower right side of my back & in the middle. I had CT done it showed 4 mm stone in my kidney. My regular family dr priscribed flomax. I’ve taken 3 so far. She just gave them to me a few days ago after I went to the er. I went back to… Read more »

Fredric Coe, MD
Admin

Hi Andrea, I think perhaps a urologist might help in this decision. Some stones that do not obstruct the main drainage of the kidney – the ureter – can obstruct interior channels. Your description of the pain does sound like the pain stone patients describe but you also have significant back trouble from fractures. The decision is complex because if you believe the pain is from the stone, the surgery to remove it is itself a major undertaking. Regards, Fred Coe

Tired and exhausted
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Tired and exhausted

I found this site after once again not feeling well. I woke up in the middle of the night with extreme mid back side pain. So I went to the er..they mention maybe kidney.. so I peed in cup.well they said urine was fine..so I told them I have ddd in my neck.so.maybe that was it. anyway I was sent home with no further information.. the next day pain was still intense so I went to see regular doc..my heart rate was up 160 so they did ekg..but it went down. While on monitor..he did blood work and sent me… Read more »

Fredric Coe, MD
Admin

Hi, I gather you have kidney stone or stones, and pain. I also gather that the stone does not seem to be obstructing the kidney, but your pain is considerable. Possibly the pain is not from the stone, or perhaps there are other causes related to the stone such as crystals in the ureters. From the little information, I cannot do much to help. If the pain remains severe and nothing is found except the one stone, perhaps your surgeons can consider if removing it would help. Regards, Fred Coe

Cindy
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Cindy

I can attest that a 4mm nonobstructing stone in the kidney CAN cause chronic kidney pain. I’m currently experiencing it. I’ve passed many kidney stones over the years and definitely know the different between “back” pain and kidney pain. Its kidney pain.
I’m looking for a good urologist near Chesterfield, MO.

Fredric Coe, MD
Admin

Hi Cindy, The closest kidney stone experts would be at Indianapolis (IUPUI); Dr James Lingeman is an outstanding surgeon there. Regards, Fred Coe

Cindy
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Cindy

I can attest that a 4mm nonobstructing stone in the kidney CAN cause chronic kidney pain. I’m currently experiencing it

Fredric Coe, MD
Admin

Hi CIndy, Few would disagree; the issue is whether surgery helps or not. Regards, Fred Coe

MANIKANDAN S
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MANIKANDAN S

My mother aged 48 yrs had upper abdominal pain and radiating towards back for past 15 days(come and go). After Ultra sound-scan, it is found that she have 2.33 mm calculus in the middle calyx of right kidney. My first doubt is whether 2.3 mm stone will cause pain in upper abdomen? Nothing else also negative in scan except fatty liver Grade 1. She don’t have any vomiting or pain during urine. Please clarify?

MANIKANDAN S
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MANIKANDAN S

My mother aged 48 yrs had upper abdominal pain and radiating towards back for past 15 days(come and go). After Ultra sound-scan, it is found that she have 2.33 mm calculus in the middle calyx of right kidney. My first doubt is whether 2.3 mm stone will cause pain in upper abdomen? Nothing else also negative in scan except fatty liver Grade 1. She dont have any vomiting or pain during urine. Please clarify?

Fredric Coe, MD
Admin

Hi Manikandan, upper abdominal pain radiating to the back is more like a gallstone or pancreatitis than a right sided kidney stone. I suspect the gall stone as most likely, but her physicians will need to sort this out. Regards, Fred Coe

Brian Gilbertson
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Brian Gilbertson

Dr. Borosky, I desperately seek help in my stone treatment. I currently have 6 stones . I had 8 but have passed two in the last 18 months. my right kidney is constantly in pain. I have seen urologist at mayo and UW health Madison being told that my stones are too small and non obstructing so my pain should be something else. i had 12 stones removed in 2015, but developed the 8 new ones by spring of 2017 and been suffering ever since. I will do anything to seek treatment to get rid of these things. I have… Read more »

Fredric Coe, MD
Admin

Hi Brian, I believe we corresponded and you are considering several surgical consultants. Regards, Fred Coe

Cindy
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Cindy

I can attest that a 4mm nonobstructing stone in the kidney CAN cause chronic kidney pain. I’m currently experiencing it. I’ve passed many kidney stones over the years and definitely know the different between “back” pain and kidney pain. Its kidney pain

Fredric Coe, MD
Admin

Hi Cindy, I missed the multiple versions of this comment. That you have passed stones and can recognize this pain as like a stone is valuable to know. I have always assumed these stones cause local internal obstruction or inflammation, but have no real data to support that assumption. Regards, Fred Coe

Paul
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Paul

Hello – (Appreciate your attentive answers and calm demeanor even with sometimes more pressing or angry posts.) I had a “one-time” kidney stone and went to the ER last October (2017) where the diagnosis by the docs there confirmed a stone (they did Ultrasound and a CT scan, etc.). I believe the cause was due to high calcium from Hyperparathyroidism which was subsequently diagnosed and I have since had correcting PTH surgery (February 2018) and my calcium is now back to normal. However, during the original ER visit they discovered an additional stone than the one suspected of causing me… Read more »

Fredric Coe, MD
Admin

Hi Paul, Given a stone and pain, I always suspect the stone. By the way, urine calcium often remains high after cure of PHPT so your physicians should check for that and treat it if present – an ongoing cause of more stones. Regards, Fred Coe

Paul Sharp
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Paul Sharp

Hello again Dr. Coe. Since the above reply I have had another urinalysis, a 24-hr. urine analysis (won’t know results until my next visit), and another ultrasound, where my urologist could subsequently see the 4mm “non-obstructing lower left pole stone” referred to in the first post. He is recommending lithotripsy. When I asked about removing it with the newer/smaller tools through the ureter up into the kidney his response was that their efficacy depends upon the location of the stone, and that mine was in a location where it was impractical or impossible to reach. He will be doing a… Read more »

Fredric Coe, MD
Admin

Hi Paul, I am not a surgeon nor your physician so I cannot venture further into your exact treatment. I worry that shock wave treatment of a lower pole stone will simply leave fragments in the lower pole that may not clear. But being what I said, my opinion is worthless in any one particular case where I know no details. If you have any uncertainties just get a second surgical opinion. Your present urologist can easily arrange for it. Regards, Fred Coe

Paul
Guest
Paul

Dr. Coe, I now have the results of the 24-hr. urine collection and also a report on the recent ultrasound. Regarding the Ultrasound, the Radiologist’s interpretation indicated a 6 mm stone in the proximal ureter/renal collection area, and another smaller non-obstructing one an upper renal area. This is quite a different situation from the Oct. 2017 original ultrasound in the ER which reported a “4mm non-obstructing lower left pole stone.” Perhaps that 4mm stone grew between then and the February 2018 hyper-parathyroid surgery and is now the “6mm” stone in the collection area, having moved form the lower left pole.… Read more »

Fredric Coe, MD
Admin

Hi Paul, I do indeed see a problem. Your urine sodium is 95 mmol/liter and 124 mmol/day; this gives a urine volume of 124/95 or 1.30 liter per day. That is woefully insufficient and could cause new stones to form given you already have some stones in the kidneys. The safe volume is above 2.25 liters, and I would vote for 2.5 liters/day. You have a lowish urine pH and high urine citrate that make we wonder if your BMI is on the high side, or you have other elements of the metabolic syndrome such as lipid or blood pressure… Read more »

Paul
Guest
Paul

Dr. Coe, I done further reading through your info about 24-hour urine tests, and then drove to the medical center to obtain the one I had done last March (2018) to compare with the one I just posted above. Surprisingly (to me at least), the ENT who ordered it only requested Urine Calcium and the rest of the items were not included in the lab report. Those results for urine calcium were: Calcium Ur mg / 39.6 Calcium 24hr / 376 Given that the later test I previously posted had urine calcium of 20.2 and 263, I am hopefully concluding… Read more »

Fredric Coe, MD
Admin

Hi Paul, I already calculated your volume in the prior comment, and it is indeed too low. No doubt the prior high calcium was from PHPT and that is not presumably cured. Yes, your sodium is high and I would reduce it. I commented on other ideas in my other note. Regards, Fred Coe

Cristi
Guest
Cristi

I have recently been diagnosed with hyperparathyroidism. My blood Ca levels have ranged from 10-11 for the past 8 years at least (as far back as I can document.) I have a consult with a surgeon next week. I have been experiencing a dull burning back pain for many years. It comes and goes, occurs almost daily and is sometimes so intense that I can barely function. It is either bilateral or unilateral and just below my rib cage along my spine. I have always considered it to be Musculoskeletal. I have been treated with chiropractic care and physical therapy… Read more »

Fredric Coe, MD
Admin

Hi Cristi, I would think your physicians might want to obtain a kidney CT in advance of surgery as stones are not at all unlikely and one might want to know about them prior to a planned surgery. Good luck, and expect a cure of the parathyroid disease. Regards, Fred Coe

Cristi
Guest
Cristi

I have been scheduled for parathyroidectomy in September and I have my first appointment with an Endocrinologist this week. I will discuss your suggestion with her. Thanks Dr Coe!

Cristi
Guest
Cristi

Just as a follow-up… My parathyroidectomy went well. There has been NO burning achy back pain since surgery!

Fredric Coe, MD
Admin

Dear Cristi, I am happy to hear this. Be sure your 24 hour urine chemistry is normal, as urine calcium can remain high despite cure of the PHPT. Regards, Fred Coe

Matt Oesterle
Guest
Matt Oesterle

In June I had a dull ache in the side that progressed into severe flank pain. After several hours it subsided and I wrote it off as something intestinal, maybe constipation. A few weeks later it happened again, but the pain lasted all day and I went to see my doctor. She examined me and we talked about it being either a kidney infection or kidney stone. She gave me a prescription for Naproxen and scheduled an ultrasound. After the ultrasound the doctors office called me back and said they had great news. The ultrasound was clear to which I… Read more »