9 Stone disease

Previous editions of this book have stated that ~10% of Caucasian men will develop a kidney stone by the age of 70. This is very much an average figure since lifetime stone risk is multifactorial, being dependent on a variety of intrinsic (inherent to the patient—sex, age, family history, comorbid conditions) and extrinsic factors (fluid intake, diet, lifestyle, climate, country of residence). In the United States of America (USA), the lifetime prevalence of stones is ~12% for men and ~7% for women. In other western countries, the lifetime risk is probably lower, but the gap between lifetime risk in the USA and that in other countries is probably narrowing as our lifestyles move closer to a USA one.

The prevalence of stone disease is increasing in all western societies. In the USA, the prevalence of stone disease increased from affecting 3.6% of the population in the period 1976–1980 to 5.2% between1988 and 1994.¹ While some of this increase may reflect better diagnostic tests (e.g. the advent of CTU) diagnosing asymptomatic stones, much of this increase is likely to be real. Certainly in the UK, rates of treatment for stones have shown a very substantial rise over the last 10y at a time when there have been no substantial changes in technology or technique of stone treatment. Thus, the use of ESWL for treating upper tract stones increased by 55% between 2000 and 2010 with a 127% increase in the number of ureteroscopic stone treatments, 49% of this increase occurring between the periods 2007–8 and 2009–10.²

Of 5047 men and women (mean age 57y) undergoing CT colonography screening in 2004–2008 and with no symptoms of stone disease, a staggering 395 (7.8%) had stones (an average of 2 stones per patient, mean stone size 3mm).³ The prevalence in men was 9.7% and in women 6.3%, but was not (surprisingly) related to diabetes, obesity, and age >60. A substantial proportion of these initially asymptomatic stones became symptomatic over time. Over 10y of follow-up, 81 of these 395 patients (21%) went on to develop at least one symptomatic stone event.

Once a stone has formed, the risk of future stone disease is very substantially increased. Within 1y of a calcium oxalate stone, 10% of men will form another calcium oxalate stone, 727–50% will have formed another stone within a mean of 7.5⁴ to 9y.⁵

Once a second stone has formed, the frequency of recurrences increases and the interval between relapses becomes smaller.

The prevalence of renal tract stone disease is determined by factors intrinsic to the individual and by extrinsic (environmental) factors. A combination of factors often contributes to risk of stone formation.

The prevalence of stone disease and incidence of new stone events is increasing. Much of this change may relate to the epidemic of obesity sweeping western societies (obesity is associated with increased urinary excretion of stone-promoting substances, e.g. calcium, oxalate, uric acid, and decreased excretion of stone-preventing substances, e.g. citrate). Obese patients have a lower urinary pH which encourages urate stone formation.

Stones may be classified according to composition (Table 9.1), X-ray appearance, size, and shape.

Other rare stone types (all of which are radiolucent): indinavir (a protease inhibitor used for treatment of HIV), triamterene (a relatively insoluble potassium-sparing diuretic, most of which is excreted in urine), xanthine.

Three broad categories of stones are described, based on their X-ray appearance. This gives some indication of the likely stone composition and helps, to some extent, to determine treatment options. However, in only 40% of cases is the stone composition correctly identified from visual estimation of the radiodensity on plain X-ray.¹

Opacity implies the presence of substantial amounts of calcium within the stone. Calcium phosphate stones are the most radiodense stones, being almost as dense as bone. Calcium oxalate stones are slightly less radiodense.

Cystine stones are relatively radiodense because they contain sulphur (Fig. 9.1). Magnesium ammonium phosphate (struvite) stones are less radiodense than calcium-containing stones.

Uric acid, triamterene, xanthine, indinavir (cannot be seen even on CTU, hence if suspected, confirm by IVU).

Stones can be characterized by their size, in mm or cm. Stones which grow to occupy the renal collecting system (the pelvis and one or more renal calyces) are known as staghorn calculi since they resemble the horns of a stag (Fig. 9.2). They are most commonly composed of struvite—magnesium ammonium phosphate (being caused by infection and forming under the alkaline conditions induced by urea-splitting bacteria), but may be composed of uric acid, cystine, or calcium oxalate monohydrate.

The driving force behind stone formation is the supersaturation of urine. Supersaturation is expressed as the ratio of urinary calcium oxalate (for example) to its solubility. Below a supersaturation of 1, crystals of calcium oxalate remain soluble. Above a supersaturation of 1, crystals of calcium oxalate nucleate and grow, thereby promoting stone formation.

Urine is said to be saturated with, for example, calcium and oxalate when the product of the concentrations of calcium and oxalate exceeds the solubility product (K_sp). Below K_sp, crystals of calcium and oxalate will not form and the urine is said to be undersaturated. Above K_sp, crystals of calcium and oxalate should form, but they do not because of the presence of inhibitors of crystal formation. However, above a certain concentration of calcium and oxalate, inhibitors of crystallization become ineffective and crystals of calcium oxalate start to form. The concentration of calcium and oxalate at which this is reached (i.e. at which crystallization starts) is known as the formation product (K_f) and the urine is said to be supersaturated with the substance or substances in question at concentrations above this level. Urine is described as being metastable for calcium and oxalate at concentrations between the K_sp of calcium and oxalate and the K_f (Box 9.1).

The ability of urine to hold more solute in solution than can pure water is due partly to the presence of various inhibitors of crystallization (e.g. citrate forms a soluble complex with calcium, preventing it from combining with oxalate or phosphate to form calcium oxalate or calcium phosphate stones). Other inhibitors of crystallization include magnesium, glycosaminoglycans, and Tamm–Horsfall protein. From a practical perspective, the only inhibitor of stone formation that is open to manipulation is citrate.

Periods of intermittent supersaturation of urine with various substances can occur as a consequence of dehydration and following meals.

The earliest phase of crystal formation is known as nucleation. Crystal nuclei usually form on the surfaces of epithelial cells or on other crystals. Crystal nuclei form into clumps—a process known as aggregation. Citrate and magnesium not only inhibit crystallization, but also inhibit aggregation. Calcium oxalate stones form over a nucleus of calcium phosphate (Randall’s plaques on the surface of a renal papilla).

Although most patients with calcium oxalate stones have at least one metabolic abnormality (e.g. hypercalciuria, hyperoxaluria, hypocitatruria), the majority of calcium oxalate stones are idiopathic, i.e. the cause of that metabolic abnormality is unknown.

Hypercalciuria: excretion of >7mmol of calcium per day in men and >6mmol per day in women. The major metabolic risk factor for calcium oxalate stone formation is that it increases the relative supersaturation of urine. Some series suggest that as many as 50% of patients with calcium stone disease have hypercalciuria although the proportion of hypercalciuric patients in other series is lower. There are three types:

Diet has a major influence on hypercalciuria.

Hypercalcaemia: almost all patients with hypercalcaemia who form stones have primary hyperparathyroidism. Of hyperparathyroid patients, about 1% form stones (the other 99% do not because of early detection of hyperparathyroidism by screening serum calcium).

Hyperoxaluria: is due to the following.

Ascorbic acid and high protein intake increase oxalate production.

Hypocitraturia: citrate forms a soluble complex with calcium (so-called chelation), thus preventing the complexing of calcium with oxalate to form calcium oxalate stones. Distal renal tubular acidosis, hypokalaemia, and carbonic anhydrase inhibitors lead to hypocitatruria.

Hyperuricosuria: high urinary uric acid levels lead to the formation of uric acid crystals on the surface of which calcium oxalate crystals form.

Humans (unlike birds) are unable to convert uric acid (which is relatively insoluble) into allantoin (which is very soluble). Human urine is supersaturated with insoluble uric acid. Uric acid exists in two forms in urine—uric acid and sodium urate. Sodium urate is 20 times more soluble than uric acid. At a urine pH of 5, <20% of uric acid is present as soluble sodium urate. At urine pH 5.5, half of the uric acid is ionized as sodium urate (soluble) and half is non-ionized as free uric acid (insoluble). At a urine pH of 6.5, >90% of uric acid is present as soluble sodium urate. Thus, uric acid is essentially insoluble in acid urine and soluble in alkaline urine. Human urine is acidic (because the end products of metabolism are acid) and this low pH, combined with supersaturation of urine with uric acid, predisposes to uric acid stone formation.

About 20% of patients with gout have uric acid stones. Patients with uric acid stones may have:

Occur in patients with renal tubular acidosis (RTA)—a defect of renal tubular H⁺ secretion resulting in an impaired ability of the kidney to acidify urine. The urine is, therefore, of high pH and the patient has a metabolic acidosis. The high urine pH increases supersaturation of the urine with calcium and phosphate, leading to their precipitation as stones.

Types of renal tubular acidosis

If urine pH is >5.5, use the ammonium chloride loading test. Urine pH that remains above 5.5 after an oral dose of ammonium chloride = incomplete distal RTA.

These stones are composed of magnesium, ammonium, and phosphate. They form as a consequence of urease-producing bacteria which produce ammonia from the breakdown of urea (urease hydrolyses urea to carbon dioxide and ammonium) and in so doing, alkalinize urine as in the following equation:

Under alkaline conditions, crystals of magnesium, ammonium, and phosphate precipitate.

Occur only in patients with cystinuria—an inherited (autosomal recessive) disorder of transmembrane cystine transport, resulting in decreased absorption of cystine from the intestine and in the proximal tubule of the kidney. Cystine is very insoluble so reduced absorption of cystine from the proximal tubule results in supersaturation with cystine and cystine crystal formation. Cystine is poorly soluble in acid urine (300mg/L at pH 5, 400mg/L at pH 7).

Determination of stone type and a metabolic evaluation allows the identification of the factors that led to stone formation so advice can be given to prevent future stone formation.

Metabolic evaluation depends, to an extent, on the stone type (Table 9.2). In many cases, a stone is retrieved. Stone type is analysed by polarizing microscopy, X-ray diffraction, and infrared spectroscopy rather than by chemical analysis. Where no stone is retrieved, its nature must be inferred from its radiological appearance (e.g. a completely radiolucent stone is likely to be composed of uric acid) or from more detailed metabolic evaluation.

In most patients, multiple factors are involved in the genesis of kidney stones and as a general guide, the following evaluation is appropriate in most patients.

Patients can be categorized as low risk and high risk for subsequent stone formation. High risk: previous history of a stone (i.e. multiple stone formers), bilateral stones, family history of stones, GI disease, uric acid stones or gout, chronic UTI, nephrocalcinosis, patients with solitary kidneys, staghorn calculi, children and young adults.

U & E, FBC (to detect undiagnosed haematological malignancy), serum calcium (corrected for serum albumin) and uric acid, urine culture, urine dipstick for pH.

As for low-risk patients plus 24h urine for calcium, oxalate, uric acid, cystine; evaluation for RTA.

Urine pH in normal individuals shows variation from pH 5–7. After a meal, pH is initially acid because of acid production from metabolism of purines (nucleic acids in, for example, meat). This is followed by an ‘alkaline tide’, pH rising to >6.5. Urine pH can help establish what type of stone the patient may have (if a stone is not available for analysis) and can help the urologist and patient in determining whether preventative measures are likely to be effective or not.

Evaluate for RTA if: calcium phosphate stones, bilateral stones, nephro-calcinosis, MSK, hypocitraturia.

Cyanide–nitroprusside colorimetric test (‘cystine spot test’): if positive, a24h urine collection is done. A 24h cystine >250mg is diagnostic of cystinuria.¹

Kidney stones may present with symptoms or be found incidentally during investigation of other problems. Presenting symptoms include pain or haematuria (microscopic or occasionally macroscopic). Struvite staghorn calculi classically present with recurrent UTIs. Malaise, weakness, and loss of appetite can also occur. Less commonly, struvite stones present with infective complications (pyonephrosis, perinephric abscess, septicaemia, xanthogranulomatous pyelonephritis).

The traditional indications for intervention are pain, infection, and obstruction. Haematuria caused by a stone is only very rarely severe or frequent enough to be the only reason to warrant treatment.

Before embarking on treatment of a stone which you think is the cause of the patient’s pain or infections, warn them that though you may be able to remove the stone successfully, their pain or infections may persist (i.e. the stone may be coincidental to their pain or infections which may be due to something else). Remember, UTIs are common in women as are stones and it is not, therefore, surprising that the two may coexist in the same patient, but be otherwise unrelated.

Options for stone management are watchful waiting, ESWL, flexible ureteroscopy, PCNL, open surgery, and medical ‘dissolution’ therapy.

It is not necessary to treat every kidney stone. As a rule of thumb, the younger the patient, the larger the stone and the more symptoms it is causing, the more inclined we are to recommend treatment. Thus, one would be inclined to do nothing about a 1cm symptomless stone in the kidney of a patient aged 95y. On the other hand, a 1cm stone in a symptomless patient aged 20y runs the risk over the remaining (many) years of the patient’s life of causing problems. It could drop into the ureter, causing ureteric colic or it could increase in size and affect kidney function or cause pain.

The results of observational studies are conflicting, some suggesting most renal stones progress—increase in size, cause symptoms, or require intervention while others suggest many do not. In a series of 80 calyceal stones followed over 7.5y (stone size not reported), 45% of the stones increased in size and the authors concluded that 80% would require intervention within 5y.¹ Conversely, 68% of patients with small renal stones remained asymptomatic over 2.5y in Glowacki’s study² and in Keeley’s RCT of ESWL vs watchful waiting for small calyceal stones, only 9% required surgery over an average follow-up of 2y.³

Burgher’s paper⁴ is helpful because it relates the risk of intervention to stone size and location, allowing a more tailored approach to decision making. Asymptomatic stones followed over a 3y period were more likely to require intervention (surgery or ESWL) or to increase in size or cause pain if they were >4mm in diameter or if located in a middle or lower pole calyx.⁴ The approximate risks over 3y of follow-up of requiring intervention, developing pain, or of increase in stone size relative to stone size is shown in Table 9.3.

Another factor determining the need for treatment is the patient’s job. Airline pilots are not allowed to fly if they have kidney stones for fear that the stones could drop into the ureter at 30 000 ft with disastrous consequences! They will only be deemed fit to fly when they are radiologically stone-free. It is sensible to warn any one whose job entrusts them with the safety of others (pilots, train drivers, drivers of buses and lorries) that they are not fit to carry out these occupations until stone-free or, at the very least, that they should contact the relevant regulatory authority to seek guidance (the Civil Aviation Authority (CAA) for pilots and the Drivers Vehicle Licensing Agency (DVLA) for drivers).⁵

Some stones are definitely not suitable for watchful waiting. Untreated struvite (i.e. infection-related) staghorn calculi will eventually destroy the kidney if untreated and are a significant risk to the patient’s life. Watchful waiting is, therefore, NOT recommended for staghorn calculi unless patient comorbidity is such that surgery would be a higher risk than watchful waiting. Historical series suggest that somewhere between 9 and 30% of patients with staghorn calculi who did not undergo surgical removal (from choice or because of comorbidity) died of renal-related causes—renal failure, urosepsis (septicaemia, pyonephrosis, perinephric abscess).⁶,⁷,⁸ A combination of a neurogenic bladder and staghorn calculus seems to be particularly associated with a poor outcome.⁹

The technique of focusing externally generated shock waves at a target (the stone). First used in humans in 1980. The first commercial lithotriptor, the Dornier HM3, became available in 1983.¹ ESWL revolutionized kidney and ureteric stone treatment.

Three methods of shock wave generation are commercially available—electrohydraulic, electromagnetic, and piezoelectric.

Electrohydraulic: application of a high voltage electrical current between two electrodes about 1mm apart under water causes discharge of a spark. Water around the tip of the electrode is vaporized by the high temperature, resulting in a rapidly expanding gas bubble. The rapid expansion and then the rapid collapse of this bubble generate a shock wave that is focused by a metal reflector shaped as a hemiellipsoid. Used in the original Dornier HM3 lithotriptor.

Electromagnetic: two electrically conducting cylindrical plates are separated by a thin membrane of insulating material. Passage of an electrical current through the plates generates a strong magnetic field between them, the subsequent movement of which generates a shock wave. An ‘acoustic’ lens is used to focus the shock wave.

Piezoelectric: a spherical dish is covered with about 3000 small ceramic elements, each of which expands rapidly when a high voltage is applied across them. This rapid expansion generates a shock wave.

X-ray, USS, or a combination of both are used to locate the stone on which the shock waves are focused. Older machines required general or regional anaesthesia because the shock waves were powerful and caused severe pain. Newer lithotriptors generate less powerful shock waves, allowing ESWL with oral or parenteral analgesia in many cases, but they are less efficient at stone fragmentation.

The likelihood of fragmentation with ESWL depends on the stone size and location, anatomy of renal collecting system, degree of obesity, and stone composition. Most effective for stones <1cm in diameter and in favourable anatomical locations. Less effective for stones >1cm diameter, in lower pole stones in a calyceal diverticulum (poor drainage), and those composed of cystine or calcium oxalate monohydrate (very hard).

Randomized studies show that a lower shock wave rate (60 vs 120 per min) achieves better stone fragmentation and clearance. Animal studies also demonstrate less renal injury and a smaller decrease in renal blood flow from lower shock wave rates.²

There have been no randomized studies comparing stone-free rates between different lithotriptors. In non-randomized studies, rather surprisingly, when it comes to the efficacy of stone fragmentation, older (the original Dornier HM3 machine) is better (but with a higher requirement for analgesia and sedation or general anaesthesia). Less powerful (modern) lithotriptors have lower stone-free rates and higher retreatment rates.

ESWL causes a certain amount of structural and functional renal damage (found more frequently the harder you look). Haematuria (microscopic, macroscopic—due to the rupture of intraparencyhmal vessels) and oedema are common, perirenal haematomas less so (0.5% detected on USS with modern machines, although reported in as many as 30% with the Dornier HM3). Effective renal plasma flow (measured by renography) has been reported to fall in ~30% of treated kidneys.

Renal injury during ESWL is significantly reduced by slowing the rate of shock wave delivery from 120 to 30 shock waves per min.³

There are data suggesting that ESWL may increase the likelihood of development of hypertension. Acute renal injury may be more likely to occur in patients with pre-existing hypertension, prolonged coagulation time, coexisting coronary heart disease, diabetes, and in those withsolitary kidneys. A retrospective case control study with 19y follow-up has raised the possibility that ESWL may cause pancreatic damage, leading to a higher risk of diabetes—diabetes developed in 16.8% of patients undergoing ESWL vs 6.6% of controls.⁴

Is ESWL more effective in the absence of pre-ESWL stenting? Probably yes.⁵ Does pre-ESWL stenting reduce the risk of ESWL complications? Probably not. When ESWL was first introduced, stones of all sizes were treated. It soon became apparent that multiple fragments from large stones could obstruct the ureter, causing a so-called steinstrasse (incidence of steinstrasse 2–3% for stones 1.5–2cm diameter; 56% for stones 3–3.5cm).

Whether stenting prior to ESWL can reduce the risk of steinstrasse remains controversial. Pre-ESWL stenting does not reduce the chances of spontaneous resolution of the steinstrasse (spontaneous passage of the stones). We nowadays see steinstrasse only rarely because ESWL tends to be reserved for smaller stones (<2cm) and PCNL for larger stones. Steinstrasse is managed expectantly (since 50% will resolve spontaneously), with ESWL of the so-called ‘lead’ fragment or ureteroscopy being required where the stones fail to pass.

The overall consensus is that pre-ESWL stenting is probably not necessary in most cases. For patients with solitary kidneys undergoing ESWL, prestenting is an option to reduce the risk of renal obstruction. The alternative is closer monitoring in the days and weeks after ESWL and emergency ureteroscopy where anuria develops.

Absolute contraindications: pregnancy, uncorrected blood clotting disorders (including anticoagulation); known renal artery stenosis.

Telescopic surgery, open surgery, or observation to allow spontaneous passage.

Clinically insignificant residual fragments (CIRFs) are residual stone fragments 4mm in size or less after ESWL. ‘Clinically insignificant’ is something of a misnomer for 12–46% of such fragments will increase in size over a period of 2–3y.⁶,⁷,⁸,⁹¹⁰ Given that there is a significant risk of increase in stone size and given our knowledge that stones that grow are likely to continue to do so and, therefore, require intervention or to become symptomatic and so require intervention, radiological follow-up of such patients seems to be sensible. How (plain X-ray if the stones are visible, USS or CT), how often and by whom (in primary care or by urologists) are contentious issues?

The first technique developed for intracorporeal lithotripsy. A high voltage applied across a concentric electrode under water generates a spark. This vaporizes water and the subsequent expansion and collapse of the gas bubble generates a shock wave. An effective form of stone fragmentation. The shock wave is not focused so the EHL probe must be applied within 1mm of the stone to optimize stone fragmentation.

EHL has a narrower safety margin than pneumatic, ultrasonic, or laser lithotripsy and should be kept as far away as possible from the wall of the ureter, renal pelvis, or bladder to limit damage to these structures and at least 2mm away from the cystoscope, ureteroscope, or nephroscope to prevent lens fracture.

Principal uses: bladder stones (wider safety margin than in the narrower ureter).

A metal projectile contained within the handpiece is propelled backwards and forwards at great speed by bursts of compressed air (Fig. 9.4a). It strikes a long, thin, metal probe at one end of the handpiece at 12Hz (12 strikes per second) transmitting shock waves to the probe which, when in contact with a rigid structure such as a stone, fragments the stone. Used for stone fragmentation in the ureter (using a thin probe to allow insertion down a ureteroscope) or kidney (a thicker probe may be used, with an inbuilt suction device—‘Lithovac’—to remove stone fragments).

Pneumatic lithotripsy is very safe since the excursion of the end of the probe is about 1mm and it bounces off the pliable wall of the ureter. Ureteric perforation is, therefore, rare. Also low cost and low maintenance. However, its ballistic effect has a tendency to cause stone migration into the proximal ureter or renal pelvis where the stone may be inaccessible to further treatment. The metal probe cannot bend around corners so it cannot be used for ureteroscopic treatment of stones within the kidney.

Principal uses: ureteric stones.

An electrical current applied across a piezoceramic plate located in the ultrasound transducer generates ultrasound waves of a specific frequency (23 000–25 000Hz). The ultrasound energy is transmitted to a hollow metal probe which, in turn, is applied to the stone (Fig. 9.4b). The stone resonates at high frequency and this causes it to break into small fragments (the opera singer breaking a glass) which are then sucked out through the centre of the hollow probe. Soft tissues do not resonate when the probe is applied to them and, therefore, are not damaged. Can only be used down straight instruments.

Principal uses: fragmentation of renal calculi during PCNL.

The holmium:YAG laser. Principally, a photothermal mechanism of action, causing stone vaporization. Minimal shock wave generation and, therefore, less risk of causing stone migration. The laser energy is delivered down fibres which vary in diameter from 200 to 360μm. The 200μm fibre is very flexible and can be used to gain access to stones even within the lower pole of the kidney (Figs. 9.5 and 9.6). A 275μm fibre delivers more laser energy at the expense of a reduction in flexibility and, therefore, a reduced chance of lower pole access. The zone of thermal injury is limited from 0.5 to 1mm from the laser tip. No stone can withstand the heat generated by the Ho:YAG laser. Laser lithotripsy takes time, however, since the thin laser fibre must be ‘painted’ over the surface of the stone to vaporize it.

Principal uses: ureteric stones, small intrarenal stones.

The development of small calibre ureteroscopes with active deflecting mechanisms and instrument channels, in combination with the development of laser technology, small diameter laser fibres, and stone baskets and graspers, has opened the way for intracorporeal, endoscopic treatment of kidney stones. Access to virtually the entire collecting system is possible with modern instruments. The holmium:YAG laser has a minimal effect on tissues at distances of 2–3mm from the laser tip and so ‘collateral’ tissue damage is minimal with this laser type.

Flexible ureteroscopy and laser fragmentation offer a more effective treatment option compared with ESWL, with a lower morbidity than PCNL, but usually requires a general anaesthetic (some patients will tolerate it with sedation alone). It can also allow access to areas of the kidney where ESWL is less efficient or where PCNL cannot reach. It is most suited to stones <2cm in diameter.

Efficacy diminishes as stone burden increases—it simply takes a long time to ‘paint’ the surface of the stone with laser energy so destroying it. A dust cloud is produced as the stone fragments and this temporarily obscures the view until it has been washed away by irrigation. Stone fragmentation rates for those expert in flexible ureteroscopy (not every stone surgeon will be able to achieve these results) are 770–80% for stones <2cm in diameter and 50% for those >2cm in diameter² and ~10% of patients will require two or more treatment sessions.²

PCNL is the removal of a kidney stone via a ‘track’ developed between the surface of the skin and the collecting system of the kidney. The first step requires ‘inflation’ of the renal collecting system (pelvis and calyces) with fluid or air instilled via a ureteric catheter inserted cystoscopically (Fig. 9.7). This makes subsequent percutaneous puncture of a renal calyx with a nephrostomy needle easier (Fig. 9.8). Once the nephrostomy needle is in the calyx, a guide wire is inserted into the renal pelvis to act as a guide over which the ‘track’ is dilated (Fig. 9.9). An access sheath is passed down the track and into the calyx and through this, a nephroscope can be advanced into the kidney (Fig. 9.10). An ultrasonic lithotripsy probe is used to fragment the stone and remove the debris.

A posterior approach is most commonly used, below the 12th rib (to avoid the pleura and far enough away from the rib to avoid the intercostals, vessels, and nerve). The preferred approach is through a posterolateral calyx rather than into the renal pelvis because this avoids damage to posterior branches of the renal artery which are closely associated with the renal pelvis. General anaesthesia is usual, though regional or even local anaesthesia (with sedation) can be used.

PCNL is generally recommended for stones >3cm in diameter, those that have failed ESWL, and/or an attempt at flexible ureteroscopy and laser treatment. It is the first-line option for staghorn calculi,¹ with ESWL and/or repeat PCNL being used for residual stone fragments. For staghorn stones, the stone-free rate of PCNL, when combined with post-operative ESWL for residual stone fragments, is in the order of 80–85%.

For middle and upper pole stones 2–3cm in diameter, options include ESWL (with a JJ stent in situ), flexible ureteroscopy and laser treatment, and PCNL. PCNL gives the best chance of complete stone clearance with a single procedure, but this is achieved at a higher risk of morbidity. Some patients will opt for several sessions of ESWL or flexible ureteroscopy/laser treatment and the possible risk of ultimately requiring PCNL because of failure of ESWL or laser treatment rather than proceeding with PCNL ‘up front’. About 50% of stones >2cm in diameter will be fragmented by flexible ureteroscopy and laser treatment.

For lower pole stones PCNL achieves substantially higher stone clearance than ESWL for all stones sizes (<1cm, 100% vs 63%; 1–2cm, 93% vs 23%; >2–3cm, 86% vs 14%)². It is also achieves superior stone-free rates compared to flexible ureteroscopy/laser treatment for lower pole stones between 1–2.5cm (71% vs 37%).³ Again, better stone-free rates must be balanced against higher morbidity.

PCNL is traditionally followed by the placement of a large bore nephrostomy tube, the rationale being to tamponade bleeding from the track (less frequently, the tube is used to keep the track patent to allow the option of check nephroscopy if post-operative imaging—a CT scan or nephrostogram—demonstrates residual stone). The disadvantage is more post-operative pain and requirement for analgesics and longer hospital stay (though some reports suggest tubed PCNL does not increase any of these parameters). As a consequence, tubeless PCNL is now in vogue—tubeless meaning no nephrostomy tube, but usually some form of ureteric drainage, e.g. a J stent or ureteric catheter (i.e. ‘tubeless’ PCNL is actually ‘relatively tubeless’; there are occasional reports of ‘totally tubeless’ PCNL).

The use of track sealants has been suggested, but there is no convincing proof that they reduce bleeding or urinary extravasation. Track diathermy and cryoablation (a 10min freeze–thaw cycle) have also been reported.

A recent review⁴ suggests that tubeless PCNL should be the default, but that the decision to place a tube should be individualized—partly based on the surgeon’s experience and erring on the side of tube placement in cases with more than two access tracks; infection stones (most staghorns); significant intraoperative bleeding; collecting system perforation (though one could argue that antegrade J stent insertion or ureteric catheter drainage might be just as effective); where a second look is anticipated (e.g. especially large stone burden).

Traditionally, PCNL is performed in the prone position (once access to the renal collecting system has been gained with the patient in the supine position, the patient is turned from supine to prone after the initial ureteric catheterization). ‘Supine’ PCNL (keeping the patient in the supine position throughout the procedure, rotated to one or other side to allow access to the appropriate flank) has recently been proposed as an alternative approach, the potential advantages being:⁵ (1) reduced operating time (no time is wasted turning the patient), (2) lower anaesthetic morbidity (the prone position reduces cardiac output), (3) easier management of airway problems (it is difficult to access the airway in a prone patient), (4) should haemorrhage occur, arterial and central venous line insertion is easier, (5) it allows the potential for manipulating the renal stone burden not only percutaneously, but also ureteroscopically (the argument being that a ‘two-handed’ approach is better than a one-handed one). Whether the supine position will become the preferred option remains to be seen.

It is more difficult to achieve a stone-free status for lower pole kidney stones compared with stones in the upper and middle pole calyces because of poor clearance of stone fragments from the dependent lower pole. Lower Pole I¹ and another randomized study comparing stone-free rates for lower pole stones treated either by flexible ureterorenoscopy vs ESWL or flexible ureterorenoscopy vs PCNL inform treatment decisions (Tables 9.4 and 9.5).

The convenience of ESWL over flexible ureterorenoscopy (outpatient procedure, no anaesthetic, much shorter recovery time) means that many patients prefer ESWL over flexible ureterorenoscopy if given the choice. Comparing flexible ureterorenoscopy vs PCNL, stone-free rates strongly favour PCNL. For stones <3cm, convalescence time is similar.

For the 1cm or smaller stones, ESWL or flexible ureterorenoscopy are reasonable first-line approaches, but warn the patient that stone clearance is relatively low for both (35% vs 50%).

For stones between 1 and 2cm, PCNL achieves higher clearance rates, although the potential for morbidity is higher. In the above well-designed study, flexible ureterorenoscopy was able to clear stones in only one-third of patients (no doubt this relatively low success rate was due to the use of very accurate non-enhanced CT scanning to determine stone-free status 3 months after treatment as opposed to plain radiography).⁶

For stones >2cm, PCNL achieves higher clearance rates than any other modality.

Where the kidney is not working, the stone may be left in situ if it is not causing symptoms (e.g. pain, recurrent urinary infection, haematuria). However, staghorn calculi should be removed unless the patient has comorbidity that would preclude safe surgery because of the substantial risk of developing serious infective complications. If the kidney is non-functioning, the simplest way of removing the stone is to remove the kidney.

Wound infection (the stones operated on are often infection stones), flank hernia, wound pain. (With PCNL these problems do not occur, blood transfusion rate is lower, analgesic requirement is less, mobilization is more rapid, and discharge earlier—all of which account for PCNL having replaced open surgery as the mainstay of treatment of large stones.) There is a significant chance of stone recurrence after open stone surgery (as for any other treatment modality) and the scar tissue that develops around the kidney will make subsequent open stone surgery technically more difficult.

Uric acid and cystine stones are potentially suitable for dissolution therapy. Calcium within either stone type reduces the chances of successful dissolution.

Urine is frequently supersaturated with uric acid (derived from a purine-rich diet, i.e. animal protein). Fifty percent of patients who form uric acid stones have gout. The other 50% do so because of a high protein and low fluid intake (‘western’ lifestyle). In patients with gout, the risk of developing stones is 71% per year after the first attack of gout.

Uric acid stones form in concentrated acid urine. Dissolution therapy is based on hydration, urine alkalinization, allopurinol, and dietary manipulation—the aim being to reduce urinary uric acid saturation. Maintain a high fluid intake (urine output 2–3L/day), ‘alkalinize’ the urine to pH 6.5–7 (sodium bicarbonate 650mg tds or qds or potassium citrate 30–60mEq day, equivalent to 15–30mL of a potassium citrate solution tds or qds). In those with hyperuricaemia or urinary uric acid excretion >1200mg/day, add allopurinol 300–600mg/day (inhibits the conversion of hypoxanthine and xanthine to uric acid). Dissolution of large stones (even staghorn calculi) is possible with this regimen.

Cystinuria is an inherited kidney and intestinal transepithelial transport defect for the amino acids cystine, ornithine, arginine, and lysine (‘COAL’), leading to excessive urinary excretion of cystine. Autosomal recessive inheritance; prevalence of 1 in 700 are homozygous (i.e. both genes defective); occurs equally in both sexes. About 3% of adult stone formers are cystinuric and 6% of stone-forming children.

Most cystinuric patients excrete about 1g of cystine per day, which is well above the solubility of cystine. Cystine solubility in acid solutions is low (300mg/L at pH 5, 400mg/L at pH 7). Patients with cystinuria present with renal calculi, often in their teens or twenties. Cystine stones are relatively radiodense because they contain sulphur atoms. The cyanide nitroprusside test will detect most homozygote stone formers and some heterozygotes (false positives occur in the presence of ketones).

The aim is to:

D-penicillamine, N-acetyl-D-penicillamine, and mercaptopropionylglycine (Tiopronin) bind to cysteine as does captopril—the compounds so formed are more soluble in urine than is cystine alone. D-penicillamine has potentially unpleasant and serious side effects (allergic reactions, nephrotic syndrome, pancytopenia, proteinuria, epidermolysis, thrombocytosis, hypogeusia). Therefore, reserved for cases where alkalinization therapy and high fluid intake fail to dissolve the stones.

Cystine stones are very hard and are, therefore, relatively resistant to ESWL. Nonetheless, for small cystine stones, a substantial proportion will still respond to ESWL. Flexible ureteroscopy (for small) and PCNL (for larger) cystine stones are used where ESWL fragmentation has failed.

Ureteric stones usually present with sudden onset of severe flank pain which is colicky (waves of increasing severity are followed by a reduction in severity, but it seldom goes away completely). It may radiate to the groin as the stone passes into the lower ureter. About 50% of patients with classic symptoms for a ureteric stone do not have a stone confirmed on subsequent imaging studies nor do they physically ever pass a stone.

Spend a few seconds looking at the patient. Ureteric stone pain is colicky—the patient moves around, trying to find a comfortable position. They may be doubled up with pain. Patients with conditions causing peritonitis (e.g. appendicitis, a ruptured ectopic pregnancy) lie very still: movement and abdominal palpation are very painful.

Arrange a pregnancy test in premenopausal women (this is mandatory in any premenopausal woman who is going to undergo imaging using ionizing radiation). If positive, refer to a gynaecologist; if negative, arrange imaging to determine whether they have a ureteric stone.

Many patients with ureteric stones have dipstick or microscopic haematuria (and more rarely, macroscopic haematuria), but 10–30% have no blood in their urine.¹,² The sensitivity of dipstick haematuria for detecting ureteric stones presenting acutely is ~95% on the first day of pain, 85% on the second day, and 65% on the third and fourth days.² Therefore, patients with a ureteric stone whose pain started 3–4 days ago may not have blood detectable in their urine. Dipstick testing is slightly more sensitive than urine microscopy for detecting stones (80% vs 70%) because blood cells lyse and, therefore, disappear if the urine specimen is not examined under the microscope within a few hours. Both ways of detecting haematuria have roughly the same specificity for diagnosing ureteric stones (~60%).

Remember, blood in the urine on dipstick testing or microscopy may be a coincidental finding because of non-stone urological disease (e.g. neoplasm, infection) or a false positive test (no abnormality is found in ~70% of patients with microscopic haematuria despite full urological investigation).

The most important aspect of examination in a patient with a ureteric stone confirmed on imaging is to measure their temperature. If the patient has a stone and a fever, they may have infection proximal to the stone. A fever in the presence of an obstructing stone is an indication for urine and blood culture, IV fluids and antibiotics, and nephrostomy drainage or J stent insertion if the fever does not resolve within a matter of hours.¹,²

The IVU, for many years the mainstay of imaging in patients with flank pain, has been superseded by CT-KUB, an unenhanced (i.e. no contrast) CT of the kidneys, ureters, and bladder (except in the rare situation of suspected indinavir stones which are not visible on CT-KUB) (Fig. 9.11). Compared with IVU, CT-KUB:

CT-KUB radiation dose: approximately 4.7mSv compared to 1.5mSv for IVU (fatal cancer risk is estimated at 1 in 2000 for a 10mSv radiation exposure). Ultra-low dose CT (ULDCT) lowers radiation exposure (0.6–2mSv), but at the expense of a lower sensitivity (68–86%) for small (<3mm) ureteric stones. Contrast-enhanced ultra-low dose CT (CEULDCT) uses contrast which increases sensitivity (97%) and specificity (100%) for detecting small ureteric stone disease while limiting radiation dose to levels comparable with IVU (1.7mSv vs 1.4mSv).⁴

If you only have access to IVU, remember it is contraindicated in patients with previous contrast reactions. Avoid in those with hay fever, a strong history of allergies or asthma who have not been pretreated with high-dose steroids 24h before the IVU. Patients taking metformin for diabetes should stop this for 48h prior to an IVU. Clearly, being able to perform an alternative test such as CT-KUB in such patients is very useful.

Where 24h CT-KUB access is not available, admit patients with suspected ureteric colic for pain relief and arrange a CT-KUB the following morning. When CTU is not immediately available, we arrange urgent abdominal ultrasonography in all patients aged >50y who present with flank pain suggestive of a possible stone to exclude serious pathology, e.g. a leaking abdominal aortic aneurysm and to demonstrate any other gross abnormalities due to non-stone associated flank pain.

Plain abdominal X-ray and renal USS are not sufficiently sensitive or specific for their routine use for diagnosing ureteric stones.

Very accurate for identifying ureteric stones.⁵ However, at the present time, cost and restricted availability limit its usefulness as a routine diagnostic method of imaging in cases of acute flank pain. This may change as MR scanners become more widely available.

While appropriate imaging studies are being organized, pain relief should be given.

There is no need to encourage the patient to drink copious amounts of fluids nor to give them large volumes of fluids intravenously in the hope that this will ‘flush’ the stone out. In a randomized trial of forced IV hydration vs minimal hydration, there was no significant difference in analgesic requirement, pain scores, or spontaneous stone passage rates.¹

Renal blood flow and urine output from the affected kidney falls during an episode of acute partial obstruction due to a stone. Excess urine output will tend to cause a greater degree of hydronephrosis in the affected kidney, which may make ureteric peristalsis^* even less efficient than it already is.

The exception to this rule may be those with radiolucent uric acid stones (suspected if low urinary pH and stones not visible on plain X-ray or with lower attenuation on CT compared with calcium, cystine, and struvite stones). High fluid intake and oral potassium citrate, sodium citrate, or sodium bicarbonate (to elevate urine pH to 6–7) may dissolve uric acid stones or at least reduce their size so increasing stone spontaneous passage rates.

In many instances, small ureteric stones will pass spontaneously within days or a few weeks, with analgesic supplements for exacerbations of pain.

Data on the rate of spontaneous stone passage are surprisingly limited.² Chances of spontaneous stone passage depend principally on stone size. Sixty-eight percent of stones 5mm or less will pass spontaneously (95% CI 46–85%; meta-analysis of 224 patients); 47% of stones 6–10mm in diameter will pass spontaneously (95% CI 36–59%; meta-analysis of 104 patients).² Average time for spontaneous stone passage for stones 4–6mm in diameter is 3 weeks.³ Stones that have not passed in 2 months are unlikely to do so. Of those stones that do eventually pass, those 2mm or less do so within 30 days and those 2–6mm in size do so within 40 days (but not all stones do pass and we cannot predict the chance of spontaneous passage in the individual patient). Therefore, accurate determination of stone size (on plain abdominal X-ray or by CTU) helps predict chances of spontaneous stone passage.

There is growing evidence for the efficacy of MET, the preferred agents being the smooth muscle relaxing A1-adrenergic adrenoceptor blockers.²,⁴ These increase spontaneous stone passage rates, reduce stone passage time, and reduce frequency of ureteric colic.⁴ The EAU/AUA Nephrolithiasis Guideline Panel meta-analysis showed that 29% more patients (CI: 20–37%) taking tamsulosin passed their stones compared with controls.² Tamsulosin has been most studied in this setting, but terazosin and doxazosin seem to be equally effective. Whether stones in all segments of the ureter are equally responsive to A-blockers remains to be determined.

Another meta-analysis (7 studies, 484 patients)⁵ suggests that tamsulosin also seems to encourage stone clearance after ESWL for ureteric (and possibly renal) stones, the pooled absolute risk difference being between 16–19% (0.2 vs 0.4mg) in favour of tamsulosin (so if 70% pass their stones spontaneously without tamsulosin, 89% pass their stones while on 0.4mg tamsulosin). Five patients needed to be treated with tamsulosin to achieve stone clearance in one. There was a mean difference of 8 days in terms of time to stone expulsion in favour of those on tamsulosin.

In the same meta-analysis, there was no significant difference in stone passage rates between those taking the calcium channel blocker, nifedipine, and control patients.

Glyceryl trinitrate patches do not aid stone passage or reduce the frequency of pain episodes and corticosteroids are of minimal, if any, benefit.⁴,⁶

A trial of MET is a very reasonable approach for many patients, but individual circumstances may dictate ‘up front’ ESWL or ureteroscopy, e.g. the possible disruption to work and daily living activities from episodes of pain occurring while a stone is progressing towards eventual spontaneous passage may prompt the patient to request ESWL or ureteroscopy (e.g. commercial airline pilots cannot fly until stone-free nor can those who fly for leisure).

MET is contraindicated where there is clinical evidence of sepsis (essentially fever) or deteriorating renal function. If you use a trial of MET, warn patients of the risks (drug side effects, possible need for intervention in the form of ESWL, ureteroscopy, or J stenting) and mention it is an ‘off-label’ (i.e. non-licensed) therapy. Arrange periodic follow-up imaging (usually a plain X-Ray) to monitor stone position.

Where the pain of a ureteric stone fails to respond to analgesics or where renal function is impaired because of the stone, then temporary relief of the obstruction can be obtained by the insertion of a JJ stent or percutaneous nephrostomy tube. (Percutaneous nephrostomy tube can restore efficient peristalsis by restoring the ability of the ureteric wall to coapt.)

JJ stent insertion or percutaneous nephrostomy tube can be done quickly, but the stone is still present (Fig. 9.13). It may pass down and out of the ureter with a stent or nephrostomy in situ, but in many instances, it simply sits where it is and subsequent definitive treatment is still required. While JJ stents can relieve stone pain, they can cause bothersome irritative bladder symptoms (pain in the bladder, frequency, and urgency) (see Table 9.6). JJ stents do make subsequent stone treatment in the form of ureteroscopy technically easier by causing passive dilatation of the ureter.

The patient may elect to proceed to definitive stone treatment by immediate ureteroscopy (for stones at any location in the ureter) or ESWL (if the stone is in the upper and lower ureter—ESWL cannot be used for stones in the mid-ureter because this region is surrounded by bone, which prevents penetration of the shock waves) (Fig. 9.14). Local facilities and expertise will determine whether definitive treatment can be offered immediately. Not all hospitals have access to ESWL or endoscopic surgeons 365 days a year.

Antibiotic delivery into an obstructed collecting system is impaired and so the septic patient with an obstructing stone should undergo urgent decompression of the collecting system and definitive stone treatment (ESWL or ureteroscopy) should be delayed until the sepsis has resolved. The rationale for performing percutaneous nephrostomy, rather than JJ stent insertion for an infected obstructed kidney, is to reduce the likelihood of septicaemia occurring as a consequence of showering bacteria into the circulation. It has been theorized that this is more likely to occur with JJ stent insertion than with percutaneous nephrostomy insertion, that J stent insertion might damage the ureter (unlikely), and that monitoring of urine output and the facility for irrigation of a viscous pyonephrosis is possible with a nephrostomy, but with not a J stent. Nephrostomy insertion has the advantage that it avoids the need for a general anaesthetic, but in fact, J stent insertion can be done with sedation and avoids the risk of bleeding from inadvertent puncture of a branch of the renal artery.¹

The EAU/AUA Nephrolithiasis Guideline Panel² recommends that the system of drainage—J stent or percutaneous nephrostomy—is left to the discretion of the urologist since both have been shown in a randomized trial of 42 patients with obstructing stones and a temperature of >38°C and/or WBC of 17 000/mm^3* to be equally effective for the management of presumed obstructive pyelonephritis or pyonephrosis³ in terms of time to normalization of temperature and WBC (which takes approximately 2–3 days) and in-hospital stay. A 6 or 7 Ch J stent was used (with a Foley bladder catheter in 70%) or 8 Ch (occasionally larger) nephrostomy (plus a urethral catheter in 33%).

Almost 70% of stones 5mm or less and almost 50% of stones 6–10mm in diameter will pass spontaneously over a period of 3–6 weeks or thereabouts.¹ Stones that have not passed in 2 months are unlikely to do so, although much to the patient’s and surgeon’s surprise, large stones do sometimes drop out of the ureter at the last moment.

These indications need to be related to the individual patient—their stone size, their renal function, the presence of a normal contralateral kidney, their tolerance of exacerbations of pain, their job and social situation, and local facilities (the availability of surgeons with appropriate skill and equipment to perform endoscopic stone treatment).

Twenty years ago, when the only options were watchful waiting or open surgical removal of a stone (open ureterolithotomy), surgeons, and patients were inclined to ‘sit it out’ for a considerable time in the hope that the stone would pass spontaneously. Nowadays, the advent of ESWL and of smaller ureteroscopes with efficient stone fragmentation devices (e.g. the holmium laser) has made stone treatment and removal a far less morbid procedure, with a far smoother and faster post-treatment recovery. It is easier for both the patient and the surgeon to opt for intervention, in the form of ESWL or surgery, as a quicker way of relieving them of their pain and a way of avoiding unpredictable and unpleasant exacerbations of pain.

It is clearly important for the surgeon to inform the patient of the outcomes and potential complications of intervention, particularly given the fact that many of stones would pass spontaneously if left a little longer, particularly now there is evidence for MET.

Basketing of stones (blind or under radiographic ‘control’) is a historical treatment (the potential for serious ureteric injury is significant).

For the purposes of decision making with regard to treatment options, the ureter can be divided into two halves (proximal and distal to the iliac vessels) or in thirds (upper third from the PUJ to the upper edge of the sacrum; middle third from the upper to the lower edge of the sacrum, i.e. the extent of the sacroiliac joint; lower third from the lower edge of the sacrum to the VUJ).

These should be interpreted in the light of local facilities and expertise. Some hospitals have access to and expertise in the whole range of treatment options. Others may have limited access to a lithotriptor or may not have surgeons skilled in the use of the ureteroscope.

Smaller ureteroscopes with improved optics and larger instrument channels and the advent of holmium laser lithotripsy have improved the efficacy of ureteroscopic stone fragmentation (to ~95% stone clearance) and reduced its morbidity. As a consequence, many surgeons and patients will opt for ureteroscopy, with its potential for a ‘one-off?’ treatment, over ESWL where more than one treatment will be required and post-treatment imaging is required to confirm stone clearance (with ureteroscopy, you can directly see that the stone has gone).

Many urology departments do not have unlimited access to ESWL and patients may, therefore, opt for ureteroscopic stone extraction.

The stone clearance rates for ESWL are stone size-dependent. ESWL is more efficient for stones <1cm in diameter compared with those >1cm in size. Conversely, the outcome of ureteroscopy is somewhat less dependent on stone size.

The bottom line seems to be that for stones <1cm in diameter, ESWL and ureteroscopy are able to achieve virtually equivalent stone-free rates, but ureteroscopy has the edge over ESWL for stones >1cm (although the difference in stone-free rates is not huge between these two treatments).²,³

RCTs comparing ESWL and ureteroscopy are generally lacking. The EAU/AUA Nephrolithiasis Guideline Panel 2007 meta-analysis suggests that:

Thus, there are no great differences in stone-free rates between ESWL and ureteroscopy (see Table 9.7). Precisely which technique one uses will depend to a considerable degree on local resources (e.g. ready access to ESWL) and local expertise at performing ureteroscopy, particularly for upper tract stones. Failed initial ESWL is associated with a low success rate for subsequent ESWL.⁴ Therefore, if no effect after one or two treatments, change tactics.

Open ureterolithotomy and laparoscopic ureterolithotomy (less invasive than open ureterolithotomy) are used in the rare cases (e.g. very impacted stones) where ESWL or ureteroscopy have been tried and failed or were not feasible.¹ Laparoscopic ureterolithotomy for large, impacted stones has a stone-free rate averaging almost 90%.

The standard advice, based on a number of RCTs, is that routine J stenting after an ‘uncomplicated’ ureteroscopy is unnecessary.⁵ ‘Uncomplicated ureteroscopy’ has not been precisely defined. Definitions include minimal or no ureteral trauma during the process of stone extraction, minimal or no ureteral dilatation required in order to allow ureteroscope access, and no or minimal residual stone burden.

Meta-analyses of post-ureteroscopy complications (emergency room visit, readmission to hospital, requirement for secondary procedures) showed no significant difference in outcome in those stented post-ureteroscopy compared with those not stented.⁶,⁷ Whether there are subgroups of patients who do benefit from stenting post-ureteroscopy remains to be determined.

It has been suggested that post-ureteroscopy stenting reduces ureteric stricture rates, but there is no convincing evidence to support this assertion.⁶,⁷

The recurrent nature of stone disease emphasizes the importance of prevention. Recurrence is more likely in those with an onset of stone disease at a young age, a family history for stones, those with an underlying metabolic predisposition (cystinuria, gout), and in those who have had an infection stone (especially in those with neuropathic bladders).

A series of landmark papers from Harvard Medical School¹ and other groups allows us to give rational advice on reducing the risk of future stone formation. The Harvard studies were carried out in those with no prior history of stone disease, but are likely to be relevant to those who have already formed a stone (which, of course, is the group most interested in how to avoid the unpleasantness of another stone). The Harvard studies stratified the risk of stone formation based on intake of calcium and other nutrients (Nurses Health Study, n = 81 000 women; equivalent male study, n = 45 000).

Low fluid intake may be the single most important risk factor for recurrent stone formation. High fluid intake is protective,² by reducing urinary saturation of calcium, oxalate, and urate. Time to recurrent stone formation is prolonged from 2 to 3y in previous stone formers randomized to high fluid vs low fluid intake (averaging 72.5 vs 1L/day) and over 5y, the risk of recurrent stones was 27% in low-volume controls compared with 12% in high-volume patients.²

Conventional teaching was that high calcium intake increases the risk of calcium oxalate stone disease. The Harvard Medical School studies have shown that low calcium intake is paradoxically associated with an increased risk of forming kidney stones in both men and women (relative risk of stone formation for the highest quintile of dietary calcium intake vs the lowest quintile = 0.65; 95% CI 0.5–0.83, i.e. high calcium intake was associated with a low risk of stone formation).

In the Harvard studies,^1,3 the relative risk of stone formation in women on supplemental calcium (most calcium supplements contain calcium carbonate) compared with those not on calcium was 1.2 (95% CI 1.02–1.4) and for men, it was 1.23 (95% CI 0.84–1.79). In 67% of women and 49% of men on supplements, the calcium was either not consumed with a meal or was consumed with a meal with low oxalate content. It is possible that consuming calcium supplements with a meal or with oxalate-containing foods could reduce this small risk of inducing kidney stones. A total of 650mg of calcium carbonate taken immediately after a meal is associated with a lower urinary oxalate and higher urinary citrate than when taken at bedtime. Urinary calcium excretion increased, but the net effect was a reduction in the activity product for calcium oxalate crystal formation.⁴ The bottom line seems to be ‘take your calcium supplement at mealtimes’.

In post-menopausal women, calcium citrate, 400 mg twice daily, increases urinary calcium and citrate excretion, reduces oxalate excretion, and does not change urine calcium oxalate saturation, which suggests calcium citrate neither increases nor decreases stone risk.⁵

Those few studies exploring the risk of calcium supplementation in those who have already formed a stone recruited so few subjects that few conclusions can be drawn. A reduction in urine saturation with calcium and oxalate was reported in 22 hyperoxaluric stone formers advised to consume calcium-containing foods or supplemental calcium citrate with meals (300–500mg of calcium), entirely in keeping with the protective effect of calcium noted in the Harvard studies (the risk of actual stone formation was not assessed).⁶ The critical factor may be taking the supplement at meal times.

Increased risk of stone formation (relative risk of stone formation shown in brackets for highest to lowest quintiles of intake of particular dietaryfactor):

High intake of animal proteins causes increased urinary excretion of calcium, reduced pH, high urinary uric acid, and reduced urinary citrate, all of which predispose to stone formation.⁷,⁸

Curhan’s studies from Harvard⁹ suggest small quantities of wine decrease the risk of stones.

Vegetable proteins contain less of the amino acids, phenylalanine, tyrosine, and tryptophan, that increase the endogenous production of oxalate. A vegetarian diet may protect against the risk of stone formation.¹⁰ A low animal protein, low sodium, and low oxalate diet with normal calcium intake (1200mg daily) is associated with a reduction in risk of stone formation of almost 50% over 5y when compared with a diet low in calcium (400mg daily) and oxalate⁷.

A small increase in urinary oxalate concentration increases calcium oxalate supersaturation much more than does an increase in urinary calcium concentration. Mild hyperoxaluria is one of the main factors leading to calcium stone formation.¹¹

Potassium citrate results in a substantial reduction in the risk of stone formation.¹²,¹³ Gastrointestinal side effects (nausea, vomiting, bloating, diarrhoea) are common. Calcium phosphate stones may form in the alkaline urine induced by citrate supplements (keep urine pH <6.5).

Reduce calcium stone disease by reducing urinary calcium excretion.¹⁴ Hypokalaemia, glucose intolerance, hyperuricaemia, and increased total cholesterol, LDL and triglycerides are potential side effects, the latter predisposing to cardiovascular disease.

Allopurinol 50–100mg daily reduces calcium oxalate stone recurrence in both urate stone formers and calcium oxalate stone formers.¹⁵

May be helpful in those with hyperoxaluria or excessive GI oxalate absorption (inflammatory bowel disease, small bowel resection).

Magnesium (an inhibitor of crystallization) and phosphate (which reduces GI calcium absorption) are probably not effective.

High fluid intake (aiming for >2.5L urine output daily); normal calcium intake; low sodium, oxalate, and protein; potassium citrate (e.g. lemon squash).

Struvite (i.e. they are infection stones) or uric acid (in non-infected urine).

Bladder calculi are predominantly a disease of men aged >50 and with BOO due to BPE. They also occur in the chronically catheterized patient (e.g. SCI patients), where the chance of developing a bladder stone is 25% over 5y (similar risk whether urethral or suprapubic location of the stone).¹

Bladder stones are still common in Thailand, Indonesia, North Africa, the Middle East, and Burma. In these endemic areas, they are usually composed of a combination of ammonium urate and calcium oxalate. A low phosphate diet in these areas (a diet of breast milk and polished rice or millet) results in high peaks of ammonia excretion in the urine.

May be symptomless (incidental finding on KUB X-ray or bladder USS or on cystoscopy)—the common presentation in spinal patients who have limited or no bladder sensation). In the neurologically intact patient—suprapubic or perineal pain, haematuria, urgency, and/or urge incontinence, recurrent UTI, LUTS (hesitancy, poor flow).

If you suspect a bladder stone, they will be visible on KUB X-ray or renal USS (Fig. 9.15).

Most stones are small enough to be removed cystoscopically (endoscopic cystolitholapaxy), using stone-fragmenting forceps for stones that can be engaged by the jaws of the forceps and EHL or pneumatic lithotripsy for those that cannot. Large stones (Fig. 9.15) can be removed by open surgery (open cystolitholapaxy).¹

While hypercalciuria and uric acid excretion increases in pregnancy (predisposing to stone formation), so too do urinary citrate and magnesium levels (protecting against stone formation). The ‘net’ effect—incidence of ureteric colic is the same as in non-pregnant women.¹ Ureteric stones occur in 1 in 1500–2500 pregnancies, mostly during second and third trimesters. They are associated with a significant risk of preterm labour² and the pain caused by ureteric stones can be difficult to distinguish from other causes.

Ureteric stone, placental abruption, appendicitis, pyelonephritis, and all the other (many) causes of flank pain in non-pregnant women.

Exposure of the fetus to ionizing radiation can cause fetal malformations, intrauterine growth retardation, malignancies in later life (leukaemia), and mutagenic effects (damage to genes, causing inherited disease in the offspring of the fetus). The fetus is most at risk during organogenesis (weeks 4–10 of gestation). Fetal radiation doses during various procedures are shown in Table 9.8. Radiation doses of <100mGy are reported as unlikely to have an adverse effect on the fetus.³ In USA, the National Council on Radiation Protection has stated that ‘fetal risk is considered to be negligible at <50mGy when compared to the other risks of pregnancy and the risk of malformations is significantly increased above control levels at doses >150mGy’.⁴ The American College of Obstetricians and Gynaecologists has stated that ‘X-ray exposure to <50mGy has not been associated with an increase in fetal anomalies or pregnancy loss’.⁵ However, every effort should be made to limit exposure of the fetus to radiation.

Limited usefulness (fetal skeleton and the enlarged uterus obscure ureteric stones; delayed excretion of contrast limits opacification of ureter; theoretical risk of fetal toxicity from the contrast material). Recommendations are for a limited IVU (e.g. control film followed by a 30min film) with fetal shielding.

Very accurate method for detecting ureteric stones, but most radiologists and urologists are unhappy to recommend this form of imaging in pregnant women due to increased fetal radiation exposure. Low and ultra-low dose CT protocols are being developed.

The American College of Obstetricians and Gynaecologists and the US National Council on Radiation Protection state that ‘although there is no evidence to suggest that the embryo is sensitive to magnetic and radio-frequency at the intensities encountered in MRI, it might be prudent to exclude pregnant women during the first trimester’.⁵,⁶ MRU can, therefore, potentially be used during the second and third trimesters, but not during the first trimester. Involves no ionizing radiation. Very accurate (100% sensitivity for detecting ureteric stones)⁷, but expensive and not readily available in most hospitals, particularly out of hours.⁸

Most (70–80%) will pass spontaneously.³

Depend on the stage of pregnancy and on local facilities and expertise:

Aim to minimize radiation exposure to the fetus and to minimize the risk of miscarriage and preterm labour. General anaesthesia can precipitate preterm labour and many urologists and obstetricians will err on the side of temporizing options such as nephrostomy tube drainage or JJ stent placement, rather than on operative treatment in the form of ureteroscopic stone removal. Avoid PCNL; ESWL is contraindicated.